Noel T. Keen--pioneer leader in molecular plant pathology.

Science.gov (United States)

Collmer, Alan; Gold, Scott

2007-01-01

Noel T. Keen (1940-2002) made pioneering contributions to molecular plant pathology during a period when the study of disease mechanisms was transformed by the new tools of molecular genetics. His primary contributions involved race-specific elicitors of plant defenses and bacterial pectic enzymes. In collaboration with Brian J. Staskawicz and Frances Jurnak, respectively, Noel cloned the first avirulence gene and determined that pectate lyase C possessed a novel structural motif, known as the parallel beta-helix. Noel received his B.S. and M.S. from Iowa State University in Ames and his Ph.D. from the Department of Plant Pathology at the University of Wisconsin in Madison in 1968. He joined the faculty of the Department of Plant Pathology at the University of California at Riverside the same year and remained there his entire career. He served as Chair of the department from 1983 to 1989 and in 1997 assumed the William and Sue Johnson Endowed Chair in Molecular Plant Pathology. He became a Fellow of the American Phytopathological Society in 1991, a Fellow of the American Association for the Advancement of Science in 1996, a Fellow of the American Academy of Microbiology in 1997, and a member of the National Academy of Sciences in 1997. He was serving as President of the American Phytopathological Society (2001-2002) at the time of his death.

Guidance for laboratories performing molecular pathology for cancer patients

Science.gov (United States)

Cree, Ian A; Deans, Zandra; Ligtenberg, Marjolijn J L; Normanno, Nicola; Edsjö, Anders; Rouleau, Etienne; Solé, Francesc; Thunnissen, Erik; Timens, Wim; Schuuring, Ed; Dequeker, Elisabeth; Murray, Samuel; Dietel, Manfred; Groenen, Patricia; Van Krieken, J Han

2014-01-01

Molecular testing is becoming an important part of the diagnosis of any patient with cancer. The challenge to laboratories is to meet this need, using reliable methods and processes to ensure that patients receive a timely and accurate report on which their treatment will be based. The aim of this paper is to provide minimum requirements for the management of molecular pathology laboratories. This general guidance should be augmented by the specific guidance available for different tumour types and tests. Preanalytical considerations are important, and careful consideration of the way in which specimens are obtained and reach the laboratory is necessary. Sample receipt and handling follow standard operating procedures, but some alterations may be necessary if molecular testing is to be performed, for instance to control tissue fixation. DNA and RNA extraction can be standardised and should be checked for quality and quantity of output on a regular basis. The choice of analytical method(s) depends on clinical requirements, desired turnaround time, and expertise available. Internal quality control, regular internal audit of the whole testing process, laboratory accreditation, and continual participation in external quality assessment schemes are prerequisites for delivery of a reliable service. A molecular pathology report should accurately convey the information the clinician needs to treat the patient with sufficient information to allow for correct interpretation of the result. Molecular pathology is developing rapidly, and further detailed evidence-based recommendations are required for many of the topics covered here. PMID:25012948

The Top 10 fungal pathogens in molecular plant pathology.

Science.gov (United States)

Dean, Ralph; Van Kan, Jan A L; Pretorius, Zacharias A; Hammond-Kosack, Kim E; Di Pietro, Antonio; Spanu, Pietro D; Rudd, Jason J; Dickman, Marty; Kahmann, Regine; Ellis, Jeff; Foster, Gary D

2012-05-01

The aim of this review was to survey all fungal pathologists with an association with the journal Molecular Plant Pathology and ask them to nominate which fungal pathogens they would place in a 'Top 10' based on scientific/economic importance. The survey generated 495 votes from the international community, and resulted in the generation of a Top 10 fungal plant pathogen list for Molecular Plant Pathology. The Top 10 list includes, in rank order, (1) Magnaporthe oryzae; (2) Botrytis cinerea; (3) Puccinia spp.; (4) Fusarium graminearum; (5) Fusarium oxysporum; (6) Blumeria graminis; (7) Mycosphaerella graminicola; (8) Colletotrichum spp.; (9) Ustilago maydis; (10) Melampsora lini, with honourable mentions for fungi just missing out on the Top 10, including Phakopsora pachyrhizi and Rhizoctonia solani. This article presents a short resumé of each fungus in the Top 10 list and its importance, with the intent of initiating discussion and debate amongst the plant mycology community, as well as laying down a bench-mark. It will be interesting to see in future years how perceptions change and what fungi will comprise any future Top 10. © 2012 THE AUTHORS. MOLECULAR PLANT PATHOLOGY © 2012 BSPP AND BLACKWELL PUBLISHING LTD.

Novel approach to improve molecular imaging research: Correlation between macroscopic and molecular pathological findings in patients

Energy Technology Data Exchange (ETDEWEB)

Boehm, Ingrid, E-mail: i.boehm@uni-bonn.de [Department of Diagnostic Radiology, ZARF Project, Center for Molecular Imaging Research MBMB, Philipps University of Marburg, Baldingerstrasse, 35039 Marburg (Germany)

2011-09-15

Purpose: Currently, clinical research approaches are sparse in molecular imaging studies. Moreover, possible links between imaging features and pathological laboratory parameters are unknown, so far. Therefore, the goal was to find a possible relationship between imaging features and peripheral blood cell apoptosis, and thereby to present a novel way to complement molecular imaging research. Materials and methods: The investigation has been done in systemic lupus erythematosus (SLE), a prototype of an autoimmune disease characterized by multiorgan involvement, autoantibody production, and disturbed apoptosis. Retrospectively, radiological findings have been compared to both autoantibody findings and percentage apoptotic blood cells. Results: Two SLE groups could be identified: patients with normal (annexin V binding < 20%), and with increased apoptosis (annexin V binding > 20%) of peripheral blood cells. The frequency of radiological examinations in SLE patients significantly correlated with an increased percentage of apoptotic cells (p < 0.005). In patients with characteristic imaging findings (e.g. lymph node swelling, pleural effusion) an elevated percentage of apoptotic cells was present. In contrast SLE-patients with normal imaging findings or uncharacteristic results of minimal severity had normal percentages of apoptotic blood cells. Conclusion: This correlation between radiographic findings and percentage of apoptotic blood cells provides (1) further insight into pathological mechanisms of SLE, (2) will offer the possibility to introduce apoptotic biomarkers as molecular probes for clinical molecular imaging approaches in future to early diagnose organ complaints in patients with SLE, and (3) is a plea to complement molecular imaging research by this clinical approach.

The long Tramp from Cellular Pathology to Molecular Pathology

Directory of Open Access Journals (Sweden)

Hans Guski

2017-05-01

Derivatives: The observation of principal identity of biological meaningful elements can be agglutinated to a ‘general theory of live’ and its manifestation. All of the investigated elements posses the same regularities, which are altered, destroyed or newly built by external influences such as disease, physical and psychological forces. Not all magnification levels that display with these elements are of the same significance. Already Virchow suggested that ‘smaller elements (molecules might be responsible for changes that are visible ‘in larger elements’ (at cellular level.  The reflection on these ideas can be associated with the implementation of molecular techniques which has been developed in the 20th century and are still ongoing today. Perspectives: Thus, cellular and molecular pathology can be integrated under one umbrella. This umbrella will lead to newly man-formed structures, such as artificial DNA and gene components or functional chip implantations.

[Diagnostic molecular pathology of lymphatic and myeloid neoplasms].

Science.gov (United States)

Klapper, W; Kreipe, H

2015-03-01

Molecular pathology has been an integral part of the diagnostics of tumors of the hematopoietic system substantially longer than for solid neoplasms. In contrast to solid tumors, the primary objective of molecular pathology in hematopoietic neoplasms is not the prediction of drug efficacy but the diagnosis itself by excluding reactive proliferation and by using molecular features for tumor classification. In the case of malignant lymphomas, the most commonly applied molecular tests are those for gene rearrangements for immunoglobulin heavy chains and T-cell receptors. However, this article puts the focus on new and diagnostically relevant assays in hematopathology. Among these are mutations of MYD88 codon 265 in lymphoplasmacytic lymphomas, B-raf V600E in hairy cell leukemia and Stat3 exon 21 in indolent T-cell lymphomas. In myeloproliferative neoplasms, MPL W515, calreticulin exon 9 and the BCR-ABL and JAK2 V617F junctions are the most frequently analyzed differentiation series. In myelodysplastic and myeloproliferative neoplasms, SRSF2, SETBP1 and CSF3R mutations provide important differential diagnostic information. Genes mutated in myelodysplastic syndromes (MDS) are particularly diverse but their analysis significantly improves the differential diagnostics between reactive conditions and MDS. The most frequent changes in MDS include mutations of TET2 and various genes encoding splicing factors.

Top 10 plant viruses in molecular plant pathology.

Science.gov (United States)

Scholthof, Karen-Beth G; Adkins, Scott; Czosnek, Henryk; Palukaitis, Peter; Jacquot, Emmanuel; Hohn, Thomas; Hohn, Barbara; Saunders, Keith; Candresse, Thierry; Ahlquist, Paul; Hemenway, Cynthia; Foster, Gary D

2011-12-01

Many scientists, if not all, feel that their particular plant virus should appear in any list of the most important plant viruses. However, to our knowledge, no such list exists. The aim of this review was to survey all plant virologists with an association with Molecular Plant Pathology and ask them to nominate which plant viruses they would place in a 'Top 10' based on scientific/economic importance. The survey generated more than 250 votes from the international community, and allowed the generation of a Top 10 plant virus list for Molecular Plant Pathology. The Top 10 list includes, in rank order, (1) Tobacco mosaic virus, (2) Tomato spotted wilt virus, (3) Tomato yellow leaf curl virus, (4) Cucumber mosaic virus, (5) Potato virus Y, (6) Cauliflower mosaic virus, (7) African cassava mosaic virus, (8) Plum pox virus, (9) Brome mosaic virus and (10) Potato virus X, with honourable mentions for viruses just missing out on the Top 10, including Citrus tristeza virus, Barley yellow dwarf virus, Potato leafroll virus and Tomato bushy stunt virus. This review article presents a short review on each virus of the Top 10 list and its importance, with the intent of initiating discussion and debate amongst the plant virology community, as well as laying down a benchmark, as it will be interesting to see in future years how perceptions change and which viruses enter and leave the Top 10. © 2011 The Authors. Molecular Plant Pathology © 2011 BSPP and Blackwell Publishing Ltd.

Pitfalls in lung cancer molecular pathology: how to limit them in routine practice?

Science.gov (United States)

Ilie, M; Hofman, P

2012-01-01

New treatment options in advanced non-small cell lung carcinoma (NSCLC) targeting activating epidermal growth factor receptor (EGFR) gene mutations and other genetic alterations demonstrated the clinical significance of the molecular features of specific subsets of tumors. Therefore, the development of personalized medicine has stimulated the routine integration into pathology departments of somatic mutation testing. However, clinical mutation testing must be optimized and standardized with regard to histological profile, type of samples, pre-analytical steps, methodology and result reporting. Routine molecular testing in NSCLC is currently moving beyond EGFR mutational analysis. Recent progress of targeted therapies will require molecular testing for a wide panel of mutations for a personalized molecular diagnosis. As a consequence, efficient testing of multiple molecular abnormalities is an urgent requirement in thoracic oncology. Moreover, increasingly limited tumor sample becomes a major challenge for molecular pathology. Continuous efforts should be made for safe, effective and specific molecular analyses. This must be based on close collaboration between the departments involved in the management of lung cancer. In this review we explored the practical issues and pitfalls surrounding the routine implementation of molecular testing in NSCLC in a pathology laboratory.

Next generation diagnostic molecular pathology: critical appraisal of quality assurance in Europe.

Science.gov (United States)

Dubbink, Hendrikus J; Deans, Zandra C; Tops, Bastiaan B J; van Kemenade, Folkert J; Koljenović, S; van Krieken, Han J M; Blokx, Willeke A M; Dinjens, Winand N M; Groenen, Patricia J T A

2014-06-01

Tumor evaluation in pathology is more and more based on a combination of traditional histopathology and molecular analysis. Due to the rapid development of new cancer treatments that specifically target aberrant proteins present in tumor cells, treatment decisions are increasingly based on the molecular features of the tumor. Not only the number of patients eligible for targeted precision medicine, but also the number of molecular targets per patient and tumor type is rising. Diagnostic molecular pathology, the discipline that determines the molecular aberrations present in tumors for diagnostic, prognostic or predictive purposes, is faced with true challenges. The laboratories have to meet the need of comprehensive molecular testing using only limited amount of tumor tissue, mostly fixed in formalin and embedded in paraffin (FFPE), in short turnaround time. Choices must be made for analytical methods that provide accurate, reliable and cost-effective results. Validation of the test procedures and results is essential. In addition, participation and good performance in internal (IQA) and external quality assurance (EQA) schemes is mandatory. In this review, we critically evaluate the validation procedure for comprehensive molecular tests as well as the organization of quality assurance and assessment of competence of diagnostic molecular pathology laboratories within Europe. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Integration of Molecular Pathology, Epidemiology, and Social Science for Global Precision Medicine

Science.gov (United States)

Nishi, Akihiro; Milner, Danny A; Giovannucci, Edward L.; Nishihara, Reiko; Tan, Andy S.; Kawachi, Ichiro; Ogino, Shuji

2015-01-01

Summary The precision medicine concept and the unique disease principle imply that each patient has unique pathogenic processes resulting from heterogeneous cellular genetic and epigenetic alterations, and interactions between cells (including immune cells) and exposures, including dietary, environmental, microbial, and lifestyle factors. As a core method field in population health science and medicine, epidemiology is a growing scientific discipline that can analyze disease risk factors, and develop statistical methodologies to maximize utilization of big data on populations and disease pathology. The evolving transdisciplinary field of molecular pathological epidemiology (MPE) can advance biomedical and health research by linking exposures to molecular pathologic signatures, enhancing causal inference, and identifying potential biomarkers for clinical impact. The MPE approach can be applied to any diseases, although it has been most commonly used in neoplastic diseases (including breast, lung and colorectal cancers) because of availability of various molecular diagnostic tests. However, use of state-of-the-art genomic, epigenomic and other omic technologies and expensive drugs in modern healthcare systems increases racial, ethnic and socioeconomic disparities. To address this, we propose to integrate molecular pathology, epidemiology, and social science. Social epidemiology integrates the latter two fields. The integrative social MPE model can embrace sociology, economics and precision medicine, address global health disparities and inequalities, and elucidate biological effects of social environments, behaviors, and networks. We foresee advancements of molecular medicine, including molecular diagnostics, biomedical imaging, and targeted therapeutics, which should benefit individuals in a global population, by means of an interdisciplinary approach of integrative MPE and social health science. PMID:26636627

Integration of molecular pathology, epidemiology and social science for global precision medicine.

Science.gov (United States)

Nishi, Akihiro; Milner, Danny A; Giovannucci, Edward L; Nishihara, Reiko; Tan, Andy S; Kawachi, Ichiro; Ogino, Shuji

2016-01-01

The precision medicine concept and the unique disease principle imply that each patient has unique pathogenic processes resulting from heterogeneous cellular genetic and epigenetic alterations and interactions between cells (including immune cells) and exposures, including dietary, environmental, microbial and lifestyle factors. As a core method field in population health science and medicine, epidemiology is a growing scientific discipline that can analyze disease risk factors and develop statistical methodologies to maximize utilization of big data on populations and disease pathology. The evolving transdisciplinary field of molecular pathological epidemiology (MPE) can advance biomedical and health research by linking exposures to molecular pathologic signatures, enhancing causal inference and identifying potential biomarkers for clinical impact. The MPE approach can be applied to any diseases, although it has been most commonly used in neoplastic diseases (including breast, lung and colorectal cancers) because of availability of various molecular diagnostic tests. However, use of state-of-the-art genomic, epigenomic and other omic technologies and expensive drugs in modern healthcare systems increases racial, ethnic and socioeconomic disparities. To address this, we propose to integrate molecular pathology, epidemiology and social science. Social epidemiology integrates the latter two fields. The integrative social MPE model can embrace sociology, economics and precision medicine, address global health disparities and inequalities, and elucidate biological effects of social environments, behaviors and networks. We foresee advancements of molecular medicine, including molecular diagnostics, biomedical imaging and targeted therapeutics, which should benefit individuals in a global population, by means of an interdisciplinary approach of integrative MPE and social health science.

New insights into molecular diagnostic pathology of primary liver cancer: Advances and challenges.

Science.gov (United States)

Cong, Wen-Ming; Wu, Meng-Chao

2015-11-01

Primary liver cancer (PLC) is one of the most common malignancies worldwide with increasing incidence and accounts for the third leading cause of cancer-related mortality. Traditional morphopathology primarily emphasizes qualitative diagnosis of PLC, which is not sufficient to resolve the major concern of increasing the long-term treatment efficacy of PLC in clinical management for the modern era. Since the beginning of the 21st century, molecular pathology has played an active role in the investigation of the evaluation of the metastatic potential of PLC, detection of drug targets, prediction of recurrence risks, analysis of clonal origins, evaluation of the malignancy trend of precancerous lesions, and determination of clinical prognosis. As a result, many new progresses have been obtained, and new strategies of molecular-pathological diagnosis have been formed. Moreover, the new types of pathobiological diagnosis indicator systems for PLC have been preliminarily established. These achievements provide valuable molecular pathology-based guide for clinical formulation of individualized therapy programs for PLC. This review article briefly summarizes some relevant progresses of molecular-pathological diagnosis of PLC from the perspective of clinical translational application other than basic experimental studies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The Molecular Pathology of Cushing Disease: Are We Nearly There?

Science.gov (United States)

Grossman, Ashley B

2017-02-01

The molecular pathology of corticotroph tumors is surveyed in the light of recent work showing the induction of aggressive corticotroph tumors by the transgenic expression of epidermal growth factor receptors.

Evaluation of the pathological response and prognosis following neoadjuvant chemotherapy in molecular subtypes of breast cancer

Directory of Open Access Journals (Sweden)

Zhao Y

2015-06-01

Full Text Available Yue Zhao,1 Xiaoqiu Dong,2 Rongguo Li,1 Xiao Ma,1 Jian Song,1 Yingjie Li,3 Dongwei Zhang1 1Department of General Surgery, Second Affiliated Hospital of Harbin Medical University, 2Department of Ultrasonography, Fourth Affiliated Hospital of Harbin Medical University, 3Department of Pathology, Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China Background: The pathological complete response of neoadjuvant chemotherapy for breast cancer correlates with the prognosis for survival. Tumors may have different prognoses according to their molecular subtypes. This study was performed to evaluate the relevance of the pathological response and prognosis following neoadjuvant chemotherapy in the molecular subtypes of breast cancer.Methods: A consecutive series of 88 patients with operable breast cancer treated with neoadjuvant chemotherapy was analyzed. Patients were classified into four molecular subtypes based on the immunohistochemistry profile of the estrogen receptor, progesterone receptor, HER2, and Ki-67. The histological response was assessed according to Miller-Payne grading (MPG and Residual Disease in Breast and Nodes (RDBN.Results: Ten patients (11.4% achieved a pathological complete response, assessed according to RDBN. The pathological complete response rate was 13.6% according to MPG. Patients with the triple-negative subtype were more likely to achieve a pathological complete response than those with luminal A breast cancer (P=0.03. MPG and RDBN are independent predictors of distant disease-free survival and local recurrence-free survival, but do not predict overall survival. Ki-67, size of invasive carcinoma, lymph nodes, molecular subtypes, MPG, and RDBN are important predictors of distant disease-free survival, local recurrence-free survival, and overall survival.Conclusion: MPG and RDBN were similarly related to the patient’s prognosis. MPG was more suitable for evaluation of distant disease

Continuing role of a frozen-tissue bank in molecular pathology.

Science.gov (United States)

Naber, S P

1996-12-01

The growth of molecular diagnostics and its application in various clinical laboratories have made it necessary to standardize the methods used to freeze and store tissues used in molecular testing. It may now be advantageous to preserve fresh tissues and other specimen types in a central frozen-tissue bank so that sample preparation and storage conditions are appropriate for molecular applications and so that the specimen inventory can be efficiently managed. The pathology laboratory is a logical site for the facility because the professional and technical expertise available is focused on the complex scientific and regulatory aspects of laboratory medicine. Organizationally, the tissue-bank program should be overseen by a surgical pathologist to integrate it into routine surgical pathology activities. A member of the laboratory technical staff can serve as the tissue-bank coordinator with responsibility for systematic storage and retrieval of specimens and routine maintenance of equipment and supplies. To facilitate the tissue-freezing procedure and efficient storage of multiple types of specimens, 2.0 ml cryogenic vials are used as the uniform storage container. All specimens are stored at -140 to -150 degrees C in the vapor phase of liquid nitrogen. The specimen inventory data are maintained with a computerized program specifically designed to manage complex specimen storage. A frozen-tissue bank is easily implemented in a pathology laboratory and is a valuable institutional asset for diagnostic and research purposes.

Molecular Pathology of Human Prion Diseases

Directory of Open Access Journals (Sweden)

2009-03-01

Full Text Available Prion diseases are fatal neurodegenerative conditions in humans and animals. In this review, we summarize the molecular background of phenotypic variability, relation of prion protein (PrP to other proteins associated with neurodegenerative diseases, and pathogenesis of neuronal vulnerability. PrP exists in different forms that may be present in both diseased and non-diseased brain, however, abundant disease-associated PrP together with tissue pathology characterizes prion diseases and associates with transmissibility. Prion diseases have different etiological background with distinct pathogenesis and phenotype. Mutations of the prion protein gene are associated with genetic forms. The codon 129 polymorphism in combination with the Western blot pattern of PrP after proteinase K digestion serves as a basis for molecular subtyping of sporadic Creutzfeldt-Jakob disease. Tissue damage may result from several parallel, interacting or subsequent pathways that involve cellular systems associated with synapses, protein processing, oxidative stress, autophagy, and apoptosis.

The Top 10 fungal pathogens in molecular plant pathology

NARCIS (Netherlands)

Dean, R.; Kan, van J.A.L.; Pretorius, Z.A.; Hammond-Kosack, K.E.; Pietro, Di A.; Spanu, P.D.; Rudd, J.J.; Dickman, M.; Kahmann, R.; Ellis, J.; Foster, G.D.

2012-01-01

The aim of this review was to survey all fungal pathologists with an association with the journal Molecular Plant Pathology and ask them to nominate which fungal pathogens they would place in a ‘Top 10’ based on scientific/economic importance. The survey generated 495 votes from the international

Molecular Pathology: A Requirement for Precision Medicine in Cancer.

Science.gov (United States)

Dietel, Manfred

2016-01-01

The increasing importance of targeting drugs and check-point inhibitors in the treatment of several tumor entities (breast, colon, lung, malignant melanoma, lymphoma, etc.) and the necessity of a companion diagnostic (HER2, (pan)RAS, EGFR, ALK, BRAF, ROS1, MET, PD-L1, etc.) is leading to new challenges for surgical pathology. Since almost all the biomarkers to be specifically detected are tissue based, a precise and reliable diagnostic is absolutely crucial. To meet this challenge surgical pathology has adapted a number of molecular methods (semi-quantitative immunohistochemistry, fluorescence in situ hybridization, PCR and its multiple variants, (pyro/Sanger) sequencing, next generation sequencing (amplicon, whole exome, whole genome), DNA arrays, methylation analyses, etc.) to be applicable for formalin-fixed paraffin-embedded tissue. Reading a patient's tissue as 'deeply' as possible and obtaining information on the morphological, genetic, proteomic and epigenetic background are the tasks of pathologists and molecular biologists and provide the clinicians with information relevant for precision medicine. Intensified cooperation between clinicians and pathologists will provide the basis of improved clinical drug selection and guide development of new cancer gene therapies and molecularly targeted drugs by research units and the pharmaceutical industry. © 2016 S. Karger GmbH, Freiburg.

Molecular pathology and prostate cancer therapeutics: from biology to bedside.

Science.gov (United States)

Rodrigues, Daniel Nava; Butler, Lisa M; Estelles, David Lorente; de Bono, Johann S

2014-01-01

Prostate cancer (PCa) is the second most commonly diagnosed malignancy in men and has an extremely heterogeneous clinical behaviour. The vast majority of PCas are hormonally driven diseases in which androgen signalling plays a central role. The realization that castration-resistant prostate cancer (CRPC) continues to rely on androgen signalling prompted the development of new, effective androgen blocking agents. As the understanding of the molecular biology of PCas evolves, it is hoped that stratification of prostate tumours into distinct molecular entities, each with its own set of vulnerabilities, will be a feasible goal. Around half of PCas harbour rearrangements involving a member of the ETS transcription factor family. Tumours without this rearrangement include SPOP mutant as well as SPINK1-over-expressing subtypes. As the number of targeted therapy agents increases, it is crucial to determine which patients will benefit from these interventions and molecular pathology will be key in this respect. In addition to directly targeting cells, therapies that modify the tumour microenvironment have also been successful in prolonging the lives of PCa patients. Understanding the molecular aspects of PCa therapeutics will allow pathologists to provide core recommendations for patient management. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Opportunities and challenges associated with clinical diagnostic genome sequencing: a report of the Association for Molecular Pathology.

Science.gov (United States)

Schrijver, Iris; Aziz, Nazneen; Farkas, Daniel H; Furtado, Manohar; Gonzalez, Andrea Ferreira; Greiner, Timothy C; Grody, Wayne W; Hambuch, Tina; Kalman, Lisa; Kant, Jeffrey A; Klein, Roger D; Leonard, Debra G B; Lubin, Ira M; Mao, Rong; Nagan, Narasimhan; Pratt, Victoria M; Sobel, Mark E; Voelkerding, Karl V; Gibson, Jane S

2012-11-01

This report of the Whole Genome Analysis group of the Association for Molecular Pathology illuminates the opportunities and challenges associated with clinical diagnostic genome sequencing. With the reality of clinical application of next-generation sequencing, technical aspects of molecular testing can be accomplished at greater speed and with higher volume, while much information is obtained. Although this testing is a next logical step for molecular pathology laboratories, the potential impact on the diagnostic process and clinical correlations is extraordinary and clinical interpretation will be challenging. We review the rapidly evolving technologies; provide application examples; discuss aspects of clinical utility, ethics, and consent; and address the analytic, postanalytic, and professional implications. Copyright © 2012 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Pathology interface for the molecular analysis of tissue by mass spectrometry

Directory of Open Access Journals (Sweden)

Jeremy L Norris

2016-01-01

Full Text Available Background: Imaging mass spectrometry (IMS generates molecular images directly from tissue sections to provide better diagnostic insights and expand the capabilities of clinical anatomic pathology. Although IMS technology has matured over recent years, the link between microscopy imaging currently used by pathologists and MS-based molecular imaging has not been established. Methods: We adapted the Vanderbilt University Tissue Core workflow for IMS into a web-based system that facilitates remote collaboration. The platform was designed to perform within acceptable web response times for viewing, annotating, and processing high resolution microscopy images. Results: We describe a microscopy-driven approach to tissue analysis by IMS. Conclusion: The Pathology Interface for Mass Spectrometry is designed to provide clinical access to IMS technology and deliver enhanced diagnostic value.

Molecular pathology of prostate cancer.

Science.gov (United States)

Cazares, L H; Drake, R R; Esquela-Kirscher, A; Lance, R S; Semmes, O J; Troyer, D A

2010-01-01

This chapter includes discussion of the molecular pathology of tissue, blood, urine, and expressed prostatic secretions. Because we are unable to reliably image the disease in vivo, a 12 core method that oversamples the peripheral zone is widely used. This generates large numbers of cores that need to be carefully processed and sampled. In spite of the large number of tissue cores, the amount of tumor available for study is often quite limited. This is a particular challenge for research, as new biomarker assays will need to preserve tissue architecture intact for histopathology. Methods of processing and reporting pathology are discussed. With the exception of ductal variants, recognized subtypes of prostate cancer are largely confined to research applications, and most prostate cancers are acinar. Biomarker discovery in urine and expressed prostatic secretions would be useful since these are readily obtained and are proximate fluids. The well-known challenges of biomarker discovery in blood and urine are referenced and discussed. Mediators of carcinogenesis can serve as biomarkers as exemplified by mutations in PTEN and TMPRSS2:ERG fusion. The use of proteomics in biomarker discovery with an emphasis on imaging mass spectroscopy of tissues is discussed. Small RNAs are of great interest, however, their usefulness as biomarkers in clinical decision making remains the subject of ongoing research. The chapter concludes with an overview of blood biomarkers such as circulating nucleic acids and tumor cells and bound/free isoforms of prostate specific antigen (PSA).

The value of cell-free DNA for molecular pathology.

Science.gov (United States)

Stewart, Caitlin M; Kothari, Prachi D; Mouliere, Florent; Mair, Richard; Somnay, Saira; Benayed, Ryma; Zehir, Ahmet; Weigelt, Britta; Dawson, Sarah-Jane; Arcila, Maria E; Berger, Michael F; Tsui, Dana Wy

2018-04-01

Over the past decade, advances in molecular biology and genomics techniques have revolutionized the diagnosis and treatment of cancer. The technological advances in tissue profiling have also been applied to the study of cell-free nucleic acids, an area of increasing interest for molecular pathology. Cell-free nucleic acids are released from tumour cells into the surrounding body fluids and can be assayed non-invasively. The repertoire of genomic alterations in circulating tumour DNA (ctDNA) is reflective of both primary tumours and distant metastatic sites, and ctDNA can be sampled multiple times, thereby overcoming the limitations of the analysis of single biopsies. Furthermore, ctDNA can be sampled regularly to monitor response to treatment, to define the evolution of the tumour genome, and to assess the acquisition of resistance and minimal residual disease. Recently, clinical ctDNA assays have been approved for guidance of therapy, which is an exciting first step in translating cell-free nucleic acid research tests into clinical use for oncology. In this review, we discuss the advantages of cell-free nucleic acids as analytes in different body fluids, including blood plasma, urine, and cerebrospinal fluid, and their clinical applications in solid tumours and haematological malignancies. We will also discuss practical considerations for clinical deployment, such as preanalytical factors and regulatory requirements. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Molecular pathological epidemiology of epigenetics: emerging integrative science to analyze environment, host, and disease.

Science.gov (United States)

Ogino, Shuji; Lochhead, Paul; Chan, Andrew T; Nishihara, Reiko; Cho, Eunyoung; Wolpin, Brian M; Meyerhardt, Jeffrey A; Meissner, Alexander; Schernhammer, Eva S; Fuchs, Charles S; Giovannucci, Edward

2013-04-01

Epigenetics acts as an interface between environmental/exogenous factors, cellular responses, and pathological processes. Aberrant epigenetic signatures are a hallmark of complex multifactorial diseases (including neoplasms and malignancies such as leukemias, lymphomas, sarcomas, and breast, lung, prostate, liver, and colorectal cancers). Epigenetic signatures (DNA methylation, mRNA and microRNA expression, etc) may serve as biomarkers for risk stratification, early detection, and disease classification, as well as targets for therapy and chemoprevention. In particular, DNA methylation assays are widely applied to formalin-fixed, paraffin-embedded archival tissue specimens as clinical pathology tests. To better understand the interplay between etiological factors, cellular molecular characteristics, and disease evolution, the field of 'molecular pathological epidemiology (MPE)' has emerged as an interdisciplinary integration of 'molecular pathology' and 'epidemiology'. In contrast to traditional epidemiological research including genome-wide association studies (GWAS), MPE is founded on the unique disease principle, that is, each disease process results from unique profiles of exposomes, epigenomes, transcriptomes, proteomes, metabolomes, microbiomes, and interactomes in relation to the macroenvironment and tissue microenvironment. MPE may represent a logical evolution of GWAS, termed 'GWAS-MPE approach'. Although epigenome-wide association study attracts increasing attention, currently, it has a fundamental problem in that each cell within one individual has a unique, time-varying epigenome. Having a similar conceptual framework to systems biology, the holistic MPE approach enables us to link potential etiological factors to specific molecular pathology, and gain novel pathogenic insights on causality. The widespread application of epigenome (eg, methylome) analyses will enhance our understanding of disease heterogeneity, epigenotypes (CpG island methylator

Using Genetic Buffering Relationships Identified in Fission Yeast To Elucidate the Molecular Pathology of Tuberous Sclerosis

Science.gov (United States)

2016-07-01

tsc1 and tsc2 loss of function mutations in Schizosaccharomyces pombe. Northeast Regional Yeast Meeting, June 16-17, University at Buffalo, The State...AWARD NUMBER: W81XWH-14-1-0169 TITLE: Using Genetic Buffering Relationships Identified in Fission Yeast To Elucidate the Molecular Pathology of...SUBTITLE Using Genetic Buffering Relationships Identified in Fission 5a. CONTRACT NUMBER W81XWH-14-1-0169 Yeast to Elucidate the Molecular Pathology

Basic pathologies of neurodegenerative dementias and their relevance for state-of-the-art molecular imaging studies

International Nuclear Information System (INIS)

Drzezga, Alexander

2008-01-01

Rising life-expectancy in the modern society has resulted in a rapidly growing prevalence of dementia, particularly of Alzheimer's disease (AD). Dementia turns into one of the most common age-related disorders with deleterious consequences for the concerned patients and their relatives, as well as worrying effects on the socio-economic systems. These facts justify strengthened scientific efforts to identify the pathologic origin of dementing disorders, to improve diagnosis, and to interfere therapeutically with the disease progression. In the recent years, remarkable progress has been made concerning the identification of molecular mechanisms underlying the pathology of neurodegenerative disorders. Growing evidence indicates that a common basis of many neurodegenerative dementias can be found in increased production, misfolding and pathological aggregation of proteins, such as ss-amyloid, tau protein, a-synuclein, or the recently described ubiquitinated TDP-43. This progressive insight in pathological processes is paralleled by the development of new therapeutic approaches. However, the exact contribution or mechanism of different pathologies with regard to the development of disease is not yet sufficiently clear. Considerable overlap of pathologies has been documented in different types of clinically defined dementias post mortem, and it has been difficult to correlate post mortem histopathology data with disease-expression during life. Molecular imaging procedures may play a valuable role to circumvent this limitation. In general, methods of molecular imaging have recently experienced an impressive advance, with numerous new and improved technologies emerging. These exciting tools may play a key role in the future regarding the evaluation of pathomechanisms, preclinical evaluation of new diagnostic procedures in animal models, selection of patients for clinical trials, and therapy monitoring. In this overview, molecular key pathologies, which are currently

Molecular pathology of adamantinomatous craniopharyngioma: review and opportunities for practice.

Science.gov (United States)

Apps, John Richard; Martinez-Barbera, Juan Pedro

2016-12-01

Since the first identification of CTNNB1 mutations in adamantinomatous craniopharyngioma (ACP), much has been learned about the molecular pathways and processes that are disrupted in ACP pathogenesis. To date this understanding has not translated into tangible patient benefit. The recent development of novel techniques and a range of preclinical models now provides an opportunity to begin to support treatment decisions and develop new therapeutics based on molecular pathology. In this review the authors summarize many of the key findings and pathways implicated in ACP pathogenesis and discuss the challenges that need to be tackled to translate these basic science findings for the benefit of patients.

Top 10 plant pathogenic bacteria in molecular plant pathology.

Science.gov (United States)

Mansfield, John; Genin, Stephane; Magori, Shimpei; Citovsky, Vitaly; Sriariyanum, Malinee; Ronald, Pamela; Dow, Max; Verdier, Valérie; Beer, Steven V; Machado, Marcos A; Toth, Ian; Salmond, George; Foster, Gary D

2012-08-01

Many plant bacteriologists, if not all, feel that their particular microbe should appear in any list of the most important bacterial plant pathogens. However, to our knowledge, no such list exists. The aim of this review was to survey all bacterial pathologists with an association with the journal Molecular Plant Pathology and ask them to nominate the bacterial pathogens they would place in a 'Top 10' based on scientific/economic importance. The survey generated 458 votes from the international community, and allowed the construction of a Top 10 bacterial plant pathogen list. The list includes, in rank order: (1) Pseudomonas syringae pathovars; (2) Ralstonia solanacearum; (3) Agrobacterium tumefaciens; (4) Xanthomonas oryzae pv. oryzae; (5) Xanthomonas campestris pathovars; (6) Xanthomonas axonopodis pathovars; (7) Erwinia amylovora; (8) Xylella fastidiosa; (9) Dickeya (dadantii and solani); (10) Pectobacterium carotovorum (and Pectobacterium atrosepticum). Bacteria garnering honourable mentions for just missing out on the Top 10 include Clavibacter michiganensis (michiganensis and sepedonicus), Pseudomonas savastanoi and Candidatus Liberibacter asiaticus. This review article presents a short section on each bacterium in the Top 10 list and its importance, with the intention of initiating discussion and debate amongst the plant bacteriology community, as well as laying down a benchmark. It will be interesting to see, in future years, how perceptions change and which bacterial pathogens enter and leave the Top 10. © 2012 The Authors. Molecular Plant Pathology © 2012 BSPP and Blackwell Publishing Ltd.

Integration of pharmacology, molecular pathology, and population data science to support precision gastrointestinal oncology.

Science.gov (United States)

Ogino, Shuji; Jhun, Iny; Mata, Douglas A; Soong, Thing Rinda; Hamada, Tsuyoshi; Liu, Li; Nishihara, Reiko; Giannakis, Marios; Cao, Yin; Manson, JoAnn E; Nowak, Jonathan A; Chan, Andrew T

2017-01-01

Precision medicine has a goal of customizing disease prevention and treatment strategies. Under the precision medicine paradigm, each patient has unique pathologic processes resulting from cellular genomic, epigenomic, proteomic, and metabolomic alterations, which are influenced by pharmacological, environmental, microbial, dietary, and lifestyle factors. Hence, to realize the promise of precision medicine, multi-level research methods that can comprehensively analyze many of these variables are needed. In order to address this gap, the integrative field of molecular pathology and population data science (i.e., molecular pathological epidemiology) has been developed to enable such multi-level analyses, especially in gastrointestinal cancer research. Further integration of pharmacology can improve our understanding of drug effects, and inform decision-making of drug use at both the individual and population levels. Such integrative research demonstrated potential benefits of aspirin in colorectal carcinoma with PIK3CA mutations, providing the basis for new clinical trials. Evidence also suggests that HPGD (15-PDGH) expression levels in normal colon and the germline rs6983267 polymorphism that relates to tumor CTNNB1 (β-catenin)/ WNT signaling status may predict the efficacy of aspirin for cancer chemoprevention. As immune checkpoint blockade targeting the CD274 (PD-L1)/ PDCD1 (PD-1) pathway for microsatellite instability-high (or mismatch repair-deficient) metastatic gastrointestinal or other tumors has become standard of care, potential modifying effects of dietary, lifestyle, microbial, and environmental factors on immunotherapy need to be studied to further optimize treatment strategies. With its broad applicability, our integrative approach can provide insights into the interactive role of medications, exposures, and molecular pathology, and guide the development of precision medicine.

Preservation of pathological tissue specimens by freeze-drying for immunohistochemical staining and various molecular biological analyses.

Science.gov (United States)

Matsuo, S; Sugiyama, T; Okuyama, T; Yoshikawa, K; Honda, K; Takahashi, R; Maeda, S

1999-05-01

Conditions of preserving DNA, RNA and protein in pathological specimens are of great importance as degradation of such macromolecules would critically affect results of molecular biological analysis. The feasibility of freeze-drying as a means of preserving pathological tissue samples for molecular analysis has previously been shown. In the present study, further tests on long-term storage conditions and analyses of freeze-dried samples by polymerase chain reaction (PCR), reverse transcriptase (RT)-PCR, western blotting and immunohistochemistry are reported. Rat chromosomal DNA of freeze-dried samples stored for 4 years showed slight degradation while RNA degradation was more prominently seen at an earlier stage of storage. However, these 4 year DNA and RNA samples were still able to serve as a template for some PCR and RT-PCR analyses, respectively. Overexpression of c-erbB-2 and p53 protein was demonstrated by western blotting and immunohistochemical staining using freeze-dried human breast cancer tissues. Although macromolecules in freeze-dried samples degrade to some extent during the preservation period, they should still be of value for certain molecular biological analyses and morphological examination; hence, providing more convenient and inexpensive ways of pathological tissue storage.

Molecular pathology of vertebral deformities in hyperthermic Atlantic salmon (Salmo salar)

OpenAIRE

Ytteborg, Elisabeth; Baeverfjord, Grete; Torgersen, Jacob; Hjelde, Kirsti; Takle, Harald

2010-01-01

Abstract Background Hyperthermia has been shown in a number of organisms to induce developmental defects as a result of changes in cell proliferation, differentiation and gene expression. In spite of this, salmon aquaculture commonly uses high water temperature to speed up developmental rate in intensive production systems, resulting in an increased frequency of skeletal deformities. In order to study the molecular pathology of vertebral deformities, Atlantic salmon was subjected to hyperther...

Expression of Tau Pathology-Related Proteins in Different Brain Regions: A Molecular Basis of Tau Pathogenesis.

Science.gov (United States)

Hu, Wen; Wu, Feng; Zhang, Yanchong; Gong, Cheng-Xin; Iqbal, Khalid; Liu, Fei

2017-01-01

Microtubule-associated protein tau is hyperphosphorylated and aggregated in affected neurons in Alzheimer disease (AD) brains. The tau pathology starts from the entorhinal cortex (EC), spreads to the hippocampus and frontal and temporal cortices, and finally to all isocortex areas, but the cerebellum is spared from tau lesions. The molecular basis of differential vulnerability of different brain regions to tau pathology is not understood. In the present study, we analyzed brain regional expressions of tau and tau pathology-related proteins. We found that tau was hyperphosphorylated at multiple sites in the frontal cortex (FC), but not in the cerebellum, from AD brain. The level of tau expression in the cerebellum was about 1/4 of that seen in the frontal and temporal cortices in human brain. In the rat brain, the expression level of tau with three microtubule-binding repeats (3R-tau) was comparable in the hippocampus, EC, FC, parietal-temporal cortex (PTC), occipital-temporal cortex (OTC), striatum, thalamus, olfactory bulb (OB) and cerebellum. However, the expression level of 4R-tau was the highest in the EC and the lowest in the cerebellum. Tau phosphatases, kinases, microtubule-related proteins and other tau pathology-related proteins were also expressed in a region-specific manner in the rat brain. These results suggest that higher levels of tau and tau kinases in the EC and low levels of these proteins in the cerebellum may accounts for the vulnerability and resistance of these representative brain regions to the development of tau pathology, respectively. The present study provides the regional expression profiles of tau and tau pathology-related proteins in the brain, which may help understand the brain regional vulnerability to tau pathology in neurodegenerative tauopathies.

Molecular pathological epidemiology: new developing frontiers of big data science to study etiologies and pathogenesis.

Science.gov (United States)

Hamada, Tsuyoshi; Keum, NaNa; Nishihara, Reiko; Ogino, Shuji

2017-03-01

Molecular pathological epidemiology (MPE) is an integrative field that utilizes molecular pathology to incorporate interpersonal heterogeneity of a disease process into epidemiology. In each individual, the development and progression of a disease are determined by a unique combination of exogenous and endogenous factors, resulting in different molecular and pathological subtypes of the disease. Based on "the unique disease principle," the primary aim of MPE is to uncover an interactive relationship between a specific environmental exposure and disease subtypes in determining disease incidence and mortality. This MPE approach can provide etiologic and pathogenic insights, potentially contributing to precision medicine for personalized prevention and treatment. Although breast, prostate, lung, and colorectal cancers have been among the most commonly studied diseases, the MPE approach can be used to study any disease. In addition to molecular features, host immune status and microbiome profile likely affect a disease process, and thus serve as informative biomarkers. As such, further integration of several disciplines into MPE has been achieved (e.g., pharmaco-MPE, immuno-MPE, and microbial MPE), to provide novel insights into underlying etiologic mechanisms. With the advent of high-throughput sequencing technologies, available genomic and epigenomic data have expanded dramatically. The MPE approach can also provide a specific risk estimate for each disease subgroup, thereby enhancing the impact of genome-wide association studies on public health. In this article, we present recent progress of MPE, and discuss the importance of accounting for the disease heterogeneity in the era of big-data health science and precision medicine.

ADVANCES AND CHALLENGES IN SUGARCANE BIOTECHNOLOY AND PLANT PATHOLOGY: A REVIEW OF THE IX PLANT PATHOLOGY WORKSHOP AND VI MOLECULAR BIOLOGY WORKSHOP

Science.gov (United States)

The IX Pathology Workshop and VI Molecular Biology Workshop of the International Society of Sugar Cane Technologists (ISSCT) were organised jointly and hosted by the Colombian Sugarcane Research Centre (CENICAÑA) from 23-27 June 2008 at the Radisson Royal Hotel in Cali, Colombia. The Workshop was we...

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Directory of Open Access Journals (Sweden)

Joel Saltz

2018-04-01

Full Text Available Summary: Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumor-infiltrating lymphocytes (TILs based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment. : Tumor-infiltrating lymphocytes (TILs were identified from standard pathology cancer images by a deep-learning-derived “computational stain” developed by Saltz et al. They processed 5,202 digital images from 13 cancer types. Resulting TIL maps were correlated with TCGA molecular data, relating TIL content to survival, tumor subtypes, and immune profiles. Keywords: digital pathology, immuno-oncology, machine learning, lymphocytes, tumor microenvironment, deep learning, tumor-infiltrating lymphocytes, artificial intelligence, bioinformatics, computer vision

System for Informatics in the Molecular Pathology Laboratory: An Open-Source End-to-End Solution for Next-Generation Sequencing Clinical Data Management.

Science.gov (United States)

Kang, Wenjun; Kadri, Sabah; Puranik, Rutika; Wurst, Michelle N; Patil, Sushant A; Mujacic, Ibro; Benhamed, Sonia; Niu, Nifang; Zhen, Chao Jie; Ameti, Bekim; Long, Bradley C; Galbo, Filipo; Montes, David; Iracheta, Crystal; Gamboa, Venessa L; Lopez, Daisy; Yourshaw, Michael; Lawrence, Carolyn A; Aisner, Dara L; Fitzpatrick, Carrie; McNerney, Megan E; Wang, Y Lynn; Andrade, Jorge; Volchenboum, Samuel L; Furtado, Larissa V; Ritterhouse, Lauren L; Segal, Jeremy P

2018-04-24

Next-generation sequencing (NGS) diagnostic assays increasingly are becoming the standard of care in oncology practice. As the scale of an NGS laboratory grows, management of these assays requires organizing large amounts of information, including patient data, laboratory processes, genomic data, as well as variant interpretation and reporting. Although several Laboratory Information Systems and/or Laboratory Information Management Systems are commercially available, they may not meet all of the needs of a given laboratory, in addition to being frequently cost-prohibitive. Herein, we present the System for Informatics in the Molecular Pathology Laboratory, a free and open-source Laboratory Information System/Laboratory Information Management System for academic and nonprofit molecular pathology NGS laboratories, developed at the Genomic and Molecular Pathology Division at the University of Chicago Medicine. The System for Informatics in the Molecular Pathology Laboratory was designed as a modular end-to-end information system to handle all stages of the NGS laboratory workload from test order to reporting. We describe the features of the system, its clinical validation at the Genomic and Molecular Pathology Division at the University of Chicago Medicine, and its installation and testing within a different academic center laboratory (University of Colorado), and we propose a platform for future community co-development and interlaboratory data sharing. Copyright © 2018. Published by Elsevier Inc.

Avoiding pitfalls in molecular genetic testing: case studies of high-resolution array comparative genomic hybridization testing in the definitive diagnosis of Mowat-Wilson syndrome.

Science.gov (United States)

Kluk, Michael Joseph; An, Yu; James, Philip; Coulter, David; Harris, David; Wu, Bai-Lin; Shen, Yiping

2011-05-01

The molecular testing options available for the diagnosis of genetic disorders are numerous and include a variety of different assay platforms. The consultative input of molecular pathologists and cytogeneticists, working closely with the ordering clinicians, is often important for definitive diagnosis. Herein, we describe two patients who had long histories of unexplained signs and symptoms with a high clinical suspicion of an underlying genetic etiology. Initial molecular testing in both cases was negative, but the application of high-resolution array comparative genomic hybridization technology lead to definitive diagnosis in both cases. We summarize the clinical findings and molecular testing in each case, discuss the differential diagnoses, and review the clinical and pathological findings of Mowat-Wilson syndrome. This report highlights the importance for those involved in molecular testing to know the nature of the underlying genetic abnormalities associated with the suspected diagnosis, to recognize the limitations of each testing platform, and to persistently pursue repeat testing using high-resolution technologies when indicated. This concept is applicable to both germline and somatic molecular genetic testing. Copyright © 2011 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Cutaneous Pythiosis in calves: An epidemiologic, pathologic, serologic and molecular characterization

Directory of Open Access Journals (Sweden)

Guilherme Konradt

2016-12-01

Full Text Available This study reports the epidemiological, pathological and mycological findings of cutaneous pythiosis in cattle in southern Brazil. 23 calves, that were kept next to a river with extensive marshy regions, presented ulcerated cutaneous lesions in thoracic and pelvic limbs, sometimes extending to the ventral thoracic region. Histopathological examination revealed multifocal pyogranulomas in the superficial and deep dermis. The Grocott-Methenamine silver, immunohistochemistry anti-Pythium insidiosum, ELISA serology and molecular characterization demonstrated the agent P. insidiosum in these cases.

Molecular epidemiology and pathology of spirorchiid infection in green sea turtles (Chelonia mydas

Directory of Open Access Journals (Sweden)

Phoebe A. Chapman

2017-04-01

Full Text Available Spirorchiid blood fluke infections affect endangered turtle populations globally, and are reported as a common cause of mortality in Queensland green sea turtles. Both the flukes and their ova are pathogenic and can contribute to the stranding or death of their host. Of particular interest are ova-associated brain lesions, which have been associated with host neurological deficits. Accurate estimations of disease frequency and the relative effect of infection relating to different spirorchiid species are made difficult by challenges in morphological identification of adults of some genera, and a lack of species-level identifying features for ova. A new specifically designed molecular assay was used to detect and identify cryptic spirorchiids and their ova in Queensland green sea turtle tissues collected from 2011 to 2014 in order to investigate epidemiology, tissue tropisms and pathology. Eight spirorchiid genotypes were detected in 14 distinct tissues, including multiple tissues for each. We found no evidence of a characteristic pathway of the eggs to the exterior; instead the results suggest that a high proportion of eggs become lost in dead-end tissues. The most common lesions observed were granulomas affecting most organs with varying severity, followed by arteritis and thrombi in the great vessels. The number of spirorchiid types detected increased with the presence and severity of granulomatous lesions. However, compared with other organs the brain showed relatively low levels of spirorchiid diversity. An inverse relationship between host age and spirorchiid diversity was evident for the liver and kidneys, but no such relationship was evident for other organs. Molecular data in this study, the first of its kind, provides the first species-level examination of spirorchiid ova and associated pathology, and paves the way for the future development of targeted ante-mortem diagnosis of spirorchiidiasis.

MRI and pathological features of different molecular subtypes of breast cancers

International Nuclear Information System (INIS)

Yu Yang; Huo Tianlong; Lai Yunyao; Hong Nan

2014-01-01

Objective: To investigate the MRI and pathological features of different molecular subtypes of breast cancer. Methods: The data of 202 patients who underwent primary breast cancer resection were retrospectively reviewed. All of the patients had MRI preoperatively. The molecular subtypes of breast cancer defined by immunohistochemistry were classified as basal-like, luminal and HER-2 overexpression. Morphology (including mass or non-mass like enhancement, shape and margin of masses, unifocal or multifocal masses) and enhancement characteristics on MRI, histologic types and grades of tumors were analyzed with Chi-square test, exact test, Fisher exact test, Kruskal-Wallis H test, and Wilcoxon test. Results: Among the 202 patients, 34 were basal-like, 144 were luminal and 24 were HER-2 overexpression. The number of mass cases in each subtype was 29, 133 and 19 respectively,making no significant difference (χ 2 =4.136, P=0.126). As for the shape of basal-like lesions,8 were round,19 were lobular and 2 were irregular, while this distribution was 23, 58, 52 in luminal subtype and 1, 11, 7 in HER-2 overexpression subtype (χ 2 =13.391, P<0.05). The margin was also strikingly different among three groups (smooth, spiculate, irregular): 20, 5, 4 respectively in basal-like, 27, 53, 53 respectively in luminal, and 4, 7, 8 respectively in HER-2 overexpression (χ 2 =28.515, P<0.01). 52.6% (10/19) of HER-2 overexpression cases were multifocal, while only 6.9% (2/29) of luminal and 8.0% (24/133) of basal-like ones were multifocal (χ 2 =16.140, P<0.01). Characteristics in dynamic contrast-enhanced MRI were statistically different, with homogeneous, heterogeneous, and rim enhancement 0, 13, 16 respectively in basal-like cases, 28, 93, 11 respectively in luminal cases and 2, 11, 6 respectively in HER-2 overexpression cases (P<0.01). However, the difference for enhancement curve did not reach significance (P =0.457). Histologic types were significantly different among molecular

Insights into the Molecular Mechanisms of Alzheimer’s and Parkinson’s Diseases with Molecular Simulations: Understanding the Roles of Artificial and Pathological Missense Mutations in Intrinsically Disordered Proteins Related to Pathology

Directory of Open Access Journals (Sweden)

Orkid Coskuner-Weber

2018-01-01

Full Text Available Amyloid-β and α-synuclein are intrinsically disordered proteins (IDPs, which are at the center of Alzheimer’s and Parkinson’s disease pathologies, respectively. These IDPs are extremely flexible and do not adopt stable structures. Furthermore, both amyloid-β and α-synuclein can form toxic oligomers, amyloid fibrils and other type of aggregates in Alzheimer’s and Parkinson’s diseases. Experimentalists face challenges in investigating the structures and thermodynamic properties of these IDPs in their monomeric and oligomeric forms due to the rapid conformational changes, fast aggregation processes and strong solvent effects. Classical molecular dynamics simulations complement experiments and provide structural information at the atomic level with dynamics without facing the same experimental limitations. Artificial missense mutations are employed experimentally and computationally for providing insights into the structure-function relationships of amyloid-β and α-synuclein in relation to the pathologies of Alzheimer’s and Parkinson’s diseases. Furthermore, there are several natural genetic variations that play a role in the pathogenesis of familial cases of Alzheimer’s and Parkinson’s diseases, which are related to specific genetic defects inherited in dominant or recessive patterns. The present review summarizes the current understanding of monomeric and oligomeric forms of amyloid-β and α-synuclein, as well as the impacts of artificial and pathological missense mutations on the structural ensembles of these IDPs using molecular dynamics simulations. We also emphasize the recent investigations on residual secondary structure formation in dynamic conformational ensembles of amyloid-β and α-synuclein, such as β-structure linked to the oligomerization and fibrillation mechanisms related to the pathologies of Alzheimer’s and Parkinson’s diseases. This information represents an important foundation for the successful and

Recent advances in molecular pathology of craniopharyngioma [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

Sarah Larkin

2017-07-01

Full Text Available Craniopharyngiomas are rare epithelial tumours arising along the path of the craniopharyngeal duct. Two major histological subtypes have been recognised, the papillary and the adamantinomatous. Craniopharyngiomas remain challenging tumours to manage and are associated with significant morbidities and mortality. Recent advances in the molecular pathology of these neoplasms have identified BRAF mutations in the papillary variant, offering promising options for targeted pharmacological treatment. The involvement of β-catenin and the Wnt pathway in the tumorigenesis of the adamantinomatous subtype has been previously established with the identification of stabilising mutations in exon 3 of CTNNB1. Further understanding of the pathogenesis of this subtype has been facilitated with the use of mouse models and xenograft experiments. It has been proposed that the clusters of cells with upregulated Wnt/β-catenin signalling induce tumour formation in a paracrine manner; the complex interactions occurring between different cell populations need to be further clarified for further expansion of this hypothesis. This review outlines recent key advances in our understanding of the molecular pathology of craniopharyngiomas and discusses some of the challenges that need to be overcome for the development of targeted therapies that will hopefully improve the management and the outcomes of these patients.

A retrospective of an unconventionally trained plant pathologist: plant diseases to molecular plant pathology.

Science.gov (United States)

Ouchi, Seiji

2006-01-01

Plant pathology evolved from its mycology-oriented origins into a science dealing with biochemical mechanisms of diseases, along with enhanced crop production through disease control. This retrospective describes first my personal experience from my introduction to plant pathology, to the establishment of the concept of accessibility as a model pertaining to genetically defined basic compatibility induced by pathogens. I then refer to the development of molecular plant pathology from physiological and biochemical plant pathology fostered by the growth in recombinant technology in the second half of the past century. This progress was best reflected by the U.S.-Japan Seminar Series held at 4-5-year intervals from 1966 to 2003 and documented by publications in major journals of our discipline. These seminars emphasized that progress in science has always been supported by the invention of novel techniques and that knowledge integrated from modern genomics and subsequent proteomics should contribute to the progress of basic life sciences and, more importantly, to the elaboration of rational measures for disease control.

Potato agriculture, late blight science, and the molecularization of plant pathology.

Science.gov (United States)

Turner, R Steven

2008-01-01

By the mid-1980s nucleic-acid based methods were penetrating the farthest reaches of biological science, triggering rivalries among practitioners, altering relationships among subfields, and transforming the research front. This article delivers a "bottom up" analysis of that transformation at work in one important area of biological science, plant pathology, by tracing the "molecularization" of efforts to understand and control one notorious plant disease -- the late blight of potatoes. It mobilizes the research literature of late blight science as a tool through which to trace the changing typography of the research front from 1983 to 2003. During these years molecularization intensified the traditional fragmentation of the late blight research community, even as it dramatically integrated study of the causal organism into broader areas of biology. In these decades the pathogen responsible for late blight, the oomycete "Phytophthora infestans," was discovered to be undergoing massive, frightening, and still largely unexplained genetic diversification -- a circumstance that lends the episode examined here an urgency that reinforces its historiographical significance as a case-study in the molecularization of the biological sciences.

MOLECULAR BIOLOGICAL AND RADIOLOGICAL TECHNOLOGIES IN THE COMPLEX DIAGNOSIS OF AUXILLARY PATHOLOGY

Directory of Open Access Journals (Sweden)

N. I. Rozhkova

2009-01-01

Full Text Available Introduction. A diversity of axillary pathologies was a prerequisite for the development of a new differential approach to diagnosing such conditions. There are new technologies (pre- and intraoperative radionuclide studies, molecular genetic techniques, that have shown themselves, along with classical methods (physical examination, mammography, X-ray and ultrasound studies.Materials and methods. The subject of the analysis is the results of a comprehensive examination of 502 women aged 22 to 84 years. Different groups were comprehensively examined using both X-ray, ultrasound, radionuclide, and molecular genetic (polymerase chain reaction studies.Results. The molecular genetic and cytological studies could provide the actual results in 95 and 84% of cases, respectively; but a com- prehensive clinical study and X-ray ultrasound computed tomography could yield them in marginal metastases in only 65.3%. Conclusion. The authors have proposed the optimal diagnostic algorithm for examination in the ambulatory-outpatient network and specialized institutions.

The pathology of familial breast cancer: Immunohistochemistry and molecular analysis

International Nuclear Information System (INIS)

Osin, Pinchas P; Lakhani, Sunil R

1999-01-01

Extensive studies of BRCA1- and BRCA2-associated breast tumours have been carried out in the few years since the identification of these familial breast cancer predisposing genes. The morphological studies suggest that BRCA1 tumours differ from BRCA2 tumours and from sporadic breast cancers. Recent progress in immunohistochemistry and molecular biology techniques has enabled in-depth investigation of molecular pathology of these tumours. Studies to date have investigated issues such as steroid hormone receptor expression, mutation status of tumour suppressor genes TP53 and c-erbB2, and expression profiles of cell cycle proteins p21, p27 and cyclin D 1 . Despite relative paucity of data, strong evidence of unique biological characteristics of BRCA1-associated breast cancer is accumulating. BRCA1-associated tumours appear to show an increased frequency of TP53 mutations, frequent p53 protein stabilization and absence of imunoreactivity for steroid hormone receptors. Further studies of larger number of samples of both BRCA1- and BRCA2-associated tumours are necessary to clarify and confirm these observations

The Geropathology Research Network: An Interdisciplinary Approach for Integrating Pathology Into Research on Aging.

Science.gov (United States)

Ladiges, Warren; Ikeno, Yuji; Niedernhofer, Laura; McIndoe, Richard A; Ciol, Marcia A; Ritchey, Jerry; Liggitt, Denny

2016-04-01

Geropathology is the study of aging and age-related lesions and diseases in the form of whole necropsies/autopsies, surgical biopsies, histology, and molecular biomarkers. It encompasses multiple subspecialties of geriatrics, anatomic pathology, molecular pathology, clinical pathology, and gerontology. In order to increase the consistency and scope of communication in the histologic and molecular pathology assessment of tissues from preclinical and clinical aging studies, a Geropathology Research Network has been established consisting of pathologists and scientists with expertise in the comparative pathology of aging, the design of aging research studies, biostatistical methods for analysis of aging data, and bioinformatics for compiling and annotating large sets of data generated from aging studies. The network provides an environment to promote learning and exchange of scientific information and ideas for the aging research community through a series of symposia, the development of uniform ways of integrating pathology into aging studies, and the statistical analysis of pathology data. The efforts of the network are ultimately expected to lead to a refined set of sentinel biomarkers of molecular and anatomic pathology that could be incorporated into preclinical and clinical aging intervention studies to increase the relevance and productivity of these types of investigations. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Pathology as the enabler of human research.

Science.gov (United States)

Crawford, James M; Tykocinski, Mark L

2005-09-01

Academic Pathology is a key player in human molecular science and in the powerful initiatives of the National Institutes of Health. Pathologists generate data crucial to virtually every molecular study of human tissue, and have the necessary skills and authority to oversee processing of human tissues for research analysis. We advocate that Academic Pathology is optimally positioned to drive the molecular revolution in study of human disease, through human tissue collection, analysis, and databasing. This can be achieved through playing a major role in human tissue procurement and management; establishing high-quality 'Pathology Resource Laboratories'; providing the scientific expertise for pathology data sharing; and recruiting and training physician scientists. Pathology should position itself to be the local institutional driver of technology implementation and development, by operating the resource laboratories, providing the expertise for technical and conceptual design of research projects, maintaining the databases that link molecular and morphological information on human tissues with the requisite clinical databases, providing education and mentorship of technology users, and nurturing new research through the development of preliminary data. We also consider that outstanding pathology journals are available for the publication of research emanating from such studies, to the benefit of the pathology profession as an academic enterprise. It is our earnest hope that Academic Pathology can play a leading role in the remarkable advances to be made as the 21st century unfolds.

Digital mammography in a screening programme and its implications for pathology: a comparative study.

LENUS (Irish Health Repository)

Feeley, Linda

2011-03-01

Most studies comparing full-field digital mammography (FFDM) with conventional screen-film mammography (SFM) have been radiology-based. The pathological implications of FFDM have received little attention in the literature, especially in the context of screening programmes. The primary objective of this retrospective study is to compare FFDM with SFM in a population-based screening programme with regard to a number of pathological parameters.

Quality control in diagnostic molecular pathology in the Netherlands; proficiency testing for patient identification in tissue samples

NARCIS (Netherlands)

Thunnissen, F. B. J. M.; Tilanus, M. G. J.; Ligtenberg, M. J. L.; Nederlof, P. M.; Dinjens, W. N. M.; Meulemans, E.; van den Brule, A. J. C.; van Noesel, C. J. M.; de Leeuw, W. J. F.; Schuuring, E.

2004-01-01

Aims: To describe the evolution of proficiency testing for molecular diagnostic pathology with respect to determining unambiguously the patient identity of tissue samples by microsatellite analysis. Method: Four rounds of quality control exchanges of samples from different patients were sent with

Incidence of sarcoma histotypes and molecular subtypes in a prospective epidemiological study with central pathology review and molecular testing.

Directory of Open Access Journals (Sweden)

Françoise Ducimetière

Full Text Available BACKGROUND: The exact overall incidence of sarcoma and sarcoma subtypes is not known. The objective of the present population-based study was to determine this incidence in a European region (Rhone-Alpes of six million inhabitants, based on a central pathological review of the cases. METHODOLOGY/PRINCIPAL FINDINGS: From March 2005 to February 2007, pathology reports and tumor blocks were prospectively collected from the 158 pathologists of the Rhone-Alpes region. All diagnosed or suspected cases of sarcoma were collected, reviewed centrally, examined for molecular alterations and classified according to the 2002 World Health Organization classification. Of the 1287 patients screened during the study period, 748 met the criteria for inclusion in the study. The overall crude and world age-standardized incidence rates were respectively 6.2 and 4.8 per 100,000/year. Incidence rates for soft tissue, visceral and bone sarcomas were respectively 3.6, 2.0 and 0.6 per 100,000. The most frequent histological subtypes were gastrointestinal stromal tumor (18%; 1.1/100,000, unclassified sarcoma (16%; 1/100,000, liposarcoma (15%; 0.9/100,000 and leiomyosarcoma (11%; 0.7/100,000. CONCLUSIONS/SIGNIFICANCE: The observed incidence of sarcomas was higher than expected. This study is the first detailed investigation of the crude incidence of histological and molecular subtypes of sarcomas.

Molecular pathology of vertebral deformities in hyperthermic Atlantic salmon (Salmo salar

Directory of Open Access Journals (Sweden)

Hjelde Kirsti

2010-07-01

Full Text Available Abstract Background Hyperthermia has been shown in a number of organisms to induce developmental defects as a result of changes in cell proliferation, differentiation and gene expression. In spite of this, salmon aquaculture commonly uses high water temperature to speed up developmental rate in intensive production systems, resulting in an increased frequency of skeletal deformities. In order to study the molecular pathology of vertebral deformities, Atlantic salmon was subjected to hyperthermic conditions from fertilization until after the juvenile stage. Results Fish exposed to the high temperature regime showed a markedly higher growth rate and a significant higher percentage of deformities in the spinal column than fish reared at low temperatures. By analyzing phenotypically normal spinal columns from the two temperature regimes, we found that the increased risk of developing vertebral deformities was linked to an altered gene transcription. In particular, down-regulation of extracellular matrix (ECM genes such as col1a1, osteocalcin, osteonectin and decorin, indicated that maturation and mineralization of osteoblasts were restrained. Moreover, histological staining and in situ hybridization visualized areas with distorted chondrocytes and an increased population of hypertrophic cells. These findings were further confirmed by an up-regulation of mef2c and col10a, genes involved in chondrocyte hypertrophy. Conclusion The presented data strongly indicates that temperature induced fast growth is severely affecting gene transcription in osteoblasts and chondrocytes; hence change in the vertebral tissue structure and composition. A disrupted bone and cartilage production was detected, which most likely is involved in the higher rate of deformities developed in the high intensive group. Our results are of basic interest for bone metabolism and contribute to the understanding of the mechanisms involved in development of temperature induced

The benefits of molecular pathology in the diagnosis of musculoskeletal disease. Part I of a two-part review: soft tissue tumors

International Nuclear Information System (INIS)

Flanagan, Adrienne M.; Delaney, David; O'Donnell, Paul

2010-01-01

Bone and soft tissue metabolic and neoplastic diseases are increasingly characterized by their molecular signatures. This has resulted from increased knowledge of the human genome, which has contributed to the unraveling of molecular pathways in health and disease. Exploitation of this information has allowed it to be used for practical diagnostic purposes. The aim of the first part of this two-part review is to provide an up-to-date review of molecular genetic investigations that are available and routinely used by specialist musculoskeletal histopathologists in the diagnosis of neoplastic disease. Herein we focus on the benefits of employing well characterized somatic mutations in soft tissue lesions that are commonly employed in diagnostic pathology today. The second part highlights the known somatic and germline mutations implicated in osteoclast-rich lesions of bone, and the genetic changes that disturb phosphate metabolism and result in a variety of musculoskeletal phenotypes. Finally, a brief practical guide of how to use and provide a molecular pathology service is given. (orig.)

[Comparative pathology of the microcirculatory bed].

Science.gov (United States)

Strukov, A I; Vorob'eva, A A

1976-11-01

This paper presents an analysis of publications, mostly by Soviet authores, on clinical studies and morphological examinations of the microcirculatory bed in different pathology. It is concluded that the microcirculatory bed should be regarded as an integral system responding to the pathological effects by a local and general reaction of its structural components and by changing the rheological properties of blood. Two types of changes develop in the microcirculatory system -- sterotyped ones, typical for extreme states (various kinds of shock, hypertensive crisis, stress situations), and those specific for certain diseases (diabetes melitus, essential hypertension, athersclerosis, collagenoses, etc.). In all the above diseases the pathological process affects the functional structures of microcirculation that undergo a rearrangement in accordance with the requirements of the body. In the initial period of the disease this re-arrangement is of a compensatory nature and passes ahead of the clinical manifestations. A comparison of the pictutrs obtained by biomicroscopy of the bulbconjunctiva of the eye and of other mucosae with film preparations of the serosae demonstrates their complete similarity. Therefore, the method of biomicroscopy of the eyeball and of the mucosae as a method reflecting the state of microcirculation in the body as a whole should become an integral part of the clinical examination of patients.

Diagnostic histochemistry and clinical-pathological testings as molecular pathways to pathogenesis and treatment of the ageing neuromuscular system: a personal view.

Science.gov (United States)

Engel, W King

2015-04-01

Ageing of the neuromuscular system in elderhood ingravescently contributes to slowness, weakness, falling and death, often accompanied by numbness and pain. This article is to put in perspective examples from a half-century of personal and team neuromuscular histochemical-pathological and clinical-pathological research, including a number of lucky and instructive accomplishments identifying new treatments and new diseases. A major focus currently is on some important, still enigmatic, aspects of the ageing neuromuscular system. It is also includes some of the newest references of others on various closely-related aspects of this ageing system. The article may help guide others in their molecular-based endeavors to identify paths leading to discovering new treatments and new pathogenic aspects. These are certainly needed - our ageing and unsteady constituents are steadily increasing. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis. Copyright © 2014. Published by Elsevier B.V.

Disrupted sensory gating in pathological gambling.

Science.gov (United States)

Stojanov, Wendy; Karayanidis, Frini; Johnston, Patrick; Bailey, Andrew; Carr, Vaughan; Schall, Ulrich

2003-08-15

Some neurochemical evidence as well as recent studies on molecular genetics suggest that pathologic gambling may be related to dysregulated dopamine neurotransmission. The current study examined sensory (motor) gating in pathologic gamblers as a putative measure of endogenous brain dopamine activity with prepulse inhibition of the acoustic startle eye-blink response and the auditory P300 event-related potential. Seventeen pathologic gamblers and 21 age- and gender-matched healthy control subjects were assessed. Both prepulse inhibition measures were recorded under passive listening and two-tone prepulse discrimination conditions. Compared to the control group, pathologic gamblers exhibited disrupted sensory (motor) gating on all measures of prepulse inhibition. Sensory motor gating deficits of eye-blink responses were most profound at 120-millisecond prepulse lead intervals in the passive listening task and at 240-millisecond prepulse lead intervals in the two-tone prepulse discrimination task. Sensory gating of P300 was also impaired in pathologic gamblers, particularly at 500-millisecond lead intervals, when performing the discrimination task on the prepulse. In the context of preclinical studies on the disruptive effects of dopamine agonists on prepulse inhibition, our findings suggest increased endogenous brain dopamine activity in pathologic gambling in line with previous neurobiological findings.

Pathological and molecular studies of the renal trematode Paratanaisia bragai in Indian peafowls (Pavo cristatus).

Science.gov (United States)

Asok Kumar, M; Kumar, Deepak; Palanivelu, Munuswamy; Annamalai, Latchumikanthan; Mathesh, Karikalan; Singh, Rajendra; Sharma, Anil Kumar; Dhama, Kuldeep

2018-03-26

Endoparasitic diseases are commonly encountered in free-ranging birds. Although not all endoparasites cause disease, persistent infection with large numbers of parasites almost always affects normal physiological functions, leading to deleterious effects on the host. This paper describes the anatomopathological alterations caused by the renal trematode Paratanaisia bragai in Indian peafowl (n = 3) and examines the phylogeny of these and related parasites. Peafowl from forests in and around the Bareilly region, Uttar Pradesh, India, were necropsied, and microscopic and molecular investigations were performed. The peafowl were confirmed to be infected with P. bragai. Significant gross pathological lesions suggested nephrosis, and microscopic findings indicated a mild-to-moderate degree of nephrosis caused by the parasites in the tissue. The parasites were identified as P. bragai by histomorphological analysis of adult and eggs in the ureters, and the identification was confirmed by PCR and phylogenetic analysis. Nucleotide sequencing of the PCR products from the renal trematodes recovered from Indian peafowl revealed a close association with P. bragai from Columbiformes in the United Kingdom and Spain. The pathology and molecular epidemiology of parasitic diseases affecting peafowl is not well understood in India. This is the first report from India and the second report worldwide to document P. bragai infection in peafowl.

Molecular pathology and age estimation.

Science.gov (United States)

Meissner, Christoph; Ritz-Timme, Stefanie

2010-12-15

Over the course of our lifetime a stochastic process leads to gradual alterations of biomolecules on the molecular level, a process that is called ageing. Important changes are observed on the DNA-level as well as on the protein level and are the cause and/or consequence of our 'molecular clock', influenced by genetic as well as environmental parameters. These alterations on the molecular level may aid in forensic medicine to estimate the age of a living person, a dead body or even skeletal remains for identification purposes. Four such important alterations have become the focus of molecular age estimation in the forensic community over the last two decades. The age-dependent accumulation of the 4977bp deletion of mitochondrial DNA and the attrition of telomeres along with ageing are two important processes at the DNA-level. Among a variety of protein alterations, the racemisation of aspartic acid and advanced glycation endproducs have already been tested for forensic applications. At the moment the racemisation of aspartic acid represents the pinnacle of molecular age estimation for three reasons: an excellent standardization of sampling and methods, an evaluation of different variables in many published studies and highest accuracy of results. The three other mentioned alterations often lack standardized procedures, published data are sparse and often have the character of pilot studies. Nevertheless it is important to evaluate molecular methods for their suitability in forensic age estimation, because supplementary methods will help to extend and refine accuracy and reliability of such estimates. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Comparative analysis of whole mount processing and systematic sampling of radical prostatectomy specimens: pathological outcomes and risk of biochemical recurrence.

Science.gov (United States)

Salem, Shady; Chang, Sam S; Clark, Peter E; Davis, Rodney; Herrell, S Duke; Kordan, Yakup; Wills, Marcia L; Shappell, Scott B; Baumgartner, Roxelyn; Phillips, Sharon; Smith, Joseph A; Cookson, Michael S; Barocas, Daniel A

2010-10-01

Whole mount processing is more resource intensive than routine systematic sampling of radical retropubic prostatectomy specimens. We compared whole mount and systematic sampling for detecting pathological outcomes, and compared the prognostic value of pathological findings across pathological methods. We included men (608 whole mount and 525 systematic sampling samples) with no prior treatment who underwent radical retropubic prostatectomy at Vanderbilt University Medical Center between January 2000 and June 2008. We used univariate and multivariate analysis to compare the pathological outcome detection rate between pathological methods. Kaplan-Meier curves and the log rank test were used to compare the prognostic value of pathological findings across pathological methods. There were no significant differences between the whole mount and the systematic sampling groups in detecting extraprostatic extension (25% vs 30%), positive surgical margins (31% vs 31%), pathological Gleason score less than 7 (49% vs 43%), 7 (39% vs 43%) or greater than 7 (12% vs 13%), seminal vesicle invasion (8% vs 10%) or lymph node involvement (3% vs 5%). Tumor volume was higher in the systematic sampling group and whole mount detected more multiple surgical margins (each p systematic sampling yield similar pathological information. Each method stratifies patients into comparable risk groups for biochemical recurrence. Thus, while whole mount is more resource intensive, it does not appear to result in improved detection of clinically important pathological outcomes or prognostication. Copyright © 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Molecular Pathological Classification of Neurodegenerative Diseases: Turning towards Precision Medicine.

Science.gov (United States)

Kovacs, Gabor G

2016-02-02

Neurodegenerative diseases (NDDs) are characterized by selective dysfunction and loss of neurons associated with pathologically altered proteins that deposit in the human brain but also in peripheral organs. These proteins and their biochemical modifications can be potentially targeted for therapy or used as biomarkers. Despite a plethora of modifications demonstrated for different neurodegeneration-related proteins, such as amyloid-β, prion protein, tau, α-synuclein, TAR DNA-binding protein 43 (TDP-43), or fused in sarcoma protein (FUS), molecular classification of NDDs relies on detailed morphological evaluation of protein deposits, their distribution in the brain, and their correlation to clinical symptoms together with specific genetic alterations. A further facet of the neuropathology-based classification is the fact that many protein deposits show a hierarchical involvement of brain regions. This has been shown for Alzheimer and Parkinson disease and some forms of tauopathies and TDP-43 proteinopathies. The present paper aims to summarize current molecular classification of NDDs, focusing on the most relevant biochemical and morphological aspects. Since the combination of proteinopathies is frequent, definition of novel clusters of patients with NDDs needs to be considered in the era of precision medicine. Optimally, neuropathological categorizing of NDDs should be translated into in vivo detectable biomarkers to support better prediction of prognosis and stratification of patients for therapy trials.

Molecular Imaging on the Cerebral Pathological Damage Target of Ketamine Dependence

Directory of Open Access Journals (Sweden)

YANG Hong-jie1,2;HU Shu1;JIA Shao-wei1;GAO Zhou1;WANG Tong3;ZHAO Zheng-qin1

2014-02-01

Full Text Available To study the cerebral pathological damage target which result from abusing ketamine through molecular imaging techniques， 20 cases of ketamine dependent patients looking for treatment at the Peking University Shenzhen Hospital and 31 healthy volunteers were included in this study, all of them got brain SPECT DAT imaging. The results were analyzed by SPSS 16.0. The bilateral caudate nucleus and putamen of healthy volunteers were roughly equally large, and the radioactive distribution of DAT in healthy volunteers were uniform and symmetrical. The bilateral corpora striatum showed typical “panda eyes” pattern. But the bilateral corpora striatum of ketamine dependent patients got smaller in shape, got disorders in pattern, and the radioactive distribution of DAT reduced or defected or even got disturbance and with much more non-specific radioactive. The V, m and Ra of bilateral corpora striatum in ketamine dependent patients were （21.03±3.15） cm3, （22.08±3.31） g and （5.37±1.08） %, respectively, which were significantly lower than the healthy volunteers (p<0.01. The cerebral pathological damage target which resulted from abusing ketamine was similar to those of compound codeine phosphate antitussive solution dependence, heroin dependence and MDMA dependence, all of these psychoactive substances damaged the function of DAT.

New approaches to the treatment of orphan genetic disorders: Mitigating molecular pathologies using chemicals

Directory of Open Access Journals (Sweden)

RENATA V. VELHO

2015-08-01

Full Text Available With the advance and popularization of molecular techniques, the identification of genetic mutations that cause diseases has increased dramatically. Thus, the number of laboratories available to investigate a given disorder and the number of subsequent diagnosis have increased over time. Although it is necessary to identify mutations and provide diagnosis, it is also critical to develop specific therapeutic approaches based on this information. This review aims to highlight recent advances in mutation-targeted therapies with chemicals that mitigate mutational pathology at the molecular level, for disorders that, for the most part, have no effective treatment. Currently, there are several strategies being used to correct different types of mutations, including the following: the identification and characterization of translational readthrough compounds; antisense oligonucleotide-mediated splicing redirection; mismatch repair; and exon skipping. These therapies and other approaches are reviewed in this paper.

New approaches to the treatment of orphan genetic disorders: Mitigating molecular pathologies using chemicals.

Science.gov (United States)

Velho, Renata V; Sperb-Ludwig, Fernanda; Schwartz, Ida V D

2015-08-01

With the advance and popularization of molecular techniques, the identification of genetic mutations that cause diseases has increased dramatically. Thus, the number of laboratories available to investigate a given disorder and the number of subsequent diagnosis have increased over time. Although it is necessary to identify mutations and provide diagnosis, it is also critical to develop specific therapeutic approaches based on this information. This review aims to highlight recent advances in mutation-targeted therapies with chemicals that mitigate mutational pathology at the molecular level, for disorders that, for the most part, have no effective treatment. Currently, there are several strategies being used to correct different types of mutations, including the following: the identification and characterization of translational readthrough compounds; antisense oligonucleotide-mediated splicing redirection; mismatch repair; and exon skipping. These therapies and other approaches are reviewed in this paper.

Current Understanding of Molecular Pathology and Treatment of Cardiomyopathy in Duchenne Muscular Dystrophy

Directory of Open Access Journals (Sweden)

Tirsa L. E. van Westering

2015-05-01

Full Text Available Duchenne muscular dystrophy (DMD is a genetic muscle disorder caused by mutations in the Dmd gene resulting in the loss of the protein dystrophin. Patients do not only experience skeletal muscle degeneration, but also develop severe cardiomyopathy by their second decade, one of the main causes of death. The absence of dystrophin in the heart renders cardiomyocytes more sensitive to stretch-induced damage. Moreover, it pathologically alters intracellular calcium (Ca2+ concentration, neuronal nitric oxide synthase (nNOS localization and mitochondrial function and leads to inflammation and necrosis, all contributing to the development of cardiomyopathy. Current therapies only treat symptoms and therefore the need for targeting the genetic defect is immense. Several preclinical therapies are undergoing development, including utrophin up-regulation, stop codon read-through therapy, viral gene therapy, cell-based therapy and exon skipping. Some of these therapies are undergoing clinical trials, but these have predominantly focused on skeletal muscle correction. However, improving skeletal muscle function without addressing cardiac aspects of the disease may aggravate cardiomyopathy and therefore it is essential that preclinical and clinical focus include improving heart function. This review consolidates what is known regarding molecular pathology of the DMD heart, specifically focusing on intracellular Ca2+, nNOS and mitochondrial dysregulation. It briefly discusses the current treatment options and then elaborates on the preclinical therapeutic approaches currently under development to restore dystrophin thereby improving pathology, with a focus on the heart.

Comorbidity, family history and personality traits in pathological gamblers compared with healthy controls.

Science.gov (United States)

Mann, K; Lemenager, T; Zois, E; Hoffmann, S; Nakovics, H; Beutel, M; Vogelgesang, M; Wölfling, K; Kiefer, F; Fauth-Bühler, M

2017-05-01

While DSM-5 classified pathological gambling as an addictive disorder, there is debate as to whether ICD-11 should follow suit. The debate hinges on scientific evidence such as neurobiological findings, family history of psychiatric disorders, psychiatric comorbidity, and personality variables. In the "Baden-Württemberg Study of Pathological Gambling", we compared a group of 515 male pathological gamblers receiving treatment with 269 matched healthy controls. We studied differences in sociodemographic characteristics, gambling-related variables, psychiatric comorbidity (lifetime), family history of psychiatric conditions, as well as personality traits such as impulsivity (Barratt Impulsiveness Scale), sensation seeking (Zuckerman's Sensation Seeking Scale) and the NEO-FFI big five. Personality traits were validated in an age- and ethnicity-matched subsample of "pure" gamblers without any psychiatric comorbidity (including nicotine dependence). Data were analyzed using two-sample t-tests, Chi 2 analyses, Fisher's exact test and Pearson correlation analysis, as appropriate. Bonferroni correction was applied to correct for multiple comparisons. Only 1% of the gamblers had been diagnosed with an impulse control disorder other than gambling (ICD-10). Notably, 88% of the gamblers in our sample had a comorbid diagnosis of substance dependence. The highest axis I comorbidity rate was for nicotine dependence (80%), followed by alcohol dependence (28%). Early age of first gambling experience was correlated with gambling severity. Compared to first-degree relatives of controls, first-degree relatives of pathological gamblers were more likely to suffer from alcohol dependence (27.0% vs. 7.4%), pathological gambling (8.3% vs. 0.7%) and suicide attempts (2.7% vs. 0.4%). Significant group differences were observed for the NEO-FFI factors neuroticism, agreeableness and conscientiousness. Gamblers were also more impulsive than controls, but did not differ from controls in terms of

Diagnostic time in digital pathology: A comparative study on 400 cases

Directory of Open Access Journals (Sweden)

Aleksandar Vodovnik

2016-01-01

Full Text Available Background: Numerous validation studies in digital pathology confirmed its value as a diagnostic tool. However, a longer time to diagnosis than traditional microscopy has been seen as a significant barrier to the routine use of digital pathology. As a part of our validation study, we compared a digital and microscopic diagnostic time in the routine diagnostic setting. Materials and Methods: One senior staff pathologist reported 400 consecutive cases in histology, nongynecological, and fine needle aspiration cytology (20 sessions, 20 cases/session, over 4 weeks. Complex, difficult, and rare cases were excluded from the study to reduce the bias. A primary diagnosis was digital, followed by traditional microscopy, 6 months later, with only request forms available for both. Microscopic slides were scanned at ×20, digital images accessed through the fully integrated laboratory information management system (LIMS and viewed in the image viewer on double 23” displays. A median broadband speed was 299 Mbps. A diagnostic time was measured from the point slides were made available to the point diagnosis was made or additional investigations were deemed necessary, recorded independently in minutes/session and compared. Results: A digital diagnostic time was 1841 and microscopic 1956 min; digital being shorter than microscopic in 13 sessions. Four sessions with shorter microscopic diagnostic time included more cases requiring extensive use of magnifications over ×20. Diagnostic time was similar in three sessions. Conclusions: A diagnostic time in digital pathology can be shorter than traditional microscopy in the routine diagnostic setting, with adequate and stable network speeds, fully integrated LIMS and double displays as default parameters. This also related to better ergonomics, larger viewing field, and absence of physical slide handling, with effects on both diagnostic and nondiagnostic time. Differences with previous studies included a design

[Detection of RAS genes mutation using the Cobas® method in a private laboratory of pathology: Medical and economical study in comparison to a public platform of molecular biology of cancer].

Science.gov (United States)

Albertini, Anne-Flore; Raoux, Delphine; Neumann, Frédéric; Rossat, Stéphane; Tabet, Farid; Pedeutour, Florence; Duranton-Tanneur, Valérie; Kubiniek, Valérie; Vire, Olivier; Weinbreck, Nicolas

In France, determination of the mutation status of RAS genes for predictive response to anti-EGFR targeted treatments is carried out by public platforms of molecular biology of cancer created by the French National Cancer Institute. This study aims to demonstrate the feasibility of these analyses by a private pathology laboratory (MEDIPATH) as per the requirements of accreditation. We retrospectively studied the mutation status of KRAS and NRAS genes in 163 cases of colorectal metastatic cancer using the Cobas ® technique. We compared our results to those prospectively obtained through pyrosequencing and allelic discrimination by the genetic laboratory of solid tumors at the Nice University Hospital (PACA-EST regional platform). The results of both series were identical: 98.7% positive correlation; negative correlation of 93.1%; overall correlation of 95.7% (Kappa=0.92). This study demonstrates the feasibility of molecular analysis in a private pathology laboratory. As this practice requires a high level of guarantee, its accreditation, according to the NF-EN-ISO15189 quality compliance French standard, is essential. Conducting molecular analysis in this context avoids the steps of routing the sample and the result between the pathology laboratory and the platform, which reduces the overall time of rendering the result. In conclusion, the transfer of some analysis from these platforms to private pathology laboratories would allow the platforms to be discharged from a part of routine testing and therefore concentrate their efforts to the development of new analyses constantly required to access personalized medicine. Copyright © 2017. Published by Elsevier Masson SAS.

Review Article: The Role of Molecular Pathological Epidemiology in the Study of Neoplastic and Non-neoplastic Diseases in the Era of Precision Medicine.

Science.gov (United States)

Ogino, Shuji; Nishihara, Reiko; VanderWeele, Tyler J; Wang, Molin; Nishi, Akihiro; Lochhead, Paul; Qian, Zhi Rong; Zhang, Xuehong; Wu, Kana; Nan, Hongmei; Yoshida, Kazuki; Milner, Danny A; Chan, Andrew T; Field, Alison E; Camargo, Carlos A; Williams, Michelle A; Giovannucci, Edward L

2016-07-01

Molecular pathology diagnostics to subclassify diseases based on pathogenesis are increasingly common in clinical translational medicine. Molecular pathological epidemiology (MPE) is an integrative transdisciplinary science based on the unique disease principle and the disease continuum theory. While it has been most commonly applied to research on breast, lung, and colorectal cancers, MPE can investigate etiologic heterogeneity in non-neoplastic diseases, such as cardiovascular diseases, obesity, diabetes mellitus, drug toxicity, and immunity-related and infectious diseases. This science can enhance causal inference by linking putative etiologic factors to specific molecular biomarkers as outcomes. Technological advances increasingly enable analyses of various -omics, including genomics, epigenomics, transcriptomics, proteomics, metabolomics, metagenomics, microbiome, immunomics, interactomics, etc. Challenges in MPE include sample size limitations (depending on availability of biospecimens or biomedical/radiological imaging), need for rigorous validation of molecular assays and study findings, and paucities of interdisciplinary experts, education programs, international forums, and standardized guidelines. To address these challenges, there are ongoing efforts such as multidisciplinary consortium pooling projects, the International Molecular Pathological Epidemiology Meeting Series, and the Strengthening the Reporting of Observational Studies in Epidemiology-MPE guideline project. Efforts should be made to build biorepository and biobank networks, and worldwide population-based MPE databases. These activities match with the purposes of the Big Data to Knowledge (BD2K), Genetic Associations and Mechanisms in Oncology (GAME-ON), and Precision Medicine Initiatives of the United States National Institute of Health. Given advances in biotechnology, bioinformatics, and computational/systems biology, there are wide open opportunities in MPE to contribute to public

Practicing pathology in the era of big data and personalized medicine.

Science.gov (United States)

Gu, Jiang; Taylor, Clive R

2014-01-01

The traditional task of the pathologist is to assist physicians in making the correct diagnosis of diseases at the earliest possible stage to effectuate the optimal treatment strategy for each individual patient. In this respect surgical pathology (the traditional tissue diagnosis) is but a tool. It is not, of itself, the purpose of pathology practice; and change is in the air. This January 2014 issue of Applied Immunohistochemistry and Molecular Morphology (AIMM) embraces that change by the incorporation of the agenda and content of the journal Diagnostic Molecular Morphology (DMP). Over a decade ago AIMM introduced and promoted the concept of "molecular morphology," and has sought to publish molecular studies that correlate with the morphologic features that continue to define cancer and many diseases. That intent is now reinforced and extended by the merger with DMP, as a logical and timely response to the growing impact of a wide range of genetic and molecular technologies that are beginning to reshape the way in which pathology is practiced. The use of molecular and genomic techniques already demonstrates clear value in the diagnosis of disease, with treatment tailored specifically to individual patients. Personalized medicine is the future, and personalized medicine demands personalized pathology. The need for integration of the flood of new molecular data, with surgical pathology, digital pathology, and the full range of pathology data in the electronic medical record has never been greater. This review describes the possible impact of these pressures upon the discipline of pathology, and examines possible outcomes. There is a sense of excitement and adventure. Active adaption and innovation are required. The new AIMM, incorporating DMP, seeks to position itself for a central role in this process.

Imaging characteristics of hepatocellular adenoma compared with pathologic findings

International Nuclear Information System (INIS)

Zhao Jing; Zhao Xinming; Ouyang Han; Huang Wenting; Zhou Chunwu

2012-01-01

Objective: To retrospectively compare CT and MR features of hepatocellular adenoma with pathologic findings. Methods: Twelve patients with histopathologically proved hepatocellular adenoma were classified on the basis of pathologic and genotype phenotype findings into four groups: steatotic type, cytological abnormality type, telangiectatic adenoma with inflammatory infiltrates type and atypical adenoma type. The CT and MR features of each type were reviewed retrospectively compared with the pathological results. Results: In this retrospective study, 12 patients were examined with CT (8 patients) and MR (8 patients). Among 12 patients, 4 patients showed a steatotic type. One patient showed hypo-density on the non-enhanced CT and 3 patients demonstrated hypo-density on all phases of the post-contrast scans. Two lesions showed iso-intense signal on the in-phase T 1 WI with signal dropout on the out-of-phase T 1 WI, and hypo-intense signal on the T 2 WI with fat suppression sequences. One lesion demonstrated moderate hypointense signal on all phases of the post-contrast MRI scans. Two patients with the telangiectatic adenoma inflammatory infiltrates type were found. One patient showed hypo-density on the non-enhanced CT scans and hyper-density on all phases of the post-contrast CT scans. One patient demonstrated iso-intense signal and the other hypo-intense signal on the T 1 WI, and both displayed moderate hyper-intense signal on the T 2 WI with fat suppression sequences and hyper-intense signal with gradual enhancement on all phases of post-contrast MR scans. There were 3 patients with a cytological abnormality type. One patient appeared hypo-density and 1 patient showed uniform iso-density on non-enhanced CT scans. All patients who had undergone contrast-enhanced CT scans were found to have hyper-density on the hepatic arterial-dominant phase and became slightly lower on the portal venous phase. On the delay phase the density reduced further. One mass showed iso

Current update on established and novel biomarkers in salivary gland carcinoma pathology and the molecular pathways involved.

Science.gov (United States)

Stenner, Markus; Klussmann, J Peter

2009-03-01

This review aims to take stock of the new information that has accumulated over the past decade on the molecular pathology of salivary gland cancer. Emphasis will be placed on established and novel immunohistochemical markers, the pathways involved, and on findings of prognostic importance as well as new therapeutic concepts. Whenever reasonable, analogies to tumors of better explored, histologically related glandular organs such as pancreas and breast are established.

Transperitoneal laparoscopic dismembered pyeloplasty in unusual circumstances--is the outcome comparable to that achieved in familiar pathologies?

Science.gov (United States)

Abraham, George P; Das, Krishanu; Ramaswami, Krishnamohan; Siddaiah, Avinash T; George, Datson P; Abraham, Jisha J; Thampan, Oppukeril S

2012-05-01

To compare the operative outcome, morbidity profile, and functional outcome after transperitoneal laparoscopic dismembered pyeloplasty for ureteropelvic junction obstruction in unusual circumstances (intrinsic pathology in anomalous kidneys or unusual extrinsic pathologies; group 1) to the outcome after this procedure in familiar pathologies (normally located kidneys with intrinsic dysfunctional segment or extrinsic compression due to a crossing vessel; group 2). The patients were evaluated in detail. All patients underwent transperitoneal laparoscopic dismembered pyeloplasty. The operative and postoperative parameters were recorded. Patients were followed up after the procedure on a 3-month protocol. Imaging was repeated at 1 year. No intervention during the follow-up period (ie, nephrostomy, ureteral stenting, or redo pyeloplasty) and improvement in the hydronephrosis grade and diuretic renogram parameters was interpreted as procedural success. The operative, postoperative, and follow-up parameters in the 2 groups were compared. Group 1 included 17 patients with intrinsic pathologic features and renal anomalies with ureteropelvic junction obstruction due to unusual extrinsic pathology. All procedures were successfully completed with the laparoscopic approach. A significant difference was noted in the mean operative duration (group 1, 196.9 ± 10.3 minutes; group 2, 125.44 minutes, P = .00). The other operative and postoperative parameters were comparable. No significant operative or postoperative events were noted. A total of 14 patients (group 1) completed the 1-year follow-up protocol. The success rate was 92.9% (13 of 14) in group 1 and 97.9% (44 of 45) in group 2 (P = .42). The procedural duration for laparoscopic dismembered pyeloplasty in unusual circumstances is longer than in familiar pathologies. However, the morbidity profile and functional outcome in these 2 scenarios were comparable. Copyright © 2012 Elsevier Inc. All rights reserved.

Molecular Pathology of Murine Ureteritis Causing Obstructive Uropathy with Hydronephrosis

Science.gov (United States)

Ichii, Osamu; Otsuka, Saori; Namiki, Yuka; Hashimoto, Yoshiharu; Kon, Yasuhiro

2011-01-01

Primary causes of urinary tract obstruction that induces urine retention and results in hydronephrosis include uroliths, inflammation, and tumors. In this study, we analyzed the molecular pathology of ureteritis causing hydronephrosis in laboratory rodents. F2 progenies of C57BL/6 and DBA/2 mice were studied histopathologically and by comprehensive gene expression analysis of their ureters. Incidence of hydronephrosis was approximately 5% in F2 progenies. Histopathologically, this hydronephrosis was caused by stenosis of the proximal ureter, which showed fibrosis and papillary malformations of the proliferative epithelium with infiltrations of B-cell-dominated lymphocytes. Additionally, CD16-positive large granular leukocytes and eosinophils infiltrated from the ureteral mucosa to the muscular layer. Eosinophilic crystals were characteristically observed in the lumen of the ureter and the cytoplasm of large granular leukocytes, eosinophils, and transitional epithelial cells. Comprehensive gene profiling revealed remarkably elevated expression of genes associated with hyperimmune responses through activation of B cells in diseased ureters. Furthermore, diseased ureters showed dramatically higher gene expression of chitinase 3-like 3, known as Ym1, which is associated with formation both of adenomas in the transitional epithelium and of eosinophilic crystals in inflammatory conditions. The Ym1 protein was mainly localized to the cytoplasm of the transitional epithelium, infiltrated cells, and eosinophilic crystals in diseased ureters. We determined that the primary cause of hydronephrosis in F2 mice was ureteritis mediated by the local hyperimmune response with malformation of the transitional epithelium. Our data provide a novel molecular pathogenesis for elucidating causes of aseptic inflammation in human upper urinary tracts. PMID:22114694

Comparison between the diagnostic accuracy of clinico-pathological and molecular tests for feline infectious peritonitis (FIP

Directory of Open Access Journals (Sweden)

Angelica Stranieri

2015-07-01

Full Text Available The aim of this study was to compare the diagnostic accuracy for feline infectious peritonitis (FIP of conventional clinic-pathological tests with that of molecular tests such as routine PCR and PCR followed by the sequencing of the Spike (S gene. Blood, effusion and tissues specimens were collected from 21 FIP suspected cats. In vivo examination consisted of CBC, serum protein electrophoresis, AGP measurement, cytological and biochemical examination and the evaluation of the ΔTNC on effusions, and of molecular tests such the screening PCR (target: 3’UTR region and the PCR directed towards the S gene followed by the amplification products sequencing in order to detect the aminoacidic substitution recently considered diagnostic for FIP1. These molecular techniques were applied to tissues collected during necropsy, which also allowed forming an FIP group (13 cats and a non-FIP group (5 cats based on histology and immunohistochemistry. The best test on tissues was immunohistochemistry (sens: 92.3%; spec: 100%, while the screening PCR suffered of low specificity (spec: 33.3% and the S gene sequencing showed low sensitivity (sens: 69.2%.On effusions, the best tests resulted screening PCR and cytology (sens and spec: 100% in comparison with the ΔTNC measurement (sens: 85.7 %; spec: 100% and the S gene sequencing (sens: 42.8%; spec: 100%.On blood, the best test resulted AGP measurement (sens: 81.8%; spec: 100%, while serum protein electrophoresis showed a surprisingly low sensitivity (sens: 41.7%. Screening PCR (sens: 55.6%; spec: 100% and S gene sequencing (sens: 33.3%; spec: 100% proved again low accuracy.

Metastatic non-small-cell lung cancer: consensus on pathology and molecular tests, first-line, second-line, and third-line therapy: 1st ESMO Consensus Conference in Lung Cancer; Lugano 2010

DEFF Research Database (Denmark)

Felip, E; Gridelli, C; Baas, P

2011-01-01

the conference, the expert panel prepared clinically relevant questions concerning five areas: early and locally advanced non-small-cell lung cancer (NSCLC), first-line metastatic NSCLC, second-/third-line NSCLC, NSCLC pathology and molecular testing, and small-cell lung cancer to be addressed through discussion......The 1st ESMO Consensus Conference on lung cancer was held in Lugano, Switzerland on 21 and 22 May 2010 with the participation of a multidisciplinary panel of leading professionals in pathology and molecular diagnostics, medical oncology, surgical oncology and radiation oncology. Before...... at the Consensus Conference. All relevant scientific literature for each question was reviewed in advance. During the Consensus Conference, the panel developed recommendations for each specific question. The consensus agreement on three of these areas: NSCLC pathology and molecular testing, the treatment of first-line...

Comparative evaluation of different methods of treatment of miners with vibration-noise pathology

Energy Technology Data Exchange (ETDEWEB)

Bel' skaya, M.L.; Nekhorosheva, M.A.; Konovalova, S.I.; Kukhtina, G.V.; Gonchar, I.G.; Terent' eva, D.P.; Grishchenko, L.A.; Soboleva, N.P.; Kharitonov, S.A.; Priklonskii, I.V.

1984-10-01

Two new therapeutic methods of treating vibration-noise pathology, needle acupuncture and hyperbaric oxygenation, are compared with established methods of medical and physical therapy. Four complexes of therapy are recommended: I complex (control), medication and physical therapy; II complex, acupuncture and medical therapy; III complex, acupuncture, medical and physical therapy; IV complex, hyperbaric oxygenation, medical and physical therapy. The four complexes were tested on a selected group of miners. II, III and IV complexes were correlated with control (I) on the basis of subjective signs, objective changes in nervous system and functional state of vegetative and peripheral nervous system. A table compares the effectiveness of II, III, IV complexes with I complex. Results confirm effectiveness of medical and physical therapy. Application of acupuncture increases benefits to cardiovascular system and hyperbaric therapy aids neurosensory hearing impairment. As a result of investigation, acupuncture and hyperbaric therapy are recommended for treatment of patients suffering vibration-noise pathology with a differential approach to their purpose. 8 references.

Splenic marginal zone lymphoma: a review of the clinical presentation, pathology, molecular biology, and management

Directory of Open Access Journals (Sweden)

Teixeira Mendes LS

2014-07-01

Full Text Available Larissa Sena Teixeira Mendes,1 Ming-Qing Du,2 Estella Matutes,3 Andrew Wotherspoon11Histopathology Department, Royal Marsden Hospital, London, UK; 2Molecular Malignancy Laboratory and Department of Histopathology, University Hospital NHS Foundation Trust/Division of Molecular Histopathology, Department of Pathology, University of Cambridge, Cambridge, UK; 3Hematopathology Unit, Hospital Clinic, Barcelona University, Barcelona, Spain Abstract: Splenic marginal zone lymphoma is a distinct low grade B-cell lymphoma primarily occurring in the spleen and separate from nodal marginal zone lymphoma and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. It is characterized by a relative indolent course, splenomegaly, moderate lymphocytosis, and an intrasinusoidal pattern of involvement, especially in the bone marrow. It is postulated that the neoplastic clone originates from persistent antigenic stimulation of marginal zone B-cells. Molecular and cytogenetic studies have failed to show specific alterations. There is no standard criterion to initiate treatment, which may include a watch and wait policy, splenectomy, or chemo/immunotherapy. This review highlights the main features of this entity, reassessing the guidelines for diagnosis, prognostic factors, staging, and management published by the SMZL Working Group (2008. Keywords: splenectomy, villous lymphocytes, guidelines

Digital pathology in nephrology clinical trials, research, and pathology practice.

Science.gov (United States)

Barisoni, Laura; Hodgin, Jeffrey B

2017-11-01

In this review, we will discuss (i) how the recent advancements in digital technology and computational engineering are currently applied to nephropathology in the setting of clinical research, trials, and practice; (ii) the benefits of the new digital environment; (iii) how recognizing its challenges provides opportunities for transformation; and (iv) nephropathology in the upcoming era of kidney precision and predictive medicine. Recent studies highlighted how new standardized protocols facilitate the harmonization of digital pathology database infrastructure and morphologic, morphometric, and computer-aided quantitative analyses. Digital pathology enables robust protocols for clinical trials and research, with the potential to identify previously underused or unrecognized clinically useful parameters. The integration of digital pathology with molecular signatures is leading the way to establishing clinically relevant morpho-omic taxonomies of renal diseases. The introduction of digital pathology in clinical research and trials, and the progressive implementation of the modern software ecosystem, opens opportunities for the development of new predictive diagnostic paradigms and computer-aided algorithms, transforming the practice of renal disease into a modern computational science.

Magnetic resonance imaging in breast cancer treated with neoadjuvant chemotherapy: radiologic-pathologic correlation of the response and disease-free survival depending on molecular subtype.

Science.gov (United States)

Cruz Ciria, S; Jiménez Aragón, F; García Mur, C; Esteban Cuesta, H; Gros Bañeres, B

2014-01-01

To evaluate the radiologic and pathologic responses to neoadjuvant chemotherapy and their correlation in the molecular subtypes of breast cancer and to analyze their impact in disease-free survival. We included 205 patients with breast cancer treated with neoadjuvant chemotherapy. We evaluated the radiologic response by comparing MRI images acquired before and after chemotherapy. The pathologic response was classified on the Miller and Payne scale. For each subtype (HER2+, TN, luminal A, luminal B HER2-, and luminal B HER2+), we used the χ(2) test, Student's t-test, ANOVA, and Kendall's Tau-b to evaluate the radiologic response and the pathologic response, the radiologic-pathologic correlation, and the disease-free survival. The subtypes HER2+ (62.1%) and TN (45.2%) had higher rates of complete radiologic response. The pathologic response was 65.5% in the HER2+ subtype, 38.1% in the TN subtype, 2.6% in the luminal A subtype, 8.2% in the luminal B HER2- subtype, and 31% in the luminal B HER2+ subtype. The rate of radiologic-pathologic correlation was significant in all subtypes, higher in TN and HER2 (Tau-b coefficients 0.805 and 0.717, respectively). Disease-free survival was higher in HER2+ (91.9±3.3 months) and lower in TN (69.5±6.3 months), with significant differences between the cases with poor and good radiologic responses (P=.040). Survival was greater in cases with good radiologic response, except in cases with luminal A subtype. MRI can be a useful tool that provides information about the evolution of breast cancer treated with neoadjuvant chemotherapy, which varies with the immunohistochemical subtype. Copyright © 2012 SERAM. Published by Elsevier Espana. All rights reserved.

Incidence of Appendicitis over Time: A Comparative Analysis of an Administrative Healthcare Database and a Pathology-Proven Appendicitis Registry

Science.gov (United States)

Clement, Fiona; Zimmer, Scott; Dixon, Elijah; Ball, Chad G.; Heitman, Steven J.; Swain, Mark; Ghosh, Subrata

2016-01-01

Importance At the turn of the 21st century, studies evaluating the change in incidence of appendicitis over time have reported inconsistent findings. Objectives We compared the differences in the incidence of appendicitis derived from a pathology registry versus an administrative database in order to validate coding in administrative databases and establish temporal trends in the incidence of appendicitis. Design We conducted a population-based comparative cohort study to identify all individuals with appendicitis from 2000 to2008. Setting & Participants Two population-based data sources were used to identify cases of appendicitis: 1) a pathology registry (n = 8,822); and 2) a hospital discharge abstract database (n = 10,453). Intervention & Main Outcome The administrative database was compared to the pathology registry for the following a priori analyses: 1) to calculate the positive predictive value (PPV) of administrative codes; 2) to compare the annual incidence of appendicitis; and 3) to assess differences in temporal trends. Temporal trends were assessed using a generalized linear model that assumed a Poisson distribution and reported as an annual percent change (APC) with 95% confidence intervals (CI). Analyses were stratified by perforated and non-perforated appendicitis. Results The administrative database (PPV = 83.0%) overestimated the incidence of appendicitis (100.3 per 100,000) when compared to the pathology registry (84.2 per 100,000). Codes for perforated appendicitis were not reliable (PPV = 52.4%) leading to overestimation in the incidence of perforated appendicitis in the administrative database (34.8 per 100,000) as compared to the pathology registry (19.4 per 100,000). The incidence of appendicitis significantly increased over time in both the administrative database (APC = 2.1%; 95% CI: 1.3, 2.8) and pathology registry (APC = 4.1; 95% CI: 3.1, 5.0). Conclusion & Relevance The administrative database overestimated the incidence of appendicitis

[Role of contemporary pathological diagnostics in the personalized treatment of cancer].

Science.gov (United States)

Tímár, József

2013-03-01

Due to the developments of pathology in the past decades (immunohistochemistry and molecular pathology) classification of cancers changed fundamentally, laying a ground for personalized management of cancer patients. Our picture of cancer is more complex today, identifying the genetic basis of the morphological variants. On the other hand, this picture has a much higher resolution enabling us to subclassify similar histological cancer types based on molecular markers. This redefined classification of cancers helps us to better predict the possible biological behavior of the disease and/or the therapeutic sensitivity, opening the way toward a more personalized treatment of this disease. The redefined molecular classification of cancer may affect the universal application of treatment protocols. To achieve this goal molecular diagnostics must be an integral and reimbursed part of the routine pathological diagnostics. On the other hand, it is time to extend the multidisciplinary team with molecular pathologist to improve the decision making process of the management of cancer patients.

Next-Generation Sequencing for Infectious Disease Diagnosis and Management: A Report of the Association for Molecular Pathology.

Science.gov (United States)

Lefterova, Martina I; Suarez, Carlos J; Banaei, Niaz; Pinsky, Benjamin A

2015-11-01

Next-generation sequencing (NGS) technologies are increasingly being used for diagnosis and monitoring of infectious diseases. Herein, we review the application of NGS in clinical microbiology, focusing on genotypic resistance testing, direct detection of unknown disease-associated pathogens in clinical specimens, investigation of microbial population diversity in the human host, and strain typing. We have organized the review into three main sections: i) applications in clinical virology, ii) applications in clinical bacteriology, mycobacteriology, and mycology, and iii) validation, quality control, and maintenance of proficiency. Although NGS holds enormous promise for clinical infectious disease testing, many challenges remain, including automation, standardizing technical protocols and bioinformatics pipelines, improving reference databases, establishing proficiency testing and quality control measures, and reducing cost and turnaround time, all of which would be necessary for widespread adoption of NGS in clinical microbiology laboratories. Copyright © 2015 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Fatal toxoplasmosis in a southern muriqui (Brachyteles arachnoides) from São Paulo state, Brazil: Pathological, immunohistochemical, and molecular characterization.

Science.gov (United States)

Santos, Stéfanie Vanessa; Pena, Hilda F J; Talebi, Mauricio G; Teixeira, Rodrigo H F; Kanamura, Cristina T; Diaz-Delgado, Josué; Gennari, Solange M; Catão-Dias, José Luiz

2018-04-01

We report the pathological, immunohistochemical, and molecular features of fatal acute systemic toxoplasmosis in an adult, female, free-living southern muriqui (Brachyteles arachnoides) from São Paulo state, Brazil. PCR-RFLP genotyping analysis identified the #21 genotype of Toxoplasma gondii. This represents the first report of acute toxoplasmosis involving this genotype in humans and animals. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A comparative cellular and molecular biology of longevity database.

Science.gov (United States)

Stuart, Jeffrey A; Liang, Ping; Luo, Xuemei; Page, Melissa M; Gallagher, Emily J; Christoff, Casey A; Robb, Ellen L

2013-10-01

Discovering key cellular and molecular traits that promote longevity is a major goal of aging and longevity research. One experimental strategy is to determine which traits have been selected during the evolution of longevity in naturally long-lived animal species. This comparative approach has been applied to lifespan research for nearly four decades, yielding hundreds of datasets describing aspects of cell and molecular biology hypothesized to relate to animal longevity. Here, we introduce a Comparative Cellular and Molecular Biology of Longevity Database, available at ( http://genomics.brocku.ca/ccmbl/ ), as a compendium of comparative cell and molecular data presented in the context of longevity. This open access database will facilitate the meta-analysis of amalgamated datasets using standardized maximum lifespan (MLSP) data (from AnAge). The first edition contains over 800 data records describing experimental measurements of cellular stress resistance, reactive oxygen species metabolism, membrane composition, protein homeostasis, and genome homeostasis as they relate to vertebrate species MLSP. The purpose of this review is to introduce the database and briefly demonstrate its use in the meta-analysis of combined datasets.

Splicing of phenylalanine hydroxylase (PAH) exon 11 is vulnerable - Molecular pathology of mutations in PAH exon 11

DEFF Research Database (Denmark)

Heintz, Caroline; Dobrowolski, Steven F.; Andersen, Henriette Skovgaard

2012-01-01

as a vulnerable exon and used patient derived lymphoblast cell lines and PAH minigenes to study the molecular defect that impacted pre-mRNA processing. We showed that the c.1144T>C and c.1066-3C>T mutations cause exon 11 skipping, while the c.1139C>T mutation is neutral or slightly beneficial. The c.1144T......In about 20-30% of phenylketonuria (PKU) patients, phenylalanine (Phe) levels can be controlled by cofactor 6R-tetrahydrobiopterin (BH(4)) administration. The phenylalanine hydroxylase (PAH) genotype has a predictive value concerning BH(4)-response and therefore a correct assessment of the mutation...... molecular pathology is important. Mutations that disturb the splicing of exons (e.g. interplay between splice site strength and regulatory sequences like exon splicing enhancers (ESEs)/exon splicing silencers (ESSs)) may cause different severity of PKU. In this study, we identified PAH exon 11...

CT presentations of colorectal cancer with chronic schistosomiasis: A comparative study with pathological findings

Energy Technology Data Exchange (ETDEWEB)

Zhang, Wei, E-mail: zhangwei976@163.com [Department of Radiology, Tongji Hospital, Tongji University, No. 389, Xincun Road, Putuo District, Shanghai 200065 (China); Wang, Pei-Jun, E-mail: peijunwang_tongji@163.com [Department of Radiology, Tongji Hospital, Tongji University, No. 389, Xincun Road, Putuo District, Shanghai 200065 (China); Shen, Xing, E-mail: shenxing1997@163.com [Department of Radiology, Traditional Chinese Hospital, No. 189, Chaoyangxi Road, Kun Shan 215300, Jiangsu Province (China); Wang, Guo-liang, E-mail: glwang1960@163.com [Department of Radiology, Tongji Hospital, Tongji University, No. 389, Xincun Road, Putuo District, Shanghai 200065 (China); Zhao, Xiao-hu, E-mail: tiger1968@163.com [Department of Radiology, Tongji Hospital, Tongji University, No. 389, Xincun Road, Putuo District, Shanghai 200065 (China); Seema, S.F., E-mail: saaaamaaaa@163.com [Department of Radiology, Tongji Hospital, Tongji University, No. 389, Xincun Road, Putuo District, Shanghai 200065 (China); Zheng, Shao-qiang, E-mail: shaoqiangzh@163.com [Department of Radiology, Tongji Hospital, Tongji University, No. 389, Xincun Road, Putuo District, Shanghai 200065 (China); Li, Ming-hua, E-mail: minghuali@163.com [Department of Radiology, Tongji Hospital, Tongji University, No. 389, Xincun Road, Putuo District, Shanghai 200065 (China)

2012-08-15

Objective: To clarify pathological basis of computed tomography (CT) presentations of colorectal cancer (CRC) with schistosomiasis for the purpose of improving the accuracy of CT diagnosis and differential diagnosis of the condition. Materials and methods: 130 patients (87 male and 43 female; age range 49-86 years, mean 71.1) were selected whose diagnoses were pathologically confirmed as CRC with schistosomiasis. All the patients underwent abdominal plain CT and contrast enhanced scanning. The location, morphology, size, calcification features and enhancement modalities (patterns) were evaluated and compared with the pathological findings by two radiologists in a blind way. Results: CT showed that in 130 patients, the tumors occurred in the large intestine, among which 109 (83.9%) were solitary and 21 (16.1%) were multifocal. The intestinal wall was irregularly thickened in 123 patients, with soft tissue masses in 7 patients. Linear, spotty and small patchy calcifications were seen in 104 (80.0%) patients, with unclear margins in 96 patients. The tumors were markedly unevenly enhanced in 92 patients. Pathological examination revealed adenocarcinoma in 114 patients and in 104 patients, calcified Shistosoma japonicum (S. japonicum) ova inside the tumors, 15 patients were mucinous adenocarcinoma, and one patient was that of adenosquamous carcinoma. Conclusion: Irregular thickening of the intestinal wall, soft tissue masses, multiple S. japonicum ova calcifications inside the tumor with obscured margins and multiple intestinal masses in some patients are important CT features of CRC with schistosomiasis.

Integrated Pathology Informatics Enables High-Quality Personalized and Precision Medicine: Digital Pathology and Beyond.

Science.gov (United States)

Volynskaya, Zoya; Chow, Hung; Evans, Andrew; Wolff, Alan; Lagmay-Traya, Cecilia; Asa, Sylvia L

2018-03-01

- The critical role of pathology in diagnosis, prognosis, and prediction demands high-quality subspecialty diagnostics that integrates information from multiple laboratories. - To identify key requirements and to establish a systematic approach to providing high-quality pathology in a health care system that is responsible for services across a large geographic area. - This report focuses on the development of a multisite pathology informatics platform to support high-quality surgical pathology and hematopathology using a sophisticated laboratory information system and whole slide imaging for histology and immunohistochemistry, integrated with ancillary tools, including electron microscopy, flow cytometry, cytogenetics, and molecular diagnostics. - These tools enable patients in numerous geographic locations access to a model of subspecialty pathology that allows reporting of every specimen by the right pathologist at the right time. The use of whole slide imaging for multidisciplinary case conferences enables better communication among members of patient care teams. The system encourages data collection using a discrete data synoptic reporting module, has implemented documentation of quality assurance activities, and allows workload measurement, providing examples of additional benefits that can be gained by this electronic approach to pathology. - This approach builds the foundation for accurate big data collection and high-quality personalized and precision medicine.

Laboratory Information Systems in Molecular Diagnostics: Why Molecular Diagnostics Data are Different.

Science.gov (United States)

Lee, Roy E; Henricks, Walter H; Sirintrapun, Sahussapont J

2016-03-01

Molecular diagnostic testing presents new challenges to information management that are yet to be sufficiently addressed by currently available information systems for the molecular laboratory. These challenges relate to unique aspects of molecular genetic testing: molecular test ordering, informed consent issues, diverse specimen types that encompass the full breadth of specimens handled by traditional anatomic and clinical pathology information systems, data structures and data elements specific to molecular testing, varied testing workflows and protocols, diverse instrument outputs, unique needs and requirements of molecular test reporting, and nuances related to the dissemination of molecular pathology test reports. By satisfactorily addressing these needs in molecular test data management, a laboratory information system designed for the unique needs of molecular diagnostics presents a compelling reason to migrate away from the current paper and spreadsheet information management that many molecular laboratories currently use. This paper reviews the issues and challenges of information management in the molecular diagnostics laboratory.

One fungus, one name promotes progressive plant pathology.

Science.gov (United States)

Wingfield, Michael J; De Beer, Z Wilhelm; Slippers, Bernard; Wingfield, Brenda D; Groenewald, Johannes Z; Lombard, Lorenzo; Crous, Pedro W

2012-08-01

The robust and reliable identification of fungi underpins virtually every element of plant pathology, from disease diagnosis to studies of biology, management/control, quarantine and, even more recently, comparative genomics. Most plant diseases are caused by fungi, typically pleomorphic organisms, for which the taxonomy and, in particular, a dual nomenclature system have frustrated and confused practitioners of plant pathology. The emergence of DNA sequencing has revealed cryptic taxa and revolutionized our understanding of relationships in the fungi. The impacts on plant pathology at every level are already immense and will continue to grow rapidly as new DNA sequencing technologies continue to emerge. DNA sequence comparisons, used to resolve a dual nomenclature problem for the first time only 19 years ago, have made it possible to approach a natural classification for the fungi and to abandon the confusing dual nomenclature system. The journey to a one fungus, one name taxonomic reality has been long and arduous, but its time has come. This will inevitably have a positive impact on plant pathology, plant pathologists and future students of this hugely important discipline on which the world depends for food security and plant health in general. This contemporary review highlights the problems of a dual nomenclature, especially its impact on plant pathogenic fungi, and charts the road to a one fungus, one name system that is rapidly drawing near. © 2011 The Authors. Molecular Plant Pathology © 2011 BSPP and Blackwell Publishing Ltd.

Deginerative changes of femoral articular cartilage in the knee : comparative study of specimen sonography and pathology

International Nuclear Information System (INIS)

Park, Ju Youn; Hong, Sung Hwan; Sohn, Jin Hee; Wee, Young Hoon; Chang, Jun Dong; Park, Hong Seok; Lee, Eil Seoung; Kang Ik Won

2001-01-01

To determine the sonographic findings of degenerative change in femoral articular cartilage of the knee by comparative study of specimen sonography and pathology. We obtained 40 specimens of cartilage of the femur (20 medial and 20 lateral condylar) from 20 patients with osteoarthritis of the knee who had undergone total knee replacement. The specimens were placed in a saline-filled container and sonography was performed using a 10-MHz linear transducer. Sonographic abnormalities were evaluated at the cartilage surface, within the cartilage, and at the bone-cartilage interface, and were compared with the corresponding pathologic findings. In addition, cartilage thickness was measured at a representative portion of each femoral cartilage specimen and was compared with the thickness determined by sonography. 'Dot' lesions, irregularity or loss of the hyperechoic line, were demonstrated by sonography at the saline-cartilage interface of 14 cartilages. Pathologic examination showed that these findings corresponded to cleft, detachment, erosion, and degeneration. Irregularities in the hyperechoic line at the bone-cartilage interface were revealed by sonography in eight cartilages and were related to irregularity or loss of tidemark, downward displacement of the cartilage, and subchondral callus formation. Dot lesions, corresponding to cleft and degeneration, were noted within one cartilage. Cartilage thickness measured on specimen and by sonography showed no significant difference (p=0.446). Specimen sonography suggested that articular cartilage underwent degenerative histopathological change. Cartilage thickness measured by sonography exactly reflected real thickness

Genetics and molecular pathology of Stargardt-like macular degeneration.

Science.gov (United States)

Vasireddy, Vidyullatha; Wong, Paul; Ayyagari, Radha

2010-05-01

Stargardt-like macular degeneration (STGD3) is an early onset, autosomal dominant macular degeneration. STGD3 is characterized by a progressive pathology, the loss of central vision, atrophy of the retinal pigment epithelium, and accumulation of lipofuscin, clinical features that are also characteristic of age-related macular degeneration. The onset of clinical symptoms in STGD3, however, is typically observed within the second or third decade of life (i.e., starting in the teenage years). The clinical profile at any given age among STGD3 patients can be variable suggesting that, although STGD3 is a single gene defect, other genetic or environmental factors may play a role in moderating the final disease phenotype. Genetic studies localized the STGD3 disease locus to a small region on the short arm of human chromosome 6, and application of a positional candidate gene approach identified protein truncating mutations in the elongation of very long chain fatty acids-4 gene (ELOVL4) in patients with this disease. The ELOVL4 gene encodes a protein homologous to the ELO group of proteins that participate in fatty acid elongation in yeast. Pathogenic mutations found in the ELOVL4 gene result in altered trafficking of the protein and behave with a dominant negative effect. Mice carrying an Elovl4 mutation developed photoreceptor degeneration and depletion of very long chain fatty acids (VLCFA). ELOVL4 protein participates in the synthesis of fatty acids with chain length longer than 26 carbons. Studies on ELOVL4 indicate that VLCFA may be necessary for normal function of the retina, and the defective protein trafficking and/or altered VLCFA elongation underlies the pathology associated with STGD3. Determining the role of VLCFA in the retina and discerning the implications of abnormal trafficking of mutant ELOVL4 and depleted VLCFA content in the pathology of STGD3 will provide valuable insight in understanding the retinal structure, function, and pathology underlying STGD3

Homo floresiensis contextualized: a geometric morphometric comparative analysis of fossil and pathological human samples.

Directory of Open Access Journals (Sweden)

Karen L Baab

Full Text Available The origin of hominins found on the remote Indonesian island of Flores remains highly contentious. These specimens may represent a new hominin species, Homo floresiensis, descended from a local population of Homo erectus or from an earlier (pre-H. erectus migration of a small-bodied and small-brained hominin out of Africa. Alternatively, some workers suggest that some or all of the specimens recovered from Liang Bua are pathological members of a small-bodied modern human population. Pathological conditions proposed to explain their documented anatomical features include microcephaly, myxoedematous endemic hypothyroidism ("cretinism" and Laron syndrome (primary growth hormone insensitivity. This study evaluates evolutionary and pathological hypotheses through comparative analysis of cranial morphology. Geometric morphometric analyses of landmark data show that the sole Flores cranium (LB1 is clearly distinct from healthy modern humans and from those exhibiting hypothyroidism and Laron syndrome. Modern human microcephalic specimens converge, to some extent, on crania of extinct species of Homo. However in the features that distinguish these two groups, LB1 consistently groups with fossil hominins and is most similar to H. erectus. Our study provides further support for recognizing the Flores hominins as a distinct species, H. floresiensis, whose affinities lie with archaic Homo.

Homo floresiensis Contextualized: A Geometric Morphometric Comparative Analysis of Fossil and Pathological Human Samples

Science.gov (United States)

Baab, Karen L.; McNulty, Kieran P.; Harvati, Katerina

2013-01-01

The origin of hominins found on the remote Indonesian island of Flores remains highly contentious. These specimens may represent a new hominin species, Homo floresiensis, descended from a local population of Homo erectus or from an earlier (pre-H. erectus) migration of a small-bodied and small-brained hominin out of Africa. Alternatively, some workers suggest that some or all of the specimens recovered from Liang Bua are pathological members of a small-bodied modern human population. Pathological conditions proposed to explain their documented anatomical features include microcephaly, myxoedematous endemic hypothyroidism (“cretinism”) and Laron syndrome (primary growth hormone insensitivity). This study evaluates evolutionary and pathological hypotheses through comparative analysis of cranial morphology. Geometric morphometric analyses of landmark data show that the sole Flores cranium (LB1) is clearly distinct from healthy modern humans and from those exhibiting hypothyroidism and Laron syndrome. Modern human microcephalic specimens converge, to some extent, on crania of extinct species of Homo. However in the features that distinguish these two groups, LB1 consistently groups with fossil hominins and is most similar to H. erectus. Our study provides further support for recognizing the Flores hominins as a distinct species, H. floresiensis, whose affinities lie with archaic Homo. PMID:23874886

Immunohistochemical Expression of Survivin in Breast Carcinoma: Relationship with Clinico pathological Parameters, Proliferation and Molecular Classification

International Nuclear Information System (INIS)

YOUSSEF, N.S.; HEWEDI, I.H.; ABD RABOH, N.M.

2008-01-01

Background and Objective: Survivin is a novel member of the inhibitor of apoptosis (IAP) gene family. It is associated with more aggressive behavior and parameters of poor prognosis in most human cancers including gastric, colorectal and bladder carcinomas. However, conflicting data exist on its prognostic effect in breast cancer. This current study is designed to assess survivin expression in breast carcinoma relating results with clinico pathological parameters, proliferation (MIB-1) and molecular classification. Material and Methods: Our retrospective study com- prised of 65 archived cases of breast carcinoma. Samples from the tumor and the adjacent normal breast tissue were immuno stained for survivin and MIB-1. Nuclear and cytoplasmic survivin expression was evaluated in normal breast tissue and carcinoma regarding both the intensity and the percentage of positive cells. ER, PR, HER2 were used as surrogate markers to classify the cases into four molecular subtypes. Results: Survivin expression was detected in 78.5% of breast carcinomas. The adjacent normal breast tissue was immuno negative. Survivin expression showed significant association with increased tumor size ( p <0.0001), high histologic grade ( p =0.04), lymph node metastases ( p <0.001), advanced tumor stage ( p <0.0001), MIB-1 expression ( p =0.02), negative estrogen receptor status ( p =0.01) and negative progesterone receptor status ( p <0.0001). The subcellular localization of survivin significantly related to histologic grade, stage and lymph node involvement. The percentage of TNP (triple negative phenotype) and HER2+/ER-PR- tumors expressing survivin were significantly higher compared to the Luminal subtypes ( p =0.01). Conclusion: Survivin expression was associated with parameters of poor prognosis in breast cancer. Moreover, the cancer-specific expression of survivin, coupled with its importance in inhibiting cell death and in regulating cell division, makes it a potential target for novel

Comparative study of radiologic-pathologic findings of experimental clonorchiasis in rabbits

International Nuclear Information System (INIS)

Ryu, Kyung Nam; Lim, Jae Hoon; Cho, You Jung; Yang, Moon Ho

1993-01-01

Radiological investigation in patients with clonorchiasis is very important as this is the only method of evaluating the severity of clonorchiasis. In order to correlate the radiologic and pathologic findings of clonorchiasis, fourteen rabbits infested with Clonorchis sinensis and five control rabbits were examined radiologically by ultrasonography, computed tomography and cholangiography and the results were correlated with pathologic findings. Dilatation of the intrahepatic small bile ducts of the liver was due to obstruction by flukes: oval or elliptical, small filling defects or irregular margin of the bile ducts on cholangiogram or intraluminal echoes on sonogram represented flukes per se; periductal thickening on sonogram and periductal enhancement of bile ducts on CT were due to inflammatory cell infiltration, adenomatous hyperplasia and periductal fibrosis; band like enhancement at the periphery of the liver on CT represented proliferated bile ducts, destruction of liver cells and resultant fibrosis. The study confirmed the pathological bases for the radiological findings of clonorchiasis in liver and bile ducts and will, perhaps, serve as a basis for the future radiologic-pathological correlation of clonorchiasis and in further clinical and experimental researches in the biliary tract diseases

Comparative study of radiologic-pathologic findings of experimental clonorchiasis in rabbits

Energy Technology Data Exchange (ETDEWEB)

Ryu, Kyung Nam; Lim, Jae Hoon; Cho, You Jung; Yang, Moon Ho [College of Medicine, Kyung Hee University, Seoul (Korea, Republic of)

1993-01-15

Radiological investigation in patients with clonorchiasis is very important as this is the only method of evaluating the severity of clonorchiasis. In order to correlate the radiologic and pathologic findings of clonorchiasis, fourteen rabbits infested with Clonorchis sinensis and five control rabbits were examined radiologically by ultrasonography, computed tomography and cholangiography and the results were correlated with pathologic findings. Dilatation of the intrahepatic small bile ducts of the liver was due to obstruction by flukes: oval or elliptical, small filling defects or irregular margin of the bile ducts on cholangiogram or intraluminal echoes on sonogram represented flukes per se; periductal thickening on sonogram and periductal enhancement of bile ducts on CT were due to inflammatory cell infiltration, adenomatous hyperplasia and periductal fibrosis; band like enhancement at the periphery of the liver on CT represented proliferated bile ducts, destruction of liver cells and resultant fibrosis. The study confirmed the pathological bases for the radiological findings of clonorchiasis in liver and bile ducts and will, perhaps, serve as a basis for the future radiologic-pathological correlation of clonorchiasis and in further clinical and experimental researches in the biliary tract diseases.

Recommendations for processing cardiovascular surgical pathology specimens: a consensus statement from the Standards and Definitions Committee of the Society for Cardiovascular Pathology and the Association for European Cardiovascular Pathology

NARCIS (Netherlands)

Stone, James R.; Basso, Cristina; Baandrup, Ulrik T.; Bruneval, Patrick; Butany, Jagdish; Gallagher, Patrick J.; Halushka, Marc K.; Miller, Dylan V.; Padera, Robert F.; Radio, Stanley J.; Sheppard, Mary N.; Suvarna, Kim; Tan, Carmela D.; Thiene, Gaetano; van der Wal, Allard C.; Veinot, John P.

2012-01-01

With the advent of molecular subclassification of diseases, much consideration should be given to the proper processing of cardiovascular surgical pathology specimens to maximize patient care. Such specimens include endomyocardial biopsies, cardiac myectomy specimens, cardiac apical core segments,

Oligodendroglioma: pathology, molecular mechanisms and markers

NARCIS (Netherlands)

Wesseling, P.; Bent, M. van den; Perry, A.

2015-01-01

For nearly a century, the diagnosis and grading of oligodendrogliomas and oligoastrocytomas has been based on histopathology alone. Roughly 20 years ago, the first glioma-associated molecular signature was found with complete chromosome 1p and 19q codeletion being particularly common in

Pathological jealousy and pathological love: Apples to apples or apples to oranges?

Science.gov (United States)

Stravogiannis, Andrea Lorena da C; Kim, Hyoun S; Sophia, Eglacy C; Sanches, Cíntia; Zilberman, Monica L; Tavares, Hermano

2018-01-01

Pathological jealousy evokes emotions, thoughts, and behaviors that cause damage to social and interpersonal relationships. On the other hand, pathological love is the uncontrollable behavior of caring for a partner that results in neglecting the needs of the self. The aim of the present research was to assess the similarities and differences between the two psychopathologies of love. To this end, thirty-two individuals with pathological jealousy and 33 individuals with pathological love were compared on demographics, aspects of romantic relationship (jealousy, satisfaction, love style), psychiatric co-morbidities, personality and psychological characteristics (e.g., impulsivity). In a univariate analysis individuals with pathological jealousy were more likely to be in a current relationship and reported greater satisfaction. The avoidant attachment and the ludus love style were associated with pathological jealousy whereas the secure attachment and agape love style was associated with pathological love. Almost three-quarters (72.3%) of the sample met criteria for a current psychiatric disorder, however no differences emerged between the pathological jealousy and pathological love groups. In a binary logistic regression, relationship status and impairments in parenting significantly differentiated the groups. While both pathological jealousy and pathological love share similarities, they also present with unique differences, which may have important treatment implications. Copyright © 2017 Elsevier B.V. All rights reserved.

Molecular pathology of breast apocrine carcinomas

DEFF Research Database (Denmark)

Celis, J.E.; Gromova, I.; Gromov, P.

2006-01-01

.5% of all invasive breast cancers according to the Danish Breast Cancer Cooperative Group Registry, and despite the fact that they are morphologically distinct from other breast lesions, there are at present no standard molecular criteria available for their diagnosis. In addition, the relationship between...

Bioenergetics molecular biology, biochemistry, and pathology

CERN Document Server

Ozawa, Takayuki

1990-01-01

The emergence of the Biochemical Sciences is underlined by the FAOB symposium in Seoul and highlighted by this Satellite meeting on the "New Bioenergetics. " Classical mitochondrial electron transfer and energy coupling is now complemented by the emerging molecular biology of the respiratory chain which is studied hand in hand with the recognition of mitochondrial disease as a major and emerging study in the basic and clinical medical sciences. Thus, this symposium has achieved an important balance of the fundamental and applied aspects of bioenergetics in the modern setting of molecular biology and mitochondrial disease. At the same time, the symposium takes note not only of the emerging excellence of Biochemical Studies in the Orient and indeed in Korea itself, but also retrospectively enjoys the history of electron transport and energy conservation as represented by the triumvirate ofYagi, King and Slater. Many thanks are due Drs. Kim and Ozawa for their elegant organization of this meeting and its juxtapo...

Endocrine pathology: past, present and future.

Science.gov (United States)

Asa, Sylvia L; Mete, Ozgur

2018-01-01

Endocrine pathology is the subspecialty of diagnostic pathology which deals with the diagnosis and characterisation of neoplastic and non-neoplastic diseases of the endocrine system. This relatively young subspecialty was initially focused mainly on thyroid and parathyroid pathology, with some participants also involved in studies of the pituitary, the endocrine pancreas, and the adrenal glands. However, the endocrine system involves much more than these traditional endocrine organs and the discipline has grown to encompass lesions of the dispersed neuroendocrine cells, including neuroendocrine tumours (NETs) of the lungs, gastrointestinal tract, thymus, breast and prostate, as well as paraganglia throughout the body, not just in the adrenals. Indeed, the production of hormones is the hallmark of the endocrine system, and some aspects of gynecological/testicular, bone and liver pathology also fall into the realm of this specialty. Many of the lesions that are the focus of this discipline are increasing in incidence and their pathology is becoming more complex with increased understanding of molecular pathology and a high incidence of familial disease. The future of endocrine pathology will demand a depth of understanding of structure, function, prognosis and prediction as pathologists play a key role in the multidisciplinary care team of patients with endocrine diseases. It is anticipated that new technologies will allow increased subspecialisation in pathology and growth of this important area of expertise. Copyright © 2017 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

A molecular network of the aging human brain provides insights into the pathology and cognitive decline of Alzheimer's disease.

Science.gov (United States)

Mostafavi, Sara; Gaiteri, Chris; Sullivan, Sarah E; White, Charles C; Tasaki, Shinya; Xu, Jishu; Taga, Mariko; Klein, Hans-Ulrich; Patrick, Ellis; Komashko, Vitalina; McCabe, Cristin; Smith, Robert; Bradshaw, Elizabeth M; Root, David E; Regev, Aviv; Yu, Lei; Chibnik, Lori B; Schneider, Julie A; Young-Pearse, Tracy L; Bennett, David A; De Jager, Philip L

2018-06-01

There is a need for new therapeutic targets with which to prevent Alzheimer's disease (AD), a major contributor to aging-related cognitive decline. Here we report the construction and validation of a molecular network of the aging human frontal cortex. Using RNA sequence data from 478 individuals, we first build a molecular network using modules of coexpressed genes and then relate these modules to AD and its neuropathologic and cognitive endophenotypes. We confirm these associations in two independent AD datasets. We also illustrate the use of the network in prioritizing amyloid- and cognition-associated genes for in vitro validation in human neurons and astrocytes. These analyses based on unique cohorts enable us to resolve the role of distinct cortical modules that have a direct effect on the accumulation of AD pathology from those that have a direct effect on cognitive decline, exemplifying a network approach to complex diseases.

Evaluation of molecular brain changes associated with environmental stress in rodent models compared to human major depressive disorder: A proteomic systems approach.

Science.gov (United States)

Cox, David Alan; Gottschalk, Michael Gerd; Stelzhammer, Viktoria; Wesseling, Hendrik; Cooper, Jason David; Bahn, Sabine

2016-11-25

Rodent models of major depressive disorder (MDD) are indispensable when screening for novel treatments, but assessing their translational relevance with human brain pathology has proved difficult. Using a novel systems approach, proteomics data obtained from post-mortem MDD anterior prefrontal cortex tissue (n = 12) and matched controls (n = 23) were compared with equivalent data from three commonly used preclinical models exposed to environmental stressors (chronic mild stress, prenatal stress and social defeat). Functional pathophysiological features associated with depression-like behaviour were identified in these models through enrichment of protein-protein interaction networks. A cross-species comparison evaluated which model(s) represent human MDD pathology most closely. Seven functional domains associated with MDD and represented across at least two models such as "carbohydrate metabolism and cellular respiration" were identified. Through statistical evaluation using kernel-based machine learning techniques, the social defeat model was found to represent MDD brain changes most closely for four of the seven domains. This is the first study to apply a method for directly evaluating the relevance of the molecular pathology of multiple animal models to human MDD on the functional level. The methodology and findings outlined here could help to overcome translational obstacles of preclinical psychiatric research.

Digitotalar dysmorphism: Molecular elucidation

African Journals Online (AJOL)

obtained for molecular studies. Since the distal arthrogryposes (DAs) are genetically heterogeneous, an unbiased approach to mutation ... Diseases and Molecular Medicine, Department of Pathology, Faculty of Health Sciences, University of Cape Town, South Africa, with an interest in molecular genetics of connective ...

Selective pathologies of the head and neck in children: a developmental perspective.

Science.gov (United States)

Ozolek, John A

2009-09-01

The range of pathology seen in the head and neck region is truly amazing and to a large extent probably mirrors the complex signaling pathways and careful orchestration of events that occurs between the primordial germ layers during the development of this region. As is true in general for the entire discipline of pediatric pathology, the head and neck pathology within this age group is as diverse and different as its adult counterpart. Cases that come across the pediatric head and neck surgical pathology bench are more heavily weighted toward developmental and congenital lesions such as branchial cleft anomalies, thyroglossal duct cysts, ectopias, heterotopias, choristomas, and primitive tumors. Many congenital "benign" lesions can cause significant morbidity and even mortality if they compress the airway or other vital structures. Exciting investigations into the molecular embryology of craniofacial development have begun to shed light on the pathogenesis of craniofacial developmental lesions and syndromes. Much more investigation is needed, however, to intertwine aberrations in the molecular ontogeny and development of the head and neck regions to the represented pathology. This review will integrate traditional morphologic embryology with some of the recent advances in the molecular pathways of head and neck development followed by a discussion of a variety of developmental lesions finishing with tumors presumed to be derived from pluripotent/progenitor cells and tumors that show anomalous or aborted development.

Expectations and essentials for the community practice of pathology.

Science.gov (United States)

Horowitz, Richard E

2006-08-01

In 3 surveys during the past 10 years, community hospital pathologists were asked what they want, need, or look for when employing a pathologist and, more specifically, what skills and knowledge a newly minted pathologist should have to be successful in the community practice of pathology. The most recent survey, done in spring of 2005, cited surgical pathology diagnosis, frozen section diagnosis, gross dissection, cytology, and fine-needle aspiration as essentials in anatomic pathology. For clinical pathology, knowledge of clinical medicine and test strategies that use the laboratory for clinical problem solving was paramount. New expectations in the latest survey were knowledge of molecular pathology and experience in quality assurance procedures. New pathologists generally meet the expectations of the community hospital workplace; however, there were some deficiencies: they were not proficient in gross pathology or autopsy pathology, they were slow, and many lack the clinical knowledge and experience to be effective consultants. The principal attribute that determines success in the practice of pathology, however, is skill in communication and interpersonal relations, and this remains the major deficiency of the fledgling pathologist.

Delayed brain radiation necrosis: pathological review and new molecular targets for treatment.

Science.gov (United States)

Furuse, Motomasa; Nonoguchi, Naosuke; Kawabata, Shinji; Miyatake, Shin-Ichi; Kuroiwa, Toshihiko

2015-12-01

Delayed radiation necrosis is a well-known adverse event following radiotherapy for brain diseases and has been studied since the 1930s. The primary pathogenesis is thought to be the direct damage to endothelial and glial cells, particularly oligodendrocytes, which causes vascular hyalinization and demyelination. This primary pathology leads to tissue inflammation and ischemia, inducing various tissue protective responses including angiogenesis. Macrophages and lymphocytes then infiltrate the surrounding areas of necrosis, releasing inflammatory cytokines such as interleukin (IL)-1α, IL-6, and tumor necrosis factor (TNF)-α. Microglia also express these inflammatory cytokines. Reactive astrocytes play an important role in angiogenesis, expressing vascular endothelial growth factor (VEGF). Some chemokine networks, like the CXCL12/CXCR4 axis, are upregulated by tissue inflammation. Hypoxia may mediate the cell-cell interactions among reactive astrocytes, macrophages, and microglial cells around the necrotic core. Recently, bevacizumab, an anti-VEGF antibody, has demonstrated promising results as an alternative treatment for radiation necrosis. The importance of VEGF in the pathophysiology of brain radiation necrosis is being recognized. The discovery of new molecular targets could facilitate novel treatments for radiation necrosis. This literature review will focus on recent work characterizing delayed radiation necrosis in the brain.

HER2 testing of gastro-oesophageal adenocarcinoma: a commentary and guidance document from the Association of Clinical Pathologists Molecular Pathology and Diagnostics Committee.

Science.gov (United States)

Wong, Newton A C S; Amary, Fernanda; Butler, Rachel; Byers, Richard; Gonzalez, David; Haynes, Harry R; Ilyas, Mohammad; Salto-Tellez, Manuel; Taniere, Philippe

2018-05-01

The use of biologics targeted to the human epidermal growth factor receptor 2 (HER2) protein is the latest addition to the armamentarium used to fight advanced gastric or gastro-oesophageal junction adenocarcinoma. The decision to treat with the biologic trastuzumab is completely dependent on HER2 testing of tumour tissue. In 2017, the College of American Pathologists, American Society for Clinical Pathology and the American Society of Clinical Oncology jointly published guidelines for HER2 testing and clinical decision making in gastro-oesophageal adenocarcinoma. The Association of Clinical Pathologists Molecular Pathology and Diagnostics Committee has issued the following document as a commentary of these guidelines and, in parallel, to provide guidance on HER2 testing in National Health Service pathology departments within the UK. This guidance covers issues related to case selection, preanalytical aspects, analysis and interpretation of such HER2 testing. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A comparative study on pathological features of transgenic rat lines expressing either three or four repeat misfolded tau.

Science.gov (United States)

Valachova, Bernadeta; Brezovakova, Veronika; Bugos, Ondrej; Jadhav, Santosh; Smolek, Tomas; Novak, Petr; Zilka, Norbert

2018-08-01

Human tauopathies represent a heterogeneous group of neurodegenerative disorders characterized by distinct clinical features, typical histopathological structures, and defined ratio(s) of three-repeat and four-repeat tau isoforms within pathological aggregates. How the optional microtubule-binding repeat of tau influences this differentiation of pathologies is understudied. We have previously generated and characterized transgenic rodent models expressing human truncated tau aa151-391 with either three (SHR24) or four microtubule-binding repeats (SHR72). Here, we compare the behavioral and neuropathological hallmarks of these two transgenic lines using a battery of tests for sensorimotor, cognitive, and neurological functions over the age range of 3.5-15 months. Progression of sensorimotor and neurological deficits was similar in both transgenic lines; however, the lifespan of transgenic line SHR72 expressing truncated four-repeat tau was markedly shorter than SHR24. Moreover, the expression of three or four-repeat tau induced distinct neurofibrillary pathology in these lines. Transgenic lines displayed different distribution of tau pathology and different type of neurofibrillary tangles. Our results suggest that three- and four-repeat isoforms of tau may display different modes of action in the diseased brain. © 2018 Wiley Periodicals, Inc.

Positron emission tomography in amyotrophic lateral sclerosis: Towards targeting of molecular pathological hallmarks

Energy Technology Data Exchange (ETDEWEB)

Willekens, Stefanie M.A.; Weehaeghe, Donatienne van [University Hospitals Leuven and KU Leuven, Division of Nuclear Medicine, Department of Imaging and Pathology, Leuven (Belgium); Damme, Philip van [University Hospitals Leuven, Department of Neurology, Leuven (Belgium); KU Leuven, Department of Neurosciences, Experimental Neurology, Leuven (Belgium); Leuven Research Institute for Neuroscience and Disease (LIND), Leuven (Belgium); VIB, Vesalius Research Center, Laboratory of Neurobiology, Leuven (Belgium); Laere, Koen van [University Hospitals Leuven and KU Leuven, Division of Nuclear Medicine, Department of Imaging and Pathology, Leuven (Belgium); Leuven Research Institute for Neuroscience and Disease (LIND), Leuven (Belgium)

2017-03-15

During the past decades, extensive efforts have been made to expand the knowledge of amyotrophic lateral sclerosis (ALS). However, clinical translation of this research, in terms of earlier diagnosis and improved therapy, remains challenging. Since more than 30% of motor neurons are lost when symptoms become clinically apparent, techniques allowing non-invasive, in vivo detection of motor neuron degeneration are needed in the early, pre-symptomatic disease stage. Furthermore, it has become apparent that non-motor signs play an important role in the disease and there is an overlap with cognitive disorders, such as frontotemporal dementia (FTD). Radionuclide imaging, such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT), form an attractive approach to quantitatively monitor the ongoing neurodegenerative processes. Although [{sup 18}F]-FDG has been recently proposed as a potential biomarker for ALS, active targeting of the underlying pathologic molecular processes is likely to unravel further valuable disease information and may help to decipher the pathogenesis of ALS. In this review, we provide an overview of radiotracers that have already been applied in ALS and discuss possible novel targets for in vivo imaging of various pathogenic processes underlying ALS onset and progression. (orig.)

Positron emission tomography in amyotrophic lateral sclerosis: Towards targeting of molecular pathological hallmarks

International Nuclear Information System (INIS)

Willekens, Stefanie M.A.; Weehaeghe, Donatienne van; Damme, Philip van; Laere, Koen van

2017-01-01

During the past decades, extensive efforts have been made to expand the knowledge of amyotrophic lateral sclerosis (ALS). However, clinical translation of this research, in terms of earlier diagnosis and improved therapy, remains challenging. Since more than 30% of motor neurons are lost when symptoms become clinically apparent, techniques allowing non-invasive, in vivo detection of motor neuron degeneration are needed in the early, pre-symptomatic disease stage. Furthermore, it has become apparent that non-motor signs play an important role in the disease and there is an overlap with cognitive disorders, such as frontotemporal dementia (FTD). Radionuclide imaging, such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT), form an attractive approach to quantitatively monitor the ongoing neurodegenerative processes. Although ["1"8F]-FDG has been recently proposed as a potential biomarker for ALS, active targeting of the underlying pathologic molecular processes is likely to unravel further valuable disease information and may help to decipher the pathogenesis of ALS. In this review, we provide an overview of radiotracers that have already been applied in ALS and discuss possible novel targets for in vivo imaging of various pathogenic processes underlying ALS onset and progression. (orig.)

The dielectric properties of neutron irradiated snake venom and its pathological impact

International Nuclear Information System (INIS)

Hanafy, M.S.; Rahmy, N.A.; Abd El-Khalek, M.M.

1999-01-01

The changes in the dielectric properties of a saline solution of Cerastes cerastes snake venom after irradiation with low-level doses of fast neutrons from a Cf-252 source, were investigated. The pathological changes in the internal organs such as liver, kidney spleen, lung and heart of the rats injected with unirradiated and irradiated venom were also studied. The changes in the molecular structure of a diluted saline solution of snake venom were measured through dielectric relaxation studies in the frequency range 0.1-10 MHz at 4±0.5 deg C. The absorption spectra of the venom solution were measured in the wavelength range 200 to 600 nm. The results indicated remarkable changes in the molecular radii, shape, relaxation time and dielectric increment of the venom molecules as a result of irradiation. Also, the intensities of the absorption bands of the venom solution decreased as a result of the irradiation process. Furthermore, the pathological examination results indicated that the toxicity of the irradiated venom decreased as compared with that of unirradiated venom, hence increasing the chance of repair of the affected organs. (author)

Trapped neutrophil syndrome in a Border Collie dog: clinical, clinico-pathologic, and molecular findings.

Science.gov (United States)

Mizukami, Keijiro; Shoubudani, Tomoaki; Nishimoto, Seira; Kawamura, Ryuta; Yabuki, Akira; Yamato, Osamu

2012-06-01

Trapped neutrophil syndrome (TNS) is an autosomal recessive inherited neutropenia known in Border Collies since the 1990's. Recently, the causative mutation has been identified in the canine VPS13B gene and a DNA-based diagnosis has now become available. The present paper describes clinical and clinico-pathologic findings in a Border Collie with TNS that was molecularly diagnosed for the first time in Japan. In a 10-week-old male Border Collie with microgenesis and symptoms related to recurrent infections, a hematological examination revealed severe leukopenia due to neutropenia, suggesting the dog to be affected by inherited neutropenic immunodeficiency. Direct DNA sequencing demonstrated that the dog was homozygous for the causative mutation of TNS and both its parents were heterozygous carriers. In addition, a simple and rapid polymerase chain reaction-based length polymorphism analysis coupled with microchip electrophoresis was developed for the genotyping of TNS. This assay could discriminate clearly all genotypes, suggesting that it was suitable for both individual diagnosis and large-scale surveys for prevention.

Molecular and pathological identification of feline coronavirus type I

African Journals Online (AJOL)

DR. NJ TONUKARI

2012-06-05

Jun 5, 2012 ... In this study, we described the isolation and molecular characterization of .... fecv2b) designed in the regions of S-protein gene were used to differentiate ..... The molecular dynamics of feline coronaviruses. Vet. Microbiol.

Recent application of PET in the pathological mechanisms of PD

International Nuclear Information System (INIS)

Tian Jiyu

2003-01-01

PET is the best method in the investigation of molecular pathology at present. In this review, the value of positron emission computed tomography for providing insight into the role of pathology mechanism, early diagnosis, differential diagnosis, mechanisms of motor fluctuations in Parkinson disease is reviewed. Especially it can be used for the early diagnosis of PD, thus being beneficial to the therapy of it

Molecular Pathology: Predictive, Prognostic, and Diagnostic Markers in Uterine Tumors.

Science.gov (United States)

Ritterhouse, Lauren L; Howitt, Brooke E

2016-09-01

This article focuses on the diagnostic, prognostic, and predictive molecular biomarkers in uterine malignancies, in the context of morphologic diagnoses. The histologic classification of endometrial carcinomas is reviewed first, followed by the description and molecular classification of endometrial epithelial malignancies in the context of histologic classification. Taken together, the molecular and histologic classifications help clinicians to approach troublesome areas encountered in clinical practice and evaluate the utility of molecular alterations in the diagnosis and subclassification of endometrial carcinomas. Putative prognostic markers are reviewed. The use of molecular alterations and surrogate immunohistochemistry as prognostic and predictive markers is also discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Prospective molecular profiling of canine cancers provides a clinically relevant comparative model for evaluating personalized medicine (PMed trials.

Directory of Open Access Journals (Sweden)

Melissa Paoloni

Full Text Available Molecularly-guided trials (i.e. PMed now seek to aid clinical decision-making by matching cancer targets with therapeutic options. Progress has been hampered by the lack of cancer models that account for individual-to-individual heterogeneity within and across cancer types. Naturally occurring cancers in pet animals are heterogeneous and thus provide an opportunity to answer questions about these PMed strategies and optimize translation to human patients. In order to realize this opportunity, it is now necessary to demonstrate the feasibility of conducting molecularly-guided analysis of tumors from dogs with naturally occurring cancer in a clinically relevant setting.A proof-of-concept study was conducted by the Comparative Oncology Trials Consortium (COTC to determine if tumor collection, prospective molecular profiling, and PMed report generation within 1 week was feasible in dogs. Thirty-one dogs with cancers of varying histologies were enrolled. Twenty-four of 31 samples (77% successfully met all predefined QA/QC criteria and were analyzed via Affymetrix gene expression profiling. A subsequent bioinformatics workflow transformed genomic data into a personalized drug report. Average turnaround from biopsy to report generation was 116 hours (4.8 days. Unsupervised clustering of canine tumor expression data clustered by cancer type, but supervised clustering of tumors based on the personalized drug report clustered by drug class rather than cancer type.Collection and turnaround of high quality canine tumor samples, centralized pathology, analyte generation, array hybridization, and bioinformatic analyses matching gene expression to therapeutic options is achievable in a practical clinical window (<1 week. Clustering data show robust signatures by cancer type but also showed patient-to-patient heterogeneity in drug predictions. This lends further support to the inclusion of a heterogeneous population of dogs with cancer into the preclinical

Molecular Regulation of the Mitochondrial F1Fo-ATPsynthase: Physiological and Pathological Significance of the Inhibitory Factor 1 (IF 1

Directory of Open Access Journals (Sweden)

Danilo Faccenda

2012-01-01

Full Text Available In mammals, the mitochondrial F1Fo-ATPsynthase sets out the energy homeostasis by producing the bulk of cellular ATP. As for every enzyme, the laws of thermodynamics command it; however, it is privileged to have a dedicated molecular regulator that controls its rotation. This is the so-called ATPase Inhibitory Factor 1 (IF1 that blocks its reversal to avoid the consumption of cellular ATP when the enzyme acts as an ATP hydrolase. Recent evidence has also demonstrated that IF1 may control the alignment of the enzyme along the mitochondrial inner membrane, thus increasing the interest for the molecule. We conceived this review to outline the fundamental knowledge of the F1Fo-ATPsynthase and link it to the molecular mechanisms by which IF1 regulates its way of function, with the ultimate goal to highlight this as an important and possibly unique means to control this indispensable enzyme in both physiological and pathological settings.

Factors involved in cardiac physiological and pathological remodeling

NARCIS (Netherlands)

Demkes, C.J.

2018-01-01

During life, the heart is exposed to different types of stresses. In response to changing demands or stimuli the heart can cope by growing in size. In this thesis, molecular changes underlying cardiac physiological and pathological adaptations are investigated. First, we validated physiological

EGFR and KRAS quality assurance schemes in pathology : generating normative data for molecular predictive marker analysis in targeted therapy

NARCIS (Netherlands)

Thunnissen, Erik; Bovée, Judith V M G; Bruinsma, Hans; van den Brule, Adriaan J C; Dinjens, Winand; Heideman, Daniëlle A M; Meulemans, Els; Nederlof, Petra; van Noesel, Carel; Prinsen, Clemens F M; Scheidel, Karen; van de Ven, Peter M; de Weger, Roel; Schuuring, Ed; Ligtenberg, Marjolijn

2011-01-01

Introduction The aim of this study was to compare the reproducibility of epidermal growth factor receptor (EGFR) immunohistochemistry (IHC), EGFR gene amplification analysis, and EGFR and KRAS mutation analysis among different laboratories performing routine diagnostic analyses in pathology in The

NMR imaging of osteoarticular pathology

International Nuclear Information System (INIS)

Frocrain, L.; Duvauferrier, R.; Gagey, N.

1987-01-01

NMR imaging is assuming an increasingly important role in the diagnosis of osteo-articular disorders. Semiological descriptions of the mean pathological disorders of the locomotor system are presented. Some investigation strategies are proposed to compare NMR imaging with other imaging techniques in various pathological states [fr

A method for normalizing pathology images to improve feature extraction for quantitative pathology

International Nuclear Information System (INIS)

Tam, Allison; Barker, Jocelyn; Rubin, Daniel

2016-01-01

Purpose: With the advent of digital slide scanning technologies and the potential proliferation of large repositories of digital pathology images, many research studies can leverage these data for biomedical discovery and to develop clinical applications. However, quantitative analysis of digital pathology images is impeded by batch effects generated by varied staining protocols and staining conditions of pathological slides. Methods: To overcome this problem, this paper proposes a novel, fully automated stain normalization method to reduce batch effects and thus aid research in digital pathology applications. Their method, intensity centering and histogram equalization (ICHE), normalizes a diverse set of pathology images by first scaling the centroids of the intensity histograms to a common point and then applying a modified version of contrast-limited adaptive histogram equalization. Normalization was performed on two datasets of digitized hematoxylin and eosin (H&E) slides of different tissue slices from the same lung tumor, and one immunohistochemistry dataset of digitized slides created by restaining one of the H&E datasets. Results: The ICHE method was evaluated based on image intensity values, quantitative features, and the effect on downstream applications, such as a computer aided diagnosis. For comparison, three methods from the literature were reimplemented and evaluated using the same criteria. The authors found that ICHE not only improved performance compared with un-normalized images, but in most cases showed improvement compared with previous methods for correcting batch effects in the literature. Conclusions: ICHE may be a useful preprocessing step a digital pathology image processing pipeline

A method for normalizing pathology images to improve feature extraction for quantitative pathology

Energy Technology Data Exchange (ETDEWEB)

Tam, Allison [Stanford Institutes of Medical Research Program, Stanford University School of Medicine, Stanford, California 94305 (United States); Barker, Jocelyn [Department of Radiology, Stanford University School of Medicine, Stanford, California 94305 (United States); Rubin, Daniel [Department of Radiology, Stanford University School of Medicine, Stanford, California 94305 and Department of Medicine (Biomedical Informatics Research), Stanford University School of Medicine, Stanford, California 94305 (United States)

2016-01-15

Purpose: With the advent of digital slide scanning technologies and the potential proliferation of large repositories of digital pathology images, many research studies can leverage these data for biomedical discovery and to develop clinical applications. However, quantitative analysis of digital pathology images is impeded by batch effects generated by varied staining protocols and staining conditions of pathological slides. Methods: To overcome this problem, this paper proposes a novel, fully automated stain normalization method to reduce batch effects and thus aid research in digital pathology applications. Their method, intensity centering and histogram equalization (ICHE), normalizes a diverse set of pathology images by first scaling the centroids of the intensity histograms to a common point and then applying a modified version of contrast-limited adaptive histogram equalization. Normalization was performed on two datasets of digitized hematoxylin and eosin (H&E) slides of different tissue slices from the same lung tumor, and one immunohistochemistry dataset of digitized slides created by restaining one of the H&E datasets. Results: The ICHE method was evaluated based on image intensity values, quantitative features, and the effect on downstream applications, such as a computer aided diagnosis. For comparison, three methods from the literature were reimplemented and evaluated using the same criteria. The authors found that ICHE not only improved performance compared with un-normalized images, but in most cases showed improvement compared with previous methods for correcting batch effects in the literature. Conclusions: ICHE may be a useful preprocessing step a digital pathology image processing pipeline.

Increased CSF Homocysteine in Pathological Gamblers Compared with Healthy Controls

Science.gov (United States)

Nordin, Conny; Sjodin, Ingemar

2009-01-01

Neurocognitive disturbances suggesting a frontal lobe dysfunction have been observed in pathological gamblers and alcohol dependents. Given that a high homocysteine level has been suggested to be a mediating factor in alcohol-related cognitive decline, we have determined homocysteine and cobalamine in cerebrospinal fluid (CSF) obtained from 11…

Laboratory practice guidelines for detecting and reporting JAK2 and MPL mutations in myeloproliferative neoplasms: a report of the Association for Molecular Pathology.

Science.gov (United States)

Gong, Jerald Z; Cook, James R; Greiner, Timothy C; Hedvat, Cyrus; Hill, Charles E; Lim, Megan S; Longtine, Janina A; Sabath, Daniel; Wang, Y Lynn

2013-11-01

Recurrent mutations in JAK2 and MPL genes are genetic hallmarks of BCR-ABL1-negative myeloproliferative neoplasms. Detection of JAK2 and MPL mutations has been incorporated into routine diagnostic algorithms for these diseases. This Special Article summarizes results from a nationwide laboratory survey of JAK2 and MPL mutation analysis. Based on the current practice pattern and the literature, this Special Article provides recommendations and guidelines for laboratory practice for detection of mutations in the JAK2 and MPL genes, including clinical manifestations for prompting the mutation analysis, current and recommended methodologies for testing the mutations, and standardization for reporting the test results. This Special Article also points to future directions for genomic testing in BCR-ABL1-negative myeloproliferative neoplasms. Copyright © 2013 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Dopamine and Opioid Neurotransmission in Behavioral Addictions: A Comparative PET Study in Pathological Gambling and Binge Eating.

Science.gov (United States)

Majuri, Joonas; Joutsa, Juho; Johansson, Jarkko; Voon, Valerie; Alakurtti, Kati; Parkkola, Riitta; Lahti, Tuuli; Alho, Hannu; Hirvonen, Jussi; Arponen, Eveliina; Forsback, Sarita; Kaasinen, Valtteri

2017-04-01

Although behavioral addictions share many clinical features with drug addictions, they show strikingly large variation in their behavioral phenotypes (such as in uncontrollable gambling or eating). Neurotransmitter function in behavioral addictions is poorly understood, but has important implications in understanding its relationship with substance use disorders and underlying mechanisms of therapeutic efficacy. Here, we compare opioid and dopamine function between two behavioral addiction phenotypes: pathological gambling (PG) and binge eating disorder (BED). Thirty-nine participants (15 PG, 7 BED, and 17 controls) were scanned with [ 11 C]carfentanil and [ 18 F]fluorodopa positron emission tomography using a high-resolution scanner. Binding potentials relative to non-displaceable binding (BP ND ) for [ 11 C]carfentanil and influx rate constant (K i ) values for [ 18 F]fluorodopa were analyzed with region-of-interest and whole-brain voxel-by-voxel analyses. BED subjects showed widespread reductions in [ 11 C]carfentanil BP ND in multiple subcortical and cortical brain regions and in striatal [ 18 F]fluorodopa K i compared with controls. In PG patients, [ 11 C]carfentanil BP ND was reduced in the anterior cingulate with no differences in [ 18 F]fluorodopa K i compared with controls. In the nucleus accumbens, a key region involved in reward processing, [ 11 C]Carfentanil BP ND was 30-34% lower and [ 18 F]fluorodopa K i was 20% lower in BED compared with PG and controls (paddiction and indicate differential mechanisms in the expression of pathological behaviors and responses to treatment.

The role of tau in the pathological process and clinical expression of Huntington's disease

DEFF Research Database (Denmark)

Vuono, Romina; Winder-Rhodes, Sophie; de Silva, Rohan

2015-01-01

and progression of Huntington's disease, the exact molecular mechanisms driving its pathogenic cascade and clinical features, especially the dementia, are not fully understood. Recently the microtubule associated protein tau, MAPT, which is associated with several neurodegenerative disorders, has been implicated......-mortem brain samples from patients with Huntington's disease (n = 16) compared to cases with a known tauopathy and healthy controls. Next, we undertook a genotype-phenotype analysis of a large cohort of patients with Huntington's disease (n = 960) with a particular focus on cognitive decline. We report...... not only on the tau pathology in the Huntington's disease brain but also the association between genetic variation in tau gene and the clinical expression and progression of the disease. We found extensive pathological inclusions containing abnormally phosphorylated tau protein that co-localized in some...

Emerging new tools to study and treat muscle pathologies: genetics and molecular mechanisms underlying skeletal muscle development, regeneration, and disease.

Science.gov (United States)

Crist, Colin

2017-01-01

Skeletal muscle is the most abundant tissue in our body, is responsible for generating the force required for movement, and is also an important thermogenic organ. Skeletal muscle is an enigmatic tissue because while on the one hand, skeletal muscle regeneration after injury is arguably one of the best-studied stem cell-dependent regenerative processes, on the other hand, skeletal muscle is still subject to many degenerative disorders with few therapeutic options in the clinic. It is important to develop new regenerative medicine-based therapies for skeletal muscle. Future therapeutic strategies should take advantage of rapidly developing technologies enabling the differentiation of skeletal muscle from human pluripotent stem cells, along with precise genome editing, which will go hand in hand with a steady and focused approach to understanding underlying mechanisms of skeletal muscle development, regeneration, and disease. In this review, I focus on highlighting the recent advances that particularly have relied on developmental and molecular biology approaches to understanding muscle development and stem cell function. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Prospective molecular profiling of canine cancers provides a clinically relevant comparative model for evaluating personalized medicine (PMed) trials.

Science.gov (United States)

Paoloni, Melissa; Webb, Craig; Mazcko, Christina; Cherba, David; Hendricks, William; Lana, Susan; Ehrhart, E J; Charles, Brad; Fehling, Heather; Kumar, Leena; Vail, David; Henson, Michael; Childress, Michael; Kitchell, Barbara; Kingsley, Christopher; Kim, Seungchan; Neff, Mark; Davis, Barbara; Khanna, Chand; Trent, Jeffrey

2014-01-01

Molecularly-guided trials (i.e. PMed) now seek to aid clinical decision-making by matching cancer targets with therapeutic options. Progress has been hampered by the lack of cancer models that account for individual-to-individual heterogeneity within and across cancer types. Naturally occurring cancers in pet animals are heterogeneous and thus provide an opportunity to answer questions about these PMed strategies and optimize translation to human patients. In order to realize this opportunity, it is now necessary to demonstrate the feasibility of conducting molecularly-guided analysis of tumors from dogs with naturally occurring cancer in a clinically relevant setting. A proof-of-concept study was conducted by the Comparative Oncology Trials Consortium (COTC) to determine if tumor collection, prospective molecular profiling, and PMed report generation within 1 week was feasible in dogs. Thirty-one dogs with cancers of varying histologies were enrolled. Twenty-four of 31 samples (77%) successfully met all predefined QA/QC criteria and were analyzed via Affymetrix gene expression profiling. A subsequent bioinformatics workflow transformed genomic data into a personalized drug report. Average turnaround from biopsy to report generation was 116 hours (4.8 days). Unsupervised clustering of canine tumor expression data clustered by cancer type, but supervised clustering of tumors based on the personalized drug report clustered by drug class rather than cancer type. Collection and turnaround of high quality canine tumor samples, centralized pathology, analyte generation, array hybridization, and bioinformatic analyses matching gene expression to therapeutic options is achievable in a practical clinical window (strategies may aid cancer drug development.

Molecular Classification of Lobular Carcinoma of the Breast

Science.gov (United States)

Fu, Denggang; Zuo, Qi; Huang, Qi; Su, Li; Ring, Huijun Z.; Ring, Brian Z.

2017-01-01

The morphology of breast tumors is complicated and diagnosis can be difficult. We present here a novel diagnostic model which we validate on both array-based and RNA sequencing platforms which reliably distinguishes this tumor type across multiple cohorts. We also examine how this molecular classification predicts sensitivity to common chemotherapeutics in cell-line based assays. A total of 1845 invasive breast cancer cases in six cohorts were collected, split into discovery and validation cohorts, and a classifier was created and compared to pathological diagnosis, grade and survival. In the validation cohorts the concordance of predicted diagnosis with a pathological diagnosis was 92%, and 97% when inconclusively classified cases were excluded. Tumor-derived cell lines were classified with the model as having predominantly ductal or lobular-like molecular physiologies, and sensitivity of these lines to relevant compounds was analyzed. A diagnostic tool can be created that reliably distinguishes lobular from ductal carcinoma and allows the classification of cell lines on the basis of molecular profiles associated with these tumor types. This tool may assist in improved diagnosis and aid in explorations of the response of lobular type breast tumor models to different compounds. PMID:28303886

Clinico-pathological features and prognosis of invasive micropapillary carcinoma compared to invasive ductal carcinoma: a population-based study from China.

Directory of Open Access Journals (Sweden)

Wen-Biao Shi

Full Text Available Invasive micropapillary carcinoma (IMPC of the breast is a rare subtype of breast cancer that is associated with a high incidence of regional lymph node metastases and a poor clinical outcome. However, the clinico-pathological features and prognostic factors of IMPC are not well understood.A total of 188 IMPC cases and 1,289 invasive ductal carcinoma (IDC cases were included. The clinical features, breast cancer-specific survival (BCSS and recurrence/metastasis-free survival (RFS of the patients were compared between these two groups.The IMPC patients exhibited more features of aggressive carcinoma than the IDC patients, including larger tumor size, higher tumor stage, a greater proportion of nodal involvement and an increased incidence of lymphovascular invasion. Patients with IMPC had lower 5-year BCSS and RFS rates (75.9% and 67.1%, respectively than patients with IDC (89.5% and 84.5%, respectively. Compared to IDC patients, the patients with IMPC had a significantly higher percentage of stage III breast cancer (51.3% versus 21.7%. In a stage-matched Kaplan-Meier analysis, the patients with stage III IMPC had lower 5-year BCSS and RFS rates than patients with stage III IDC (BCSS, P = 0.004; RFS, P = 0.034. A multivariate analysis revealed that TNM stage was an independent prognostic factor for patients with IMPC. The proportion of cancers with a luminal-like subtype was significantly higher in IMPC than in IDC (P<0.001. However, after matching by molecular subtype, the patients with IMPC had significantly worse clinical outcomes than patients with IDC.In Chinese women, IMPCs displayed more aggressive behaviors than IDCs, resulting in poorer clinical outcomes for patients with IMPC, regardless of a favorable molecular subtype. Our findings illustrate that the poorer survival of patients with IMPC might be due to an increased incidence and aggressiveness of tumors in TNM stage III.

Metastatic non-small-cell lung cancer: consensus on pathology and molecular tests, first-line, second-line, and third-line therapy: 1st ESMO Consensus Conference in Lung Cancer; Lugano 2010

DEFF Research Database (Denmark)

Felip, E; Gridelli, C; Baas, P

2011-01-01

The 1st ESMO Consensus Conference on lung cancer was held in Lugano, Switzerland on 21 and 22 May 2010 with the participation of a multidisciplinary panel of leading professionals in pathology and molecular diagnostics, medical oncology, surgical oncology and radiation oncology. Before the confer...

Comparative molecular analysis of old olive ( Olea europaea L ...

African Journals Online (AJOL)

We compared the genetic profiles of six old olive cultivars from an Eastern Mediterranean Region of Turkey to 15 modern Turkish olive cultivars from different geographical origins. The RAPD profiles successfully clarified the molecular relationships among the genotypes tested. Seventeen RAPD primers generated 153 ...

Hip joint pathology

DEFF Research Database (Denmark)

Tijssen, M; van Cingel, R E H; de Visser, E

2017-01-01

The purpose of this retrospective cohort study was to (a) describe the clinical presentation of femoroacetabular impingement (FAI) and hip labral pathology; (b) describe the accuracy of patient history and physical tests for FAI and labral pathology as confirmed by hip arthroscopy. Patients (18......-65 years) were included if they were referred to a physical therapist to gather pre-operative data and were then diagnosed during arthroscopy. Results of pre-operative patient history and physical tests were collected and compared to arthroscopy. Data of 77 active patients (mean age: 37 years) were...

Translational analysis of mouse and human placental protein and mRNA reveals distinct molecular pathologies in human preeclampsia.

Science.gov (United States)

Cox, Brian; Sharma, Parveen; Evangelou, Andreas I; Whiteley, Kathie; Ignatchenko, Vladimir; Ignatchenko, Alex; Baczyk, Dora; Czikk, Marie; Kingdom, John; Rossant, Janet; Gramolini, Anthony O; Adamson, S Lee; Kislinger, Thomas

2011-12-01

Preeclampsia (PE) adversely impacts ~5% of pregnancies. Despite extensive research, no consistent biomarkers or cures have emerged, suggesting that different molecular mechanisms may cause clinically similar disease. To address this, we undertook a proteomics study with three main goals: (1) to identify a panel of cell surface markers that distinguish the trophoblast and endothelial cells of the placenta in the mouse; (2) to translate this marker set to human via the Human Protein Atlas database; and (3) to utilize the validated human trophoblast markers to identify subgroups of human preeclampsia. To achieve these goals, plasma membrane proteins at the blood tissue interfaces were extracted from placentas using intravascular silica-bead perfusion, and then identified using shotgun proteomics. We identified 1181 plasma membrane proteins, of which 171 were enriched at the maternal blood-trophoblast interface and 192 at the fetal endothelial interface with a 70% conservation of expression in humans. Three distinct molecular subgroups of human preeclampsia were identified in existing human microarray data by using expression patterns of trophoblast-enriched proteins. Analysis of all misexpressed genes revealed divergent dysfunctions including angiogenesis (subgroup 1), MAPK signaling (subgroup 2), and hormone biosynthesis and metabolism (subgroup 3). Subgroup 2 lacked expected changes in known preeclampsia markers (sFLT1, sENG) and uniquely overexpressed GNA12. In an independent set of 40 banked placental specimens, GNA12 was overexpressed during preeclampsia when co-incident with chronic hypertension. In the current study we used a novel translational analysis to integrate mouse and human trophoblast protein expression with human microarray data. This strategy identified distinct molecular pathologies in human preeclampsia. We conclude that clinically similar preeclampsia patients exhibit divergent placental gene expression profiles thus implicating divergent

Clinical and Pathological Characteristics of Mucinous Colorectal Adenocarcinoma: A Comparative Study

Directory of Open Access Journals (Sweden)

Hosseini

2016-03-01

Full Text Available Background Mucinous adenocarcinoma accounts for approximately 5% - 15% of all colorectal cancers. Objectives The aim of this study was to investigate the clinicopathological characteristics of patients with mucinous colorectal adenocarcinoma. Patients and Methods This retrospective study was carried out by reviewing the medical records of 70 mucinous colorectal cancer (MCC patients who were diagnosed and treated at a tertiary academic hospital between 2005 and 2010. For the comparative analysis, 491 patients with non-mucinous colorectal cancer (NMCC were included. Results Of 561 patients with colorectal adenocarcinoma, 70 patients (12.5% had the mucinous type. There were 42 (60% men and 28 (40% women, with a median age of 55 years old (range 24 - 81 years included in the study. We did not find any differences regarding the patients’ mean age (P = 0.408 and male/female ratio (P = 0.700 between the MCC and NMCC; however, there was a predilection for the right colon and sigmoid colon in the MCC, when compared to the NMCC (P = 0.012. In addition, the MCC tended to have a larger tumor size (P = 0.004, higher histological grade (P < 0.001, higher node stage (P < 0.001, higher number of dissected nodes (P = 0.013, higher number of positive nodes (P < 0.001, and a higher rate of perineural invasion (P = 0.013 compared to the NMCC. Conclusions This study indicates that most clinicopathological characteristics of MCC are different from those of NMCC. In addition, there was an association between the mucinous subtype and adverse pathological features in the patients with colorectal cancer.

Overview of silkworm pathology in China | Guo-Ping | African ...

African Journals Online (AJOL)

In this study, we elaborated the history and progress of studies on silkworm diseases in China through summarizing and reviewing the achievements on silkworm pathology, pathogenic molecular biology, epidemiology, pathogen detection and diagnostic techniques, damage from non-infectious silkworm diseases and ...

Mapping pathological phenotypes in a mouse model of CDKL5 disorder.

Directory of Open Access Journals (Sweden)

Elena Amendola

Full Text Available Mutations in cyclin-dependent kinase-like 5 (CDKL5 cause early-onset epileptic encephalopathy, a neurodevelopmental disorder with similarities to Rett Syndrome. Here we describe the physiological, molecular, and behavioral phenotyping of a Cdkl5 conditional knockout mouse model of CDKL5 disorder. Behavioral analysis of constitutive Cdkl5 knockout mice revealed key features of the human disorder, including limb clasping, hypoactivity, and abnormal eye tracking. Anatomical, physiological, and molecular analysis of the knockout uncovered potential pathological substrates of the disorder, including reduced dendritic arborization of cortical neurons, abnormal electroencephalograph (EEG responses to convulsant treatment, decreased visual evoked responses (VEPs, and alterations in the Akt/rpS6 signaling pathway. Selective knockout of Cdkl5 in excitatory and inhibitory forebrain neurons allowed us to map the behavioral features of the disorder to separable cell-types. These findings identify physiological and molecular deficits in specific forebrain neuron populations as possible pathological substrates in CDKL5 disorder.

Mapping pathological phenotypes in a mouse model of CDKL5 disorder.

Science.gov (United States)

Amendola, Elena; Zhan, Yang; Mattucci, Camilla; Castroflorio, Enrico; Calcagno, Eleonora; Fuchs, Claudia; Lonetti, Giuseppina; Silingardi, Davide; Vyssotski, Alexei L; Farley, Dominika; Ciani, Elisabetta; Pizzorusso, Tommaso; Giustetto, Maurizio; Gross, Cornelius T

2014-01-01

Mutations in cyclin-dependent kinase-like 5 (CDKL5) cause early-onset epileptic encephalopathy, a neurodevelopmental disorder with similarities to Rett Syndrome. Here we describe the physiological, molecular, and behavioral phenotyping of a Cdkl5 conditional knockout mouse model of CDKL5 disorder. Behavioral analysis of constitutive Cdkl5 knockout mice revealed key features of the human disorder, including limb clasping, hypoactivity, and abnormal eye tracking. Anatomical, physiological, and molecular analysis of the knockout uncovered potential pathological substrates of the disorder, including reduced dendritic arborization of cortical neurons, abnormal electroencephalograph (EEG) responses to convulsant treatment, decreased visual evoked responses (VEPs), and alterations in the Akt/rpS6 signaling pathway. Selective knockout of Cdkl5 in excitatory and inhibitory forebrain neurons allowed us to map the behavioral features of the disorder to separable cell-types. These findings identify physiological and molecular deficits in specific forebrain neuron populations as possible pathological substrates in CDKL5 disorder.

Slot Machine Response Frequency Predicts Pathological Gambling

DEFF Research Database (Denmark)

Linnet, Jakob; Rømer Thomsen, Kristine; Møller, Arne

2013-01-01

Slot machines are among the most addictive forms of gambling, and pathological gambling slot machine players represent the largest group of treatment seekers, accounting for 35% to 93% of the population. Pathological gambling sufferers have significantly higher response frequency (games / time......) on slot machines compared with non-problem gamblers, which may suggest increased reinforcement of the gambling behavior in pathological gambling. However, to date it is unknown whether or not the increased response frequency in pathological gambling is associated with symptom severity of the disorder....... This study tested the hypothesis that response frequency is associated with symptom severity in pathological gambling. We tested response frequency among twenty-two pathological gambling sufferers and twenty-one non-problem gamblers on a commercially available slot machine, and screened for pathological...

Hitchhiker's guide to multi-dimensional plant pathology.

Science.gov (United States)

Saunders, Diane G O

2015-02-01

Filamentous pathogens pose a substantial threat to global food security. One central question in plant pathology is how pathogens cause infection and manage to evade or suppress plant immunity to promote disease. With many technological advances over the past decade, including DNA sequencing technology, an array of new tools has become embedded within the toolbox of next-generation plant pathologists. By employing a multidisciplinary approach plant pathologists can fully leverage these technical advances to answer key questions in plant pathology, aimed at achieving global food security. This review discusses the impact of: cell biology and genetics on progressing our understanding of infection structure formation on the leaf surface; biochemical and molecular analysis to study how pathogens subdue plant immunity and manipulate plant processes through effectors; genomics and DNA sequencing technologies on all areas of plant pathology; and new forms of collaboration on accelerating exploitation of big data. As we embark on the next phase in plant pathology, the integration of systems biology promises to provide a holistic perspective of plant–pathogen interactions from big data and only once we fully appreciate these complexities can we design truly sustainable solutions to preserve our resources.

[Comparative double-blind study of Bi-Profenid and oxyphenbutazone in sports pathology].

Science.gov (United States)

Commandré, F A; Fornaris, E; Fourré, J M; Raybaud, A; Colonna, P; Pirdas, C

1983-12-12

Effectiveness and tolerance of ketoprofen in sustained-release tablets (Bi-Profenid 150 mg) were investigated in a double blind trial in 44 athletes who had recently sprained an ankle. Patients were given either 300 mg Bi-Profenid or 400 mg oxyphenbutazone daily for seven days. Treatment regimens were assigned at random. Results were assessed as excellent or good in 85% of patients given Bi-Profenid and 50% of those given oxyphenbutazone. Spontaneous pain resolved in 19 patients receiving Bi-Profenid and in 6 under oxyphenbutazone. Decrease in pain upon physical examination and in articular circumference was significantly greater with Bi-Profenid as compared with oxyphenbutazone. The chance of rapidly resuming sport was better with Bi-Profenid. Tolerance was excellent in 68.2% of patients with Bi-Profenid and 59% of those with oxyphenbutazone. This investigation thus emphasizes the value of Bi-Profenid in sport pathology.

Molecular Pathology and Personalized Medicine: The Dawn of a New Era in Companion Diagnostics-Practical Considerations about Companion Diagnostics for Non-Small-Cell-Lung-Cancer.

Science.gov (United States)

Plönes, Till; Engel-Riedel, Walburga; Stoelben, Erich; Limmroth, Christina; Schildgen, Oliver; Schildgen, Verena

2016-01-15

Companion diagnostics (CDx) have become a major tool in molecular pathology and assist in therapy decisions in an increasing number of various cancers. Particularly, the developments in lung cancer have been most impressing in the last decade and consequently lung cancer mutation testing and molecular profiling has become a major business of diagnostic laboratories. However, it has become difficult to decide which biomarkers are currently relevant for therapy decisions, as many of the new biomarkers are not yet approved as therapy targets, remain in the status of clinical studies, or still have not left the experimental phase. The current review is focussed on those markers that do have current therapy implications, practical implications arising from the respective companion diagnostics, and thus is focused on daily practice.

European Consensus Conference for external quality assessment in molecular pathology

NARCIS (Netherlands)

van Krieken, J. H.; Siebers, A. G.; Normanno, N.; Timens, Wim

Molecular testing of tumor samples to guide treatment decisions is of increasing importance. Several drugs have been approved for treatment of molecularly defined subgroups of patients, and the number of agents requiring companion diagnostics for their prescription is expected to rapidly increase.

Computational Pathology

Science.gov (United States)

Louis, David N.; Feldman, Michael; Carter, Alexis B.; Dighe, Anand S.; Pfeifer, John D.; Bry, Lynn; Almeida, Jonas S.; Saltz, Joel; Braun, Jonathan; Tomaszewski, John E.; Gilbertson, John R.; Sinard, John H.; Gerber, Georg K.; Galli, Stephen J.; Golden, Jeffrey A.; Becich, Michael J.

2016-01-01

Context We define the scope and needs within the new discipline of computational pathology, a discipline critical to the future of both the practice of pathology and, more broadly, medical practice in general. Objective To define the scope and needs of computational pathology. Data Sources A meeting was convened in Boston, Massachusetts, in July 2014 prior to the annual Association of Pathology Chairs meeting, and it was attended by a variety of pathologists, including individuals highly invested in pathology informatics as well as chairs of pathology departments. Conclusions The meeting made recommendations to promote computational pathology, including clearly defining the field and articulating its value propositions; asserting that the value propositions for health care systems must include means to incorporate robust computational approaches to implement data-driven methods that aid in guiding individual and population health care; leveraging computational pathology as a center for data interpretation in modern health care systems; stating that realizing the value proposition will require working with institutional administrations, other departments, and pathology colleagues; declaring that a robust pipeline should be fostered that trains and develops future computational pathologists, for those with both pathology and non-pathology backgrounds; and deciding that computational pathology should serve as a hub for data-related research in health care systems. The dissemination of these recommendations to pathology and bioinformatics departments should help facilitate the development of computational pathology. PMID:26098131

A Comparative Study of Activity-Based Costing vs. Current Pricing System for Pathology Examinations at Okmeydani Training and Research Hospital, Turkey

Directory of Open Access Journals (Sweden)

Enver YARIKKAYA

2017-01-01

Full Text Available Objective: To provide real cost data for pathology examinations by using activity-based costing method, in order to provide means to departments, health administrators and the social security institution to achieve improvements in financial planning, quality and cost control. Material and Method: The cost of the histopathological examinations, which were accepted by the Department of Pathology at Okmeydanı Training and Research Hospital during August 2014, was calculated using the activity-based costing method. The costs were compared with the amounts specified in the Healthcare Implementation Notification Tariff and the conventional volume-based costing. Results: Most pathology examinations listed within a given band in the Healthcare Implementation Notification Tariff show variations in unit costs. The study found that the costs of 77.4% of the examinations were higher than the prices listed in the Healthcare Implementation Notification Tariff. Conclusion: The pathology examination tariffs specified in the Healthcare Implementation Notification do not reflect the real costs of the examinations. The costs that are calculated using the activity-based costing system may vary according to the service types and levels of health care institutions. However, the main parameters of the method used in the study reflect the necessity of a more accurate banding of pathology examinations. The banding specified by the Healthcare Implementation Notification Tariff needs to be revised to reflect the real costs in Turkey.

A Comparative Study of Activity-Based Costing vs. Current Pricing System for Pathology Examinations at Okmeydani Training and Research Hospital, Turkey.

Science.gov (United States)

Yarikkaya, Enver; Özekinci, Selver; Sargan, Aytül; Durmuş, Şenay Erdoğan; Yildiz, Fetin Rüştü

2017-01-01

To provide real cost data for pathology examinations by using activity-based costing method, in order to provide means to departments, health administrators and the social security institution to achieve improvements in financial planning, quality and cost control. The cost of the histopathological examinations, which were accepted by the Department of Pathology at Okmeydanı Training and Research Hospital during August 2014, was calculated using the activity-based costing method. The costs were compared with the amounts specified in the Healthcare Implementation Notification Tariff and the conventional volume-based costing. Most pathology examinations listed within a given band in the Healthcare Implementation Notification Tariff show variations in unit costs. The study found that the costs of 77.4% of the examinations were higher than the prices listed in the Healthcare Implementation Notification Tariff. The pathology examination tariffs specified in the Healthcare Implementation Notification do not reflect the real costs of the examinations. The costs that are calculated using the activity-based costing system may vary according to the service types and levels of health care institutions. However, the main parameters of the method used in the study reflect the necessity of a more accurate banding of pathology examinations. The banding specified by the Healthcare Implementation Notification Tariff needs to be revised to reflect the real costs in Turkey.

Evidence-Based Diagnostic Algorithm for Glioma: Analysis of the Results of Pathology Panel Review and Molecular Parameters of EORTC 26951 and 26882 Trials.

Science.gov (United States)

Kros, Johan M; Huizer, Karin; Hernández-Laín, Aurelio; Marucci, Gianluca; Michotte, Alex; Pollo, Bianca; Rushing, Elisabeth J; Ribalta, Teresa; French, Pim; Jaminé, David; Bekka, Nawal; Lacombe, Denis; van den Bent, Martin J; Gorlia, Thierry

2015-06-10

With the rapid discovery of prognostic and predictive molecular parameters for glioma, the status of histopathology in the diagnostic process should be scrutinized. Our project aimed to construct a diagnostic algorithm for gliomas based on molecular and histologic parameters with independent prognostic values. The pathology slides of 636 patients with gliomas who had been included in EORTC 26951 and 26882 trials were reviewed using virtual microscopy by a panel of six neuropathologists who independently scored 18 histologic features and provided an overall diagnosis. The molecular data for IDH1, 1p/19q loss, EGFR amplification, loss of chromosome 10 and chromosome arm 10q, gain of chromosome 7, and hypermethylation of the promoter of MGMT were available for some of the cases. The slides were divided in discovery (n = 426) and validation sets (n = 210). The diagnostic algorithm resulting from analysis of the discovery set was validated in the latter. In 66% of cases, consensus of overall diagnosis was present. A diagnostic algorithm consisting of two molecular markers and one consensus histologic feature was created by conditional inference tree analysis. The order of prognostic significance was: 1p/19q loss, EGFR amplification, and astrocytic morphology, which resulted in the identification of four diagnostic nodes. Validation of the nodes in the validation set confirmed the prognostic value (P diagnostic algorithm for anaplastic glioma based on multivariable analysis of consensus histopathology and molecular parameters. © 2015 by American Society of Clinical Oncology.

Alzheimer's disease amyloid-beta links lens and brain pathology in Down syndrome.

Directory of Open Access Journals (Sweden)

Juliet A Moncaster

2010-05-01

Full Text Available Down syndrome (DS, trisomy 21 is the most common chromosomal disorder and the leading genetic cause of intellectual disability in humans. In DS, triplication of chromosome 21 invariably includes the APP gene (21q21 encoding the Alzheimer's disease (AD amyloid precursor protein (APP. Triplication of the APP gene accelerates APP expression leading to cerebral accumulation of APP-derived amyloid-beta peptides (Abeta, early-onset AD neuropathology, and age-dependent cognitive sequelae. The DS phenotype complex also includes distinctive early-onset cerulean cataracts of unknown etiology. Previously, we reported increased Abeta accumulation, co-localizing amyloid pathology, and disease-linked supranuclear cataracts in the ocular lenses of subjects with AD. Here, we investigate the hypothesis that related AD-linked Abeta pathology underlies the distinctive lens phenotype associated with DS. Ophthalmological examinations of DS subjects were correlated with phenotypic, histochemical, and biochemical analyses of lenses obtained from DS, AD, and normal control subjects. Evaluation of DS lenses revealed a characteristic pattern of supranuclear opacification accompanied by accelerated supranuclear Abeta accumulation, co-localizing amyloid pathology, and fiber cell cytoplasmic Abeta aggregates (approximately 5 to 50 nm identical to the lens pathology identified in AD. Peptide sequencing, immunoblot analysis, and ELISA confirmed the identity and increased accumulation of Abeta in DS lenses. Incubation of synthetic Abeta with human lens protein promoted protein aggregation, amyloid formation, and light scattering that recapitulated the molecular pathology and clinical features observed in DS lenses. These results establish the genetic etiology of the distinctive lens phenotype in DS and identify the molecular origin and pathogenic mechanism by which lens pathology is expressed in this common chromosomal disorder. Moreover, these findings confirm increased Abeta

Molecular pathology in adult gliomas: diagnostic, prognostic, and predictive markers.

LENUS (Irish Health Repository)

Jansen, Michael

2010-07-01

Over the past 10 years, there has been an increasing use of molecular markers in the assessment and management of adult malignant gliomas. Some molecular signatures are used diagnostically to help pathologists classify tumours, whereas others are used to estimate prognosis for patients. Most crucial, however, are those markers that are used to predict response to certain therapies, thereby directing clinicians to a particular treatment while avoiding other potentially deleterious therapies. Recently, large-scale genome-wide surveys have been used to identify new biomarkers that have been rapidly developed as diagnostic and prognostic tools. Given these developments, the pace of discovery of new molecular assays will quicken to facilitate personalised medicine in the setting of malignant glioma.

How can the postgraduate training program in pathology departments in India be improved?

Directory of Open Access Journals (Sweden)

Shivayogi R Bhusnurmath

2011-01-01

Full Text Available There exists a wide variation in the competence of the postgraduate residents trained in pathology in different institutions across India. This results in strong disparities in the clinical diagnostic skills, teaching skills, research capabilities and the managerial skills of the graduates. The end users of this training, namely the community, clinicians and health care institutions would benefit from a more uniform and better trained pathologist. The article reviews the reasons for the variation in the quality of the training programs. The main deficiencies include, lack of well-defined criteria for recruitment of residents, training facilities, faculty resources, curriculum with well-defined learning objectives and competencies, hands-on experiences in diagnostic and research activities, diagnostic specimens and medical autopsies, exposure to molecular pathology, pathology informatics, electron microscopy, research experiences, communication skills, professional behavior and bioethics, business practices in pathology and quality assurance. There is also a lack of defined career tracks in various disciplines in laboratory medicine, standard protocols for evaluation and regional and national oversight of the programs. The steps for rectification should include defining the competencies and learning objectives, development of the curriculum including teaching methods, facilities and evaluation strategies, communication skills, professional behavior skills, teaching skills, legal aspects of practicing pathology and the various career pathways to subspecialties in pathology. The training should include defined exposure to molecular pathology, electron microscopy, quality control and assurance, laboratory accreditation, business aspects of pathology practice, review of literature, evidence-based medicine, medical autopsy and medical informatics. Efforts should be made to share human and laboratory resources between regional cooperation. The

Molecular Pathology and Personalized Medicine: The Dawn of a New Era in Companion Diagnostics—Practical Considerations about Companion Diagnostics for Non-Small-Cell-Lung-Cancer

Directory of Open Access Journals (Sweden)

Till Plönes

2016-01-01

Full Text Available Companion diagnostics (CDx have become a major tool in molecular pathology and assist in therapy decisions in an increasing number of various cancers. Particularly, the developments in lung cancer have been most impressing in the last decade and consequently lung cancer mutation testing and molecular profiling has become a major business of diagnostic laboratories. However, it has become difficult to decide which biomarkers are currently relevant for therapy decisions, as many of the new biomarkers are not yet approved as therapy targets, remain in the status of clinical studies, or still have not left the experimental phase. The current review is focussed on those markers that do have current therapy implications, practical implications arising from the respective companion diagnostics, and thus is focused on daily practice.

Predictability in Pathological Gambling? Applying the Duplication of Purchase Law to the Understanding of Cross-Purchases Between Regular and Pathological Gamblers.

Science.gov (United States)

Lam, Desmond; Mizerski, Richard

2017-06-01

The objective of this study is to explore the gambling participations and game purchase duplication of light regular, heavy regular and pathological gamblers by applying the Duplication of Purchase Law. Current study uses data collected by the Australian Productivity Commission for eight different types of games. Key behavioral statistics on light regular, heavy regular, and pathological gamblers were computed and compared. The key finding is that pathological gambling, just like regular gambling, follows the Duplication of Purchase Law, which states that the dominant factor of purchase duplication between two brands is their market shares. This means that gambling between any two games at pathological level, like any regular consumer purchases, exhibits "law-like" regularity based on the pathological gamblers' participation rate of each game. Additionally, pathological gamblers tend to gamble more frequently across all games except lotteries and instant as well as make greater cross-purchases compared to heavy regular gamblers. A better understanding of the behavioral traits between regular (particularly heavy regular) and pathological gamblers can be useful to public policy makers and social marketers in order to more accurately identify such gamblers and better manage the negative impacts of gambling.

Curriculum Guidelines for Pathology and Oral Pathology.

Science.gov (United States)

Journal of Dental Education, 1985

1985-01-01

Guidelines for dental school pathology courses describe the interrelationships of general, systemic, and oral pathology; primary educational goals; prerequisites; a core curriculum outline and behavioral objectives for each type of pathology. Notes on sequencing, faculty, facilities, and occupational hazards are included. (MSE)

The comparative study of radiograph, MRI and pathology in degeneration of lumbar intervertebral disc

International Nuclear Information System (INIS)

Shang Tiesong; Wang Yunzhao

2002-01-01

Objective: To investigate the pathology, and MRI features of the degeneration of lumbar intervertebral discs (IVD). Methods: Thirteen human lumbar spine segments with 31 IVDs were harvested from fresh cadavers. High quality radiographs were taken for all specimens. Five segments with 20 IVD underwent MRl. Then, the radiographic and MRI findings were correlated with corresponding 87 pathologic sections. Results: Variant degeneration was observed in pathologic sections in all 31 IVDs. With MRI T 2 WI images, 20 IVDs showed linear and spotty high signal in the annular fibers, or most of the IVD showed high signal. On pathologic cuts, 22 of 31 IVDs showed infolding of annular fibers, 18 of 31 showed outfolding of annular fibers. On MRI T 1 WI and T 2 WI images, infolding and outfolding of annular fibers were seen as low signal. 20 of 31 IVDs had necrotic debris of cells in the nucleus pulposus. 14 of 20 demonstrated spotty low signal areas on MRI T 2 WI images. 7 Schmorl nodules were found. On pathologic sections Schmorl nodules were seen as IVD tissue protruding into vertebral endplates, they were seen as high signal on T 2 WI images. Two large fissures found on sections were seen as low signal on T 2 WI. Degenerative fibrosis seen on 6 IVD, which showed intermediate signal on T 2 WI images. However, radiographs only demonstrated osteophytes on 3 vertebrae, 7 Schmorl's nodules. Sclerotic, concave and irregular endplates were seen in 11 IVDs, the tatter is the indication of cartilaginous endplate disruption, Conclusion: MRI is very useful in demonstrating the degeneration of IVD, radiograph is able to indirectly show the disappearance of cartilaginous endplate

Acute sciatic nerve crush injuries in rabbits: MRI and pathological comparative study

International Nuclear Information System (INIS)

Li Xinchun; Chen Jianyu; Wang Xinlu; Shen Jun; Liu Qingyu; Liang Biling

2004-01-01

Objective: Simulating injury mechanism in human peripheral nerve, acute sciatic nerve crush injuries model was produced in rabbits to investigate the relationship between the manifestations of MRI and pathology in order to provide the information for clinical therapy and operative plan. Methods: Thirty-two adult rabbits were randomly divided into two groups: group A (n=16) and B (n=16). In group A, the left sciatic nerves were crushed with a stress of 3.61 kg; In group B, with a stress of 10.50 kg. 4 time intervals in each group were observed in 1, 2, 4, and 8 weeks, respectively, and each time interval contained 4 rabbits. Left sciatic nerves were served as injured sides, right sciatic nerves were regarded as control sides. MRI was performed at different time interval after crush injury. Then the nerves were examined pathologically. Results: There were no obvious changes on T 1 WI in injured sides, but the injured distal segment of sciatic nerve thickened and twisted, showing high signal intensity on 3D T 2 WI, T 2 WI/SPIR, B-FFE, and T 2 WI/STIR. MRI could show abnormality of 30 sciatic nerves, the correct diagnostic rate was 93.75% and false negative rate was 6.25%. The distal sciatic nerve/muscle signal intensity ratio (SIR) of the injured sides was significantly higher than that of the control sides (P 0.05). SIR in injured side increased at 1 week, reached the peak at 2 weeks, at this time, nerve axons disappeared and lots of myelin degenerated, abduction function disappeared. SIR decreased during 4-8 weeks, the myelin sheath breakdown and Schwann cell proliferated obviously, and abduction functions were observed. The control sciatic nerves showed no abnormality in MRI and pathology. Conclusion: MRI can make the diagnosis of crush injury of sciatic nerve, and dynamic SIR measurement of nerve injury correlates well with the pathological and functional recovery process. MRI is an effective method to monitor degeneration, regeneration, and prognosis after

Interaction of pathology and molecular characterization of thyroid cancers

International Nuclear Information System (INIS)

Williams, E.D.; Cherstvoy, E.; Egloff, B.; Hoefler, H.; Vecchio, G.; Bogdanova, T.; Bragarnik, M.; Tronko, N.D.

1996-01-01

This paper presents the results of joint studies of thyroid cancer in children under 15 years of age between departments in Cambridge, Brussels, Naples and Munich in the European Union, and departments in Minsk, Kiev and Obninsk in the newly independent states of Eastern Europe. The pathology of 264 cases of childhood thyroid cancer out of 430 that have occurred since 1990 in the 3 countries in which high levels of fallout from the Chernobyl accident occurred has been restudied by NIS and EU pathologists. The overall level of agreement reached was about 97%. The diagnosis was supported by immunocytochemistry and ISH for the differentiation markers, thyroglobulin and calcitonin, and the tumors were classified according to the WHO, with papillary carcinomas being further subclassified. 99% of the 134 Belarussian cases were papillary carcinomas, as were 94% of the 114 Ukrainian tumors. All 9 of the Russian cases available for study were papillary in type. 76 of 154 cases of childhood thyroid cancer reviewed over a 30 year period in England and Wales and were also studied, 68% of these were papillary carcinoma. Histological study showed that a subtype of papillary carcinoma, rarely found in adults, with a solid/follicular architecture occurred in children. It was found in 72% of the Belarussian papillary carcinomas, 76% of the Ukrainian cases, but only 40% of the England and Wales cases. Molecular biological studies showed that the proportion of cases of papillary carcinoma expressing the ret gene was not significantly different in the exposed and the unexposed tumors, studies of the type of translocation leading to ret gene expression are not yet conclusive. Ras gene mutations were found as expected in follicular carcinoma, but were absent from any papillary carcinoma, whether from exposed or unexposed cases. TSH receptor mutations, normally found in follicular tumors were not found in any papillary carcinomas, nor were any p53 mutations identified. All these results

EORTC recommended protocol for melanoma sentinel lymph node sectioning misclassifies up to 50% of the patients compared with complete step sectioning. Danish Society for Pathological Anatomy and Clinical Cytology

DEFF Research Database (Denmark)

Riber-Hansen, Rikke; Hastrup, N; Clemmensen, O.

2010-01-01

EORTC recommended protocol for melanoma sentinel lymph node sectioning misclassifies up to 50% of the patients compared with complete step sectioning. Danish Society for Pathological Anatomy and Clinical Cytology......EORTC recommended protocol for melanoma sentinel lymph node sectioning misclassifies up to 50% of the patients compared with complete step sectioning. Danish Society for Pathological Anatomy and Clinical Cytology...

Hybrid Imaging Labels: Providing the Link Between Mass Spectrometry-Based Molecular Pathology and Theranostics

Science.gov (United States)

Buckle, Tessa; van der Wal, Steffen; van Malderen, Stijn J.M.; Müller, Larissa; Kuil, Joeri; van Unen, Vincent; Peters, Ruud J.B.; van Bemmel, Margaretha E.M.; McDonnell, Liam A.; Velders, Aldrik H.; Koning, Frits; Vanhaeke, Frank; van Leeuwen, Fijs W. B.

2017-01-01

Background: Development of theranostic concepts that include inductively coupled plasma mass spectrometry (ICP-MS) and laser ablation ICP-MS (LA-ICP-MS) imaging can be hindered by the lack of a direct comparison to more standardly used methods for in vitro and in vivo evaluation; e.g. fluorescence or nuclear medicine. In this study a bimodal (or rather, hybrid) tracer that contains both a fluorescent dye and a chelate was used to evaluate the existence of a direct link between mass spectrometry (MS) and in vitro and in vivo molecular imaging findings using fluorescence and radioisotopes. At the same time, the hybrid label was used to determine whether the use of a single isotope label would allow for MS-based diagnostics. Methods: A hybrid label that contained both a DTPA chelate (that was coordinated with either 165Ho or 111In) and a Cy5 fluorescent dye was coupled to the chemokine receptor 4 (CXCR4) targeting peptide Ac-TZ14011 (hybrid-Cy5-Ac-TZ4011). This receptor targeting tracer was used to 1) validate the efficacy of (165Ho-based) mass-cytometry in determining the receptor affinity via comparison with fluorescence-based flow cytometry (Cy5), 2) evaluate the microscopic binding pattern of the tracer in tumor cells using both fluorescence confocal imaging (Cy5) and LA-ICP-MS-imaging (165Ho), 3) compare in vivo biodistribution patterns obtained with ICP-MS (165Ho) and radiodetection (111In) after intravenous administration of hybrid-Cy5-Ac-TZ4011 in tumor-bearing mice. Finally, LA-ICP-MS-imaging (165Ho) was linked to fluorescence-based analysis of excised tissue samples (Cy5). Results: Analysis with both mass-cytometry and flow cytometry revealed a similar receptor affinity, respectively 352 ± 141 nM and 245 ± 65 nM (p = 0.08), but with a much lower detection sensitivity for the first modality. In vitro LA-ICP-MS imaging (165Ho) enabled clear discrimination between CXCR4 positive and negative cells, but fluorescence microscopy was required to determine the

Bioinformatics Education in Pathology Training: Current Scope and Future Direction

Directory of Open Access Journals (Sweden)

Michael R Clay

2017-04-01

Full Text Available Training anatomic and clinical pathology residents in the principles of bioinformatics is a challenging endeavor. Most residents receive little to no formal exposure to bioinformatics during medical education, and most of the pathology training is spent interpreting histopathology slides using light microscopy or focused on laboratory regulation, management, and interpretation of discrete laboratory data. At a minimum, residents should be familiar with data structure, data pipelines, data manipulation, and data regulations within clinical laboratories. Fellowship-level training should incorporate advanced principles unique to each subspecialty. Barriers to bioinformatics education include the clinical apprenticeship training model, ill-defined educational milestones, inadequate faculty expertise, and limited exposure during medical training. Online educational resources, case-based learning, and incorporation into molecular genomics education could serve as effective educational strategies. Overall, pathology bioinformatics training can be incorporated into pathology resident curricula, provided there is motivation to incorporate, institutional support, educational resources, and adequate faculty expertise.

Pathology economic model tool: a novel approach to workflow and budget cost analysis in an anatomic pathology laboratory.

Science.gov (United States)

Muirhead, David; Aoun, Patricia; Powell, Michael; Juncker, Flemming; Mollerup, Jens

2010-08-01

The need for higher efficiency, maximum quality, and faster turnaround time is a continuous focus for anatomic pathology laboratories and drives changes in work scheduling, instrumentation, and management control systems. To determine the costs of generating routine, special, and immunohistochemical microscopic slides in a large, academic anatomic pathology laboratory using a top-down approach. The Pathology Economic Model Tool was used to analyze workflow processes at The Nebraska Medical Center's anatomic pathology laboratory. Data from the analysis were used to generate complete cost estimates, which included not only materials, consumables, and instrumentation but also specific labor and overhead components for each of the laboratory's subareas. The cost data generated by the Pathology Economic Model Tool were compared with the cost estimates generated using relative value units. Despite the use of automated systems for different processes, the workflow in the laboratory was found to be relatively labor intensive. The effect of labor and overhead on per-slide costs was significantly underestimated by traditional relative-value unit calculations when compared with the Pathology Economic Model Tool. Specific workflow defects with significant contributions to the cost per slide were identified. The cost of providing routine, special, and immunohistochemical slides may be significantly underestimated by traditional methods that rely on relative value units. Furthermore, a comprehensive analysis may identify specific workflow processes requiring improvement.

Speed-accuracy tradeoff in decision-making performance among pathological gamblers.

Science.gov (United States)

Kertzman, Semion; Vainder, Michael; Vishne, Tali; Aizer, Anat; Kotler, Moshe; Dannon, Pinhas N

2010-01-01

Pathological gambling is classified as an impulse control disorder in the DSM-IV-TR; however, few studies have investigated the relationship between gambling behavior and impulsive decision-making in time-non-limited situations. The subjects performed the Matching Familiar Figures Test (MFFT). The MFFT investigated the reflection-impulsivity dimension in pathological gamblers (n = 82) and demographically matched healthy subjects (n = 82). Our study demonstrated that pathological gamblers had a significantly higher rate of errors than healthy controls (p = 0.01) but were not different in terms of response time (p = 0.49). We found a similar power of correlation between the number of errors and response time in both pathological gamblers and controls. We may conclude that impaired performance of our pathological gamblers as compared to controls in a situation without time limit pressure cannot be explained by a trade-off of greater speed at the cost of less accuracy. The results of our study showed that pathological gamblers tend to make more errors but do not exhibit quicker responses as compared to the control group. Diminished MFFT performance in pathological gamblers as compared to controls supports findings of previous studies which show that pathological gamblers have impaired decision-making. Further controlled studies with a larger sample size which examine MFFT performance in pathological gamblers are necessary to confirm our results. Copyright 2009 S. Karger AG, Basel.

Pathological video-gaming among Singaporean youth.

Science.gov (United States)

Choo, Hyekyung; Gentile, Douglas A; Sim, Timothy; Li, Dongdong; Khoo, Angeline; Liau, Albert K

2010-11-01

Increase in internet use and video-gaming contributes to public concern on pathological or obsessive play of video games among children and adolescents worldwide. Nevertheless, little is known about the prevalence of pathological symptoms in video-gaming among Singaporean youth and the psychometric properties of instruments measuring pathological symptoms in video-gaming. A total of 2998 children and adolescents from 6 primary and 6 secondary schools in Singapore responded to a comprehensive survey questionnaire on sociodemographic characteristics, video-gaming habits, school performance, somatic symptoms, various psychological traits, social functioning and pathological symptoms of video-gaming. After weighting, the survey data were analysed to determine the prevalence of pathological video-gaming among Singaporean youth and gender differences in the prevalence. The construct validity of instrument used to measure pathological symptoms of video-gaming was tested. Of all the study participants, 8.7% were classified as pathological players with more boys reporting more pathological symptoms than girls. All variables, including impulse control problem, social competence, hostility, academic performance, and damages to social functioning, tested for construct validity, were significantly associated with pathological status, providing good evidence for the construct validity of the instrument used. The prevalence rate of pathological video-gaming among Singaporean youth is comparable with that from other countries studied thus far, and gender differences are also consistent with the findings of prior research. The positive evidence of construct validity supports the potential use of the instrument for future research and clinical screening on Singapore children and adolescents' pathological video-gaming.

Musculoskeletal ultrasound including definitions for ultrasonographic pathology

DEFF Research Database (Denmark)

Wakefield, RJ; Balint, PV; Szkudlarek, Marcin

2005-01-01

pathologies. This article presents the first report from the OMERACT ultrasound special interest group, which has compared US against the criteria of the OMERACT filter. Also proposed for the first time are consensus US definitions for common pathological lesions seen in patients with inflammatory arthritis....

Central pathology review with two-stage quality assurance for pathological response after neoadjuvant chemotherapy in the ARTemis Trial.

Science.gov (United States)

Thomas, Jeremy St John; Provenzano, Elena; Hiller, Louise; Dunn, Janet; Blenkinsop, Clare; Grybowicz, Louise; Vallier, Anne-Laure; Gounaris, Ioannis; Abraham, Jean; Hughes-Davies, Luke; McAdam, Karen; Chan, Stephen; Ahmad, Rizvana; Hickish, Tamas; Houston, Stephen; Rea, Daniel; Caldas, Carlos; Bartlett, John Ms; Cameron, David Allan; Hayward, Richard Laurence; Earl, Helena Margaret

2017-08-01

The ARTemis Trial tested standard neoadjuvant chemotherapy±bevacizumab in the treatment of HER2-negative early breast cancer. We compare data from central pathology review with report review and also the reporting behavior of the two central pathologists. Eight hundred women with HER2-negative early invasive breast cancer were recruited. Response to chemotherapy was assessed from local pathology reports for pathological complete response in breast and axillary lymph nodes. Sections from the original core biopsy and surgical excision were centrally reviewed by one of two trial pathologists blinded to the local pathology reports. Pathologists recorded response to chemotherapy descriptively and also calculated residual cancer burden. 10% of cases were double-reported to compare the central pathologists' reporting behavior. Full sample retrieval was obtained for 681 of the 781 patients (87%) who underwent surgery within the trial and were evaluable for pathological complete response. Four hundred and eighty-three (71%) were assessed by JSJT, and 198 (29%) were assessed by EP. Residual cancer burden calculations were possible in 587/681 (86%) of the centrally reviewed patients, as 94/681 (14%) had positive sentinel nodes removed before neoadjuvant chemotherapy invalidating residual cancer burden scoring. Good concordance was found between the two pathologists for residual cancer burden classes within the 65-patient quality assurance exercise (kappa 0.63 (95% CI: 0.57-0.69)). Similar results were obtained for the between-treatment arm comparison both from the report review and the central pathology review. For pathological complete response, report review was as good as central pathology review but for minimal residual disease, report review overestimated the extent of residual disease. In the ARTemis Trial central pathology review added little in the determination of pathological complete response but had a role in evaluating low levels of residual disease. Calculation

The Transcriptional Coactivator Bob1 Is Associated With Pathologic B Cell Responses in Autoimmune Tissue Inflammation

NARCIS (Netherlands)

Levels, Maria J.; Van Tok, Melissa N.; Cantaert, Tineke; Canete, Juan D.; Kroese, Frans G. M.; Germar, Kristine; Spits, Hergen; Baeten, Dominique L. P.; Yeremenko, Nataliya G.

Objective. The molecular mechanisms steering abnormal B cell responses in autoimmune diseases remain poorly understood. We undertook this study to identify molecular switches controlling pathologic B cell responses in rheumatoid arthritis (RA). Methods. Candidate molecules were identified by gene

How to read a pathology report of a bone tumor

International Nuclear Information System (INIS)

Guinebretière, Jean-Marc; Kreshak, Jennifer; Suciu, Voichita; Maulmont, Charles De; Mascard, Eric; Missenard, Gilles; Larousserie, Frederique; Vanel, Daniel

2013-01-01

The interpretation of a biopsy specimen involving bone is one of the most challenging feats for a pathologist, as it is often difficult to distinguish between benign or reactive lesions and malignant tumors on microscopic analysis. Therefore, correlation with the clinical data and imaging is essential and sometimes it is only the evolution of certain characteristics over time or information garnered from molecular analysis that can provide an accurate diagnosis. The pathology report is critical in that it will define subsequent patient management; its wording must precisely reflect those elements that are known with certainty and those that are diagnostic hypotheses. It must be systematic, thorough, and complete and should not be limited to a simple conclusion. The pathologist must first ensure the completeness and correct transcription of the information provided with the specimen, then describe and analyze the histology as well as the quality and representative nature of the sample (as they relate to the radiographic findings and preliminary/final diagnoses), and finally, compare what is seen under the microscope with the assessment made by the radiologist and/or surgeon. This analysis helps to identify difficult cases requiring further consultation between the radiologist and pathologist. There are multiple reasons for misinterpretation of a pathology report. An important and largely underestimated reason is varied interpretations of terms used by the pathologist. Standardized pathology reports with concise phrases as well as multidisciplinary meetings may limit errors and should be encouraged for optimal diagnostic accuracy

How to read a pathology report of a bone tumor

Energy Technology Data Exchange (ETDEWEB)

Guinebretière, Jean-Marc, E-mail: jean-marc.guinebretiere@curie.net [Department of Pathology, Hôpital René-Huguenin, Institut Curie, 35 rue Dailly, 92210 Saint Cloud (France); Kreshak, Jennifer [Department of Research, Istituto Ortopedico Rizzoli, Bologna (Italy); Suciu, Voichita [Department of Pathology, Hôpital René-Huguenin, Institut Curie, 35 rue Dailly, 92210 Saint Cloud (France); Maulmont, Charles De [Department of Radiology, Hôpital René-Huguenin, Institut Curie, 35 rue Dailly, 92210 Saint Cloud (France); Mascard, Eric; Missenard, Gilles [Institut Gustave-Roussy, 35 rue Camille Desmoulins, 94805 Villejuif (France); Larousserie, Frederique [Department of Research, Istituto Ortopedico Rizzoli, Bologna (Italy); Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris (France); Vanel, Daniel [Department of Research, Istituto Ortopedico Rizzoli, Bologna (Italy)

2013-12-01

The interpretation of a biopsy specimen involving bone is one of the most challenging feats for a pathologist, as it is often difficult to distinguish between benign or reactive lesions and malignant tumors on microscopic analysis. Therefore, correlation with the clinical data and imaging is essential and sometimes it is only the evolution of certain characteristics over time or information garnered from molecular analysis that can provide an accurate diagnosis. The pathology report is critical in that it will define subsequent patient management; its wording must precisely reflect those elements that are known with certainty and those that are diagnostic hypotheses. It must be systematic, thorough, and complete and should not be limited to a simple conclusion. The pathologist must first ensure the completeness and correct transcription of the information provided with the specimen, then describe and analyze the histology as well as the quality and representative nature of the sample (as they relate to the radiographic findings and preliminary/final diagnoses), and finally, compare what is seen under the microscope with the assessment made by the radiologist and/or surgeon. This analysis helps to identify difficult cases requiring further consultation between the radiologist and pathologist. There are multiple reasons for misinterpretation of a pathology report. An important and largely underestimated reason is varied interpretations of terms used by the pathologist. Standardized pathology reports with concise phrases as well as multidisciplinary meetings may limit errors and should be encouraged for optimal diagnostic accuracy.

Crowdsourcing the General Public for Large Scale Molecular Pathology Studies in Cancer

Directory of Open Access Journals (Sweden)

Francisco J. Candido dos Reis

2015-07-01

Interpretation: Crowdsourcing of the general public to classify cancer pathology data for research is viable, engages the public and provides accurate ER data. Crowdsourced classification of research data may offer a valid solution to problems of throughput requiring human input.

Emerging and Future Applications of Matrix-Assisted Laser Desorption Ionization Time-of-Flight (MALDI-TOF) Mass Spectrometry in the Clinical Microbiology Laboratory: A Report of the Association for Molecular Pathology.

Science.gov (United States)

Doern, Christopher D; Butler-Wu, Susan M

2016-11-01

The performance of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MS) for routine bacterial and yeast identification as well as direct-from-blood culture bottle identification has been thoroughly evaluated in the peer-reviewed literature. Microbiologists are now moving beyond these methods to apply MS to other areas of the diagnostic process. This review discusses the emergence of advanced matrix-assisted laser desorption ionization time-of-flight MS applications, including the identification of filamentous fungi and mycobacteria and the current and future state of antimicrobial resistance testing. Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

How does it feel to be a pathology resident? Results of a survey on experiences and job satisfaction during pathology residency.

Science.gov (United States)

Pehlivanoglu, Burcin; Hassoy, Hur; Calle, Catarina; Dendooven, Amelie; Nalbantoglu, ILKe; Reshchikova, Lidiya; Gul, Gulen; Doganavsargil, Basak

2017-09-01

Residents' career choices and professional motivation can be affected from perception of their role and recognition within a medical team as well as their educational and workplace experiences. To evaluate pathology trainees' perceptions of their pathology residency, we conducted a 42-item survey via a web-based link questioning respondents' personal and institutional background, workplace, training conditions, and job satisfaction level. For the 208 residents from different European countries who responded, personal expectations in terms of quality of life (53%) and scientific excitement (52%) were the most common reasons why they chose and enjoy pathology. Sixty-six percent were satisfied about their relationship with other people working in their department, although excessive time spent on gross examination appeared less satisfactory. A set residency training program (core curriculum), a set annual scientific curriculum, and a residency program director existed in the program of 58, 60, and 69% respondents, respectively. Most respondents (76%) considered that pathologists have a direct and high impact on patient management, but only 32% agreed that pathologists cooperate with clinicians/surgeons adequately. Most (95%) found that patients barely know what pathologists do. Only 22% considered pathology and pathologists to be adequately positioned in their country's health care system. Almost 84% were happy to have chosen pathology, describing it as "puzzle solving," "a different fascinating world," and "challenging while being crucial for patient management." More than two thirds (72%) considered pathology and pathologists to face a bright future. However, a noticeable number of respondents commented on the need for better physical working conditions, a better organized training program, more interaction with experienced pathologists, and deeper knowledge on molecular pathology.

Surgical pathology in the 20th century at the Mount Sinai Hospital, New York.

Science.gov (United States)

Geller, Stephen A

2008-08-01

, immunohistochemistry, cytogenetics, molecular pathology) gain place, the increasing tendency to select investigators, including basic scientists, as teaching department chairs and the financial constraints requiring increasing use of nonphysician workers all speak to the relegation of the Otani-Kaneko era to history. Is this a loss to Pathology? It is certainly a style of practice that has been lost. However, there is no reason to bemoan the state of Pathology in the beginning years of the 21st century. Pathology practice is outstanding at many medical centers throughout the world, including at Mount Sinai under the very able and creative leadership of Alan Schiller, who has presided over great enhancements of the department in both anatomic and clinical pathology, including significant advances in the study of diseases by molecular methods. Surgical Pathology at Mount Sinai has been led by James Strauchen, a renowned hematopathologist recruited by Schiller's predecessor, Jerome Kleinerman, and is currently directed by Ira Bleiweiss, a student of Kaneko. Other techniques and technologies have, to a degree, compensated for some of the changes since the Otani-Kaneko years and it is almost certain that advances in molecular pathology will allow for increasing sophistication in establishing diagnoses, and likely even grading and staging, probably even on blood, rather than tissue, samples. The science of Pathology will advance, as the art declines. Those who learned at Mount Sinai during the Otani-Kaneko years will, however, very likely tell you that they were privileged to have learned Pathology there and, especially, to have learned a distinct philosophy of Pathology under the guidance of caring, thoughtful, and especially gifted pathologists.

Direct-Conversion Molecular Breast Imaging of Invasive Breast Cancer: Imaging Features, Extent of Invasive Disease, and Comparison Between Invasive Ductal and Lobular Histology.

Science.gov (United States)

Conners, Amy Lynn; Jones, Katie N; Hruska, Carrie B; Geske, Jennifer R; Boughey, Judy C; Rhodes, Deborah J

2015-09-01

The purposes of this study were to compare the tumor appearance of invasive breast cancer on direct-conversion molecular breast imaging using a standardized lexicon and to determine how often direct-conversion molecular breast imaging identifies all known invasive tumor foci in the breast, and whether this differs for invasive ductal versus lobular histologic profiles. Patients with prior invasive breast cancer and concurrent direct-conversion molecular breast imaging examinations were retrospectively reviewed. Blinded review of direct-conversion molecular breast imaging examinations was performed by one of two radiologists, according to a validated lexicon. Direct-conversion molecular breast imaging findings were matched with lesions described on the pathology report to exclude benign reasons for direct-conversion molecular breast imaging findings and to document direct-conversion molecular breast imaging-occult tumor foci. Associations between direct-conversion molecular breast imaging findings and tumor histologic profiles were examined using chi-square tests. In 286 patients, 390 invasive tumor foci were present in 294 breasts. A corresponding direct-conversion molecular breast imaging finding was present for 341 of 390 (87%) tumor foci described on the pathology report. Invasive ductal carcinoma (IDC) tumor foci were more likely to be a mass (40% IDC vs 15% invasive lobular carcinoma [ILC]; p < 0.001) and to have marked intensity than were ILC foci (63% IDC vs 32% ILC; p < 0.001). Direct-conversion molecular breast imaging correctly revealed all pathology-proven foci of invasive disease in 79.8% of cases and was more likely to do so for IDC than for ILC (86.1% vs 56.7%; p < 0.0001). Overall, direct-conversion molecular breast imaging showed all known invasive foci in 249 of 286 (87%) patients. Direct-conversion molecular breast imaging features of invasive cancer, including lesion type and intensity, differ by histologic subtype. Direct-conversion molecular

Pathology Gross Photography: The Beginning of Digital Pathology.

Science.gov (United States)

Rampy, B Alan; Glassy, Eric F

2015-06-01

The underutilized practice of photographing anatomic pathology specimens from surgical pathology and autopsies is an invaluable benefit to patients, clinicians, pathologists, and students. Photographic documentation of clinical specimens is essential for the effective practice of pathology. When considering what specimens to photograph, all grossly evident pathology, absent yet expected pathologic features, and gross-only specimens should be thoroughly documented. Specimen preparation prior to photography includes proper lighting and background, wiping surfaces of blood, removing material such as tubes or bandages, orienting the specimen in a logical fashion, framing the specimen to fill the screen, positioning of probes, and using the right-sized scale. Copyright © 2015 Elsevier Inc. All rights reserved.

Quantum Dot-based Immunohistochemistry for Pathological Applications

Directory of Open Access Journals (Sweden)

Li Zhou

2016-01-01

Full Text Available Quantum dots (QDs are novel light emitting semiconductor nanocrystals with diameter ranging from 2 to 20 nm. In comparison with traditional organic dyes and fluorescent proteins, QDs possess unique optical properties including extremely high fluorescence efficiency and minimal photobleaching which make them emerge as a new class of fluorescent labels for molecular imaging and biomedical analysis. Herein, recent advances in fundamental mechanisms and pathological applications of QD were reviewed.

Claudin-Low Breast Cancer; Clinical & Pathological Characteristics.

Directory of Open Access Journals (Sweden)

Kay Dias

Full Text Available Claudin-low breast cancer is a molecular type of breast cancer originally identified by gene expression profiling and reportedly associated with poor survival. Claudin-low tumors have been recognised to preferentially display a triple-negative phenotype, however only a minority of triple-negative breast cancers are claudin-low. We sought to identify an immunohistochemical profile for claudin-low tumors that could facilitate their identification in formalin fixed paraffin embedded tumor material. First, an in silico collection of ~1600 human breast cancer expression profiles was assembled and all claudin-low tumors identified. Second, genes differentially expressed between claudin-low tumors and all other molecular subtypes of breast cancer were identified. Third, a number of these top differentially expressed genes were tested using immunohistochemistry for expression in a diverse panel of breast cancer cell lines to determine their specificity for claudin-low tumors. Finally, the immunohistochemical panel found to be most characteristic of claudin-low tumors was examined in a cohort of 942 formalin fixed paraffin embedded human breast cancers with >10 years clinical follow-up to evaluate the clinico-pathologic and survival characteristics of this tumor subtype. Using this approach we determined that claudin-low breast cancer is typically negative for ER, PR, HER2, claudin 3, claudin 4, claudin 7 and E-cadherin. Claudin-low tumors identified with this immunohistochemical panel, were associated with young age of onset, higher tumor grade, larger tumor size, extensive lymphocytic infiltrate and a circumscribed tumor margin. Patients with claudin-low tumors had a worse overall survival when compared to patients with luminal A type breast cancer. Interestingly, claudin-low tumors were associated with a low local recurrence rate following breast conserving therapy. In conclusion, a limited panel of antibodies can facilitate the identification of

Molecular markers for urothelial bladder cancer prognosis: toward implementation in clinical practice.

Science.gov (United States)

van Rhijn, Bas W G; Catto, James W; Goebell, Peter J; Knüchel, Ruth; Shariat, Shahrokh F; van der Poel, Henk G; Sanchez-Carbayo, Marta; Thalmann, George N; Schmitz-Dräger, Bernd J; Kiemeney, Lambertus A

2014-10-01

To summarize the current status of clinicopathological and molecular markers for the prediction of recurrence or progression or both in non-muscle-invasive and survival in muscle-invasive urothelial bladder cancer, to address the reproducibility of pathology and molecular markers, and to provide directions toward implementation of molecular markers in future clinical decision making. Immunohistochemistry, gene signatures, and FGFR3-based molecular grading were used as molecular examples focussing on prognostics and issues related to robustness of pathological and molecular assays. The role of molecular markers to predict recurrence is limited, as clinical variables are currently more important. The prediction of progression and survival using molecular markers holds considerable promise. Despite a plethora of prognostic (clinical and molecular) marker studies, reproducibility of pathology and molecular assays has been understudied, and lack of reproducibility is probably the main reason that individual prediction of disease outcome is currently not reliable. Molecular markers are promising to predict progression and survival, but not recurrence. However, none of these are used in the daily clinical routine because of reproducibility issues. Future studies should focus on reproducibility of marker assessment and consistency of study results by incorporating scoring systems to reduce heterogeneity of reporting. This may ultimately lead to incorporation of molecular markers in clinical practice. Copyright © 2014 Elsevier Inc. All rights reserved.

Blood-based biomarkers of microvascular pathology in Alzheimer's disease.

LENUS (Irish Health Repository)

Ewers, Michael

2012-02-01

Sporadic Alzheimer\\'s disease (AD) is a genetically complex and chronically progressive neurodegenerative disorder with molecular mechanisms and neuropathologies centering around the amyloidogenic pathway, hyperphosphorylation and aggregation of tau protein, and neurofibrillary degeneration. While cerebrovascular changes have not been traditionally considered to be a central part of AD pathology, a growing body of evidence demonstrates that they may, in fact, be a characteristic feature of the AD brain as well. In particular, microvascular abnormalities within the brain have been associated with pathological AD hallmarks and may precede neurodegeneration. In vivo assessment of microvascular pathology provides a promising approach to develop useful biological markers for early detection and pathological characterization of AD. This review focuses on established blood-based biological marker candidates of microvascular pathology in AD. These candidates include plasma concentration of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) that are increased in AD. Measures of endothelial vasodilatory function including endothelin (ET-1), adrenomedullin (ADM), and atrial natriuretic peptide (ANP), as well as sphingolipids are significantly altered in mild AD or during the predementia stage of mild cognitive impairment (MCI), suggesting sensitivity of these biomarkers for early detection and diagnosis. In conclusion, the emerging clinical diagnostic evidence for the value of blood-based microvascular biomarkers in AD is promising, however, still requires validation in phase II and III diagnostic trials. Moreover, it is still unclear whether the described protein dysbalances are early or downstream pathological events and how the detected systemic microvascular alterations relate to cerebrovascular and neuronal pathologies in the AD brain.

Comparing Dimensional Models Assessing Personality Traits and Personality Pathology Among Adult ADHD and Borderline Personality Disorder.

Science.gov (United States)

Koerting, Johanna; Pukrop, Ralf; Klein, Philipp; Ritter, Kathrin; Knowles, Mark; Banzhaf, Anke; Gentschow, Laura; Vater, Aline; Heuser, Isabella; Colla, Michael; Roepke, Stefan

2016-08-01

This pilot study was a comparison of dimensional models assessing personality traits and personality pathology in a clinical sample of adults diagnosed with ADHD and adults diagnosed with borderline personality disorder (BPD), and a nonclinical control sample of healthy adults. Personality traits were assessed using the NEO-Personality Inventory-Revised (NEO-PI-R) and dimensional personality pathology with the Dimensional Assessment of Personality Pathology-Basic Questionnaire (DAPP-BQ). Adults with ADHD and BPD produced higher Emotional Dysregulation/Neuroticism and Dissocial Behavior scores than controls. For the Extraversion/Inhibitedness scale, adults with BPD produced significantly lower scores than adults with ADHD and controls. On the Conscientiousness/Compulsivity domains, Conscientiousness scores were lower for both disorders, whereas low Compulsivity values were specific to adult ADHD. Our results suggest that patients with adult ADHD and BPD have distinguishable profiles of personality traits and personality pathology. © The Author(s) 2012.

Pathology Assistant (C - Gamechanger Of Pathology Diagnostic

Directory of Open Access Journals (Sweden)

Asel Kudaybergenova

2016-06-01

When the competition ended, we received many favor- able reviews and we decided to start another project a little bit similar to the competition. Every month we show three interesting and difficult to diagnose cases provided by the leading Russian pathologists. The participants can look through the clinical data and digitized histological slides, and then discuss what they see among their professional society. There are 400  specialists  from  post  USSR countries.  Moreover, we get a few proposal of partnership to start a similar project in EU. And the last product in line is Pathology Assistant. It is a game changer. Pathology Assistant is a Digital Pathology©technology driven application for pathology diagnostics, tool to innovate pathology diagnostics in more simple, proven by analytical algo- rithm, automatically delivering anticipated support way. The service provides vast and structured database of validated cases, intuitive interface, fast and convenient system of analytical search. Pathology Assistant will streamline and simplify pathologist’s way to the right decision. Pathologists from Memorial Sloan Catering and biggest EU labs are working on preparing the con- tent for the project.  

Laboratory of Cell and Molecular Biology

Data.gov (United States)

Federal Laboratory Consortium — The Laboratory of Cell and Molecular Biology investigates the organization, compartmentalization, and biochemistry of eukaryotic cells and the pathology associated...

Tau pathology in Creutzfeldt-Jakob disease revisited.

Science.gov (United States)

Kovacs, Gabor G; Rahimi, Jasmin; Ströbel, Thomas; Lutz, Mirjam I; Regelsberger, Günther; Streichenberger, Nathalie; Perret-Liaudet, Armand; Höftberger, Romana; Liberski, Pawel P; Budka, Herbert; Sikorska, Beata

2017-05-01

Creutzfeldt-Jakob disease (CJD) is a human prion disease with different etiologies. To determine the spectrum of tau pathologies in CJD, we assessed phospho-Tau (pTau) immunoreactivities in 75 sporadic CJD cases including an evaluation of the entorhinal cortex and six hippocampal subregions. Twelve cases (16%) showed only small tau-immunoreactive neuritic profiles. Fifty-two (69.3%) showed additional tau pathology in the medial temporal lobe compatible with primary age related tauopathy (PART). In 22/52 cases the lower pTau immunoreactivity load in the entorhinal cortex as compared to subiculum, dentate gyrus or CA4 region of the hippocampus was significantly different from the typical distribution of the Braak staging. A further 11 cases (14.7%) showed widespread tau pathologies compatible with features of primary tauopathies or the gray matter type of ageing-related tau astrogliopathy (ARTAG). Prominent gray matter ARTAG was also observed in two out of three additionally examined V203I genetic CJD cases. Analysis of cerebrospinal fluid revealed prominent increase of total tau protein in cases with widespread tau pathology, while pTau (T181) level was increased only in four. This correlated with immunohistochemical observations showing less pathology with anti-pTau T181 antibody when compared to anti-pTau S202/T205, T212/S214 and T231. The frequency of tau pathologies is not unusually high in sporadic CJD and does not precisely relate to PrP deposition. However, the pattern of hippocampal tau pathology often deviates from the stages of Braak. Currently applied examination of cerebrospinal fluid pTau (T181) level does not reliably reflect primary tauopathies, PART and ARTAG seen in CJD brains. © 2016 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.

Comparative Evaluation of C-reactive Proteins in Pregnant Women with and without Periodontal Pathologies: A Prospective Cohort Analysis.

Science.gov (United States)

Mannava, Padmakanth; Gokhale, Sunil; Pujari, Sudarshan; Biswas, Krishna P; Kaliappan, Satish; Vijapure, Shashank

2016-06-01

Inflammation of tooth supporting structures is referred to as periodontitis. C-reactive proteins (CRP) levels are usually increased in case of chronic inflammatory process like periodontitis. Association of CRP with pregnancy has been observed in the past, which includes most commonly preterm delivery, preeclampsia, etc. Therefore, it can be hypothesized that CRP may act as a link between periodontitis and adverse pregnancy outcomes. Hence, we aim to evaluate the plasma CRP levels in pregnant women with and without periodontal pathologies. The study included 210 pregnant women who reported to the hospital with periodontal problems and for routine checkups. All the patients were divided into three groups based on the presence and absence of periodontal pathologies. Russell's Periodontal Index Score was used for the evaluation of periodontal status of the subjects. While comparing the mean CRP levels in all the three study groups, statistically significant results were obtained. Statistically significant results were obtained while comparing the mean CRP levels in group C patients before treatment and after treatment therapy. The CRP levels were estimated by taking blood samples. Paired t-test and one-way analysis of variance was used to assess the correlation between the two parameters. Casual association might exist between the CRP levels and periodontal diseases in pregnant women and the CRP levels may also get elevated in pregnant women.

Imaging of Cerebrovascular Pathology in Animal Models of Alzheimer`s Disease

Directory of Open Access Journals (Sweden)

Jan eKlohs

2014-03-01

Full Text Available In Alzheimer’s disease (AD, vascular pathology may interact with neurodegeneration and thus aggravate cognitive decline. As the relationship between these two processes is poorly understood, research has been increasingly focused on understanding the link between cerebrovascular alterations and AD. This has at last been spurred by the engineering of transgenic animals, which display pathological features of AD and develop cerebral amyloid angiopathy to various degrees. Transgenic models are versatile for investigating the role of amyloid deposition and vascular dysfunction, and for evaluating novel therapeutic concepts. In addition, research has benefited from the development of novel imaging techniques, which are capable of characterizing vascular pathology in vivo. They provide vascular structural read-outs and have the ability to assess the functional consequences of vascular dysfunction as well as to visualize and monitor the molecular processes underlying these pathological alterations. This article focusses on recent in vivo small animal imaging studies addressing vascular aspects related to AD. With the technical advances of imaging modalities such as magnetic resonance, nuclear and microscopic imaging, molecular, functional and structural information related to vascular pathology can now be visualized in vivo in small rodents. Imaging vascular and parenchymal amyloid-β (Aβ deposition as well as Aβ transport pathways have been shown to be useful to characterize their dynamics and to elucidate their role in the development of cerebral amyloid angiopathy and AD. Structural and functional imaging read-outs have been employed to describe the deleterious affects of Aβ on vessel morphology, hemodynamics and vascular integrity. More recent imaging studies have also addressed how inflammatory processes partake in the pathogenesis of the disease. Moreover, imaging can be pivotal in the search for novel therapies targeting the vasculature.

Impaired decisional impulsivity in pathological videogamers.

Directory of Open Access Journals (Sweden)

Michael A Irvine

Full Text Available Pathological gaming is an emerging and poorly understood problem. Impulsivity is commonly impaired in disorders of behavioural and substance addiction, hence we sought to systematically investigate the different subtypes of decisional and motor impulsivity in a well-defined pathological gaming cohort.Fifty-two pathological gaming subjects and age-, gender- and IQ-matched healthy volunteers were tested on decisional impulsivity (Information Sampling Task testing reflection impulsivity and delay discounting questionnaire testing impulsive choice, and motor impulsivity (Stop Signal Task testing motor response inhibition, and the premature responding task. We used stringent diagnostic criteria highlighting functional impairment.In the Information Sampling Task, pathological gaming participants sampled less evidence prior to making a decision and scored fewer points compared with healthy volunteers. Gaming severity was also negatively correlated with evidence gathered and positively correlated with sampling error and points acquired. In the delay discounting task, pathological gamers made more impulsive choices, preferring smaller immediate over larger delayed rewards. Pathological gamers made more premature responses related to comorbid nicotine use. Greater number of hours played also correlated with a Motivational Index. Greater frequency of role playing games was associated with impaired motor response inhibition and strategy games with faster Go reaction time.We show that pathological gaming is associated with impaired decisional impulsivity with negative consequences in task performance. Decisional impulsivity may be a potential target in therapeutic management.

Oral pathology diagnosis by means of micro-Raman spectroscopy on biopsies and blood serum

Science.gov (United States)

Zenone, F.; Lepore, M.; Perna, G.; Carmone, P.; Delfino, I.; Gaeta, G. M.; Capozzi, V.

2007-02-01

Pemphigus vulgaris is a chronic, autoimmune, blistering disease of the skin and mucous membranes with a potentially fatal outcome. In this case micro-Raman spectroscopy (μ-RS) can provide a powerful tool for a not invasive analysis of biological tissue for biopsy and in vivo investigation. Based on the evaluation of molecular vibration frequencies, the μ-RS is able to detect the main molecular bonds of protein constituents, as the C-H and C-C ones. Changes in frequency or in the relative intensity of the vibration modes revealed by μ-RS can be related to changes of chemical bond and of protein structure induced by pathology. Quantitative information on the intensity variation of specific Raman lines can be extracted by Partial Least Square (PLS) analysis. μ-RS was performed on some samples of oral tissue and blood serum from informed patients affected by pemphigus vulgaris (an oral pathology) at different pathology stages. The spectra were measured by means of a Raman confocal microspectrometer apparatus using the 633 nm line of a He- Ne laser source. The main protein bonds are clearly detectable in the considered samples giving important information on the integrity and on the state of tissue and blood serum components (lipids and proteins), and consequently on the occurrence of pathology.

A comparative study of postmortem MR imaging and pathological examination of human brain specimens

International Nuclear Information System (INIS)

Shiga, Tohru

1998-01-01

This study was designed to assess the value of MRI of the postmortem brain specimens by comparing MRI findings with neuropathological findings. Postmortem MRI was performed in 17 consecutive formalin-fixed whole brains comprising 3 with primary CNS neoplasm, 1 with metastatic brain tumor, 6 with cerebral vascular disease (CVD), 1 with degenerative disease, 1 with spongy state in thalamus, and 5 with no abnormality. Postmortem T2WI detected all neuropathological abnormalities but sparsely distributed tumor cells without edema. In one case of CNS neoplasm, the tumor lesions with little necrosis or edema showed isointensity to brain tissue, while others with large amounts of necrosis and edema showed high signal intensity on T2WI. In the cases of CVD, the major signal changes on T2WI were due to edema, necrosis, and damage of the organization as observed on neuropathological studies. There was one case in which both MRI and neuropathological examination showed an abnormality, which was pathologically unexplainable. In two cases, findings of postmortem MRI were more apparent than those of macroscopic examination. Postmortem MRI appeared different from premortem MRI in one of the rest three cases whereas the postmortem MRI correlated well with neuropathological findings. Progression of the disease immediately before death may have caused this difference. In conclusion, the correlations between MRI and neuropathological findings facilitate understanding the mechanisms responsible for MRI abnormalities. An increase in free water in edema, necrosis, and damage in brain tissue can explain an increased signal intensity on T2WI. Postmortem MRI may contribute to the effective pathological examination by pointing out subtle abnormalities before brain cutting. (author)

Molecular testing practices and perceptions among dermatopathologists.

Science.gov (United States)

Torre, Kristin; Jhorar, Preeti; Wu, Rong; Pfeifer, John; Elaba, Zendee; Murphy, Michael

2018-02-13

We evaluated how dermatopathologists are employing molecular testing in the setting of neoplastic skin diseases, and assessed their opinions of the broader role and utility of molecular technologies in clinical practice. A 15-question online survey was sent to Fellows of the American Society of Dermatopathology in April 2017. One hundred and thirty-six dermatopathologists completed the survey (response rate = 16%). A majority (94%) of respondents reported experience with one or more molecular testing strategies. Sixty-two percent of dermatopathologists order 12 or more molecular tests per year, while 5% of respondents order 2 or fewer assays per year. More frequent utilization of molecular testing is associated with relevant instruction during residency training (P = .009), primary board certification in pathology (P = .008), academic medical center affiliation (P = molecular pathology/cytogenetics laboratory (P = .007), and greater physician confidence incorporating test results into histopathological assessments (P = molecular testing in dermatopathology may be limited by factors such as physician training, test costs/insurance coverage, logistical issues and lack of evidence-based clinical practice guidelines. Dermatopathologists have concerns regarding clinical validity/utility and inappropriate/overuse of some molecular tests. The importance of longitudinal education in molecular technologies and their applications for trainee and practicing physicians is highlighted. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Evolution of the Pathology Residency Curriculum

Directory of Open Access Journals (Sweden)

Wesley Y. Naritoku MD, PhD

2016-10-01

Full Text Available The required medical knowledge and skill set for the pathologist of 2020 are different than in 2005. Pathology residency training curriculum must accordingly change to fulfill the needs of these ever-changing requirements. In order to make rational curricular adjustments, it is important for us to know the current trajectory of resident training in pathology—where we have been, what our actual current training curriculum is now—to understand how that might change in anticipation of meeting the needs of a changing patient and provider population and to fit within the evolving future biomedical and socioeconomic health-care setting. In 2013, there were 143 Accreditation Council for Graduate Medical Education-accredited pathology residency training programs in the United States, with approximately 2400 residents. There is diversity among residency training programs not only with respect to the number of residents but also in training venue(s. To characterize this diversity among pathology residency training programs, a curriculum survey was conducted of pathology residency program directors in 2013 and compared with a similar survey taken almost 9 years previously in 2005 to identify trends in pathology residency curriculum. Clinical pathology has not changed significantly in the number of rotations over 9 years; however, anatomic pathology has changed dramatically, with an increase in the number of surgical pathology rotations coupled with a decline in stand-alone autopsy rotations. With ever-expanding medical knowledge that the graduating pathology resident must know, it is necessary to (1 reflect upon what are the critical need subjects, (2 identify areas that have become of lesser importance, and then (3 prioritize training accordingly.

Evolution of the Pathology Residency Curriculum

Science.gov (United States)

Powell, Suzanne Z.; Black-Schaffer, W. Stephen

2016-01-01

The required medical knowledge and skill set for the pathologist of 2020 are different than in 2005. Pathology residency training curriculum must accordingly change to fulfill the needs of these ever-changing requirements. In order to make rational curricular adjustments, it is important for us to know the current trajectory of resident training in pathology—where we have been, what our actual current training curriculum is now—to understand how that might change in anticipation of meeting the needs of a changing patient and provider population and to fit within the evolving future biomedical and socioeconomic health-care setting. In 2013, there were 143 Accreditation Council for Graduate Medical Education-accredited pathology residency training programs in the United States, with approximately 2400 residents. There is diversity among residency training programs not only with respect to the number of residents but also in training venue(s). To characterize this diversity among pathology residency training programs, a curriculum survey was conducted of pathology residency program directors in 2013 and compared with a similar survey taken almost 9 years previously in 2005 to identify trends in pathology residency curriculum. Clinical pathology has not changed significantly in the number of rotations over 9 years; however, anatomic pathology has changed dramatically, with an increase in the number of surgical pathology rotations coupled with a decline in stand-alone autopsy rotations. With ever-expanding medical knowledge that the graduating pathology resident must know, it is necessary to (1) reflect upon what are the critical need subjects, (2) identify areas that have become of lesser importance, and then (3) prioritize training accordingly. PMID:28725779

Thrombotic thrombocytopenic purpura presenting with pathologic fracture: a case report.

Science.gov (United States)

Berber, Ilhami; Erkurt, Mehmet Ali; Kuku, Irfan; Kaya, Emin; Unlu, Serkan; Ertem, Kadir; Nizam, Ilknur

2014-08-01

Thrombotic thrombocytopenic purpura is an acute syndrome with abnormalities in multiple organ systems, which becomes manifest with microangiopathic hemolytic anemia and thrombocytopenia. The hereditary or acquired deficiency of ADAMTS-13 activity leads to an excess of high molecular weight von Willebrand factor multimers in plasma, leading to platelet aggregation and diffuse intravascular thrombus formation, resulting in thrombotic thrombocytopenic purpura. Thrombotic lesions occurring in TTP leads to ischemia and convulsion. Depending on the properties of the bony tissue, fractures are divided into three groups as traumatic, pathological, and stress fractures. A pathologic fracture is a broken bone caused by disease leading to weakness of the bone. This process is most commonly due to osteoporosis, but may also be due to other pathologies such as cancer, infections, inherited bone disorders, or a bone cyst. We herein report a case with a pathologic fracture due to convulsion secondary to thrombotic thrombocytopenic pupura. Thrombotic lesions occurring in TTP may lead to ischemia and convulsion, as in our patient and pathological fractures presented in our case report may occur as a result of severe muscle contractions associated with convulsive activity. Thrombotic thrombocytopenic pupura is a disease that involves many organ systems and thus may have a very wide spectrum of clinical presentations. Copyright © 2014. Published by Elsevier Ltd.

A comparative study of the SVM and K-nn machine learning algorithms for the diagnosis of respiratory pathologies using pulmonary acoustic signals.

Science.gov (United States)

Palaniappan, Rajkumar; Sundaraj, Kenneth; Sundaraj, Sebastian

2014-06-27

Pulmonary acoustic parameters extracted from recorded respiratory sounds provide valuable information for the detection of respiratory pathologies. The automated analysis of pulmonary acoustic signals can serve as a differential diagnosis tool for medical professionals, a learning tool for medical students, and a self-management tool for patients. In this context, we intend to evaluate and compare the performance of the support vector machine (SVM) and K-nearest neighbour (K-nn) classifiers in diagnosis respiratory pathologies using respiratory sounds from R.A.L.E database. The pulmonary acoustic signals used in this study were obtained from the R.A.L.E lung sound database. The pulmonary acoustic signals were manually categorised into three different groups, namely normal, airway obstruction pathology, and parenchymal pathology. The mel-frequency cepstral coefficient (MFCC) features were extracted from the pre-processed pulmonary acoustic signals. The MFCC features were analysed by one-way ANOVA and then fed separately into the SVM and K-nn classifiers. The performances of the classifiers were analysed using the confusion matrix technique. The statistical analysis of the MFCC features using one-way ANOVA showed that the extracted MFCC features are significantly different (p < 0.001). The classification accuracies of the SVM and K-nn classifiers were found to be 92.19% and 98.26%, respectively. Although the data used to train and test the classifiers are limited, the classification accuracies found are satisfactory. The K-nn classifier was better than the SVM classifier for the discrimination of pulmonary acoustic signals from pathological and normal subjects obtained from the RALE database.

Food insecurity and eating disorder pathology.

Science.gov (United States)

Becker, Carolyn Black; Middlemass, Keesha; Taylor, Brigitte; Johnson, Clara; Gomez, Francesca

2017-09-01

The primary aim of this study was to investigate eating disorder (ED) pathology in those living with food insecurity. A secondary aim was to investigate whether any-reason dietary restraint, weight self-stigma, and worry increased as level of food insecurity increased. Participants (N = 503) seeking food from food pantries completed questionnaires assessing level of food insecurity, demographics, ED pathology, dietary restraint, weight self-stigma, and worry. Consistent with hypotheses, participants with the highest level of food insecurity (i.e., adults who reported having hungry children in their household) also endorsed significantly higher levels of binge eating, overall ED pathology, any-reason dietary restraint, weight self-stigma, and worry compared to participants with lower levels of food insecurity. Contrary to hypotheses, compensatory behaviors also increased as level of food insecurity worsened. Overall, 17% of those in the child hunger food insecurity group reported clinically significant ED pathology. This is the first study to assess the full spectrum of ED pathology in a low-income, marginalized population with food insecurity. Given that food insecurity is a global concern, results from this study suggest that greater attention to the association between ED pathology and food insecurity is warranted by researchers around the world. © 2017 Wiley Periodicals, Inc.

Comparing staging by positron emission tomography with contrast-enhanced computed tomography and by pathology in head and neck squamous cell carcinoma.

Science.gov (United States)

Qualliotine, J R; Mydlarz, W K; Chan, J Y K; Zhou, X; Wang, H; Agrawal, N

2015-12-01

This study aimed to evaluate the ability of positron emission tomography with contrast-enhanced computed tomography to correctly stage head and neck squamous cell carcinomas, in comparison with pathological staging. Positron emission tomography computed tomography was used to determine the tumour-node-metastasis classification and overall cancer stage in 85 head and neck squamous cell carcinoma patients who underwent pre-operative imaging using this modality and primary surgery between July 2010 and January 2013. Staging by positron emission tomography computed tomography was retrospectively compared with staging using pathological specimens. Agreement between imaging stage and pathological stage was examined by univariate and multivariate analysis both overall and for each primary tumour site. This imaging modality was 87.5 per cent sensitive and 44.8 per cent specific in identifying regional cervical metastases, and had false positive and false negative rates of 18.8 per cent and 8.2 per cent, respectively. The positive predictive and negative predictive values were 75.4 per cent and 65.0 per cent, respectively. Univariate and multivariate analyses revealed a significant agreement between positron emission tomography computed tomography and pathological node classification in older patients and for the oral cavity primary tumour site. There was significant agreement between both methods in the overall classification only for tumours classified as T3 or greater. Positron emission tomography computed tomography should be used with caution for the pre-operative staging of head and neck cancers because of its high false positive and false negative rates.

Video game addiction in emerging adulthood: Cross-sectional evidence of pathology in video game addicts as compared to matched healthy controls.

Science.gov (United States)

Stockdale, Laura; Coyne, Sarah M

2018-01-01

The Internet Gaming Disorder Scale (IGDS) is a widely used measure of video game addiction, a pathology affecting a small percentage of all people who play video games. Emerging adult males are significantly more likely to be video game addicts. Few researchers have examined how people who qualify as video game addicts based on the IGDS compared to matched controls based on age, gender, race, and marital status. The current study compared IGDS video game addicts to matched non-addicts in terms of their mental, physical, social-emotional health using self-report, survey methods. Addicts had poorer mental health and cognitive functioning including poorer impulse control and ADHD symptoms compared to controls. Additionally, addicts displayed increased emotional difficulties including increased depression and anxiety, felt more socially isolated, and were more likely to display internet pornography pathological use symptoms. Female video game addicts were at unique risk for negative outcomes. The sample for this study was undergraduate college students and self-report measures were used. Participants who met the IGDS criteria for video game addiction displayed poorer emotional, physical, mental, and social health, adding to the growing evidence that video game addictions are a valid phenomenon. Copyright © 2017 Elsevier B.V. All rights reserved.

The diagnosis of chronic endometritis in infertile asymptomatic women: a comparative study of histology, microbial cultures, hysteroscopy, and molecular microbiology.

Science.gov (United States)

Moreno, Inmaculada; Cicinelli, Ettore; Garcia-Grau, Iolanda; Gonzalez-Monfort, Marta; Bau, Davide; Vilella, Felipe; De Ziegler, Dominique; Resta, Leonardo; Valbuena, Diana; Simon, Carlos

2018-06-01

Chronic endometritis is a persistent inflammation of the endometrial mucosa caused by bacterial pathogens such as Enterobacteriaceae, Enterococcus, Streptococcus, Staphylococcus, Mycoplasma, and Ureaplasma. Although chronic endometritis can be asymptomatic, it is found in up to 40% of infertile patients and is responsible for repeated implantation failure and recurrent miscarriage. Diagnosis of chronic endometritis is based on hysteroscopy of the uterine cavity, endometrial biopsy with plasma cells being identified histologically, while specific treatment is determined based on microbial culture. However, not all microorganisms implicated are easily or readily culturable needing a turnaround time of up to 1 week. We sought to develop a molecular diagnostic tool for chronic endometritis based on real-time polymerase chain reaction equivalent to using the 3 classic methods together, overcoming the bias of using any of them alone. Endometrial samples from patients assessed for chronic endometritis (n = 113) using at least 1 or several conventional diagnostic methods namely histology, hysteroscopy, and/or microbial culture, were blindly evaluated by real-time polymerase chain reaction for the presence of 9 chronic endometritis pathogens: Chlamydia trachomatis, Enterococcus, Escherichia coli, Gardnerella vaginalis, Klebsiella pneumoniae, Mycoplasma hominis, Neisseria gonorrhoeae, Staphylococcus, and Streptococcus. The sensitivity and specificity of the molecular analysis vs the classic diagnostic techniques were compared in the 65 patients assessed by all 3 recognized classic methods. The molecular method showed concordant results with histological diagnosis in 30 samples (14 double positive and 16 double negative) with a matching accuracy of 46.15%. Concordance of molecular and hysteroscopic diagnosis was observed in 38 samples (37 double positive and 1 double negative), with an accuracy of 58.46%. When the molecular method was compared to microbial culture

Metals and cholesterol: two sides of the same coin in Alzheimer’s disease pathology

Science.gov (United States)

Wong, Bruce X.; Hung, Ya Hui; Bush, Ashley I.; Duce, James A.

2014-01-01

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disease. It begins years prior to the onset of clinical symptoms, such as memory loss and cognitive decline. Pathological hallmarks of AD include the accumulation of β-amyloid in plaques and hyperphosphorylated tau in neurofibrillary tangles. Copper, iron, and zinc are abnormally accumulated and distributed in the aging brain. These metal ions can adversely contribute to the progression of AD. Dysregulation of cholesterol metabolism has also been implicated in the development of AD pathology. To date, large bodies of research have been carried out independently to elucidate the role of metals or cholesterol on AD pathology. Interestingly, metals and cholesterol affect parallel molecular and biochemical pathways involved in AD pathology. The possible links between metal dyshomeostasis and altered brain cholesterol metabolism in AD are reviewed. PMID:24860500

Pathology in Greece.

Science.gov (United States)

Sakellariou, S; Patsouris, E

2015-11-01

Pathology is the field of medicine that studies diseases. Ancient Greece hosted some of the earliest societies that laid the structural foundations of pathology. Initially, knowledge was based on observations but later on the key elements of pathology were established based on the dissection of animals and the autopsy of human cadavers. Christianized Greece under Ottoman rule (1453-1821) was not conducive to the development of pathology. After liberation, however, a series of events took place that paved the way for the establishment and further development of the specialty. The appointment in 1849 of two Professors of Pathology at the Medical School of Athens for didactical purposes proved to be the most important step in fostering the field of pathology in modern Greece. Presently in Greece there are seven university departments and 74 pathology laboratories in public hospitals, employing 415 specialized pathologists and 90 residents. The First Department of Pathology at the Medical School of Athens University is the oldest (1849) and largest in Greece, encompassing most pathology subspecialties.

Guidance for laboratories performing molecular pathology for cancer patients

NARCIS (Netherlands)

Cree, Ian A.; Deans, Zandra; Ligtenberg, Marjolijn J. L.; Normanno, Nicola; Edsjo, Anders; Rouleau, Etienne; Sole, Francesc; Thunnissen, Erik; Timens, Wim; Schuuring, Ed; Dequeker, Elisabeth; Murray, Samuel; Dietel, Manfred; Groenen, Patricia; Van Krieken, J. Han

2014-01-01

Molecular testing is becoming an important part of the diagnosis of any patient with cancer. The challenge to laboratories is to meet this need, using reliable methods and processes to ensure that patients receive a timely and accurate report on which their treatment will be based. The aim of this

Guidance for laboratories performing molecular pathology for cancer patients

NARCIS (Netherlands)

Cree, Ian A.; Deans, Zandra; Ligtenberg, Marjolijn J. L.; Normanno, Nicola; Edsjo, Anders; Rouleau, Etienne; Sole, Francesc; Thunnissen, Erik; Timens, Wim; Schuuring, Ed; Dequeker, Elisabeth; Murray, Samuel; Dietel, Manfred; Groenen, Patricia; Van Krieken, J. Han

Molecular testing is becoming an important part of the diagnosis of any patient with cancer. The challenge to laboratories is to meet this need, using reliable methods and processes to ensure that patients receive a timely and accurate report on which their treatment will be based. The aim of this

Current state of molecular imaging research

International Nuclear Information System (INIS)

Grimm, J.; Wunder, A.

2005-01-01

The recent years have seen significant advances in both molecular biology, allowing the identification of genes and pathways related to disease, and imaging technologies that allow for improved spatial and temporal resolution, enhanced sensitivity, better depth penetration, improved image processing, and beneficial combinations of different imaging modalities. These advances have led to a paradigm shift in the scope of diagnostic imaging. The traditional role of radiological diagnostic imaging is to define gross anatomy and structure in order to detect pathological abnormalities. Available contrast agents are mostly non-specific and can be used to image physiological processes such as changes in blood volume, flow, and perfusion but not to demonstrate pathological alterations at molecular levels. However, alterations at the anatomical-morphological level are relatively late manifestations of underlying molecular changes. Using molecular probes or markers that bind specifically to molecular targets allows for the non-invasive visualization and quantitation of biological processes such as gene expression, apoptosis, or angiogenesis at the molecular level within intact living organisms. This rapidly evolving, multidisciplinary approach, referred to as molecular imaging, promises to enable early diagnosis, can provide improved classification of stage and severity of disease, an objective assessment of treatment efficacy, and a reliable prognosis. Furthermore, molecular imaging is an important tool for the evaluation of physiological and pathophysiological processes, and for the development of new therapies. This article comprises a review of current technologies of molecular imaging, describes the development of contrast agents and various imaging modalities, new applications in specific disease models, and potential future developments. (orig.)

Exploring the Neural Basis of Avatar Identification in Pathological Internet Gamers and of Self-Reflection in Pathological Social Network Users.

Science.gov (United States)

Leménager, Tagrid; Dieter, Julia; Hill, Holger; Hoffmann, Sabine; Reinhard, Iris; Beutel, Martin; Vollstädt-Klein, Sabine; Kiefer, Falk; Mann, Karl

2016-09-01

Background and aims Internet gaming addiction appears to be related to self-concept deficits and increased angular gyrus (AG)-related identification with one's avatar. For increased social network use, a few existing studies suggest striatal-related positive social feedback as an underlying factor. However, whether an impaired self-concept and its reward-based compensation through the online presentation of an idealized version of the self are related to pathological social network use has not been investigated yet. We aimed to compare different stages of pathological Internet game and social network use to explore the neural basis of avatar and self-identification in addictive use. Methods About 19 pathological Internet gamers, 19 pathological social network users, and 19 healthy controls underwent functional magnetic resonance imaging while completing a self-retrieval paradigm, asking participants to rate the degree to which various self-concept-related characteristics described their self, ideal, and avatar. Self-concept-related characteristics were also psychometrically assessed. Results Psychometric testing indicated that pathological Internet gamers exhibited higher self-concept deficits generally, whereas pathological social network users exhibit deficits in emotion regulation only. We observed left AG hyperactivations in Internet gamers during avatar reflection and a correlation with symptom severity. Striatal hypoactivations during self-reflection (vs. ideal reflection) were observed in social network users and were correlated with symptom severity. Discussion and conclusion Internet gaming addiction appears to be linked to increased identification with one's avatar, evidenced by high left AG activations in pathological Internet gamers. Addiction to social networks seems to be characterized by emotion regulation deficits, reflected by reduced striatal activation during self-reflection compared to during ideal reflection.

Exploring the Neural Basis of Avatar Identification in Pathological Internet Gamers and of Self-Reflection in Pathological Social Network Users

Science.gov (United States)

Leménager, Tagrid; Dieter, Julia; Hill, Holger; Hoffmann, Sabine; Reinhard, Iris; Beutel, Martin; Vollstädt-Klein, Sabine; Kiefer, Falk; Mann, Karl

2016-01-01

Background and aims Internet gaming addiction appears to be related to self-concept deficits and increased angular gyrus (AG)-related identification with one’s avatar. For increased social network use, a few existing studies suggest striatal-related positive social feedback as an underlying factor. However, whether an impaired self-concept and its reward-based compensation through the online presentation of an idealized version of the self are related to pathological social network use has not been investigated yet. We aimed to compare different stages of pathological Internet game and social network use to explore the neural basis of avatar and self-identification in addictive use. Methods About 19 pathological Internet gamers, 19 pathological social network users, and 19 healthy controls underwent functional magnetic resonance imaging while completing a self-retrieval paradigm, asking participants to rate the degree to which various self-concept-related characteristics described their self, ideal, and avatar. Self-concept-related characteristics were also psychometrically assessed. Results Psychometric testing indicated that pathological Internet gamers exhibited higher self-concept deficits generally, whereas pathological social network users exhibit deficits in emotion regulation only. We observed left AG hyperactivations in Internet gamers during avatar reflection and a correlation with symptom severity. Striatal hypoactivations during self-reflection (vs. ideal reflection) were observed in social network users and were correlated with symptom severity. Discussion and conclusion Internet gaming addiction appears to be linked to increased identification with one’s avatar, evidenced by high left AG activations in pathological Internet gamers. Addiction to social networks seems to be characterized by emotion regulation deficits, reflected by reduced striatal activation during self-reflection compared to during ideal reflection. PMID:27415603

The development and evaluation of an audit tool for measuring reporting accuracy of radiographers compared with radiologists for intra-luminal pathology detected at computed tomography colonography (CTC)

International Nuclear Information System (INIS)

Rimes, Susan Jane; Fox, Danial; Knapp, Karen M.; Meertens, Robert

2015-01-01

Objective: To design and test an audit tool to measure the reporting accuracy of radiographers using radiologist reports as the gold standard. Design: A database was designed to capture radiographer and radiologist report data. The radiographer preliminary evaluation of intraluminal pathology was given a score (PDS score) by the reporting radiologist based on the pathology present, the discrepancy between the preliminary evaluation and the final report and the significance of that discrepancy on the clinical management of the patient. To test the reliability of this scoring system, 30 randomly selected cases (n = 1815) were retrospectively compared and assessed for accuracy using the PDS score by 3 independent practitioners. Inter rater reliability was assessed using percentage agreement and kappa scores. Results: There was 100% agreement between participants for all significant pathologies. Inter rater agreement was 80–93% for normal studies and insignificant pathologies. Conclusion: Results indicate that the tool provides a practical, easy to use and reliable method to record, monitor and evaluate a preliminary evaluation of the colon by radiographers. - Highlights: • Radiographers issue a preliminary clinical evaluation of computed tomography colonography. • A database was set up to collate and audit radiographer preliminary clinical evaluation. • Radiographer primary clinical evaluations were scored for accuracy against the radiology report. • Radiographer accuracy was high when compared with the radiology report. • Radiographers can support radiologists through double reporting of intraluminal pathology

The effectiveness of annotated (vs. non-annotated) digital pathology slides as a teaching tool during dermatology and pathology residencies.

Science.gov (United States)

Marsch, Amanda F; Espiritu, Baltazar; Groth, John; Hutchens, Kelli A

2014-06-01

With today's technology, paraffin-embedded, hematoxylin & eosin-stained pathology slides can be scanned to generate high quality virtual slides. Using proprietary software, digital images can also be annotated with arrows, circles and boxes to highlight certain diagnostic features. Previous studies assessing digital microscopy as a teaching tool did not involve the annotation of digital images. The objective of this study was to compare the effectiveness of annotated digital pathology slides versus non-annotated digital pathology slides as a teaching tool during dermatology and pathology residencies. A study group composed of 31 dermatology and pathology residents was asked to complete an online pre-quiz consisting of 20 multiple choice style questions, each associated with a static digital pathology image. After completion, participants were given access to an online tutorial composed of digitally annotated pathology slides and subsequently asked to complete a post-quiz. A control group of 12 residents completed a non-annotated version of the tutorial. Nearly all participants in the study group improved their quiz score, with an average improvement of 17%, versus only 3% (P = 0.005) in the control group. These results support the notion that annotated digital pathology slides are superior to non-annotated slides for the purpose of resident education. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Necroptosis: Molecular Signalling and Translational Implications

Directory of Open Access Journals (Sweden)

Claudia Giampietri

2014-01-01

Full Text Available Necroptosis is a form of programmed necrosis whose molecular players are partially shared with apoptotic cell death. Here we summarize what is known about molecular signalling of necroptosis, particularly focusing on fine tuning of FLIP and IAP proteins in the apoptosis/necroptosis balance. We also emphasize necroptosis involvement in physiological and pathological conditions, particularly in the regulation of immune homeostasis.

THE COMPARATIVE ANALYSIS OF THE ULTRASONIC EXAMINATION AND Х-RAY MAMMOGRAPHY OF THE MEN WITH MASS PATHOLOGY IN THE MAMMARY GLAND PROJECTION

Directory of Open Access Journals (Sweden)

V. B. Akimova

2015-01-01

Full Text Available Based on the scientific materials of domestic and foreign authors as well as on own observations, the results of the ultrasonic and mammographic research of the man’s mass pathology in the mammary gland projection being found in the process of differential diagnosis between malignant and benign tumors with similar clinical picture are presented in the article. Methodologically there has been carried out the analysis of the distinctive and rare signs of the benign process and malignant transformation of the man’s mass pathology in the mammary gland projection. In order to compare X-Ray and ultrasonic characteristics of the mass pathology in the patients’ mammary gland projection similar visual effects in the process of the prebiopsy clinical diagnosis forming has been studied in pairs. Mammography pictures and visualization in B-regime have been studied critically: shape correctness, localization, irregularity and obscurity of contours, presence of pathological inclusions, data of the colour and spectral Doppler sonography and 3D-regime scanning. According to the results of visual examinaion objective indications for needle biopsy of the man’s mass pathology in the mammary gland projection have been presented to the reader. The calculation of operation characteristics of different research methods of the mammary gland and combination of these methods has been done. The regularity of the information increase with an increase of the methods applied has been revealed. Based on the catamnesis examples of 317 men, the analysis of the necessity to make a combined examination variants of the mammary gland as the only definite opportunity to get a clinical diagnosis has been done.

Molecular pathology of intraductal papillary mucinous neoplasms of the pancreas.

Science.gov (United States)

Paini, Marina; Crippa, Stefano; Partelli, Stefano; Scopelliti, Filippo; Tamburrino, Domenico; Baldoni, Andrea; Falconi, Massimo

2014-08-07

Since the first description of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas in the eighties, their identification has dramatically increased in the last decades, hand to hand with the improvements in diagnostic imaging and sampling techniques for the study of pancreatic diseases. However, the heterogeneity of IPMNs and their malignant potential make difficult the management of these lesions. The objective of this review is to identify the molecular characteristics of IPMNs in order to recognize potential markers for the discrimination of more aggressive IPMNs requiring surgical resection from benign IPMNs that could be observed. We briefly summarize recent research findings on the genetics and epigenetics of intraductal papillary mucinous neoplasms, identifying some genes, molecular mechanisms and cellular signaling pathways correlated to the pathogenesis of IPMNs and their progression to malignancy. The knowledge of molecular biology of IPMNs has impressively developed over the last few years. A great amount of genes functioning as oncogenes or tumor suppressor genes have been identified, in pancreatic juice or in blood or in the samples from the pancreatic resections, but further researches are required to use these informations for clinical intent, in order to better define the natural history of these diseases and to improve their management.

CYP polymorphisms and pathological conditions related to chronic exposure to organochlorine pesticides

Directory of Open Access Journals (Sweden)

Anca Oana Docea

Full Text Available The association between genetic variations in the cytochrome P450 (CYP family genes and pathological conditions related to long-term exposure to organochlorine compounds (OCs deserves further elucidation. OCs are persistent organic pollutants with bioaccumulative and lipophilic characteristics. They can act as endocrine disruptors and perturb cellular mechanisms. Prolonged exposure to OCs has been associated with different pathological manifestations. CYP genes are responsible for transcribing enzymes essential in xenobiotic metabolism. Therefore, polymorphisms in these genetic sequences a. alter the metabolic pathways, b. induce false cellular responses, and c. may provoke pathological conditions. The main aim of this review is to define the interaction between parameters a, b and c at a mechanistic/molecular level, with references in clinical cases. Keywords: Organochlorine compounds, Cytochrome P450, Genetic polymorphisms, Pathogenesis, Environmental pollutants

INHERITED PATHOLOGY OF β2-LAMININ (PIERSON SYNDROME: CLINICAL AND GENETIC ASPECTS

Directory of Open Access Journals (Sweden)

M.Yu. Kagan

2010-01-01

Full Text Available For the last decade a great successes were attained in the study of molecular bases of glomerular diseases. It was certain that the most frequent reasons of congenital and infantile nephrotic syndrome are mutations in the genes of NPHS1, NPHS2, and WT1. Nevertheless, until now, a number of patients, having combination of early nephrotic syndrome with inherent pathology of other organs, which etiology remains un known. These cases continue to be intensively probed. One of the most important recent achievements in understanding of molecular mechanisms of early nephrotic syndrome is the discovery of mutations of gene of LAMB2, encoding β2 laminin, as the cause of Pearson syndrome (OMIM#609049. In this article the author presents the basic genetic and clinical descriptions of this recently identified pathology. Key words: Pearson syndrome, congenital nephrotic syndrome, β2 laminin, malformation of organ of vision. (Pediatric Pharmacology. – 2010; 7(3:114-117

Lungscape: resected non-small-cell lung cancer outcome by clinical and pathological parameters.

Science.gov (United States)

Peters, Solange; Weder, Walter; Dafni, Urania; Kerr, Keith M; Bubendorf, Lukas; Meldgaard, Peter; O'Byrne, Kenneth J; Wrona, Anna; Vansteenkiste, Johan; Felip, Enriqueta; Marchetti, Antonio; Savic, Spasenija; Lu, Shun; Smit, Egbert; Dingemans, Anne-Marie; Blackhall, Fiona H; Baas, Paul; Camps, Carlos; Rosell, Rafael; Stahel, Rolf A

2014-11-01

The Lungscape project was designed to address the impact of clinical, pathological, and molecular characteristics on outcome in resected non-small- cell lung cancer (NSCLC). A decentralized biobank with fully annotated tissue samples was established. Selection criteria for participating centers included sufficient number of cases, tissue microarray building capability, and documented ethical approval. Patient selection was based on availability of comprehensive clinical data, radical resection between 2003 and 2009 with adequate follow-up, and adequate quantity and quality of formalin-fixed tissue. Fifteen centers contributed 2449 cases. The 5-year overall survival (OS) was 69.6% and 63.6% for stages IA and IB, 51.6% and 47.7% for stages IIA and IIB, and 29.0% and 13.0% for stages IIIA and IIIB, respectively (p < 0.001). Median and 5-year relapse-free survival (RFS) were 52.8 months and 47.3%, respectively. Distant relapse was recorded for 44.4%, local for 26.0%, and both for 16.9% of patients. Based on multivariate analysis for the OS, RFS, and time to relapse, the factors significantly associated with all of them are performance status and pathological stage. The aim of this report is to present the results from Lungscape, the first large series reporting on NSCLC surgical outcome measured not only by OS but also by RFS and time to relapse and including multivariate analysis by significant clinical and pathological prognostic parameters. As tissue from all patients is preserved locally and is available for detailed molecular investigations, Lungscape provides an excellent basis to evaluate the influence of molecular parameters on the disease outcome after radical resection, besides providing an overview of the molecular landscape of stage I to III NSCLC.

Diagnostic Efficiency in Digital Pathology: A Comparison of Optical Versus Digital Assessment in 510 Surgical Pathology Cases.

Science.gov (United States)

Mills, Anne M; Gradecki, Sarah E; Horton, Bethany J; Blackwell, Rebecca; Moskaluk, Christopher A; Mandell, James W; Mills, Stacey E; Cathro, Helen P

2018-01-01

Prior work has shown that digital images and microscopic slides can be interpreted with comparable diagnostic accuracy. Although accuracy has been well-validated, the interpretative time for digital images has scarcely been studied and concerns about efficiency remain a major barrier to adoption. We investigated the efficiency of digital pathology when compared with glass slide interpretation in the diagnosis of surgical pathology biopsy and resection specimens. Slides were pulled from 510 surgical pathology cases from 5 organ systems (gastrointestinal, gynecologic, liver, bladder, and brain). Original diagnoses were independently confirmed by 2 validating pathologists. Diagnostic slides were scanned using the Philips IntelliSite Pathology Solution. Each case was assessed independently on digital and optical by 3 reading pathologists, with a ≥6 week washout period between modalities. Reading pathologists recorded assessment times for each modality; digital times included time to load the case. Diagnostic accuracy was determined based on whether a rendered diagnosis differed significantly from the original diagnosis. Statistical analysis was performed to assess for differences in interpretative times across modalities. All 3 reading pathologists showed comparable diagnostic accuracy across optical and digital modalities (mean major discordance rates with original diagnosis: 4.8% vs. 4.4%, respectively). Mean assessment times ranged from 1.2 to 9.1 seconds slower on digital versus optical. The slowest reader showed a significant learning effect during the course of the study so that digital assessment times decreased over time and were comparable with optical times by the end of the series. Organ site and specimen type did not significantly influence differences in interpretative times. In summary, digital image reading times compare favorably relative to glass slides across a variety of organ systems and specimen types. Mean increase in assessment time is 4

Evolutionary developmental pathology and anthropology: A new field linking development, comparative anatomy, human evolution, morphological variations and defects, and medicine.

Science.gov (United States)

Diogo, Rui; Smith, Christopher M; Ziermann, Janine M

2015-11-01

We introduce a new subfield of the recently created field of Evolutionary-Developmental-Anthropology (Evo-Devo-Anth): Evolutionary-Developmental-Pathology-and-Anthropology (Evo-Devo-P'Anth). This subfield combines experimental and developmental studies of nonhuman model organisms, biological anthropology, chordate comparative anatomy and evolution, and the study of normal and pathological human development. Instead of focusing on other organisms to try to better understand human development, evolution, anatomy, and pathology, it places humans as the central case study, i.e., as truly model organism themselves. We summarize the results of our recent Evo-Devo-P'Anth studies and discuss long-standing questions in each of the broader biological fields combined in this subfield, paying special attention to the links between: (1) Human anomalies and variations, nonpentadactyly, homeotic transformations, and "nearest neighbor" vs. "find and seek" muscle-skeleton associations in limb+facial muscles vs. other head muscles; (2) Developmental constraints, the notion of "phylotypic stage," internalism vs. externalism, and the "logic of monsters" vs. "lack of homeostasis" views about human birth defects; (3) Human evolution, reversions, atavisms, paedomorphosis, and peromorphosis; (4) Scala naturae, Haeckelian recapitulation, von Baer's laws, and parallelism between phylogeny and development, here formally defined as "Phylo-Devo parallelism"; and (5) Patau, Edwards, and Down syndrome (trisomies 13, 18, 21), atavisms, apoptosis, heart malformations, and medical implications. © 2015 Wiley Periodicals, Inc.

Metals and cholesterol: two sides of the same coin in Alzheimer’s disease pathology

Directory of Open Access Journals (Sweden)

Bruce Xue Wen Wong

2014-05-01

Full Text Available Alzheimer’s disease (AD is a multifactorial neurodegenerative disease. It begins years prior to the onset of clinical symptoms, such as memory loss and cognitive decline. Pathological hallmarks of AD include the accumulation of β-amyloid in plaques and hyperphosphorylated tau in neurofibrillary tangles. Copper, iron and zinc are abnormally accumulated and distributed in the aging brain. These metal ions can adversely contribute to the progression of AD. Dysregulation of cholesterol metabolism has also been implicated in the development of AD pathology. To date, large bodies of research have been carried out independently to elucidate the role of metals or cholesterol on AD pathology. Interestingly, metals and cholesterol affect parallel molecular and biochemical pathways involved in AD pathology. The possible links between metal dyshomeostasis and altered brain cholesterol metabolism in AD are reviewed.

Pathology-Dependent Effects Linked to Small Heat Shock Proteins Expression: An Update

Directory of Open Access Journals (Sweden)

A.-P. Arrigo

2012-01-01

Full Text Available Small heat shock proteins (small Hsps are stress-induced molecular chaperones that act as holdases towards polypeptides that have lost their folding in stress conditions or consequently of mutations in their coding sequence. A cellular protection against the deleterious effects mediated by damaged proteins is thus provided to cells. These chaperones are also highly expressed in response to protein conformational and inflammatory diseases and cancer pathologies. Through specific and reversible modifications in their phospho-oligomeric organization, small Hsps can chaperone appropriate client proteins in order to provide cells with resistance to different types of injuries or pathological conditions. By helping cells to better cope with their pathological status, their expression can be either beneficial, such as in diseases characterized by pathological cell degeneration, or deleterious when they are required for tumor cell survival. Moreover, small Hsps are actively released by cells and can act as immunogenic molecules that have dual effects depending on the pathology. The cellular consequences linked to their expression levels and relationships with other Hsps as well as therapeutic strategies are discussed in view of their dynamic structural organization required to interact with specific client polypeptides.

Frozen section pathology for decision making in parotid surgery.

Science.gov (United States)

Olsen, Kerry D; Moore, Eric J; Lewis, Jean E

2013-12-01

For parotid lesions, the high accuracy and utility of intraoperative frozen section (FS) pathology, compared with permanent section pathology, facilitates intraoperative decision making about the extent of surgery required. To demonstrate the accuracy and utility of FS pathology of parotid lesions as one factor in intraoperative decision making. Retrospective review of patients undergoing parotidectomy at a tertiary care center. Evaluation of the accuracy of FS pathology for parotid surgery by comparing FS pathology results with those of permanent section. Documented changes from FS to permanent section in 1339 parotidectomy pathology reports conducted from January 1, 2000, through December 31, 2009, included 693 benign and 268 primary and metastatic malignant tumors. Changes in diagnosis were found from benign to malignant (n = 11) and malignant to benign (n = 2). Sensitivity and specificity of a malignant diagnosis were 98.5% and 99.0%, respectively. Other changes were for lymphoma vs inflammation or lymphoma typing (n = 89) and for confirmation of or change in tumor type for benign (n = 36) or malignant (n = 69) tumors. No case changed from low- to high-grade malignant tumor. Only 4 cases that changed from FS to permanent section would have affected intraoperative decision making. Three patients underwent additional surgery 2 to 3 weeks later. Overall, only 1 patient was overtreated (lymphoma initially deemed carcinoma). Frozen section pathology for parotid lesions has high accuracy and utility in intraoperative decision making, facilitating timely complete procedures.

Tinnitus: pathology of synaptic plasticity at the cellular and system levels

Directory of Open Access Journals (Sweden)

Matthieu J Guitton

2012-03-01

Full Text Available Despite being more and more common, and having a high impact on the quality of life of sufferers, tinnitus does not yet have a cure. This has been mostly the result of limited knowledge of the biological mechanisms underlying this adverse pathology. However, the last decade has witnessed tremendous progress in our understanding on the pathophysiology of tinnitus. Animal models have demonstrated that tinnitus is a pathology of neural plasticity, and has two main components: a molecular, peripheral component related to the initiation phase of tinnitus; and a system-level, central component related to the long-term maintenance of tinnitus. Using the most recent experimental data and the molecular/system dichotomy as a framework, we describe here the biological basis of tinnitus. We then discuss these mechanisms from an evolutionary perspective, highlighting similarities with memory. Finally, we consider how these discoveries can translate into therapies, and we suggest operative strategies to design new and effective combined therapeutic solutions using both pharmacological (local and systemic and behavioral tools (e.g., using tele-medicine and virtual reality settings.

Molecular, Pathological, Radiological, and Immune Profiling of Non-brainstem Pediatric High-Grade Glioma from the HERBY Phase II Randomized Trial.

Science.gov (United States)

Mackay, Alan; Burford, Anna; Molinari, Valeria; Jones, David T W; Izquierdo, Elisa; Brouwer-Visser, Jurriaan; Giangaspero, Felice; Haberler, Christine; Pietsch, Torsten; Jacques, Thomas S; Figarella-Branger, Dominique; Rodriguez, Daniel; Morgan, Paul S; Raman, Pichai; Waanders, Angela J; Resnick, Adam C; Massimino, Maura; Garrè, Maria Luisa; Smith, Helen; Capper, David; Pfister, Stefan M; Würdinger, Thomas; Tam, Rachel; Garcia, Josep; Thakur, Meghna Das; Vassal, Gilles; Grill, Jacques; Jaspan, Tim; Varlet, Pascale; Jones, Chris

2018-05-14

The HERBY trial was a phase II open-label, randomized, multicenter trial evaluating bevacizumab (BEV) in addition to temozolomide/radiotherapy in patients with newly diagnosed non-brainstem high-grade glioma (HGG) between the ages of 3 and 18 years. We carried out comprehensive molecular analysis integrated with pathology, radiology, and immune profiling. In post-hoc subgroup analysis, hypermutator tumors (mismatch repair deficiency and somatic POLE/POLD1 mutations) and those biologically resembling pleomorphic xanthoastrocytoma ([PXA]-like, driven by BRAF_V600E or NF1 mutation) had significantly more CD8 + tumor-infiltrating lymphocytes, and longer survival with the addition of BEV. Histone H3 subgroups (hemispheric G34R/V and midline K27M) had a worse outcome and were immune cold. Future clinical trials will need to take into account the diversity represented by the term "HGG" in the pediatric population. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Low HER2/neu gene expression is associated with pathological response to concurrent paclitaxel and radiation therapy in locally advanced breast cancer

International Nuclear Information System (INIS)

Formenti, Silvia C.; Spicer, Darcy; Skinner, Kristin; Cohen, Deidre; Groshen, Susan; Bettini, Anna; Naritoku, Wesley; Press, Michael; Salonga, Dennis; Tsao-Wei, Denice; Danenberg, Kathy; Danenberg, Peter

2002-01-01

Purpose: The objective of this study was twofold: first, to identify patients with locally advanced breast cancer (LABC) who will achieve a pathological response to a preoperative regimen of concurrent paclitaxel and radiation; and second, to explore associations between molecular markers from the original tumors and pathological response. Methods and Materials: Patients with previously untreated LABC were eligible to receive a regimen of preoperative concurrent paclitaxel, 30 mg/m 2 twice a week for a total of 8 weeks, and radiation delivered Weeks 2-6, 45 Gy at 1.8 Gy per fraction to the breast, ipsilateral axilla, and supraclavicular nodes. At mastectomy, pathologic findings were classified as pathological complete response (pCR) no residual invasive cells in the breast and axillary contents; pathological partial response (pPR) = presence of ≤10 microscopic foci of invasive cells; no pathological response (pNR) = pathological persistence of tumor. For each patient, pretreatment breast cancer biopsies were prospectively analyzed by immunohistochemistry (IHC) for estrogen and progesterone (ER/PR) hormonal receptors, HER2/neu and p53 overexpression. Estrogen receptor (ER), HER2/neu, metablastin, β-tubulin III and IV, microtubule-associated protein-4 (MAP-4), bcl-2, bax, and cyclooxygenase-2 (COX-2) gene expression were measured using real-time quantitative polymerase chain reaction (PCR). Results: A total of 36 patients had pretreatment biopsies and were evaluable for the analysis of the association of molecular markers with pathological response. Pathological response in the mastectomy specimen was achieved in 12 of these 36 patients (33%). Only HER2/neu and ER gene expression were found to be significantly associated with the extent of pathological response to the regimen, i.e., tumors with low HER2/neu gene expression and negative estrogen receptors were more likely to respond to the tested regimen (p=0.009 and p=0.006, respectively). Conversely, p53 protein

New developments in digital pathology: from telepathology to virtual pathology laboratory.

Science.gov (United States)

Kayser, Klaus; Kayser, Gian; Radziszowski, Dominik; Oehmann, Alexander

2004-01-01

To analyse the present status and future development of computerized diagnostic pathology in terms of work-flow integrative telepathology and virtual laboratory. Telepathology has left its childhood. The technical development of telepathology is mature, in contrast to that of virtual pathology. Two kinds of virtual pathology laboratories are emerging: a) those with distributed pathologists and distributed (>=1) laboratories associated to individual biopsy stations/surgical theatres, and b) distributed pathologists working in a centralized laboratory. Both are under technical development. Telepathology can be used for e-learning and e-training in pathology, as exemplarily demonstrated on Digital Lung Pathology Pathology (www.pathology-online.org). A virtual pathology institution (mode a) accepts a complete case with the patient's history, clinical findings, and (pre-selected) images for first diagnosis. The diagnostic responsibility is that of a conventional institution. The internet serves as platform for information transfer, and an open server such as the iPATH (http://telepath.patho.unibas.ch) for coordination and performance of the diagnostic procedure. The size of images has to be limited, and usual different magnifications have to be used. A group of pathologists is "on duty", or selects one member for a predefined duty period. The diagnostic statement of the pathologist(s) on duty is retransmitted to the sender with full responsibility. First experiences of a virtual pathology institution group working with the iPATH server (Dr. L. Banach, Dr. G. Haroske, Dr. I. Hurwitz, Dr. K. Kayser, Dr. K.D. Kunze, Dr. M. Oberholzer,) working with a small hospital of the Salomon islands are promising. A centralized virtual pathology institution (mode b) depends upon the digitalisation of a complete slide, and the transfer of large sized images to different pathologists working in one institution. The technical performance of complete slide digitalisation is still under

Eulimdana clava (Nematoda: Filarioidea) infection in domestic pigeons (Columba livia domestica): Molecular characterization and pathological changes.

Science.gov (United States)

Šupić, Jovana; Alić, Alma Šeho; Hasanić, Melida; Goletić, Šejla; Duscher, Georg G; Hodžić, Adnan; Alić, Amer

2018-02-15

Filarial nematodes of the Eulimdana genus inhabit subcutaneous tissue of various avian species, mostly Charadriiforme birds. In domestic pigeons, E. clava is the only species recorded in the subcutaneous tissue in a number of isolated cases. In the present study, we discuss the morphology and histopathology of filarial nematodes recovered from subcutaneous tissue of domestic pigeons in Bosnia and Herzegovina. In total 110 pigeons were submitted to necropsy at the Department of Pathology of the Faculty of Veterinary Medicine in Sarajevo. At necropsy, in four pigeons (3.6%) numerous thread-like 0.9-2.1 cm long nematode parasites were observed in the subcutaneous tissue, peritracheal and periesophageal connective tissue. In one pigeon, the parasites were also found free in the body cavity around the heart and lungs. In addition, several 80-90 μm long microfilariae were noted in the tissue cross-sections. No significant lesions were observed associated with adult parasites or microfilariae. Based on morphology, host species and localization detected parasites were identified as E. clava. Molecular analyses of the cox1 and 12S rRNA nucleotide sequences herein generated revealed the close genetic relationship to other filarioid nematodes. The importance of the nematodes in pigeons and the lack of sequences in genetic databases for comparison of avian filarial parasites are emphasized. Copyright © 2018 Elsevier B.V. All rights reserved.

COMPARISON OF RETINAL PATHOLOGY VISUALIZATION IN MULTISPECTRAL SCANNING LASER IMAGING.

Science.gov (United States)

Meshi, Amit; Lin, Tiezhu; Dans, Kunny; Chen, Kevin C; Amador, Manuel; Hasenstab, Kyle; Muftuoglu, Ilkay Kilic; Nudleman, Eric; Chao, Daniel; Bartsch, Dirk-Uwe; Freeman, William R

2018-03-16

To compare retinal pathology visualization in multispectral scanning laser ophthalmoscope imaging between the Spectralis and Optos devices. This retrospective cross-sectional study included 42 eyes from 30 patients with age-related macular degeneration (19 eyes), diabetic retinopathy (10 eyes), and epiretinal membrane (13 eyes). All patients underwent retinal imaging with a color fundus camera (broad-spectrum white light), the Spectralis HRA-2 system (3-color monochromatic lasers), and the Optos P200 system (2-color monochromatic lasers). The Optos image was cropped to a similar size as the Spectralis image. Seven masked graders marked retinal pathologies in each image within a 5 × 5 grid that included the macula. The average area with detected retinal pathology in all eyes was larger in the Spectralis images compared with Optos images (32.4% larger, P < 0.0001), mainly because of better visualization of epiretinal membrane and retinal hemorrhage. The average detection rate of age-related macular degeneration and diabetic retinopathy pathologies was similar across the three modalities, whereas epiretinal membrane detection rate was significantly higher in the Spectralis images. Spectralis tricolor multispectral scanning laser ophthalmoscope imaging had higher rate of pathology detection primarily because of better epiretinal membrane and retinal hemorrhage visualization compared with Optos bicolor multispectral scanning laser ophthalmoscope imaging.

Mapping thalamocortical network pathology in temporal lobe epilepsy.

Science.gov (United States)

Bernhardt, Boris C; Bernasconi, Neda; Kim, Hosung; Bernasconi, Andrea

2012-01-10

Although experimental work has provided evidence that the thalamus is a crucial relay structure in temporal lobe epilepsy (TLE), the relation of the thalamus to neocortical pathology remains unclear. To assess thalamocortical network pathology in TLE, we mapped pointwise patterns of thalamic atrophy and statistically related them to neocortical thinning. We studied cross-sectionally 36 patients with drug-resistant TLE and 19 age- and sex-matched healthy control subjects using high-resolution MRI. To localize thalamic pathology, we converted manual labels into surface meshes using the spherical harmonic description and calculated local deformations relative to a template. In addition, we measured cortical thickness by means of the constrained Laplacian anatomic segmentation using proximity algorithm. Compared with control subjects, patients with TLE showed ipsilateral thalamic atrophy that was located along the medial surface, encompassing anterior, medial, and posterior divisions. Unbiased analysis correlating the degree of medial thalamic atrophy with cortical thickness measurements mapped bilateral frontocentral, lateral temporal, and mesiotemporal cortices. These areas overlapped with those of cortical thinning found when patients were compared with control subjects. Thalamic atrophy intensified with a longer duration of epilepsy and was more severe in patients with a history of febrile convulsions. The degree and distribution of thalamic pathology relates to the topography and extent of neocortical atrophy, lending support to the concept that the thalamus is an important hub in the pathologic network of TLE.

Highlights from the 7th European Meeting on Molecular Diagnostics

NARCIS (Netherlands)

Dr. A.J.C. van den Brule, van den; Drs A.J.M. Loonen; Dr. R. Schuurman

2012-01-01

This report presents the highlights of the 7th European Meeting on Molecular Diagnostics held in Scheveningen, The Hague, The Netherlands, 12-14 October 2011. The areas covered included molecular diagnostics applications in medical microbiology, virology, pathology, hemato-oncology,clinical genetics

Phosphoproteomic analysis for the identification of predictive molecular factors and new molecular targets in breast, colorectal, ovary, and lung cancer

International Nuclear Information System (INIS)

Belluco, C.; De Paoli, P.

2009-01-01

Neoadjuvant chemotherapy is a standard therapeutic approach for several types of locally advanced and metastatic tumors. Molecular factors predictive of response to therapy are highly needed for exploiting the potential benefit of properative chemotherapy. Moreover, neoadjuvant chemotherapy represents an ideal clinical model for studying predictive factors since it allows to obtain pre-treatment tissue biopsies which can be analyzed and the results compared to clinical and pathological response. Protein kinases represent some of the most important drug targets in medicine today and their aberrant activation are involved in many disease processes including cancer development and progression

Error-free pathology: applying lean production methods to anatomic pathology.

Science.gov (United States)

Condel, Jennifer L; Sharbaugh, David T; Raab, Stephen S

2004-12-01

The current state of our health care system calls for dramatic changes. In their pathology department, the authors believe these changes may be accomplished by accepting the long-term commitment of applying a lean production system. The ideal state of zero pathology errors is one that should be pursued by consistently asking, "Why can't we?" The philosophy of lean production systems began in the manufacturing industry: "All we are doing is looking at the time from the moment the customer gives us an order to the point when we collect the cash. And we are reducing that time line by removing non-value added wastes". The ultimate goals in pathology and overall health care are not so different. The authors' intention is to provide the patient (customer) with the most accurate diagnostic information in a timely and efficient manner. Their lead histotechnologist recently summarized this philosophy: she indicated that she felt she could sleep better at night knowing she truly did the best job she could. Her chances of making an error (in cutting or labeling) were dramatically decreased in the one-by-one continuous flow work process compared with previous practices. By designing a system that enables employees to be successful in meeting customer demand, and by empowering the frontline staff in the development and problem solving processes, one can meet the challenges of eliminating waste and build an improved, efficient system.

Selective pathology fellowships: diverse, innovative, and valuable subspecialty training.

Science.gov (United States)

Iezzoni, Julia C; Ewton, April; Chévez-Barrios, Patricia; Moore, Stephen; Thorsen, Linda M; Naritoku, Wesley Y

2014-04-01

Although selective pathology fellowships have a long-standing history of developing trainees with advanced expertise in specific areas of pathology other than those of the American Board of Pathology-certified subspecialties, the widespread interest in this training continues to grow. To describe the historical background and current status of selective pathology fellowships, and to provide examples of 3 programs. In addition, Accreditation Council for Graduate Medical Education (ACGME)-accredited programs and nonaccredited programs in Selective Pathology are compared. ACGME data banks and publicly available online materials were used. Program directors of the fellowships examples in this paper provided program-specific information. Additionally, an online survey of the program directors and program coordinators of ACGME-accredited programs and nonaccredited programs in selective pathology was performed. There are currently 76 ACGME-accredited selective pathology programs. The programs are distributed between 3 major categories: surgical pathology, focused anatomic pathology, and focused clinical pathology. Although the vast majority of programs are concerned that their funding source may be cut in the next 3 years, most programs will not change the number of fellowship positions in their programs. Program requirements devoted specifically and solely to selective pathology have been developed and are in effect. The value of this training is recognized not only by pathologists, but by clinicians as well, in both academia and private practice. Importantly, the diversity and innovation inherent in selective pathology allow these programs to adeptly address new subspecialty areas and technologic advances in the current and evolving practice of pathology.

Eighteen cases of small breast cancer: a comparative study of mammography, CT scan and pathology

International Nuclear Information System (INIS)

Wu Yaopan; Lin Haogao; Cai Peiqiang; Ouyang Yi; Zhang Weizhang; Lu Bingui

2003-01-01

Objective: To improve the early diagnosis of breast cancer through a study of the mammography and CT findings of small breast cancer. Methods: The mammography and CT findings of 18 cases of small breast cancer (φ≤2.0 cm in diameter) were studied and compared with pathological results. Results: The diagnostic accuracy of CT and mammography was 83% and 61%, respectively. There was a statistical difference between both modalities (P<0.05), CT scan was superior to mammography. However, there was no difference between them when assessing the lesion arising in F-type breast. In detecting breast fine cluster of calcification, the sensitivity of mammography was better than CT scan. Conclusion: The patient suspected of small breast cancer should take mammography as the first evaluation. CT scan is reserved for the further investigation. The mammography combined with CT scan can improve the early diagnostic rate of breast cancer

Bacterial pathogenesis of plants: future challenges from a microbial perspective: Challenges in Bacterial Molecular Plant Pathology.

Science.gov (United States)

Pfeilmeier, Sebastian; Caly, Delphine L; Malone, Jacob G

2016-10-01

secretion systems (T3SSs) are important and well-studied contributors to bacterial disease. Several key unanswered questions will shape future investigations of these systems. We need to define the mechanism of hierarchical and temporal control of effector secretion. For successful infection, effectors need to interact with host components to exert their function. Advanced biochemical, proteomic and cell biological techniques will enable us to study the function of effectors inside the host cell in more detail and on a broader scale. Population genomics analyses provide insight into evolutionary adaptation processes of phytopathogens. The determination of the diversity and distribution of type III effectors (T3Es) and other virulence genes within and across pathogenic species, pathovars and strains will allow us to understand how pathogens adapt to specific hosts, the evolutionary pathways available to them, and the possible future directions of the evolutionary arms race between effectors and molecular plant targets. Although pathogenic bacteria employ a host of different virulence and proliferation strategies, as a result of the space constraints, this review focuses mainly on the hemibiotrophic pathogens. We discuss the process of plant infection from the perspective of these important phytopathogens, and highlight new approaches to address the outstanding challenges in this important and fast-moving field. © 2016 The Authors. Molecular Plant Pathology Published by British Society for Plant Pathology and John Wiley & Sons Ltd.

Hsp90 molecular chaperone: structure, functions and participation in cardio-vascular pathologies

Directory of Open Access Journals (Sweden)

Kroupskaya I. V.

2009-10-01

Full Text Available The review is devoted to the analysis of structural and functional properties of molecular chaperon Hsp90. Hsp90 is a representative of highly widespread family of heat shock proteins. The protein is found in eubacteria and all branches of eukarya, but it is apparently absent in archaea. It is one of key regulators of numerous signalling pathways, cell growth and development, apoptosis, induction of autoimmunity, and progression of heart failure. The full functional activity of Hsp90 shows up in a complex with other molecular chaperones and co-chaperones. Molecular interactions between chaperones, different signalling proteins and protein-partners are highly crucial for the normal functioning of signalling pathways and their destruction causes an alteration in the cell physiology up to its death.

[Psychopathology and achievement motivation in adolescents with pathological internet use].

Science.gov (United States)

Wartberg, Lutz; Sack, Peter-Michael; Petersen, Kay-Uwe; Thomasius, Rainer

2011-01-01

In Germany, the internet is used by 69.4% of the population or 49 million people, and 100% of adolescents (between 14 to 19 years of age) spend time in the internet at least occasionally. An excessive use of the internet may lead to negative psychosocial consequences and changes in behaviour. This phenomenon is named "pathological internet use". Until now, there are only few studies published that investigate mental well being in German adolescents with pathological internet use. 16 participants of an outpatient treatment program for pathological internet use and 16 healthy adolescents were compared on self-reported levels of psychopathology (SPS-J), achievement motivation (FLM 7-13) and personal experience of attention deficit (FEDA). There were no differences in age, gender, intelligence or education between the two groups. Pathological internet users exhibited significantly elevated scores on self-esteem problems and the summary score of the SPS-J and significantly lower scores on FLM 7-13-dimensions "achievement ambition" and "perseverance/diligence" compared to controls. The results revealed that adolescents with pathological internet use report a higher level of psychopathology and lower levels of achievement motivation and drive. These findings should be taken into account when conceptualizing treatments for pathological internet users.

Exploring gender differences in body image, eating pathology, and sexual harassment.

Science.gov (United States)

Buchanan, Nicole T; Bluestein, Brooke M; Nappa, Alexa C; Woods, Krystle C; Depatie, Melissa M

2013-06-01

This study examines the relationship between body image (weight/shape concerns), eating pathology, and sexual harassment among men and women (N=2446). Hierarchical regressions controlling for depression revealed main effects of gender such that women reported greater weight/shape concerns, eating pathology, dietary restraint, eating concerns, and binge eating compared to men. Main effects for sexual harassment indicated that as harassment increased, participants reported increased weight/shape concerns, eating pathology, dietary restraint, eating concerns, binge eating, and compensatory behaviors. There were small but significant interactions between gender and harassment for eating pathology total score (which included each of the domains listed above), weight/shape concerns, dietary restraint, and eating concerns such that the relationship between increased harassment and increased pathology was stronger for women compared to men. The largest interaction was found for compensatory behaviors, such that while women and men's scores both increased as harassment increased, the relationship was stronger for men. Copyright © 2013 Elsevier Ltd. All rights reserved.

[Allergy and autoimmunity: Molecular diagnostics, therapy, and presumable pathogenesis].

Science.gov (United States)

Arefieva, A S; Smoldovskaya, O V; Tikhonov, A A; Rubina, A Yu

2017-01-01

Allergic and autoimmune diseases represent immunopathological reactions of an organism to antigens. Despite that the allergy is a result of exaggerated immune response to foreign antigens (allergens) and autoimmune diseases are characterized by the pathological response to internal antigens (autoantigens), the underlying mechanisms of these diseases are probably common. Thus, both types of diseases represent variations in the hypersensitivity reaction. A large percentage of both the adult and pediatric population is in need of early diagnostics of these pathologies of the immune system. Considering the diversity of antibodies produced in allergic and autoimmune disease and the difficulties accompanying clinical diagnosing, molecular diagnostics of these pathological processes should be carried out in several stages, including screening and confirmatory studies. In this review, we summarize the available data on the molecular diagnostics and therapy of allergic and autoimmune diseases and discuss the basic similarities and differences in the mechanisms of their development.

Pathological Gambling among Italian Nursing Students.

Science.gov (United States)

Cicolini, Giancarlo; Della Pelle, Carlo; Simonetti, Valentina; Comparcini, Dania; Sepede, Gianna; Cipollone, Francesco

2018-04-01

To investigate the role of psychiatric dimensions, behavioral or substance addictions and demographical variables as determinants of pathological gambling among nursing students. Multicenter cross-sectional study. From June to October 2015 a survey was carried out among Italian Nursing students. Data were collected using a six-section tool. Nursing students who completed the survey numbered 1083, 902 (83.3%) had some problems with gambling and 29 (2.7%) showed pathological gambling. Percentage of pathological gambling was significantly associate with illicit drug/alcohol use (65.5%; p=0.001) and with male gender (58.6%) comparing to student nurse with non-pathological gambling (20%) and those with some problem (24.2%). Significant main effect was observed for IAT score (Beta=0.119, t=3.28, p=0.001): higher IAT scores were associated with higher SOGS scores. Italian nursing students have some problems with gambling and pathological gambling problem, and males are those who have more problems. Results might be useful for faculties of health professionals to identify students at risk in an early stage, to direct prevention tailored interventions. Nursing faculties should be aware of the prevalence of Gambling among students. Prevention interventions should be planned to minimize the risk of gambling behavior in the future nurses' health care workers. Copyright © 2017 Elsevier Inc. All rights reserved.

Time for change: a new training programme for morpho-molecular pathologists?

Science.gov (United States)

Moore, David A; Oien, Karin A; Lee, Jessica L; Jones, J Louise; Salto-Tellez, Manuel

2018-01-01

The evolution of cellular pathology as a specialty has always been driven by technological developments and the clinical relevance of incorporating novel investigations into diagnostic practice. In recent years, the molecular characterisation of cancer has become of crucial relevance in patient treatment both for predictive testing and subclassification of certain tumours. Much of this has become possible due to the availability of next-generation sequencing technologies and the whole-genome sequencing of tumours is now being rolled out into clinical practice in England via the 100 000 Genome Project. The effective integration of cellular pathology reporting and genomic characterisation is crucial to ensure the morphological and genomic data are interpreted in the relevant context, though despite this, in many UK centres molecular testing is entirely detached from cellular pathology departments. The CM-Path initiative recognises there is a genomics knowledge and skills gap within cellular pathology that needs to be bridged through an upskilling of the current workforce and a redesign of pathology training. Bridging this gap will allow the development of an integrated ‘morphomolecular pathology’ specialty, which can maintain the relevance of cellular pathology at the centre of cancer patient management and allow the pathology community to continue to be a major influence in cancer discovery as well as playing a driving role in the delivery of precision medicine approaches. Here, several alternative models of pathology training, designed to address this challenge, are presented and appraised. PMID:29113995

Protection by neuroglobin expression in brain pathologies

Directory of Open Access Journals (Sweden)

Eliana Baez

2016-09-01

Full Text Available Astrocytes play an important role in physiological, metabolic and structural functions and, when impaired, they can be involved in various pathologies including Alzheimer, focal ischemic stroke and traumatic brain injury. These disorders involve an imbalance in the blood flow and nutrients such as glucose and lactacte, leading to biochemical and molecular changes that cause neuronal damage, which is followed by loss of cognitive and motor functions. Previous studies have shown that astrocytes are more resilient than neurons during brain insults as a consequence of their more effective antioxidant systems, transporters and enzymes, which made them less susceptible to excitotoxicity. In addition, astrocytes synthesize and release different protective molecules for neurons, including neuroglobin, a member of the globin family of proteins. After brain injury neuroglobin expression is induced in astrocytes. Since neuroglobin promotes neuronal survival, its increased expression in astrocytes after brain injury may represent an endogenous neuroprotective mechanism. Here, we review the role of neuroglobin in the CNS, its relationship with different pathologies, and the role of different factors that regulate its expression in astrocytes.

Pathologic contrast enhancement of cerebral lesions: A comparative study using stereotactic CT, stereotactic MR imaging, and stereotactic biopsy

International Nuclear Information System (INIS)

Earnest, F. IV; Kelly, P.J.; Scheithauer, B.; Kall, B.; Cascino, T.L.; Ehman, R.L.; Forbes, G.

1986-01-01

The author compared the pattern and degree of Gd-DTPA dimeglumine contrast enhancement demonstrated on stereotactic MR images with that seen on stereotactic CT images obtained after conventional iodinated contrast agent enhancement and with histopathologic findings on sequential stereotactic brain biopsies. Stereotactic biopsies of the areas that enhanced on CT or MR imaging revealed tumor tissue with neovascularity. Tumor tissue with no or mild neovascularity did not enhance with contrast agent administration. Isolated tumor cells were frequently found beyond the margins of some primary brain neoplasms defined by contrast agent-enhanced MR imaging and CT. The histopathologic findings associated with pathologic contrast agent enhancement are presented

Mutational myriad of tumor suppressor p53 in Filipino breast cancer: results and perspectives in molecular pathology and epidemiology

Energy Technology Data Exchange (ETDEWEB)

Deocaris, Custer C

2000-04-01

The p53 tumor suppressor is by far the most widely mutated gene in human cancers. p53 encodes a 53-kDa phosphoprotein, transcription-activator whose targets include genes and gene products that orchestrate genomic stability, cellular response to DNA damage, cell cycle progression apoptosis and aging (senescence). Analysis of the p53 gene profile has previously resulted in identifying several cancer-causative factors in the human setting, as well as, in creating a unique molecular profile of a tumor useful in the design of tailored-therapies for individual cancer patients. Our results in screening for p53 abnormalities in 140 Filipino patients with primary breast lesions confined from 1997-1998 in 5 major hospitals in Manila reveal that p53 plays an important role in the development and progression of breast cancer in at least 48% of all cases. Two methods of p53 analysis are employed, enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction-temporal temperature gradient electrophoresis (PCR-TTGE). Inter-comparisons of method exhibit 63.3% concordance in 21 fresh breast carcinoma samples, with ELISA demonstrating 14% false-positives and 10% false-negatives. Only mutations in exon 7 (p=0.063) in the tumor samples how significant correlation with abnormal cellular elevation of p53. PCR-TTGE screening in a large series of 140 patients show that most genetic lesions are localized in exons 5 (41% of the total cases) and 6 (27% of the total cases). No mutations are, however, detected in the transactivation (exons 2-4) and oligomerization (exons 10-11) domains. Invasive carcinomas (stages II and III) are characterized with more frequent and diverse genetic alterations compared with benign tumors, most significantly at exon 5B (p=0.066) and at independently multiple sites (p=0.066). Earlier-onset cases (age of diagnosis < 50 yrs), known to be more clinico-pathologically aggressive, are diagnosed harboring more frequent p53 mutations centered at exon 7 (p=0

Mutational myriad of tumor suppressor p53 in Filipino breast cancer: results and perspectives in molecular pathology and epidemiology

International Nuclear Information System (INIS)

Deocaris, Custer C.

2000-04-01

The p53 tumor suppressor is by far the most widely mutated gene in human cancers. p53 encodes a 53-kDa phosphoprotein, transcription-activator whose targets include genes and gene products that orchestrate genomic stability, cellular response to DNA damage, cell cycle progression apoptosis and aging (senescence). Analysis of the p53 gene profile has previously resulted in identifying several cancer-causative factors in the human setting, as well as, in creating a unique molecular profile of a tumor useful in the design of tailored-therapies for individual cancer patients. Our results in screening for p53 abnormalities in 140 Filipino patients with primary breast lesions confined from 1997-1998 in 5 major hospitals in Manila reveal that p53 plays an important role in the development and progression of breast cancer in at least 48% of all cases. Two methods of p53 analysis are employed, enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction-temporal temperature gradient electrophoresis (PCR-TTGE). Inter-comparisons of method exhibit 63.3% concordance in 21 fresh breast carcinoma samples, with ELISA demonstrating 14% false-positives and 10% false-negatives. Only mutations in exon 7 (p=0.063) in the tumor samples how significant correlation with abnormal cellular elevation of p53. PCR-TTGE screening in a large series of 140 patients show that most genetic lesions are localized in exons 5 (41% of the total cases) and 6 (27% of the total cases). No mutations are, however, detected in the transactivation (exons 2-4) and oligomerization (exons 10-11) domains. Invasive carcinomas (stages II and III) are characterized with more frequent and diverse genetic alterations compared with benign tumors, most significantly at exon 5B (p=0.066) and at independently multiple sites (p=0.066). Earlier-onset cases (age of diagnosis < 50 yrs), known to be more clinico-pathologically aggressive, are diagnosed harboring more frequent p53 mutations centered at exon 7 (p=0

Pathological gambling in women: a review

Directory of Open Access Journals (Sweden)

Martins Silvia Saboia

2002-01-01

Full Text Available Pathological gambling was only recently recognized as a psychiatric disorder (DSM-III, APA, 1980. Most studies of pathological gambling include only male subjects. Despite the paucity of information, it is likely that at least one-third of pathological gamblers are women. The objective of this article is to review clinical and epidemiological characteristics of female gamblers as compared to their male counterparts. MEDLINE and PsycINFO were searched for investigational studies and reviews of the past 10 years on clinical (sociodemographic, course and progression, psychiatric comorbidities, genetics, and personality and epidemiological aspects of female gamblers. Other relevant articles were also selected from reference lists. It is concluded that the current literature indicates some common characteristics in female and male gamblers, but it also indicates the possibility that each gender may carry etiopathogenic differences that when better understood should lead to improved treatment and prevention strategies.

Integrating molecular diagnostics into histopathology training: the Belfast model.

Science.gov (United States)

Flynn, C; James, J; Maxwell, P; McQuaid, S; Ervine, A; Catherwood, M; Loughrey, M B; McGibben, D; Somerville, J; McManus, D T; Gray, M; Herron, B; Salto-Tellez, M

2014-07-01

Molecular medicine is transforming modern clinical practice, from diagnostics to therapeutics. Discoveries in research are being incorporated into the clinical setting with increasing rapidity. This transformation is also deeply changing the way we practise pathology. The great advances in cell and molecular biology which have accelerated our understanding of the pathogenesis of solid tumours have been embraced with variable degrees of enthusiasm by diverse medical professional specialties. While histopathologists have not been prompt to adopt molecular diagnostics to date, the need to incorporate molecular pathology into the training of future histopathologists is imperative. Our goal is to create, within an existing 5-year histopathology training curriculum, the structure for formal substantial teaching of molecular diagnostics. This specialist training has two main goals: (1) to equip future practising histopathologists with basic knowledge of molecular diagnostics and (2) to create the option for those interested in a subspecialty experience in tissue molecular diagnostics to pursue this training. It is our belief that this training will help to maintain in future the role of the pathologist at the centre of patient care as the integrator of clinical, morphological and molecular information. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Teaching digital pathology: The international school of digital pathology and proposed syllabus

Directory of Open Access Journals (Sweden)

Vincenzo Della Mea

2017-01-01

Full Text Available Digital pathology is an interdisciplinary field where competency in pathology, laboratory techniques, informatics, computer science, information systems, engineering, and even biology converge. This implies that teaching students about digital pathology requires coverage, expertise, and hands-on experience in all these disciplines. With this in mind, a syllabus was developed for a digital pathology summer school aimed at professionals in the aforementioned fields, as well as trainees and doctoral students. The aim of this communication is to share the context, rationale, and syllabus for this school of digital pathology.

Dimensions of personality pathology in adolescents: Relations to DSM-IV personality disorder symptoms

NARCIS (Netherlands)

Tromp, N.B.; Koot, H.M.

2009-01-01

The aim of the present study was to relate and compare two approaches to personality pathology in adolescents. Dimensions of personality pathology, assessed by the Dimensional Assessment of Personality Pathology-Basic Questionnaire for Adolescents (DAPP-BQ-A; Tromp & Koot, 2008), were related to

Cortical Pathology in RRMS: Taking a Cue from Four Sisters

Directory of Open Access Journals (Sweden)

Massimiliano Calabrese

2012-01-01

Full Text Available Background. Although grey matter pathology is a relevant aspect of multiple sclerosis (MS both with physical and cognitive rebounds, its pathogenesis is still under investigation. To what extent the familial and sporadic cases of MS differ in cortical pathology has not been elucidated yet. Here we present a multiple case report of four sisters affected by MS, all of them having a very high burden of cortical pathology. Methods. The clinical and grey matter MRI parameters of the patients were compared with those of twenty-five-aged matched healthy women and 25 women affected by sporadic MS (matched for age, disease duration, EDSS, and white matter lesion load. Results. Despite their short disease duration (<5 years, the four sisters showed a significant cortical thinning compared to healthy controls ( and sporadic MS ( and higher CLs number ( and volume ( compared to sporadic MS. Discussion. Although limited to a single family, our observation is worth of interest since it suggests that familial factors may account for a peculiar involvement of the cortex in MS pathology. This hypothesis should be further evaluated in a large number of multiplex MS families.

The Danish Pathology Register

DEFF Research Database (Denmark)

Bjerregaard, Beth; Larsen, Ole B

2011-01-01

The National Board of Health, Denmark in 1997 published guidelines for reporting of pathology data and the Danish Pathology Register (DPR) was established.......The National Board of Health, Denmark in 1997 published guidelines for reporting of pathology data and the Danish Pathology Register (DPR) was established....

Pathological gambling and criminality.

Science.gov (United States)

Folino, Jorge Oscar; Abait, Patricia Estela

2009-09-01

To review research results on the relationship between pathological gambling and criminality, published in 2007 and 2008, in English and in Spanish. An important association between pathological gambling and criminality was confirmed in populations of anonymous gamblers, helpline callers and substance abusers. Helplines provide a timely service to gamblers who have not reached the maximum stages in the development of a pathological gambling pattern. Pathological gambling is associated with violence in couples and dysfunctional families. Inversely, violence is also an antecedent promoting vulnerability toward pathological gambling. Impulsiveness shows diverse relationships with pathological gambling and violence as well. A pathological gambler's involvement in crime is exceptionally considered without responsibility by justice, but it may be an indicator of the disorder severity and the need for special therapeutic tactics. While reviewing the present study, research work was published that contributed to a better understanding of the association between pathological gambling and criminality and went further into their complex relationship and the formulation of explanatory models related to impulsiveness.

Lipidomics of human brain aging and Alzheimer's disease pathology.

Science.gov (United States)

Naudí, Alba; Cabré, Rosanna; Jové, Mariona; Ayala, Victoria; Gonzalo, Hugo; Portero-Otín, Manuel; Ferrer, Isidre; Pamplona, Reinald

2015-01-01

Lipids stimulated and favored the evolution of the brain. Adult human brain contains a large amount of lipids, and the largest diversity of lipid classes and lipid molecular species. Lipidomics is defined as "the full characterization of lipid molecular species and of their biological roles with respect to expression of proteins involved in lipid metabolism and function, including gene regulation." Therefore, the study of brain lipidomics can help to unravel the diversity and to disclose the specificity of these lipid traits and its alterations in neural (neurons and glial) cells, groups of neural cells, brain, and fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of human brain aging and Alzheimer disease. This review will discuss the lipid composition of the adult human brain. We first consider a brief approach to lipid definition, classification, and tools for analysis from the new point of view that has emerged with lipidomics, and then turn to the lipid profiles in human brain and how lipids affect brain function. Finally, we focus on the current status of lipidomics findings in human brain aging and Alzheimer's disease pathology. Neurolipidomics will increase knowledge about physiological and pathological functions of brain cells and will place the concept of selective neuronal vulnerability in a lipid context. © 2015 Elsevier Inc. All rights reserved.

[Quality of DNA from archival pathological samples of gallbladder cancer].

Science.gov (United States)

Roa, Iván; de Toro, Gonzalo; Sánchez, Tamara; Slater, Jeannie; Ziegler, Anne Marie; Game, Anakaren; Arellano, Leonardo; Schalper, Kurt; de Aretxabala, Xabier

2013-12-01

The quality of the archival samples stored at pathology services could be a limiting factor for molecular biology studies. To determine the quality of DNA extracted from gallbladder cancer samples at different institutions. One hundred ninety four samples coming from five medical centers in Chile, were analyzed. DNA extraction was quantified determining genomic DNA concentration. The integrity of DNA was determined by polymerase chain reaction amplification of different length fragments of a constitutive gene (β-globin products of 110, 268 and 501 base pairs). The mean DNA concentration obtained in 194 gallbladder cancer samples was 48 ± 43.1 ng/µl. In 22% of samples, no amplification was achieved despite obtaining a mean DNA concentration of 58.3 ng/ul. In 81, 67 and 22% of samples, a DNA amplification of at least 110, 268 or 501 base pairs was obtained, respectively. No differences in DNA concentration according to the source of the samples were demonstrated. However, there were marked differences in DNA integrity among participating centers. Samples from public hospitals were of lower quality than those from private clinics. Despite some limitations, in 80% of cases, the integrity of DNA in archival samples from pathology services in our country would allow the use of molecular biology techniques.

Cue-induced craving in pathological buying: empirical evidence and clinical implications.

Science.gov (United States)

Trotzke, Patrick; Starcke, Katrin; Pedersen, Anya; Brand, Matthias

2014-01-01

Pathological buying is associated with marked distress and impaired functioning in important life domains. It is currently under debate whether pathological buying can be considered a behavioral addiction. In analogy to results reported in addicted individuals, craving reactions elicited by addiction-related cues might be an underlying mechanism for the etiology and pathogenesis of pathological buying. In the present study, 30 pathological buyers and 30 matched control participants were examined with a cue-reactivity paradigm consisting of shopping and control cues. Skin conductance responses, as well as subjective ratings for arousal, valence, and urge to buy, were assessed. Subjective craving reactions were measured before and after the cue-reactivity paradigm. On a physiological level, skin conductance responses toward shopping cues were higher in pathological buyers (mean [M; standard deviation {SD}] = 0.26 [0.13]) compared with control participants (M [SD] = 0.19 [0.09]; t(58) = 2.29, p = .025, d = 0.60). On a behavioral level, the individuals with pathological buying rated the shopping cues as more arousing and more positive, and reported a greater urge to buy compared with control participants and with control cues. An increase in subjective craving after completing the cue-reactivity paradigm was observed only in the pathological buyers (Mpre [SD] = 1.95 [1.47], Mpost [SD] = 2.87 [1.79]; t(29) = 5.07, p buying. The results demonstrate similarities between pathological buying and substance or behavioral addictions and provide implications for clinical treatment.

Comparative Molecular Analysis of Gastrointestinal Adenocarcinomas

NARCIS (Netherlands)

Liu, Yang; Sethi, Nilay S; Hinoue, Toshinori; Schneider, Barbara G; Cherniack, Andrew D; Sanchez-Vega, Francisco; Seoane, Jose A; Farshidfar, Farshad; Bowlby, Reanne; Islam, Mirazul; Kim, Jaegil; Chatila, Walid; Akbani, Rehan; Kanchi, Rupa S; Rabkin, Charles S; Willis, Joseph E; Wang, Kenneth K; McCall, Shannon J; Mishra, Lopa; Ojesina, Akinyemi I; Bullman, Susan; Pedamallu, Chandra Sekhar; Lazar, Alexander J; Sakai, Ryo; Thorsson, Vésteinn; Bass, Adam J; Laird, Peter W; de Krijger, RR

2018-01-01

We analyzed 921 adenocarcinomas of the esophagus, stomach, colon, and rectum to examine shared and distinguishing molecular characteristics of gastrointestinal tract adenocarcinomas (GIACs). Hypermutated tumors were distinct regardless of cancer type and comprised those enriched for

Pathologic fracture in childhood and adolescent osteosarcoma: A single-institution experience.

Science.gov (United States)

Haynes, Lindsay; Kaste, Sue C; Ness, Kirsten K; Wu, Jianrong; Ortega-Laureano, Lucia; Bishop, Michael; Neel, Michael; Rao, Bhaskar; Fernandez-Pineda, Israel

2017-04-01

Pathologic fractures occur in 5-10% of pediatric osteosarcoma (OS) cases and have historically been considered a contraindication to limb salvage. Our purpose was to describe the radiographic features of pathologic fracture and examine its impact on local recurrence rates, functional outcomes, and overall survival. We retrospectively analyzed patients at our institution from 1990 to 2015 with pathologic fracture at diagnosis or during neoadjuvant chemotherapy. We selected a control group of 50 OS patients of similar age and gender without pathologic fracture from 1990 to 2015. Functional outcomes were scored using Musculoskeletal Tumor Society criteria. Chi-square test was used for comparative analysis of groups. Thirty-six patients with 37 pathologic fractures form the study cohort. Of patients who received surgery, 18 of 34 patients with fracture underwent amputation compared to 8 of 48 patients in the nonfracture group (P = 0.007). Indications for amputation in fracture patients were tumor size (n = 7), neurovascular involvement (n = 6), and tumor progression during neoadjuvant chemotherapy (n = 5). Only one patient (2.9%) in the fracture group who underwent limb salvage suffered local recurrence. Of patients who received neoadjuvant chemotherapy, 25 of 34 fracture patients showed poor histological response compared to 24 of 47 nonfracture patients (P = 0.044). There was no statistically significant difference in overall survival (P = 0.96). Functional outcomes were significantly lower in fracture patients (median = 17.5) than nonfracture patients (median = 24) (P = 0.023). Radiographic features of pathologic fractures were highly variable in this population. Limb salvage surgery can be performed without increased risk of local recurrence. Patients with pathologic fracture suffer worse functional outcomes but no decrease in overall survival. © 2016 Wiley Periodicals, Inc.

Molecular magnetic resonance imaging of atherosclerotic vessel wall disease

Energy Technology Data Exchange (ETDEWEB)

Noerenberg, Dominik [Charite - University Medicine Berlin, Department of Radiology, Berlin (Germany); University of Munich - Grosshadern, Department of Clinical Radiology, Munich (Germany); Ebersberger, Hans U. [Heart Center Munich-Bogenhausen, Department of Cardiology and Intensive Care Medicine, Munich (Germany); Diederichs, Gerd; Hamm, Bernd [Charite - University Medicine Berlin, Department of Radiology, Berlin (Germany); Botnar, Rene M. [King' s College London, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); Makowski, Marcus R. [Charite - University Medicine Berlin, Department of Radiology, Berlin (Germany); King' s College London, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom)

2016-03-15

Molecular imaging aims to improve the identification and characterization of pathological processes in vivo by visualizing the underlying biological mechanisms. Molecular imaging techniques are increasingly used to assess vascular inflammation, remodeling, cell migration, angioneogenesis and apoptosis. In cardiovascular diseases, molecular magnetic resonance imaging (MRI) offers new insights into the in vivo biology of pathological vessel wall processes of the coronary and carotid arteries and the aorta. This includes detection of early vascular changes preceding plaque development, visualization of unstable plaques and assessment of response to therapy. The current review focuses on recent developments in the field of molecular MRI to characterise different stages of atherosclerotic vessel wall disease. A variety of molecular MR-probes have been developed to improve the non-invasive detection and characterization of atherosclerotic plaques. Specifically targeted molecular probes allow for the visualization of key biological steps in the cascade leading to the development of arterial vessel wall lesions. Early detection of processes which lead to the development of atherosclerosis and the identification of vulnerable atherosclerotic plaques may enable the early assessment of response to therapy, improve therapy planning, foster the prevention of cardiovascular events and may open the door for the development of patient-specific treatment strategies. (orig.)

Molecular magnetic resonance imaging of atherosclerotic vessel wall disease

International Nuclear Information System (INIS)

Noerenberg, Dominik; Ebersberger, Hans U.; Diederichs, Gerd; Hamm, Bernd; Botnar, Rene M.; Makowski, Marcus R.

2016-01-01

Molecular imaging aims to improve the identification and characterization of pathological processes in vivo by visualizing the underlying biological mechanisms. Molecular imaging techniques are increasingly used to assess vascular inflammation, remodeling, cell migration, angioneogenesis and apoptosis. In cardiovascular diseases, molecular magnetic resonance imaging (MRI) offers new insights into the in vivo biology of pathological vessel wall processes of the coronary and carotid arteries and the aorta. This includes detection of early vascular changes preceding plaque development, visualization of unstable plaques and assessment of response to therapy. The current review focuses on recent developments in the field of molecular MRI to characterise different stages of atherosclerotic vessel wall disease. A variety of molecular MR-probes have been developed to improve the non-invasive detection and characterization of atherosclerotic plaques. Specifically targeted molecular probes allow for the visualization of key biological steps in the cascade leading to the development of arterial vessel wall lesions. Early detection of processes which lead to the development of atherosclerosis and the identification of vulnerable atherosclerotic plaques may enable the early assessment of response to therapy, improve therapy planning, foster the prevention of cardiovascular events and may open the door for the development of patient-specific treatment strategies. (orig.)

Multimodal PET Imaging of Amyloid and Tau Pathology in Alzheimer Disease and Non-Alzheimer Disease Dementias.

Science.gov (United States)

Xia, Chenjie; Dickerson, Bradford C

2017-07-01

Biomarkers of the molecular pathology underpinning dementia syndromes are increasingly recognized as crucial for diagnosis and development of disease-modifying treatments. Amyloid PET imaging is an integral part of the diagnostic assessment of Alzheimer disease. Its use has also deepened understanding of the role of amyloid pathology in Lewy body disorders and aging. Tau PET imaging is an imaging biomarker that will likely play an important role in the diagnosis, monitoring, and treatment in dementias. Using tau PET imaging to examine how tau pathology relates to amyloid and other markers of neurodegeneration will serve to better understand the pathophysiologic cascade that leads to dementia. Copyright © 2017 Elsevier Inc. All rights reserved.

[Protocol for the study of bone tumours and standardization of pathology reports].

Science.gov (United States)

Machado, Isidro; Pozo, José Juan; Marcilla, David; Cruz, Julia; Tardío, Juan C; Astudillo, Aurora; Bagué, Sílvia

Primary bone neoplasms represent a rare and heterogeneous group of mesenchymal tumours. The prevalence of benign and malignant tumours varies; the latter (sarcomas) account for less than 0.2% of all malignant tumours. Primary bone neoplasms are usually diagnosed and classified according to the criteria established and published by the World Health Organization (WHO 2013). These criteria are a result of advances in molecular pathology, which complements the histopathological diagnosis. Bone tumours should be diagnosed and treated in referral centers by a multidisciplinary team including pathologists, radiologists, orthopedic surgeons and oncologists. We analyzed different national and international protocols in order to provide a guide of recommendations for the improvement of pathological evaluation and management of bone tumours. We include specific recommendations for the pre-analytical, analytical, and post-analytical phases, as well as protocols for gross and microscopic pathology. Copyright © 2016 Sociedad Española de Anatomía Patológica. Publicado por Elsevier España, S.L.U. All rights reserved.

MOLECULAR CYTOGENETICS OF LYMPHOMA. WHERE DO WE STAND IN 2010?

OpenAIRE

2011-01-01

Abstract Since approximately 20 years most malignant lymphomas are classified by the recognition of clinico-pathologic entities, each with its own combination of clinical, morphologic, immunophenotypic and molecular genetic characteristics. Obviously, in many instances molecular cytogenetics is of great help for classification and in some lymphomas it is even a prerequisite. Molecular cytogenetic alterations can be detected by a large variety of techniques, ranging from conventiona...

Evaluation of pathological features of hepatocellular carcinoma by contrast-enhanced ultrasonography: Comparison with pathology on resected specimen

International Nuclear Information System (INIS)

Ogawa, Sadanobu; Kumada, Takashi; Toyoda, Hidenori; Ichikawa, Hideo; Kawachi, Toshiaki; Otobe, Katsuhiko; Hibi, Toshio; Takeshima, Kenji; Kiriyama, Seiki; Sone, Yasuhiro; Tanikawa, Makoto; Hisanaga, Yasuhiro; Yamaguchi, Akihiro; Isogai, Masatoshi; Kaneoka, Yuji; Washizu, Junji

2006-01-01

Features of hepatocellular carcinoma (HCC) observed by contrast-enhanced ultrasonography (CEUS) were compared to pathological features of corresponding resected HCC specimens, to evaluate the ability of CEUS to depict the pathological features of HCC. We investigated 50 HCC nodules that were treated by surgical resection. All nodules had been examined by CEUS with intravenous contrast agent (Levovist) before surgery. CEUS findings were divided into three phases for evaluation and classification of enhancement patterns: two vascular phases (arterial phase and portal venous phase) and the delayed phase. Pathological examination focused on differentiation and on the presence or absence of a tumor capsule, intratumoral septum, and intratumoral necrosis. All 21 nodules that showed a linear or annular vessel around the tumor margin in the arterial phase had capsular formation. Of the 27 nodules that showed heterogeneous perfusion in the portal venous phase, 21 (77.8%) had an intratumoral septum and 23 (85.2%) showed intratumoral necrosis. All nodules that were depicted as a defect with an unclear margin in the delayed phase were well-differentiated HCCs, whereas all nodules that were depicted as a defect with a clear margin were moderately or poorly differentiated HCCs. From our observations, the arterial, portal venous, and delayed phases of CEUS could reflect different pathological aspects of HCC. Some pathological characteristics of HCC might be evaluated preoperatively and non-invasively, by means of combined analysis of three phases of CEUS findings

Molecular markers in bladder cancer: Novel research frontiers.

Science.gov (United States)

Sanguedolce, Francesca; Cormio, Antonella; Bufo, Pantaleo; Carrieri, Giuseppe; Cormio, Luigi

2015-01-01

Bladder cancer (BC) is a heterogeneous disease encompassing distinct biologic features that lead to extremely different clinical behaviors. In the last 20 years, great efforts have been made to predict disease outcome and response to treatment by developing risk assessment calculators based on multiple standard clinical-pathological factors, as well as by testing several molecular markers. Unfortunately, risk assessment calculators alone fail to accurately assess a single patient's prognosis and response to different treatment options. Several molecular markers easily assessable by routine immunohistochemical techniques hold promise for becoming widely available and cost-effective tools for a more reliable risk assessment, but none have yet entered routine clinical practice. Current research is therefore moving towards (i) identifying novel molecular markers; (ii) testing old and new markers in homogeneous patients' populations receiving homogeneous treatments; (iii) generating a multimarker panel that could be easily, and thus routinely, used in clinical practice; (iv) developing novel risk assessment tools, possibly combining standard clinical-pathological factors with molecular markers. This review analyses the emerging body of literature concerning novel biomarkers, ranging from genetic changes to altered expression of a huge variety of molecules, potentially involved in BC outcome and response to treatment. Findings suggest that some of these indicators, such as serum circulating tumor cells and tissue mitochondrial DNA, seem to be easily assessable and provide reliable information. Other markers, such as the phosphoinositide-3-kinase (PI3K)/AKT (serine-threonine kinase)/mTOR (mammalian target of rapamycin) pathway and epigenetic changes in DNA methylation seem to not only have prognostic/predictive value but also, most importantly, represent valuable therapeutic targets. Finally, there is increasing evidence that the development of novel risk assessment tools

The rise of a novel classification system for endometrial carcinoma; integration of molecular subclasses.

Science.gov (United States)

McAlpine, Jessica; Leon-Castillo, Alicia; Bosse, Tjalling

2018-04-01

Endometrial cancer is a clinically heterogeneous disease and it is becoming increasingly clear that this heterogeneity may be a function of the diversity of the underlying molecular alterations. Recent large-scale genomic studies have revealed that endometrial cancer can be divided into at least four distinct molecular subtypes, with well-described underlying genomic aberrations. These subtypes can be reliably delineated and carry significant prognostic as well as predictive information; embracing and incorporating them into clinical practice is thus attractive. The road towards the integration of molecular features into current classification systems is not without obstacles. Collaborative studies engaging research teams from across the world are working to define pragmatic assays, improve risk stratification systems by combining molecular features and traditional clinicopathological parameters, and determine how molecular classification can be optimally utilized to direct patient care. Pathologists and clinicians caring for women with endometrial cancer need to engage with and understand the possibilities and limitations of this new approach, because integration of molecular classification of endometrial cancers is anticipated to become an essential part of gynaecological pathology practice. This review will describe the challenges in current systems of endometrial carcinoma classification, the evolution of new molecular technologies that define prognostically distinct molecular subtypes, and potential applications of molecular classification as a step towards precision medicine and refining care for individuals with the most common gynaecological cancer in the developed world. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

A Century of Plant Pathology: A Retrospective View on Understanding Host-Parasite Interactions.

Science.gov (United States)

Keen, N T

2000-09-01

▪ Abstract  The twentieth century has been productive for the science of plant pathology and the field of host-parasite interactions-both in understanding how pathogens and plant defense work and in developing more effective means of disease control. Early in the twentieth century, plant pathology adopted a philosophy that encouraged basic scientific investigation of pathogens and disease defense. That philosophy led to the strategy of developing disease-resistant plants as a prima facie disease-control measure-and in the process saved billions of dollars and avoided the use of tons of pesticides. Plant pathology rapidly adopted molecular cloning and its spin-off technologies, and these have fueled major advances in our basic understanding of plant diseases. This knowledge and the development of efficient technologies for producing transgenic plants convey optimism that plant diseases will be more efficiently controlled in the twenty-first century.

Molecular classification of endometrial carcinoma on diagnostic specimens is highly concordant with final hysterectomy: Earlier prognostic information to guide treatment.

Science.gov (United States)

Talhouk, Aline; Hoang, Lien N; McConechy, Melissa K; Nakonechny, Quentin; Leo, Joyce; Cheng, Angela; Leung, Samuel; Yang, Winnie; Lum, Amy; Köbel, Martin; Lee, Cheng-Han; Soslow, Robert A; Huntsman, David G; Gilks, C Blake; McAlpine, Jessica N

2016-10-01

Categorization and risk stratification of endometrial carcinomas is inadequate; histomorphologic assessment shows considerable interobserver variability, and risk of metastases and recurrence can only be derived after surgical staging. We have developed a Proactive Molecular Risk classification tool for Endometrial cancers (ProMisE) that identifies four distinct prognostic subgroups. Our objective was to assess whether molecular classification could be performed on diagnostic endometrial specimens obtained prior to surgical staging and its concordance with molecular classification performed on the subsequent hysterectomy specimen. Sequencing of tumors for exonuclease domain mutations (EDMs) in POLE and immunohistochemistry for mismatch repair (MMR) proteins and p53 were applied to both pre- and post-staging archival specimens from 60 individuals to identify four molecular subgroups: MMR-D, POLE EDM, p53 wild type, p53 abn (abnormal). Three gynecologic subspecialty pathologists assigned histotype and grade to a subset of samples. Concordance of molecular and clinicopathologic subgroup assignments were determined, comparing biopsy/curetting to hysterectomy specimens. Complete molecular and pathologic categorization was achieved in 57 cases. Concordance metrics for pre- vs. post-staging endometrial samples categorized by ProMisE were highly favorable; average per ProMisE class sensitivity(0.9), specificity(0.96), PPV(0.9), NPV(0.96) and kappa statistic 0.86(95%CI, 0.72-0.93), indicating excellent agreement. We observed the highest level of concordance for 'p53 abn' tumors, the group associated with the worst prognosis. In contrast, grade and histotype assignment from original pathology reports pre- vs. post-staging showed only moderate levels of agreement (kappa=0.55 and 0.44 respectively); even with subspecialty pathology review only moderate levels of agreement were observed. Molecular classification can be achieved on diagnostic endometrial samples and accurately

VEGF-A, cytoskeletal dynamics, and the pathological vascular phenotype

International Nuclear Information System (INIS)

Nagy, Janice A.; Senger, Donald R.

2006-01-01

Normal angiogenesis is a complex process involving the organization of proliferating and migrating endothelial cells (ECs) into a well-ordered and highly functional vascular network. In contrast, pathological angiogenesis, which is a conspicuous feature of tumor growth, ischemic diseases, and chronic inflammation, is characterized by vessels with aberrant angioarchitecture and compromised barrier function. Herein we review the subject of pathological angiogenesis, particularly that driven by vascular endothelial growth factor (VEGF-A), from a new perspective. We propose that the serious structural and functional anomalies associated with VEGF-A-elicited neovessels, reflect, at least in part, imbalances in the internal molecular cues that govern the ordered assembly of ECs into three dimensional vascular networks and preserve vessel barrier function. Adopting such a viewpoint widens the focus from solely on specific pro-angiogenic stimuli such as VEGF-A to include a key set of cytoskeletal regulatory molecules, the Rho GTPases, which are known to direct multiple aspects of vascular morphogenesis including EC motility, alignment, multi-cellular organization, as well as intercellular junction integrity. We offer this perspective to draw attention to the importance of endothelial cytoskeletal dynamics for proper neovascularization and to suggest new therapeutic strategies with the potential to improve the pathological vascular phenotype

Molecular epidemiology of mastitis pathogens of dairy cattle and comparative relevance to humans.

Science.gov (United States)

Zadoks, Ruth N; Middleton, John R; McDougall, Scott; Katholm, Jorgen; Schukken, Ynte H

2011-12-01

Mastitis, inflammation of the mammary gland, can be caused by a wide range of organisms, including gram-negative and gram-positive bacteria, mycoplasmas and algae. Many microbial species that are common causes of bovine mastitis, such as Escherichia coli, Klebsiella pneumoniae, Streptococcus agalactiae and Staphylococcus aureus also occur as commensals or pathogens of humans whereas other causative species, such as Streptococcus uberis, Streptococcus dysgalactiae subsp. dysgalactiae or Staphylococcus chromogenes, are almost exclusively found in animals. A wide range of molecular typing methods have been used in the past two decades to investigate the epidemiology of bovine mastitis at the subspecies level. These include comparative typing methods that are based on electrophoretic banding patterns, library typing methods that are based on the sequence of selected genes, virulence gene arrays and whole genome sequencing projects. The strain distribution of mastitis pathogens has been investigated within individual animals and across animals, herds, countries and host species, with consideration of the mammary gland, other animal or human body sites, and environmental sources. Molecular epidemiological studies have contributed considerably to our understanding of sources, transmission routes, and prognosis for many bovine mastitis pathogens and to our understanding of mechanisms of host-adaptation and disease causation. In this review, we summarize knowledge gleaned from two decades of molecular epidemiological studies of mastitis pathogens in dairy cattle and discuss aspects of comparative relevance to human medicine.

Comparison of Pathologic Response Evaluation Systems after Anthracycline with/without Taxane-Based Neoadjuvant Chemotherapy among Different Subtypes of Breast Cancers.

Directory of Open Access Journals (Sweden)

Hee Jin Lee

Full Text Available Several methods are used to assess the pathologic response of breast cancer after neoadjuvant chemotherapy (NAC to predict clinical outcome. However, the clinical utility of these systems for each molecular subtype of breast cancer is unclear. Therefore, we applied six pathologic response assessment systems to specific subtypes of breast cancer and compared the results.Five hundred and eighty eight breast cancer patients treated with anthracycline with/without taxane-based NAC were retrospectively analyzed, and the ypTNM stage, residual cancer burden (RCB, residual disease in breast and nodes (RDBN, tumor response ratio, Sataloff's classification, and Miller-Payne grading system were evaluated. The results obtained for each assessment system were analyzed in terms of patient survival.In triple-negative tumors, all systems were significantly associated with disease-free survival and Kaplan-Meier survival curves for disease-free survival were clearly separated by all assessment methods. For HR+/HER2- tumors, systems assessing the residual tumor (ypTNM stage, RCB, and RDBN had prognostic significance. However, for HER2+ tumors, the association between patient survival and the pathologic response assessment results varied according to the system used, and none resulted in distinct Kaplan-Meier curves.Most of the currently available pathologic assessment systems used after anthracycline with/without taxane-based NAC effectively classified triple-negative breast cancers into groups showing different prognoses. The pathologic assessment systems evaluating residual tumors only also had prognostic significance in HR+/HER2- tumors. However, new assessment methods are required to effectively evaluate the pathologic response of HR+/HER2+ and HR-/HER2+ tumors to anthracycline with/without taxane-based NAC.

Pharmacokinetics of Active Components From Guhong Injection in Normal and Pathological Rat Models of Cerebral Ischemia: A Comparative Study

Directory of Open Access Journals (Sweden)

Li Yu

2018-05-01

Full Text Available Background and Objectives: Guhong Injection (GHI is usually administered for the treatment of stroke in clinics. Aceglutamide and hydroxyl safflower yellow A (HSYA are its key ingredients for brain protective effect. To investigate the pharmacokinetics of aceglutamide and HSYA under pathological and normal conditions, the pharmacokinetic parameters and characteristics of middle cerebral artery occlusion (MCAO and normal rats given the same dosage of GHI were studied compared.Methods: 12 SD rats were divided into two groups, namely, MCAO and normal groups. Both groups were treated with GHI in the same dosage. Plasma samples were collected from the jaw vein at different time points and subsequently tested by high-performance liquid chromatography (HPLC.Results: After administration of GHI, both aceglutamide and HSYA were immediately detected in the plasma. Ninety percent of aceglutamide and HSYA was eliminated within 3 h. For aceglutamide, statistically significant differences in the parameters including AUC(0−t, AUC(0−∞, AUMC(0−t, AUMC(0−∞, Cmax (P < 0.01, and Vz (P < 0.05. Meanwhile, compared with the MCAO group, in the normal group, the values of AUC(0−t, AUMC(0−t, VRT(0−t, and Cmax (P < 0.01 for HSYA were significantly higher, whereas the value of MRT(0−t was significantly lower in the normal group.Conclusions: The in vivo trials based on the different models showed that, the pharmacokinetic behaviors and parameters of aceglutamide and HSYA in GHI were completely different. These results suggest that the pathological damage of ischemia-reperfusion has a significant impact on the pharmacokinetic traits of aceglutamide and HSYA.

Comparative studies on molecular structure, vibrational spectra and hyperpolarizabilies of NLO chromophore Ethyl 4-Dimethylaminobenzoate

Science.gov (United States)

Amalanathan, M.; Jasmine, G. Femina; Roy, S. Dawn Dharma

2017-08-01

The molecular structure, vibrational spectra and polarizabilities of Ethyl 4-Dimethylaminobenzoate (EDAB) was investigated by density functional theory employing Becke's three parameter hybrid exchange functional with Lee-Yang-Parr (B3LYP) co-relational functional involving 6-311++G(d,p) basis set and compared with some other levels. A detailed interpretation of the IR and Raman spectra of EDBA have been reported and analyzed. Complete vibrational assignments of the vibrational modes have been done on the basis of the potential energy distribution (TED) using VEDA software. The molecular electrostatic potential mapped onto total density surface has been obtained. A study on the electronic properties, such as absorption wavelength, and frontier molecular orbitals energy, was performed using DFT approach. The stability of the molecule arising from hyper conjugative interactions and accompanying charge delocalization has been analyzed using natural bond orbital (NBO) analysis. The natural and Mulliken charge also calculated and compared with different level of calculation. The dipole moment, polarizability and first, second order hyperpolarizabilities of the title molecule were calculated and compared with the experimental values. The energy gap between frontier orbitals has been used along with electric moments and first order hyperpolarizability, to understand the non linear optical (NLO) activity of the molecule. The NLO activity of molecule was confirmed by SHG analysis.

PATHOLOGICAL AND MOLECULAR GENETIC STUDIES ON SOME SOYBEAN MUTANTS INDUCED BY GAMMA RAYS IN RELATION TO CHARCOAL ROT DISEASE

International Nuclear Information System (INIS)

ASHRY, N.A.; EL-DEMERDASH, H.M.; ABD EL-RAHMAN, S.S.

2008-01-01

The Egyptian soybean cultivar Giza-22 was used to induce resistant mutants for charcoal rot disease using gamma rays. Sixteen mutants and their parental cultivar were evaluated in M3 generation for their agronomic traits and for resistance to charcoal rot disease. Four mutants showed superiority in their agronomic traits as compared with their parental cultivar. Three mutants were significantly resistant to the disease than their parental cultivar (Giza-22). These three resistant mutants showed non-significant improvement in their agronomic traits as compared with Giza-22 cultivar. DNA extractions from the three resistant mutants and their parent were used to test the differences on the molecular level. Seven random amplified polymorphic DNA (RAPD) primers were used to detect RAPD markers related to charcoal rot resistance in soybean, and to differentiate these mutants. Six RAPD-primers showed molecular markers associated with resistance to charcoal rot in soybean, where five RAPD-primers could differentiate each of the three mutants from each other and from their parental cultivar

Pathology in Undergraduate Training Program

Directory of Open Access Journals (Sweden)

Shiva Raj K.C.

2018-04-01

Full Text Available Pathology is a study of disease which deals with etiology, pathogenesis and morphological features and the associated clinical features. Pathology acts as a bridge that fills the gap between basic sciences and clinical medicine. With proper understanding of pathological processes, one can understand the disease process. In Nepal, since the beginning of medical school teaching, Pathology as a basic science discipline and is a component of the preclinical medical school curriculum.Pathology teaching in 19th century was vague, disorganized and very little, though precious. The lectures used to be conducted by surgeons. At Barts, surgeon Sir James Paget had taught surgical pathology. The real revolution in pathology teaching began in the early 1900s when, spurred on by increasing understanding of disease mechanisms, pathology began to be accepted as a specialty in its own right.During the early and mid of 20th century, pathology teaching was a part of clinical teaching with daily, autopsy demonstration. By the late 1980s, significant change had taken place. In many medical schools, debate started regarding relevance of vigorous preclinical teaching. Then system-based approach was incorporated and traditional preclinical course had been abandoned. With this pathology teaching also began to change with pathologists being involved in teaching histology, often alongside pathology to highlight its clinical relevance. In medical schools the pathology teaching time was cut. Autopsy demonstrations, which had been so popular with generations of medical students, were becoming irregular and less well attended.Though teaching of pathology in blocks to ‘avoid fragmentation’ has disappeared in western countries; it is still practice in Nepal. In western countries there was traditional practice of teaching general pathology in the first two years and systemic pathology in the clinical years. Now pathology teaching is integrated throughout the course. A

Panning artifacts in digital pathology images

Science.gov (United States)

Avanaki, Ali R. N.; Lanciault, Christian; Espig, Kathryn S.; Xthona, Albert; Kimpe, Tom R. L.

2017-03-01

In making a pathologic diagnosis, a pathologist uses cognitive processes: perception, attention, memory, and search (Pena and Andrade-Filho, 2009). Typically, this involves focus while panning from one region of a slide to another, using either a microscope in a traditional workflow or software program and display in a digital pathology workflow (DICOM Standard Committee, 2010). We theorize that during panning operation, the pathologist receives information important to diagnosis efficiency and/or correctness. As compared to an optical microscope, panning in a digital pathology image involves some visual artifacts due to the following: (i) the frame rate is finite; (ii) time varying visual signals are reconstructed using imperfect zero-order hold. Specifically, after pixel's digital drive is changed, it takes time for a pixel to emit the expected amount of light. Previous work suggests that 49% of navigation is conducted in low-power/overview with digital pathology (Molin et al., 2015), but the influence of display factors has not been measured. We conducted a reader study to establish a relationship between display frame rate, panel response time, and threshold panning speed (above which the artifacts become noticeable). Our results suggest visual tasks that involve tissue structure are more impacted by the simulated panning artifacts than those that only involve color (e.g., staining intensity estimation), and that the panning artifacts versus normalized panning speed has a peak behavior which is surprising and may change for a diagnostic task. This is work in progress and our final findings should be considered in designing future digital pathology systems.

Increased Pathological Worry Levels in Patients with Alopecia Areata

Directory of Open Access Journals (Sweden)

Basak Sahin

2017-01-01

Full Text Available Aim: Alopecia Areata (AA is a type of hair loss that has been considered to have associations with various psychiatric disorders. In this study, we aimed to compare pathological worry levels between patients with AA and healthy controls (HC. Material and Method: Sixty-three patients with AA and 90 HCs were included in the present study after applying inclusion and exclusion criteria. The socio-demographic characteristics, some clinical characteristics, and the scores from the Penn State Worry Questionnaire (PSWQ were compared between groups. Results: The demographic characteristics were found to be similar between groups except for gender. The family history of AA was significantly higher in the AA group. The mean score of PSWQ in the AA group was 44.02 ± 11.59, compared to 39.71 ± 7.77 in the HC group. The mean score of PSWQ was significantly higher in the AA group (t=-3.27, p= 0.001.Discussion: The present study is the first to compare pathological worry between patients with AA and HCs. We suggest that pathological worry should be more thoroughly investigated in patients with AA to improve their quality of life. Also, this can be an effective approach to targeting the patients who may develop anxiety disorder.

Quantitative image variables reflect the intratumoral pathologic heterogeneity of lung adenocarcinoma.

Science.gov (United States)

Choi, E-Ryung; Lee, Ho Yun; Jeong, Ji Yun; Choi, Yoon-La; Kim, Jhingook; Bae, Jungmin; Lee, Kyung Soo; Shim, Young Mog

2016-10-11

We aimed to compare quantitative radiomic parameters from dual-energy computed tomography (DECT) of lung adenocarcinoma and pathologic complexity.A total 89 tumors with clinical stage I/II lung adenocarcinoma were prospectively included. Fifty one radiomic features were assessed both from iodine images and non-contrast images of DECT datasets. Comprehensive histologic subtyping was evaluated with all surgically resected tumors. The degree of pathologic heterogeneity was assessed using pathologic index and the number of mixture histologic subtypes in a tumor. Radiomic parameters were correlated with pathologic index. Tumors were classified as three groups according to the number of mixture histologic subtypes and radiomic parameters were compared between the three groups.Tumor density and 50th through 97.5th percentile Hounsfield units (HU) of histogram on non-contrast images showed strong correlation with the pathologic heterogeneity. Radiomic parameters including 75th and 97.5th percentile HU of histogram, entropy, and inertia on 1-, 2- and 3 voxel distance on non-contrast images showed incremental changes while homogeneity showed detrimental change according to the number of mixture histologic subtypes (all Ps heterogeneity, which may help in the prediction of intratumoral heterogeneity of the whole tumor.

Correlations of behavioral deficits with brain pathology assessed through longitudinal MRI and histopathology in the R6/1 mouse model of Huntington's disease.

Directory of Open Access Journals (Sweden)

Ivan Rattray

Full Text Available Huntington's disease (HD is caused by the expansion of a CAG repeat in the huntingtin (HTT gene. The R6 mouse models of HD express a mutant version of exon 1 HTT and typically develop motor and cognitive impairments, a widespread huntingtin (HTT aggregate pathology and brain atrophy. Unlike the more commonly used R6/2 mouse line, R6/1 mice have fewer CAG repeats and, subsequently, a less rapid pathological decline. Compared to the R6/2 line, fewer descriptions of the progressive pathologies exhibited by R6/1 mice exist. The association between the molecular and cellular neuropathology with brain atrophy, and with the development of behavioral phenotypes remains poorly understood in many models of HD. In attempt to link these factors in the R6/1 mouse line, we have performed detailed assessments of behavior and of regional brain abnormalities determined through longitudinal, in vivo magnetic resonance imaging (MRI, as well as an end-stage, ex vivo MRI study and histological assessment. We found progressive decline in both motor and non-motor related behavioral tasks in R6/1 mice, first evident at 11 weeks of age. Regional brain volumes were generally unaffected at 9 weeks, but by 17 weeks there was significant grey matter atrophy. This age-related brain volume loss was validated using a more precise, semi-automated Tensor Based morphometry assessment. As well as these clear progressive phenotypes, mutant HTT (mHTT protein, the hallmark of HD molecular pathology, was widely distributed throughout the R6/1 brain and was accompanied by neuronal loss. Despite these seemingly concomitant, robust pathological phenotypes, there appeared to be little correlation between the three main outcome measures: behavioral performance, MRI-detected brain atrophy and histopathology. In conclusion, R6/1 mice exhibit many features of HD, but the underlying mechanisms driving these clear behavioral disturbances and the brain volume loss, still remain unclear.

Progressive Motor Neuron Pathology and the Role of Astrocytes in a Human Stem Cell Model of VCP-Related ALS

Directory of Open Access Journals (Sweden)

Claire E. Hall

2017-05-01

Full Text Available Motor neurons (MNs and astrocytes (ACs are implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS, but their interaction and the sequence of molecular events leading to MN death remain unresolved. Here, we optimized directed differentiation of induced pluripotent stem cells (iPSCs into highly enriched (> 85% functional populations of spinal cord MNs and ACs. We identify significantly increased cytoplasmic TDP-43 and ER stress as primary pathogenic events in patient-specific valosin-containing protein (VCP-mutant MNs, with secondary mitochondrial dysfunction and oxidative stress. Cumulatively, these cellular stresses result in synaptic pathology and cell death in VCP-mutant MNs. We additionally identify a cell-autonomous VCP-mutant AC survival phenotype, which is not attributable to the same molecular pathology occurring in VCP-mutant MNs. Finally, through iterative co-culture experiments, we uncover non-cell-autonomous effects of VCP-mutant ACs on both control and mutant MNs. This work elucidates molecular events and cellular interplay that could guide future therapeutic strategies in ALS.

Structure of sulfamidase provides insight into the molecular pathology of mucopolysaccharidosis IIIA

International Nuclear Information System (INIS)

Sidhu, Navdeep S.; Schreiber, Kathrin; Pröpper, Kevin; Becker, Stefan; Usón, Isabel; Sheldrick, George M.; Gärtner, Jutta; Krätzner, Ralph; Steinfeld, Robert

2014-01-01

Mucopolysaccharidosis IIIA is a fatal neurodegenerative disease that typically manifests itself in childhood and is caused by mutations in the gene for the lysosomal enzyme sulfamidase. The first structure of this enzyme is presented, which provides insight into the molecular basis of disease-causing mutations, and the enzymatic mechanism is proposed. Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). More than 100 mutations in the SGSH gene have been found to reduce or eliminate its enzymatic activity. However, the molecular understanding of the effect of these mutations has been confined by a lack of structural data for this enzyme. Here, the crystal structure of glycosylated SGSH is presented at 2 Å resolution. Despite the low sequence identity between this unique N-sulfatase and the group of O-sulfatases, they share a similar overall fold and active-site architecture, including a catalytic formylglycine, a divalent metal-binding site and a sulfate-binding site. However, a highly conserved lysine in O-sulfatases is replaced in SGSH by an arginine (Arg282) that is positioned to bind the N-linked sulfate substrate. The structure also provides insight into the diverse effects of pathogenic mutations on SGSH function in mucopolysaccharidosis type IIIA and convincing evidence for the molecular consequences of many missense mutations. Further, the molecular characterization of SGSH mutations will lay the groundwork for the development of structure-based drug design for this devastating neurodegenerative disorder

Structure of sulfamidase provides insight into the molecular pathology of mucopolysaccharidosis IIIA

Energy Technology Data Exchange (ETDEWEB)

Sidhu, Navdeep S. [University of Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen (Germany); University of Göttingen, Tammannstrasse 4, 37077 Göttingen (Germany); Schreiber, Kathrin [University of Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen (Germany); Pröpper, Kevin [University of Göttingen, Tammannstrasse 4, 37077 Göttingen (Germany); Becker, Stefan [Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen (Germany); Usón, Isabel [Instituto de Biologia Molecular de Barcelona (IBMB–CSIC), Barcelona Science Park, Baldiri Reixach 15, 08028 Barcelona (Spain); Institucio Catalana de Recerca i Estudis Avancats (ICREA), (Spain); Sheldrick, George M. [University of Göttingen, Tammannstrasse 4, 37077 Göttingen (Germany); Gärtner, Jutta; Krätzner, Ralph, E-mail: rkraetz@gwdg.de; Steinfeld, Robert, E-mail: rkraetz@gwdg.de [University of Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen (Germany)

2014-05-01

Mucopolysaccharidosis IIIA is a fatal neurodegenerative disease that typically manifests itself in childhood and is caused by mutations in the gene for the lysosomal enzyme sulfamidase. The first structure of this enzyme is presented, which provides insight into the molecular basis of disease-causing mutations, and the enzymatic mechanism is proposed. Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). More than 100 mutations in the SGSH gene have been found to reduce or eliminate its enzymatic activity. However, the molecular understanding of the effect of these mutations has been confined by a lack of structural data for this enzyme. Here, the crystal structure of glycosylated SGSH is presented at 2 Å resolution. Despite the low sequence identity between this unique N-sulfatase and the group of O-sulfatases, they share a similar overall fold and active-site architecture, including a catalytic formylglycine, a divalent metal-binding site and a sulfate-binding site. However, a highly conserved lysine in O-sulfatases is replaced in SGSH by an arginine (Arg282) that is positioned to bind the N-linked sulfate substrate. The structure also provides insight into the diverse effects of pathogenic mutations on SGSH function in mucopolysaccharidosis type IIIA and convincing evidence for the molecular consequences of many missense mutations. Further, the molecular characterization of SGSH mutations will lay the groundwork for the development of structure-based drug design for this devastating neurodegenerative disorder.

Comparative evaluation of differential laser-induced perturbation spectroscopy as a technique to discriminate emerging skin pathology

Science.gov (United States)

Kozikowski, Raymond T.; Smith, Sarah E.; Lee, Jennifer A.; Castleman, William L.; Sorg, Brian S.; Hahn, David W.

2012-06-01

Fluorescence spectroscopy has been widely investigated as a technique for identifying pathological tissue; however, unrelated subject-to-subject variations in spectra complicate data analysis and interpretation. We describe and evaluate a new biosensing technique, differential laser-induced perturbation spectroscopy (DLIPS), based on deep ultraviolet (UV) photochemical perturbation in combination with difference spectroscopy. This technique combines sequential fluorescence probing (pre- and post-perturbation) with sub-ablative UV perturbation and difference spectroscopy to provide a new spectral dimension, facilitating two improvements over fluorescence spectroscopy. First, the differential technique eliminates significant variations in absolute fluorescence response within subject populations. Second, UV perturbations alter the extracellular matrix (ECM), directly coupling the DLIPS response to the biological structure. Improved biosensing with DLIPS is demonstrated in vivo in a murine model of chemically induced skin lesion development. Component loading analysis of the data indicates that the DLIPS technique couples to structural proteins in the ECM. Analysis of variance shows that DLIPS has a significant response to emerging pathology as opposed to other population differences. An optimal likelihood ratio classifier for the DLIPS dataset shows that this technique holds promise for improved diagnosis of epithelial pathology. Results further indicate that DLIPS may improve diagnosis of tissue by augmenting fluorescence spectra (i.e. orthogonal sensing).

Molecular MR imaging

International Nuclear Information System (INIS)

Fleige, G.; Hamm, B.

2000-01-01

Basic medicobiological research in recent years has made rapid advances in the functional understanding of normal and pathological processes down to the molecular level. At the same time, various imaging modalities have developed from the depiction of organs to approaching the depiction of the cellular level and are about to make the visualization of molecular processes an established procedure. Besides other modalities like PET and near-infrared fluorescence, MR imaging offers some promising options for molecular imaging as well as some applications that have already been tested such as the visualization of enzyme activity, the depiction of the expression of certain genes, the visualization of surface receptors, or the specific demonstration of cells involved in the body's immune response. A major advantage of molecular magnetic resonance imaging (mMRI) over other more sensitive modalities is its high spatial resolution. However, the establishment of mMRI crucially relies on further improvements in resolution and the development of molecular markers for improving its sensitivity and specificity. The state of the art of mMRI is presented by giving a survey of the literature on experimental studies and reporting the results our study group obtained during investigation on gliomas. (orig.) [de

Mammary gland pathologies in the parturient buffalo

Directory of Open Access Journals (Sweden)

G N Purohit

2014-12-01

Full Text Available Parturition related mammary gland pathologies in the buffalo appear to be low on accord of anatomic (longer teat length, thicker streak canal and physiologic (lower cisternal storage of secreted milk, lower milk production differences with cattle. Hemolactia, udder edema and hypogalactia usually occur in the buffalo due to physiologic changes around parturition however mastitis involves pathologic changes in the udder and teats; the incidence of mastitis is however lower compared to cattle. The incidence and therapy of hemolactia, udder edema and hypogalactia are mentioned and the risk factors, incidence, diagnosis, therapy and prevention for mastitis in buffalo are also described.

Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome.

Science.gov (United States)

Tothill, Richard W; Tinker, Anna V; George, Joshy; Brown, Robert; Fox, Stephen B; Lade, Stephen; Johnson, Daryl S; Trivett, Melanie K; Etemadmoghadam, Dariush; Locandro, Bianca; Traficante, Nadia; Fereday, Sian; Hung, Jillian A; Chiew, Yoke-Eng; Haviv, Izhak; Gertig, Dorota; DeFazio, Anna; Bowtell, David D L

2008-08-15

The study aim to identify novel molecular subtypes of ovarian cancer by gene expression profiling with linkage to clinical and pathologic features. Microarray gene expression profiling was done on 285 serous and endometrioid tumors of the ovary, peritoneum, and fallopian tube. K-means clustering was applied to identify robust molecular subtypes. Statistical analysis identified differentially expressed genes, pathways, and gene ontologies. Laser capture microdissection, pathology review, and immunohistochemistry validated the array-based findings. Patient survival within k-means groups was evaluated using Cox proportional hazards models. Class prediction validated k-means groups in an independent dataset. A semisupervised survival analysis of the array data was used to compare against unsupervised clustering results. Optimal clustering of array data identified six molecular subtypes. Two subtypes represented predominantly serous low malignant potential and low-grade endometrioid subtypes, respectively. The remaining four subtypes represented higher grade and advanced stage cancers of serous and endometrioid morphology. A novel subtype of high-grade serous cancers reflected a mesenchymal cell type, characterized by overexpression of N-cadherin and P-cadherin and low expression of differentiation markers, including CA125 and MUC1. A poor prognosis subtype was defined by a reactive stroma gene expression signature, correlating with extensive desmoplasia in such samples. A similar poor prognosis signature could be found using a semisupervised analysis. Each subtype displayed distinct levels and patterns of immune cell infiltration. Class prediction identified similar subtypes in an independent ovarian dataset with similar prognostic trends. Gene expression profiling identified molecular subtypes of ovarian cancer of biological and clinical importance.

Temporal Patterns of Fatigue Predict Pathologic Response in Patients Treated With Preoperative Chemoradiation Therapy for Rectal Cancer

International Nuclear Information System (INIS)

Park, Hee Chul; Janjan, Nora A.; Mendoza, Tito R.; Lin, Edward H.; Vadhan-Raj, Saroj; Hundal, Mandeep; Zhang Yiqun; Delclos, Marc E.; Crane, Christopher H.; Das, Prajnan; Wang, Xin Shelley; Cleeland, Charles S.; Krishnan, Sunil

2009-01-01

Purpose: To investigate whether symptom burden before and during preoperative chemoradiation therapy (CRT) for rectal cancer predicts for pathologic tumor response. Methods and Materials: Fifty-four patients with T3/T4/N+ rectal cancers were treated on a Phase II trial using preoperative capecitabine and concomitant boost radiotherapy. Symptom burden was prospectively assessed before (baseline) and weekly during CRT by patient self-reported questionnaires, the MD Anderson Symptom Inventory (MDASI), and Brief Fatigue Inventory (BFI). Survival probabilities were estimated using the Kaplan-Meier method. Symptom scores according to tumor downstaging (TDS) were compared using Student's t tests. Logistic regression was used to determine whether symptom burden levels predicted for TDS. Lowess curves were plotted for symptom burden across time. Results: Among 51 patients evaluated for pathologic response, 26 patients (51%) had TDS. Fatigue, pain, and drowsiness were the most common symptoms. All symptoms increased progressively during treatment. Patients with TDS had lower MDASI fatigue scores at baseline and at completion (Week 5) of CRT (p = 0.03 for both) and lower levels of BFI 'usual fatigue' at baseline. Conclusion: Lower levels of fatigue at baseline and completion of CRT were significant predictors of pathologic tumor response gauged by TDS, suggesting that symptom burden may be a surrogate for tumor burden. The relationship between symptom burden and circulating cytokines merits evaluation to characterize the molecular basis of this phenomenon.

Whole Genome Sequencing Increases Molecular Diagnostic Yield Compared with Current Diagnostic Testing for Inherited Retinal Disease.

Science.gov (United States)

Ellingford, Jamie M; Barton, Stephanie; Bhaskar, Sanjeev; Williams, Simon G; Sergouniotis, Panagiotis I; O'Sullivan, James; Lamb, Janine A; Perveen, Rahat; Hall, Georgina; Newman, William G; Bishop, Paul N; Roberts, Stephen A; Leach, Rick; Tearle, Rick; Bayliss, Stuart; Ramsden, Simon C; Nemeth, Andrea H; Black, Graeme C M

2016-05-01

To compare the efficacy of whole genome sequencing (WGS) with targeted next-generation sequencing (NGS) in the diagnosis of inherited retinal disease (IRD). Case series. A total of 562 patients diagnosed with IRD. We performed a direct comparative analysis of current molecular diagnostics with WGS. We retrospectively reviewed the findings from a diagnostic NGS DNA test for 562 patients with IRD. A subset of 46 of 562 patients (encompassing potential clinical outcomes of diagnostic analysis) also underwent WGS, and we compared mutation detection rates and molecular diagnostic yields. In addition, we compared the sensitivity and specificity of the 2 techniques to identify known single nucleotide variants (SNVs) using 6 control samples with publically available genotype data. Diagnostic yield of genomic testing. Across known disease-causing genes, targeted NGS and WGS achieved similar levels of sensitivity and specificity for SNV detection. However, WGS also identified 14 clinically relevant genetic variants through WGS that had not been identified by NGS diagnostic testing for the 46 individuals with IRD. These variants included large deletions and variants in noncoding regions of the genome. Identification of these variants confirmed a molecular diagnosis of IRD for 11 of the 33 individuals referred for WGS who had not obtained a molecular diagnosis through targeted NGS testing. Weighted estimates, accounting for population structure, suggest that WGS methods could result in an overall 29% (95% confidence interval, 15-45) uplift in diagnostic yield. We show that WGS methods can detect disease-causing genetic variants missed by current NGS diagnostic methodologies for IRD and thereby demonstrate the clinical utility and additional value of WGS. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Dopamine release in ventral striatum of pathological gamblers losing money

DEFF Research Database (Denmark)

Linnet, J; Peterson, E; Doudet, D J

2010-01-01

Linnet J, Peterson E, Doudet DJ, Gjedde A, Møller A. Dopamine release in ventral striatum of pathological gamblers losing money. Objective: To investigate dopaminergic neurotransmission in relation to monetary reward and punishment in pathological gambling. Pathological gamblers (PG) often continue...... gambling despite losses, known as 'chasing one's losses'. We therefore hypothesized that losing money would be associated with increased dopamine release in the ventral striatum of PG compared with healthy controls (HC). Method: We used Positron Emission Tomography (PET) with [(11)C]raclopride to measure...... dopamine release in the ventral striatum of 16 PG and 15 HC playing the Iowa Gambling Task (IGT). Results: PG who lost money had significantly increased dopamine release in the left ventral striatum compared with HC. PG and HC who won money did not differ in dopamine release. Conclusion: Our findings...

APOEε2 is associated with milder clinical and pathological Alzheimer's disease

Science.gov (United States)

Serrano-Pozo, Alberto; Qian, Jing; Monsell, Sarah E.; Betensky, Rebecca A.; Hyman, Bradley T.

2015-01-01

Objective The Alzheimer disease (AD) APOEε4 risk allele associates with an earlier age of onset and increased amyloid-β deposition, whereas the protective APOEε2 allele delays the onset and appears to prevent amyloid-β deposition. Yet the clinical and pathological effects of APOEε2 remain uncertain because of its relative rarity. We investigated the effects of APOE ε2 and ε4 alleles on AD pathology and cognition in a large US dataset of well characterized AD patients. Methods We studied individuals from the National Alzheimer's Coordinating Center (NACC) autopsy cohort across the entire clinico-pathological continuum of AD. Multivariable models were built to examine the associations between APOE alleles and AD neuropathological changes, using the APOEε3/ε3 group as comparator. Mediation analysis was used to estimate the direct and indirect effects of APOE alleles on AD pathology and cognition (CDR-SOB and MMSE). Results Compared to APOEε3/ε3, APOEε2 is independently associated with lower Braak NFT stages and, possibly, fewer neuritic plaques, but has no direct effect on CAA severity, whereas APOEε4 is associated with more neuritic plaques and CAA, but has no independent effect on Braak NFT stage. Unadjusted analyses showed marked differences among APOE genotypes with respect to cognitive performance (ε2>ε3>ε4). Mediation analysis suggests that this is largely explained through effects on pathology. Interpretation Even when adjusted for age of onset, symptom duration and other demographic variables, APOEε2 is associated with milder AD pathology and less severe antemortem cognitive impairment compared to APOE ε3 and ε4 alleles, suggesting a relative neuroprotective effect of APOEε2 in AD. PMID:25623662

BRCA mutations and their influence on pathological complete response and prognosis in a clinical cohort of neoadjuvantly treated breast cancer patients.

Science.gov (United States)

Wunderle, Marius; Gass, Paul; Häberle, Lothar; Flesch, Vivien M; Rauh, Claudia; Bani, Mayada R; Hack, Carolin C; Schrauder, Michael G; Jud, Sebastian M; Emons, Julius; Erber, Ramona; Ekici, Arif B; Hoyer, Juliane; Vasileiou, Georgia; Kraus, Cornelia; Reis, Andre; Hartmann, Arndt; Lux, Michael P; Beckmann, Matthias W; Fasching, Peter A; Hein, Alexander

2018-05-03

BRCA1/2 mutations influence the molecular characteristics and the effects of systemic treatment of breast cancer. This study investigates the impact of germline BRCA1/2 mutations on pathological complete response and prognosis in patients receiving neoadjuvant systemic chemotherapy. Breast cancer patients were tested for a BRCA1/2 mutation in clinical routine work and were treated with anthracycline-based or platinum-based neoadjuvant chemotherapy between 1997 and 2015. These patients were identified in the tumor registry of the Breast Center of the University of Erlangen (Germany). Logistic regression and Cox regression analyses were performed to investigate the associations between BRCA1/2 mutation status, pathological complete response, disease-free survival, and overall survival. Among 355 patients, 59 had a mutation in BRCA1 or in BRCA2 (16.6%), 43 in BRCA1 (12.1%), and 16 in BRCA2 (4.5%). Pathological complete response defined as "ypT0; ypN0" was observed in 54.3% of BRCA1/2 mutation carriers, but only in 22.6% of non-carriers. The adjusted odds ratio was 2.48 (95% CI 1.26-4.91) for BRCA1/2 carriers versus non-carriers. Patients who achieved a pathological complete response had better disease-free survival and overall survival rates compared with those who did not achieve a pathological complete response, regardless of BRCA1/2 mutation status. BRCA1/2 mutation status leads to better responses to neoadjuvant chemotherapy in breast cancer. Pathological complete response is the main predictor of disease-free survival and overall survival, independently of BRCA1/2 mutation status.

Molecularly targeted therapeutic radiopharmaceuticals

International Nuclear Information System (INIS)

Saw, M.M.

2007-01-01

Full text: It is generally agreed that current focus of nuclear medicine development should be on molecular imaging and therapy. Though, the widespread use of the terminology 'molecular imaging' is quite recent, nuclear medicine has used molecular imaging techniques for more than 20 years ago. A variety of radiopharmaceuticals have been introduced for the internal therapy of malignant and inflammatory lesions in nuclear medicine. In the field of bio/medical imaging, nuclear medicine is one of the disciplines which has the privilege of organized and well developed chemistry/ pharmacy section; radio-chemistry/radiopharmacy. Fundamental principles have been developed more than 40 years ago and advanced research is going well into postgenomic era. The genomic revolution and dramatically increased insight in the molecular mechanisms underlying pathology have led to paradigm shift in drug development. Likewise does in the nuclear medicine. Here, the author will present current clinical and pre-clinical therapeutic radiopharmaceuticals based on molecular targets such as membrane-bound receptors, enzymes, nucleic acids, sodium iodide symporter, etc, in correlation with fundamentals of radiopharmacy. (author)

Defining the molecular pathologies in cloaca malformation: similarities between mouse and human

Directory of Open Access Journals (Sweden)

Laura A. Runck

2014-04-01

Full Text Available Anorectal malformations are congenital anomalies that form a spectrum of disorders, from the most benign type with excellent functional prognosis, to very complex, such as cloaca malformation in females in which the rectum, vagina and urethra fail to develop separately and instead drain via a single common channel into the perineum. The severity of this phenotype suggests that the defect occurs in the early stages of embryonic development of the organs derived from the cloaca. Owing to the inability to directly investigate human embryonic cloaca development, current research has relied on the use of mouse models of anorectal malformations. However, even studies of mouse embryos lack analysis of the earliest stages of cloaca patterning and morphogenesis. Here we compared human and mouse cloaca development and retrospectively identified that early mis-patterning of the embryonic cloaca might underlie the most severe forms of anorectal malformation in humans. In mouse, we identified that defective sonic hedgehog (Shh signaling results in early dorsal-ventral epithelial abnormalities prior to the reported defects in septation. This is manifested by the absence of Sox2 and aberrant expression of keratins in the embryonic cloaca of Shh knockout mice. Shh knockout embryos additionally develop a hypervascular stroma, which is defective in BMP signaling. These epithelial and stromal defects persist later, creating an indeterminate epithelium with molecular alterations in the common channel. We then used these animals to perform a broad comparison with patients with mild-to-severe forms of anorectal malformations including cloaca malformation. We found striking parallels with the Shh mouse model, including nearly identical defective molecular identity of the epithelium and surrounding stroma. Our work strongly suggests that early embryonic cloacal epithelial differentiation defects might be the underlying cause of severe forms of anorectal malformations

Appendiceal pathology at the time of oophorectomy for ovarian neoplasms.

Science.gov (United States)

Timofeev, Julia; Galgano, Mary T; Stoler, Mark H; Lachance, Jason A; Modesitt, Susan C; Jazaeri, Amir A

2010-12-01

To investigate the prevalence of appendiceal pathology in women undergoing surgery for a suspected ovarian neoplasm and the predictive value of intraoperative findings to determine the need for appendectomy at the time of surgery. Retrospective analysis of patients who underwent oophorectomy and appendectomy during the same surgical procedures at the University of Virginia Health System from 1992 to 2007. Observations were stratified based on the nature (benign, borderline, or malignant) and histology (serous compared with mucinous) of the ovarian neoplasm, frozen compared with final pathological diagnosis, and the gross appearance of the appendix. Among the 191 patients identified, frozen section was consistent with seven mucinous and 35 serous carcinomas, 16 serous and 33 mucinous borderline tumors, 71 mucinous and serous cystadenomas, and 29 cases of suspected metastatic tumor from a gastrointestinal primary. The highest rates of coexisting appendiceal pathology were associated with serous ovarian cancers (94.4% of grossly abnormal and 35.3% of normal appendices) and ovarian tumors suspected to be of primary gastrointestinal origin (83.3% grossly abnormal and 60.0% normal appendices harbored coexisting mucinous neoplasms). Linear regression analysis revealed that appearance of the appendix and frozen section diagnosis of the ovarian pathology were statistically significant predictors of coexisting appendiceal pathology, but the latter was more important. The prevalence of coexisting, clinically significant appendiceal pathology is low with a frozen section diagnosis of serous or mucinous cystadenoma. Appendectomy is recommended when frozen section diagnosis is mucinous or serous ovarian carcinoma, borderline tumor or metastatic carcinoma of suspected gastrointestinal origin.

[Psychopathology in online pathological gamblers: a preliminary study].

Science.gov (United States)

Barrault, S; Varescon, I

2012-04-01

The rapidly expanding gambling offline and online have resulted in an increasing number of gamblers and the problem is likely to get worse in the future. However, online pathological gambling is a not well known. This rapidly developing modality of gambling, which requires to be studied, notably in its links with regular pathological gambling and Internet addiction. Depression and personality disorders are known to be often associated with pathological gambling. Personality disorders have an influence on pathological gambling, increasing its severity. Online gamblers seem to have a particular personality profile, compared to offline gamblers, and could present different personality disorders. Depression is a common comorbidity among online gamblers, as well as offline gamblers. Both types of gamblers have personality disorders, but the nature of these disorders differs: prevalency of personality disorders of cluster B (dramatic, emotional or erratic disorders) is more important in offline gamblers, whereas cluster C (anxious or fearful disorders) is more present in online pathological gamblers. In France, few studies have specifically examined this subject. The objective of the study is to evaluate scores on depression, personality disorders and internet addiction in online pathological gamblers. The South Oaks Gambling Screen (SOGS) is used to assess pathological gambling, Beck's Depression Inventory (BDI) to measure depression, the Personality Disorders Questionnaire (PDQ 4) to assess personality disorders and the Internet Addiction Test (IAT) to assess internet addiction. Participants completed the self-report scales. Questionnaires were strictly confidential. The participants were recruited in gambling places (cafés) and Internet forums. Two groups of pathological gamblers were formed: online gamblers (N=15) and offline gamblers (N=15). Participants gave their informed consent. Participation was voluntary and anonymous and no payment was made. ANALYSIS OF THE

Digital pathology: DICOM-conform draft, testbed, and first results.

Science.gov (United States)

Zwönitzer, Ralf; Kalinski, Thomas; Hofmann, Harald; Roessner, Albert; Bernarding, Johannes

2007-09-01

Hospital information systems are state of the art nowadays. Therefore, Digital Pathology, also labelled as Virtual Microscopy, has gained increased attention. Triggered by radiology, standardized information models and workflows were world-wide defined based on DICOM. However, DICOM-conform integration of Digital Pathology into existing clinical information systems imposes new problems requiring specific solutions concerning the huge amount of data as well as the special structure of the data to be managed, transferred, and stored. We implemented a testbed to realize and evaluate the workflow of digitized slides from acquisition to archiving. The experiences led to the draft of a DICOM-conform information model that accounted for extensions, definitions, and technical requirements necessary to integrate digital pathology in a hospital-wide DICOM environment. Slides were digitized, compressed, and could be viewed remotely. Real-time transfer of the huge amount of data was optimized using streaming techniques. Compared to a recent discussion in the DICOM Working Group for Digital Pathology (WG26) our experiences led to a preference of a JPEG2000/JPIP-based streaming of the whole slide image. The results showed that digital pathology is feasible but strong efforts by users and vendors are still necessary to integrate Digital Pathology into existing information systems.

Ultrasonographic and pathologic correlation in cases of gynecomastia

Energy Technology Data Exchange (ETDEWEB)

Kook, Shin Ho; Lee, Seung Hee; Kim, Myung Sook; Pae, Won Kil [Kangbuk Samsung Hospital, Seoul (Korea, Republic of)

1996-07-01

To define and correlate characteristic sonographic and pathologic findings in men with gynecomastia. We reviewed medical records and sonographic findings of 26 patients with pathologically proven gynecomastia. All of the chief symptoms, physical findings and causes were categorized. Characteristic sonographic patterns of gynecomastia were analyzed and compared with pathologic findings. Gynecomastia was most common in the 20- to 40-year-old age group (50%)6; palpable mass was found in 62% of all those cases. Gynecomastia was unilateral or asymmetrical in 22 men (85%), and was caused idiopathically in 21 (81%). The characteristic sonographic patterns correlated with pathologic findings were as follows:(1) focal subareolar smooth oval (or triangular) indistinct margined homogeneous hypoechoic (or isoechoic) patterns were found in 14 cases (54%). Eight of these (57%) were of the florid type of gynecomastia (67%);(2) diffuse homogeneous hyperechoic (or isoechoic) patterns were found in five cases (19%);four of these (80%) were of the intermediate or fibrotic type:(3) involuting female breast parenchymal patterns were found in seven cases (27%), of which six (86%) were of the intermediate or fibrotic type. The characteristic sonographic patterns of gynecomastia correlate closely with pathologic types related to the duration of the condition. Ultrasonography is a useful primary diagnostic modality for the evaluation of gynecomastia.

Optical diagnostics of tumour cells at different stages of pathology development

Energy Technology Data Exchange (ETDEWEB)

Shcheglova, L S; Maryakhina, V S [Orenburg State University, Orenburg (Russian Federation); Abramova, L L [Orenburg State Agrarian University, Orenburg (Russian Federation)

2013-11-30

The differences in optical and biophysical properties between the cells of mammary gland tumour extracted from tumours of different diameter are described. It is shown that the spectral and spectrokinetic properties of fluorescent probes in the cells extracted from the tumours 1 – 3 cm in diameter are essentially different. Thus, the extinction coefficient of rhodamine 6G gradually increases with the pathology development. At the same time the rate of interaction of the triplet states of molecular probes with the oxygen, diluted in the tumour cells cytoplasm, decreases with the growth of the tumour capsule diameter. The observed regularities can be due to the changes in the cell structure, biochemical and biophysical properties. The reported data may be useful for developing optical methods of diagnostics of biotissue pathological conditions. (optical methods in biology and medicine)

Stem Cell Pathology.

Science.gov (United States)

Fu, Dah-Jiun; Miller, Andrew D; Southard, Teresa L; Flesken-Nikitin, Andrea; Ellenson, Lora H; Nikitin, Alexander Yu

2018-01-24

Rapid advances in stem cell biology and regenerative medicine have opened new opportunities for better understanding disease pathogenesis and the development of new diagnostic, prognostic, and treatment approaches. Many stem cell niches are well defined anatomically, thereby allowing their routine pathological evaluation during disease initiation and progression. Evaluation of the consequences of genetic manipulations in stem cells and investigation of the roles of stem cells in regenerative medicine and pathogenesis of various diseases such as cancer require significant expertise in pathology for accurate interpretation of novel findings. Therefore, there is an urgent need for developing stem cell pathology as a discipline to facilitate stem cell research and regenerative medicine. This review provides examples of anatomically defined niches suitable for evaluation by diagnostic pathologists, describes neoplastic lesions associated with them, and discusses further directions of stem cell pathology.

Comparative transcriptome analyses indicate molecular homology of zebrafish swimbladder and mammalian lung.

Directory of Open Access Journals (Sweden)

Weiling Zheng

Full Text Available The fish swimbladder is a unique organ in vertebrate evolution and it functions for regulating buoyancy in most teleost species. It has long been postulated as a homolog of the tetrapod lung, but the molecular evidence is scarce. In order to understand the molecular function of swimbladder as well as its relationship with lungs in tetrapods, transcriptomic analyses of zebrafish swimbladder were carried out by RNA-seq. Gene ontology classification showed that genes in cytoskeleton and endoplasmic reticulum were enriched in the swimbladder. Further analyses depicted gene sets and pathways closely related to cytoskeleton constitution and regulation, cell adhesion, and extracellular matrix. Several prominent transcription factor genes in the swimbladder including hoxc4a, hoxc6a, hoxc8a and foxf1 were identified and their expressions in developing swimbladder during embryogenesis were confirmed. By comparison of enriched transcripts in the swimbladder with those in human and mouse lungs, we established the resemblance of transcriptome of the zebrafish swimbladder and mammalian lungs. Based on the transcriptomic data of zebrafish swimbladder, the predominant functions of swimbladder are in its epithelial and muscular tissues. Our comparative analyses also provide molecular evidence of the relatedness of the fish swimbladder and mammalian lung.

Validation of a next-generation sequencing assay for clinical molecular oncology.

Science.gov (United States)

Cottrell, Catherine E; Al-Kateb, Hussam; Bredemeyer, Andrew J; Duncavage, Eric J; Spencer, David H; Abel, Haley J; Lockwood, Christina M; Hagemann, Ian S; O'Guin, Stephanie M; Burcea, Lauren C; Sawyer, Christopher S; Oschwald, Dayna M; Stratman, Jennifer L; Sher, Dorie A; Johnson, Mark R; Brown, Justin T; Cliften, Paul F; George, Bijoy; McIntosh, Leslie D; Shrivastava, Savita; Nguyen, Tudung T; Payton, Jacqueline E; Watson, Mark A; Crosby, Seth D; Head, Richard D; Mitra, Robi D; Nagarajan, Rakesh; Kulkarni, Shashikant; Seibert, Karen; Virgin, Herbert W; Milbrandt, Jeffrey; Pfeifer, John D

2014-01-01

Currently, oncology testing includes molecular studies and cytogenetic analysis to detect genetic aberrations of clinical significance. Next-generation sequencing (NGS) allows rapid analysis of multiple genes for clinically actionable somatic variants. The WUCaMP assay uses targeted capture for NGS analysis of 25 cancer-associated genes to detect mutations at actionable loci. We present clinical validation of the assay and a detailed framework for design and validation of similar clinical assays. Deep sequencing of 78 tumor specimens (≥ 1000× average unique coverage across the capture region) achieved high sensitivity for detecting somatic variants at low allele fraction (AF). Validation revealed sensitivities and specificities of 100% for detection of single-nucleotide variants (SNVs) within coding regions, compared with SNP array sequence data (95% CI = 83.4-100.0 for sensitivity and 94.2-100.0 for specificity) or whole-genome sequencing (95% CI = 89.1-100.0 for sensitivity and 99.9-100.0 for specificity) of HapMap samples. Sensitivity for detecting variants at an observed 10% AF was 100% (95% CI = 93.2-100.0) in HapMap mixes. Analysis of 15 masked specimens harboring clinically reported variants yielded concordant calls for 13/13 variants at AF of ≥ 15%. The WUCaMP assay is a robust and sensitive method to detect somatic variants of clinical significance in molecular oncology laboratories, with reduced time and cost of genetic analysis allowing for strategic patient management. Copyright © 2014 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

The Oral Pathology Related Articles Published in Iranian Journal of Pathology from 2006 to 2015.

Science.gov (United States)

Shamim, Thorakkal

2016-01-01

There is a paucity of information about the oral pathology related articles published in a pathology journal. This study aimed to audit the oral pathology related articles published in Iranian Journal of Pathology (Iran J Pathol) from 2006 to 2015. Bibliometric analysis of issues of Iran J Pathol from 2006 to 2015 was performed using web-based search. The articles published were analyzed for type of article and individual topic of oral pathology. The articles published were also checked for authorship trends. Out of the total 49 published articles related to oral pathology, case reports (21) and original articles (18) contributed the major share. The highest number of oral pathology related articles was published in 2011, 2014 and 2015 with 8 articles each and the least published year was 2012 with 1 article. Among the oral pathology related articles published, spindle cell neoplasms (7) followed by salivary gland tumors (5), jaw tumors (4), oral granulomatous conditions (4), lymphomas (4), oral cancer (3) and odontogenic cysts (3) form the major attraction of the contributors. The largest numbers of published articles related to oral pathology were received from Tehran University of Medical Sciences; Tehran (7) followed by Mashhad University of Medical Sciences, Mashhad (6) and Shahid Beheshti University of Medical Sciences, Tehran (5). This paper may be considered as a baseline study for the bibliometric information regarding oral pathology related articles published in a pathology journal.

Genetics and pathological mechanisms of Usher syndrome.

Science.gov (United States)

Yan, Denise; Liu, Xue Z

2010-06-01

Usher syndrome (USH) comprises a group of autosomal recessively inherited disorders characterized by a dual sensory impairment of the audiovestibular and visual systems. Three major clinical subtypes (USH type I, USH type II and USH type III) are distinguished on the basis of the severity of the hearing loss, the presence or absence of vestibular dysfunction and the age of onset of retinitis pigmentosa (RP). Since the cloning of the first USH gene (MYO7A) in 1995, there have been remarkable advances in elucidating the genetic basis for this disorder, as evidence for 11 distinct loci have been obtained and genes for 9 of them have been identified. The USH genes encode proteins of different classes and families, including motor proteins, scaffold proteins, cell adhesion molecules and transmembrane receptor proteins. Extensive information has emerged from mouse models and molecular studies regarding pathogenesis of this disorder and the wide phenotypic variation in both audiovestibular and/or visual function. A unifying hypothesis is that the USH proteins are integrated into a protein network that regulates hair bundle morphogenesis in the inner ear. This review addresses genetics and pathological mechanisms of USH. Understanding the molecular basis of phenotypic variation and pathogenesis of USH is important toward discovery of new molecular targets for diagnosis, prevention and treatment of this debilitating disorder.

[Editorial] Environmental and occupational risk factors associated with different pathological conditions.

Science.gov (United States)

Signorelli, Salvatore Santo; Ferrante, Margherita

2017-05-01

A wide body of evidence indicates that environmental and occupational risk factors are associated with the development of pathological disorders. The pathogenic role of many environmental pollutants or occupational contaminants is already known and has been extensively investigated. However, the molecular mechanisms of action and the pathogenic effects of many substances remain unknown. Therefore, there is a need to better investigate the role of new environmental and occupational risk factors that may cause the development of several diseases.

Decision making in pathological gambling: A comparison between pathological gamblers, alcohol dependents, persons with Tourette syndrome, and normal controls

NARCIS (Netherlands)

Goudriaan, Anna E.; Oosterlaan, Jaap; de Beurs, Edwin; van den Brink, Wim

2005-01-01

Decision making deficits play an important role in the definition of pathological gambling (PG). However, only few empirical studies are available regarding decision making processes in PG. This study therefore compares decision making processes in PG and normal controls in detail using three

Image analysis and machine learning in digital pathology: Challenges and opportunities.

Science.gov (United States)

Madabhushi, Anant; Lee, George

2016-10-01

. We also briefly review some of the state of the art in fusion of radiology and pathology images and also combining digital pathology derived image measurements with molecular "omics" features for better predictive modeling. The review ends with a brief discussion of some of the technical and computational challenges to be overcome and reflects on future opportunities for the quantitation of histopathology. Copyright © 2016 Elsevier B.V. All rights reserved.

Genetic basis of endocrine pathology

Directory of Open Access Journals (Sweden)

T.V. Sorokman

2017-05-01

Full Text Available The purpose of the review was analysis of literature data relating to the molecular genetic basis and diagnosis of endocrine pathology. We searched for published and unpublished researches using Pubmed as the search engine by the keywords: ‘genes’, ‘endocrine diseases’, ‘molecular diagnostics’, ‘prohormones’, ‘nuclear receptors and transcription factors’, taking into consideration studies conducted over the last 10 years, citation review of relevant primary and review articles, conference abstracts, personal files, and contact with expert informants. The criterion for the selection of articles for the study was based on their close relevance to the topic, thus out of 144 analyzed articles, the findings of the researchers covered in 32 articles were crucial. The described nosologies presented various heredi­tary forms of hypopituitarism, disturbances of steroid hormone biosynthesis, abnormal gender formation, monogenic forms of diabetes mellitus, endocrine tumors, etc. Pathology is identified that is associated with a mutation of genes encoding protein prohormones, receptors, steroid biosynthesis enzymes, intracellular signaling molecules, transport proteins, ion channels, and transcription factors. Among the endocrine diseases associated with defects in genes encoding protein prohormones, the defects of the GH1 gene are most common, the defects in the gene CYP21A2 (21-hydroxylase are among diseases associated with defects in genes encoding enzymes. More often mutations of genes encoding proteins belong to the class of G-protein coupled receptors. Most of the mutations associated with MEN-2A are concentrated in the rich cysteine region of the Ret receptor. More than 70 monogenic syndromes are known, in which there is a marked tolerance to glucose and some form of diabetes mellitus is diagnosed, diabetes mellitus caused by mutation of the mitochondrial gene (mutation tRNALeu, UUR is also detected. Of all the monogenic forms of

Duodenal pathologies in children: a single‐center experience

Directory of Open Access Journals (Sweden)

Ulas Emre Akbulut

2018-05-01

Full Text Available Objective: Several studies have been performed concerning pathologies of the stomach and esophagus in the pediatric age group. However, there have been very few studies of duodenal pathologies in children. The authors aimed to examine the clinical, endoscopic, and histopathological characteristics, as well as the etiology of duodenal pathologies in children. Method: Patients aged between 1 and 17 years undergoing esophagogastroduodenoscopy during two years at this unit, were investigated retrospectively. Demographic, clinical, endoscopic data, and the presence of duodenal pathologies, gastritis, and esophagitis were recorded in all of the children. Results: Out of 747 children who underwent endoscopy, duodenal pathology was observed in 226 (30.3% patients. Pathology was also present in the esophagus in 31.6% of patients and in the stomach in 58.4%. The level of chronic diarrhea was higher in patients with duodenal pathology when compared with those without duodenal pathology (p = 0.002, OR: 3.91, 95% CI: 1.59–9.57. Helicobacter pylori infection was more common in patients with pathology in the duodenum (59.3%. Conclusion: Duodenal pathology was detected in 30.3% of the present patients. A significantly higher level of chronic diarrhea was observed in subjects with duodenal pathologies compared to those with no such pathology. The rate of Helicobacter pylori infection was considerably higher than that in previous studies. In addition, there is a weak correlation between endoscopic appearance and histology of duodenitis. Resumo: Objetivo: Foram feitos vários estudos com relação a patologias do estômago e esôfago na faixa etária pediátrica. Contudo, poucos estudos das patologias duodenais em crianças. Visamos a examinar as características clínicas, endoscópicas e histopatológicas, juntamente com a etiologia, das patologias duodenais em crianças. Método: Foram investigados retrospectivamente pacientes entre 1 e 17 anos submetidos a

The pathology and pathophysiology of vascular dementia.

Science.gov (United States)

Kalaria, Raj N

2017-12-19

Vascular dementia (VaD) is widely recognised as the second most common type of dementia. Consensus and accurate diagnosis of clinically suspected VaD relies on wide-ranging clinical, neuropsychological and neuroimaging measures in life but more importantly pathological confirmation. Factors defining subtypes of VaD include the nature and extent of vascular pathologies, degree of involvement of extra and intracranial vessels and the anatomical location of tissue changes as well as time after the initial vascular event. Atherosclerotic and cardioembolic diseases combined appear the most common subtypes of vascular brain injury. In recent years, cerebral small vessel disease (SVD) has gained prominence worldwide as an important substrate of cognitive impairment. SVD is characterised by arteriolosclerosis, lacunar infarcts and cortical and subcortical microinfarcts and diffuse white matter changes, which involve myelin loss and axonal abnormalities. Global brain atrophy and focal degeneration of the cerebrum including medial temporal lobe atrophy are also features of VaD similar to Alzheimer's disease. Hereditary arteriopathies have provided insights into the mechanisms of dementia particularly how arteriolosclerosis, a major contributor of SVD promotes cognitive impairment. Recently developed and validated neuropathology guidelines indicated that the best predictors of vascular cognitive impairment were small or lacunar infarcts, microinfarcts, perivascular space dilation, myelin loss, arteriolosclerosis and leptomeningeal cerebral amyloid angiopathy. While these substrates do not suggest high specificity, VaD is likely defined by key neuronal and dendro-synaptic changes resulting in executive dysfunction and related cognitive deficits. Greater understanding of the molecular pathology is needed to clearly define microvascular disease and vascular substrates of dementia. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pathological and molecular based study of pneumonic pasteurellosis in cattle and buffalo (bubalus bubalis)

International Nuclear Information System (INIS)

Hussain, R.

2014-01-01

In present study the clinico-pathological findings were recorded in naturally infected cattle and buffaloes due to pasteurella multocida during an outbreak at different livestock herds. There was no significant difference in mortality among various groups of buffaloes (p>0.78) and cattle (p>0.49). The infected animals showed clinical signs of moderate to acute anorexia, salivation, fever, depression, dysponea, submandibular edema, mucopurulent nasal discharge and respiratory grunts. Few of infected animals died due to septicemia. the necropsy of dead animals was performed and visceral organs lungs, kidneys, heart and lymph nodes were observed for gross and histopathological lesions. The tissue samples from these organs were fixed in formalin for pathological changes. Necropsy of dead animals revealed severe pneumonia, consolidation of lungs and intense pleural adhesions. serosanguinous fluid was accumulated in pericardium and peritoneal cavities. Histopathologically affected lungs exhibited severe congestion, mononuclear cell infiltration, thick interlobular septae punctuated with macrophages, plasma cells and peri-vascular cuffing. Liver, kidneys and lymph nodes had degenerative changes in histological sections. The specificity of p. multocida was determined by colony characteristics on macconkey's agar and morphological features with gram's iodine. The pcr product size approximately 511bp from lung tissues confirmed a total of 82% (19/23) bacterial isolates from dead animals. (author)

[Pathological gambling: risk factors].

Science.gov (United States)

Bouju, G; Grall-Bronnec, M; Landreat-Guillou, M; Venisse, J-L

2011-09-01

In France, consumption of gambling games increased by 148% between 1960 and 2005. In 2004, gamblers lost approximately 0.9% of household income, compared to 0.4% in 1960. This represents approximately 134 Euros per year and per head. In spite of this important increase, the level remains lower than the European average (1%). However, gambling practices may continue to escalate in France in the next few years, particularly with the recent announce of the legalisation of online games and sports betting. With the spread of legalised gambling, pathological gambling rates may increase in France in the next years, in response to more widely available and more attractive gambling opportunities. In this context, there is a need for better understanding of the risk factors that are implicated in the development and maintenance of pathological gambling. This paper briefly describes the major risk factors for pathological gambling by examining the recent published literature available during the first quarter of 2008. This documentary basis was collected by Inserm for the collective expert report procedure on Gambling (contexts and addictions). Seventy-two articles focusing on risk factors for pathological gambling were considered in this review. Only 47 of them were taken into account for analysis. The selection of these 47 publications was based on the guide on literature analysis established by the French National Agency for Accreditation and Assessment in Health (ANAES, 2000). Some publications from more recent literature have also been added, mostly about Internet gambling. We identify three major types of risk factors implicated in gambling problems: some of them are related to the subject (individual factors), others are related to the object of the addiction, here the gambling activity by itself (structural factors), and the last are related to environment (contextual or situational factors). Thus, the development and maintenance of pathological gambling seems to be

Pathology of the vestibulocochlear nerve

Energy Technology Data Exchange (ETDEWEB)

De Foer, Bert [Department of Radiology, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail: bert.defoer@GZA.be; Kenis, Christoph [Department of Radiology, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail: christophkenis@hotmail.com; Van Melkebeke, Deborah [Department of Neurology, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail: Deborah.vanmelkebeke@Ugent.be; Vercruysse, Jean-Philippe [University Department of ENT, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail: jphver@yahoo.com; Somers, Thomas [University Department of ENT, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail: Thomas.somers@GZA.be; Pouillon, Marc [Department of Radiology, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail: marc.pouillon@GZA.be; Offeciers, Erwin [University Department of ENT, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail: Erwin.offeciers@GZA.be; Casselman, Jan W. [Department of Radiology, AZ Sint-Jan AV Hospital, Ruddershove 10, Bruges (Belgium); Consultant Radiologist, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium); Academic Consultent, University of Ghent (Belgium)], E-mail: jan.casselman@azbrugge.be

2010-05-15

There is a large scala of pathology affecting the vestibulocochlear nerve. Magnetic resonance imaging is the method of choice for the investigation of pathology of the vestibulocochlear nerve. Congenital pathology mainly consists of agenesis or hypoplasia of the vestibulocochlear nerve. Tumoral pathology affecting the vestibulocochlear nerve is most frequently located in the internal auditory canal or cerebellopontine angle. Schwannoma of the vestibulocochlear nerve is the most frequently found tumoral lesion followed by meningeoma, arachnoid cyst and epidermoid cyst. The most frequently encountered pathologies as well as some more rare entities are discussed in this chapter.

Pathology of the vestibulocochlear nerve

International Nuclear Information System (INIS)

De Foer, Bert; Kenis, Christoph; Van Melkebeke, Deborah; Vercruysse, Jean-Philippe; Somers, Thomas; Pouillon, Marc; Offeciers, Erwin; Casselman, Jan W.

2010-01-01

There is a large scala of pathology affecting the vestibulocochlear nerve. Magnetic resonance imaging is the method of choice for the investigation of pathology of the vestibulocochlear nerve. Congenital pathology mainly consists of agenesis or hypoplasia of the vestibulocochlear nerve. Tumoral pathology affecting the vestibulocochlear nerve is most frequently located in the internal auditory canal or cerebellopontine angle. Schwannoma of the vestibulocochlear nerve is the most frequently found tumoral lesion followed by meningeoma, arachnoid cyst and epidermoid cyst. The most frequently encountered pathologies as well as some more rare entities are discussed in this chapter.

Update on pathology of ocular parasitic disease.

Science.gov (United States)

Das, Dipankar; Ramachandra, Varsha; Islam, Saidul; Bhattacharjee, Harsha; Biswas, Jyotirmay; Koul, Akanksha; Deka, Panna; Deka, Apurba

2016-11-01

Parasites are a group of eukaryotic organisms that may be free-living or form a symbiotic or parasitic relationship with the hosts. Consisting of over 800,000 recognized species, parasites may be unicellular (Protozoa) or multicellular (helminths and arthropods). The association of parasites with human population started long before the emergence of civilization. Parasitic zoonotic diseases are prevalent worldwide including India. Appropriate epidemiological data are lacking on existing zoonotic parasitic diseases, and newer diseases are emerging in our scenario. Systemic diseases such as cysticercosis, paragonimiasis, hydatidosis, and toxoplasmosis are fairly common. Acquired Toxoplasma infections are rising in immune-deficient individuals. Amongst the ocular parasitic diseases, various protozoas such as Cystoidea, trematodes, tissue flagellates, sporozoas etc. affect humans in general and eyes in particular, in different parts of the world. These zoonoses seem to be a real health related problem globally. Recent intensification of research throughout the world has led to specialization in biological fields, creating a conducive situation for researchers interested in this subject. The basics of parasitology lie in morphology, pathology, and with recent updates in molecular parasitology, the scope has extended further. The current review is to address the recent update in ophthalmic parasites with special reference to pathology and give a glimpse of further research in this field.

Update on pathology of ocular parasitic disease

Directory of Open Access Journals (Sweden)

Dipankar Das

2016-01-01

Full Text Available Parasites are a group of eukaryotic organisms that may be free-living or form a symbiotic or parasitic relationship with the hosts. Consisting of over 800,000 recognized species, parasites may be unicellular (Protozoa or multicellular (helminths and arthropods. The association of parasites with human population started long before the emergence of civilization. Parasitic zoonotic diseases are prevalent worldwide including India. Appropriate epidemiological data are lacking on existing zoonotic parasitic diseases, and newer diseases are emerging in our scenario. Systemic diseases such as cysticercosis, paragonimiasis, hydatidosis, and toxoplasmosis are fairly common. Acquired Toxoplasma infections are rising in immune-deficient individuals. Amongst the ocular parasitic diseases, various protozoas such as Cystoidea, trematodes, tissue flagellates, sporozoas etc. affect humans in general and eyes in particular, in different parts of the world. These zoonoses seem to be a real health related problem globally. Recent intensification of research throughout the world has led to specialization in biological fields, creating a conducive situation for researchers interested in this subject. The basics of parasitology lie in morphology, pathology, and with recent updates in molecular parasitology, the scope has extended further. The current review is to address the recent update in ophthalmic parasites with special reference to pathology and give a glimpse of further research in this field.

[Adolescent pathological gambling].

Science.gov (United States)

Petit, A; Karila, L; Lejoyeux, M

2015-05-01

Although experts have long thought that the problems of gambling involved only adults, recent studies tend to show that teenagers are also affected. The objective of this paper is to show the characteristics of pathological gambling in adolescents. This review focuses on the clinical features, prevalence, psychopathology, prevention and treatment of this disorder. A review of the medical literature was conducted, using PubMed, using the following keywords alone or combined: pathological gambling, dependence, addiction and adolescents. We selected 12 English articles from 1997 to 2014. Recent work estimate that between 4 and 8% of adolescents suffer from problem gambling, and the prevalence of pathological gambling is 2-4 times higher in adolescents than in adults. The term adolescent pathological gambler starts early around the age of 10-12 years, with a quick change of status from casual to that of problem gambler and player. Complications appear quickly and comorbidities are common. There is no curative pharmacological treatment approved by health authorities. Pathological gambling among adolescents has grown significantly in recent years and should be promptly taken care of. Further studies must be performed to improve our understanding of this problem among adolescents. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Pathological gambling: comorbid psychiatric diagnoses in patients and their families.

Science.gov (United States)

Dannon, Pinhas N; Lowengrub, Katherine; Aizer, Anat; Kotler, Moshe

2006-01-01

Pathological gambling is a highly prevalent and disabling impulse control disorder. Recent studies have consistently demonstrated that pathological gamblers respond well to treatment with selective serotonin reuptake inhibitors, mood stabilizers and opioid antagonists. These findings have supported the observation that pathological gambling is associated with anxiety and mood spectrum disorders as well as addictive disorders. Fifty-two male pathological gamblers and their first-degree relatives (n=93) completed a semi-structured DSM-IV-based diagnostic interview as well as a series of data collection instruments including the South Oaks Gambling Scale, the Hamilton Rating Scale for Depression, the Hamilton Rating Scale for Anxiety, the Yale-Brown Obsessive-Compulsive Scale, and the Young Mania Rating Scale. The study subjects and their first-degree relative were compared to demographically matched normal controls (n=96). We found higher prevalence of alcohol, substance abuse, problematic gambling, depression, and anxiety disorders in the pathological gamblers and their first-degree relatives than in the control group. In particular, the scores on the Hamilton Rating Scale for Depression, the Hamilton Rating Scale for Anxiety, and the Yale-Brown Obsessive-Compulsive Scale were higher in the study group than in the control group. Our finding of a high prevalence of psychiatric comorbidity in pathological gamblers and their families raises the question of the proper classification of pathological gambling in the DSM-IV. Furthermore, the pattern of psychiatric disorders seen in the first-degree relatives can lead to new insights about the etiopathology of pathological gambling.

Investigation of a dual modal method for bone pathologies using quantitative ultrasound and photoacoustics

Science.gov (United States)

Steinberg, Idan; Gannot, Israel; Eyal, Avishay

2015-03-01

Osteoporosis is a widespread disease that has a catastrophic impact on patient's lives and overwhelming related healthcare costs. In recent works, we have developed a multi-spectral, frequency domain photoacoustic method for the evaluation of bone pathologies. This method has great advantages over pure ultrasonic or optical methods as it provides both molecular information from the bone absorption spectrum and bone mechanical status from the characteristics of the ultrasound propagation. These characteristics include both the Speed of Sound (SOS) and Broadband Ultrasonic Attenuation (BUA). To test the method's quantitative predictions, we have constructed a combined ultrasound and photoacoustic setup. Here, we experimentally present a dual modality system, and compares between the methods on bone samples in-vitro. The differences between the two modalities are shown to provide valuable insight into the bone structure and functional status.

Clinical and molecular features of high-grade osteosarcoma

NARCIS (Netherlands)

Anninga, Jakob Klaas

2013-01-01

It can be concluded from this thesis that high-grade osteosarcoma is at clinical, pathological and molecular level a heterogeneous disease. To treat high-grade osteosarcoma, neo-adjuvant chemotherapy should be combined with radical surgery, irrespective the localization. There are only 4 effective

Future-proofing pathology: the case for clinical adoption of digital pathology.

Science.gov (United States)

Williams, Bethany Jill; Bottoms, David; Treanor, Darren

2017-12-01

This document clarifies the strategic context of digital pathology adoption, defines the different use cases a healthcare provider may wish to consider as part of a digital adoption and summarises existing reasons for digital adoption and its potential benefits. The reader is provided with references to the relevant literature, and illustrative case studies. The authors hope this report will be of interest to healthcare providers, pathology managers, departmental heads, pathologists and biomedical scientists that are considering digital pathology, deployments or preparing business cases for digital pathology adoption in clinical settings. The information contained in this document can be shared and used in any documentation the reader wishes to present for their own institutional case for adoption report or business case. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Next-Generation Pathology.

Science.gov (United States)

Caie, Peter D; Harrison, David J

2016-01-01

The field of pathology is rapidly transforming from a semiquantitative and empirical science toward a big data discipline. Large data sets from across multiple omics fields may now be extracted from a patient's tissue sample. Tissue is, however, complex, heterogeneous, and prone to artifact. A reductionist view of tissue and disease progression, which does not take this complexity into account, may lead to single biomarkers failing in clinical trials. The integration of standardized multi-omics big data and the retention of valuable information on spatial heterogeneity are imperative to model complex disease mechanisms. Mathematical modeling through systems pathology approaches is the ideal medium to distill the significant information from these large, multi-parametric, and hierarchical data sets. Systems pathology may also predict the dynamical response of disease progression or response to therapy regimens from a static tissue sample. Next-generation pathology will incorporate big data with systems medicine in order to personalize clinical practice for both prognostic and predictive patient care.

A comparative pathological finding in pigs exposed to fumonisin B1 and/or Mycoplasma hyopneumoniae.

Science.gov (United States)

Pósa, Roland; Stoev, Stoycho; Kovács, Melinda; Donkó, Tamás; Repa, Imre; Magyar, Tibor

2016-06-01

A more complicated pathology was observed in female pigs infected with Mycoplasma hyopneumoniae, when the same were exposed to 20 ppm dietary levels of fumonisin B1 (FB1) starting 14 days before infection for a period of 42 days as was assessed by gross pathology and pathomorphological examinations or computed tomography, and also manifested by the strong deterioration of the pneumonic process in two pigs and the subsequent euthanizing of one pig. Typical damages in FB1-fed pigs were a strong oedema in the lung and slight oedema in the other internal organs and mild degenerative changes in the kidneys, whereas the typical pathomorphological changes in M. hyopneumoniae-infected pigs corresponded to the morphologic pattern of a catarrhal bronchointerstitial pneumonia more pronounced in the cranial and middle lobes or in the cranial third of the caudal lobe of the lung. The pigs treated by both pathogens (toxic and infectious) revealed strong oedematous changes in the interstitium of lung in addition to deteriorated and extended bronchointerstitial pneumonic process. © The Author(s) 2014.

A comparative molecular dynamics study on thermostability of human and chicken prion proteins

International Nuclear Information System (INIS)

Ji, Hong-Fang; Zhang, Hong-Yu

2007-01-01

To compare the thermostabilities of human and chicken normal cellular prion proteins (HuPrP C and CkPrP C ), molecular dynamics (MD) simulations were performed for both proteins at an ensemble level (10 parallel simulations at 400 K and 5 parallel simulations at 300 K as a control). It is found that the thermostability of HuPrP C is comparable with that of CkPrP C , which implicates that the non-occurrence of prion diseases in non-mammals cannot be completely attributed to the thermodynamic properties of non-mammalian PrP C

SurfaceSlide: a multitouch digital pathology platform.

Directory of Open Access Journals (Sweden)

Yinhai Wang

Full Text Available BACKGROUND: Digital pathology provides a digital environment for the management and interpretation of pathological images and associated data. It is becoming increasing popular to use modern computer based tools and applications in pathological education, tissue based research and clinical diagnosis. Uptake of this new technology is stymied by its single user orientation and its prerequisite and cumbersome combination of mouse and keyboard for navigation and annotation. METHODOLOGY: In this study we developed SurfaceSlide, a dedicated viewing platform which enables the navigation and annotation of gigapixel digitised pathological images using fingertip touch. SurfaceSlide was developed using the Microsoft Surface, a 30 inch multitouch tabletop computing platform. SurfaceSlide users can perform direct panning and zooming operations on digitised slide images. These images are downloaded onto the Microsoft Surface platform from a remote server on-demand. Users can also draw annotations and key in texts using an on-screen virtual keyboard. We also developed a smart caching protocol which caches the surrounding regions of a field of view in multi-resolutions thus providing a smooth and vivid user experience and reducing the delay for image downloading from the internet. We compared the usability of SurfaceSlide against Aperio ImageScope and PathXL online viewer. CONCLUSION: SurfaceSlide is intuitive, fast and easy to use. SurfaceSlide represents the most direct, effective and intimate human-digital slide interaction experience. It is expected that SurfaceSlide will significantly enhance digital pathology tools and applications in education and clinical practice.

Feasibility of using microbeads with holographic barcodes to track DNA specimens in the clinical molecular laboratory

Directory of Open Access Journals (Sweden)

Jason D. Merker

2013-07-01

Full Text Available We demonstrate the feasibility of using glass microbeads with a holographic barcode identifier to track DNA specimens in the molecular pathology laboratory. These beads can be added to peripheral blood specimens and are carried through automated DNA extraction protocols that use magnetic glass particles. We found that an adequate number of microbeads are consistently carried over during genomic DNA extraction to allow specimen identification, that the beads do not interfere with the performance of several different molecular assays, and that the beads and genomic DNA remain stable when stored together under regular storage conditions in the molecular pathology laboratory. The beads function as an internal, easily readable specimen barcode. This approach may be useful for identifying DNA specimens and reducing errors associated with molecular laboratory testing.

Investigation of arc repressor DNA-binding specificity by comparative molecular dynamics simulations.

Science.gov (United States)

Song, Wei; Guo, Jun-Tao

2015-01-01

Transcription factors regulate gene expression through binding to specific DNA sequences. How transcription factors achieve high binding specificity is still not well understood. In this paper, we investigated the role of protein flexibility in protein-DNA-binding specificity by comparative molecular dynamics (MD) simulations. Protein flexibility has been considered as a key factor in molecular recognition, which is intrinsically a dynamic process involving fine structural fitting between binding components. In this study, we performed comparative MD simulations on wild-type and F10V mutant P22 Arc repressor in both free and complex conformations. The F10V mutant has lower DNA-binding specificity though both the bound and unbound main-chain structures between the wild-type and F10V mutant Arc are highly similar. We found that the DNA-binding motif of wild-type Arc is structurally more flexible than the F10V mutant in the unbound state, especially for the six DNA base-contacting residues in each dimer. We demonstrated that the flexible side chains of wild-type Arc lead to a higher DNA-binding specificity through forming more hydrogen bonds with DNA bases upon binding. Our simulations also showed a possible conformational selection mechanism for Arc-DNA binding. These results indicate the important roles of protein flexibility and dynamic properties in protein-DNA-binding specificity.

Distinctive serum miRNA profile in mouse models of striated muscular pathologies.

Directory of Open Access Journals (Sweden)

Nicolas Vignier

Full Text Available Biomarkers are critically important for disease diagnosis and monitoring. In particular, close monitoring of disease evolution is eminently required for the evaluation of therapeutic treatments. Classical monitoring methods in muscular dystrophies are largely based on histological and molecular analyses of muscle biopsies. Such biopsies are invasive and therefore difficult to obtain. The serum protein creatine kinase is a useful biomarker, which is however not specific for a given pathology and correlates poorly with the severity or course of the muscular pathology. The aim of the present study was the systematic evaluation of serum microRNAs (miRNAs as biomarkers in striated muscle pathologies. Mouse models for five striated muscle pathologies were investigated: Duchenne muscular dystrophy (DMD, limb-girdle muscular dystrophy type 2D (LGMD2D, limb-girdle muscular dystrophy type 2C (LGMD2C, Emery-Dreifuss muscular dystrophy (EDMD and hypertrophic cardiomyopathy (HCM. Two-step RT-qPCR methodology was elaborated, using two different RT-qPCR miRNA quantification technologies. We identified miRNA modulation in the serum of all the five mouse models. The most highly dysregulated serum miRNAs were found to be commonly upregulated in DMD, LGMD2D and LGMD2C mouse models, which all exhibit massive destruction of striated muscle tissues. Some of these miRNAs were down rather than upregulated in the EDMD mice, a model without massive myofiber destruction. The dysregulated miRNAs identified in the HCM model were different, with the exception of one dysregulated miRNA common to all pathologies. Importantly, a specific and distinctive circulating miRNA profile was identified for each studied pathological mouse model. The differential expression of a few dysregulated miRNAs in the DMD mice was further evaluated in DMD patients, providing new candidates of circulating miRNA biomarkers for DMD.

[When history meets molecular medicine: molecular history of human tuberculosis].

Science.gov (United States)

Ottini, Laura; Falchetti, Mario

2010-01-01

Tuberculosis represents one of the humankind's most socially devastating diseases. Despite a long history of medical research and the development of effective therapies, this disease remains a global health danger even in the 21st century. Tuberculosis may cause death but infected people with effective immunity may remain healthy for years, suggesting long-term host-pathogen co-existence. Because of its antiquity, a supposed association with human settlements and the tendency to leave typical lesions on skeletal and mummified remains, tuberculosis has been the object of intensive multidisciplinary studies, including paleo-pathological research. During the past 10 years molecular paleo-pathology developed as a new scientific discipline allowing the study of ancient pathogens by direct detection of their DNA. In this work, we reviewed evidences for tuberculosis in ancient human remains, current methods for identifying ancient mycobacterial DNA and explored current theories of Mycobacterium tuberculosis evolution and their implications in the global development of tuberculosis looking into the past and present at the same time.

Comparing hair-morphology and molecular methods to identify fecal samples from Neotropical felids.

Directory of Open Access Journals (Sweden)

Carlos C Alberts

Full Text Available To avoid certain problems encountered with more-traditional and invasive methods in behavioral-ecology studies of mammalian predators, such as felids, molecular approaches have been employed to identify feces found in the field. However, this method requires a complete molecular biology laboratory, and usually also requires very fresh fecal samples to avoid DNA degradation. Both conditions are normally absent in the field. To address these difficulties, identification based on morphological characters (length, color, banding, scales and medullar patterns of hairs found in feces could be employed as an alternative. In this study we constructed a morphological identification key for guard hairs of eight Neotropical felids (jaguar, oncilla, Geoffroy's cat, margay, ocelot, Pampas cat, puma and jaguarundi and compared its efficiency to that of a molecular identification method, using the ATP6 region as a marker. For this molecular approach, we simulated some field conditions by postponing sample-conservation procedures. A blind test of the identification key obtained a nearly 70% overall success rate, which we considered equivalent to or better than the results of some molecular methods (probably due to DNA degradation found in other studies. The jaguar, puma and jaguarundi could be unequivocally discriminated from any other Neotropical felid. On a scale ranging from inadequate to excellent, the key proved poor only for the margay, with only 30% of its hairs successfully identified using this key; and have intermediate success rates for the remaining species, the oncilla, Geoffroy's cat, ocelot and Pampas cat, were intermediate. Complementary information about the known distributions of felid populations may be necessary to substantially improve the results obtained with the key. Our own molecular results were even better, since all blind-tested samples were correctly identified. Part of these identifications were made from samples kept in suboptimal

Physician supply and demand in anatomical pathology in Taiwan.

Science.gov (United States)

Hsu, Chih-Yi; Jung, Shih-Ming; Chuang, Shih-Sung

2011-02-01

Anatomical pathology was not popular in Taiwan a few decades ago, with a severe shortage of pathologists. However, there has been a steady increase in recent years, and now there is a threat of oversupply We evaluated supply and demand over the past three decades and compared the findings with other countries. We collected the enrollment data of pathologists and physicians from the Taiwan Society of Pathology, the Department of Health, Executive Yuan, and Taiwan Medical Association, and analyzed equivalent data from other countries. We sent questionnaires to pathology chiefs to inquire about future job vacancies. The number of pathologists has increased at an annual rate of 4.93% between 2004 and 2008, in contrast to 3.7% for all physicians. There has been a net annual increase of 12 pathologists in the past 13 years. The estimated average number of consultant posts per year was nine, which was only one-third of the average number of first-year residents (R1s). The number of pathologists/million population in Taiwan was 14.83, which was comparable to that in Japan and South Korea but much smaller than that in Canada and the United States. The ratio of pathologists to physicians in Taiwan was 0.97%, which was higher than that in Japan (0.68%) and South Korea (0.64%), but lower than in Canada (1.32%) and the United States (1.46%). On average, 1.79% of medical graduates chose pathology for their R1 training in Taiwan, which was higher than that in the United States (1.50%) and Canada (1.10-1.20%). Anatomical pathology is no longer a specialty that is facing a physician shortage in Taiwan, and there is now a relatively high pathologist/physician ratio among Asian countries. We suggest that a decrease in the number of R1s in pathology is needed to maintain a balance between supply and demand. Copyright © 2011 Formosan Medical Association & Elsevier. Published by Elsevier B.V. All rights reserved.

Dimensions of personality pathology in adolescents: Relations to DSM-IV personality disorder symptoms

OpenAIRE

Tromp, N.B.; Koot, H.M.

2009-01-01

The aim of the present study was to relate and compare two approaches to personality pathology in adolescents. Dimensions of personality pathology, assessed by the Dimensional Assessment of Personality Pathology-Basic Questionnaire for Adolescents (DAPP-BQ-A; Tromp & Koot, 2008), were related to DSM-IV personality disorder (PD) symptoms in 168 adolescents referred for mental health services. Correlational analyses revealed that the DAPP-BQ-A higher- and lower-order dimensions were related to ...

The Molecular Biology of Soft-Tissue Sarcomas and Current Trends in Therapy

Directory of Open Access Journals (Sweden)

Jorge Quesada

2012-01-01

Full Text Available Basic research in sarcoma models has been fundamental in the discovery of scientific milestones leading to a better understanding of the molecular biology of cancer. Yet, clinical research in sarcoma has lagged behind other cancers because of the multiple clinical and pathological entities that characterize sarcomas and their rarity. Sarcomas encompass a very heterogeneous group of tumors with diverse pathological and clinical overlapping characteristics. Molecular testing has been fundamental in the identification and better definition of more specific entities among this vast array of malignancies. A group of sarcomas are distinguished by specific molecular aberrations such as somatic mutations, intergene deletions, gene amplifications, reciprocal translocations, and complex karyotypes. These and other discoveries have led to a better understanding of the growth signals and the molecular pathways involved in the development of these tumors. These findings are leading to treatment strategies currently under intense investigation. Disruption of the growth signals is being targeted with antagonistic antibodies, tyrosine kinase inhibitors, and inhibitors of several downstream molecules in diverse molecular pathways. Preliminary clinical trials, supported by solid basic research and strong preclinical evidence, promises a new era in the clinical management of these broad spectrum of malignant tumors.

Comparative studies on different molecular methods for ...

African Journals Online (AJOL)

The present study aims to evaluate two molecular methods for epidemiological typing of multi drug resistant Klebsiella pneumoniae isolated from Mansoura Hospitals. In this study, a total of 300 clinical isolates were collected from different patients distributed among Mansoura Hospitals, Dakahlia governorate, Egypt.

Molecular profiling--a tool for addressing emerging gaps in the comparative risk assessment of GMOs.

Science.gov (United States)

Heinemann, Jack A; Kurenbach, Brigitta; Quist, David

2011-10-01

Assessing the risks of genetically modified organisms (GMOs) is required by both international agreement and domestic legislation. Many view the use of the "omics" tools for profiling classes of molecules as useful in risk assessment, but no consensus has formed on the need or value of these techniques for assessing the risks of all GMOs. In this and many other cases, experts support case-by-case use of molecular profiling techniques for risk assessment. We review the latest research on the applicability and usefulness of molecular profiling techniques for GMO risk assessment. As more and more kinds of GMOs and traits are developed, broader use of molecular profiling in a risk assessment may be required to supplement the comparative approach to risk assessment. The literature-based discussions on the use of profiling appear to have settled on two findings: 1. profiling techniques are reliable and relevant, at least no less so than other techniques used in risk assessment; and 2. although not required routinely, regulators should be aware of when they are needed. The dismissal of routine molecular profiling may be confusing to regulators who then lack guidance on when molecular profiling might be worthwhile. Molecular profiling is an important way to increase confidence in risk assessments if the profiles are properly designed to address relevant risks and are applied at the correct stage of the assessment. Copyright © 2011 Elsevier Ltd. All rights reserved.

Alzheimer's disease pathological lesions activate the spleen tyrosine kinase.

Science.gov (United States)

Schweig, Jonas Elias; Yao, Hailan; Beaulieu-Abdelahad, David; Ait-Ghezala, Ghania; Mouzon, Benoit; Crawford, Fiona; Mullan, Michael; Paris, Daniel

2017-09-06

The pathology of Alzheimer's disease (AD) is characterized by dystrophic neurites (DNs) surrounding extracellular Aβ-plaques, microgliosis, astrogliosis, intraneuronal tau hyperphosphorylation and aggregation. We have previously shown that inhibition of the spleen tyrosine kinase (Syk) lowers Aβ production and tau hyperphosphorylation in vitro and in vivo. Here, we demonstrate that Aβ-overexpressing Tg PS1/APPsw, Tg APPsw mice, and tau overexpressing Tg Tau P301S mice exhibit a pathological activation of Syk compared to wild-type littermates. Syk activation is occurring in a subset of microglia and is age-dependently increased in Aβ-plaque-associated dystrophic neurites of Tg PS1/APPsw and Tg APPsw mice. In Tg Tau P301S mice, a pure model of tauopathy, activated Syk occurs in neurons that show an accumulation of misfolded and hyperphosphorylated tau in the cortex and hippocampus. Interestingly, the tau pathology is exacerbated in neurons that display high levels of Syk activation supporting a role of Syk in the formation of tau pathological species in vivo. Importantly, human AD brain sections show both pathological Syk activation in DNs around Aβ deposits and in neurons immunopositive for pathological tau species recapitulating the data obtained in transgenic mouse models of AD. Additionally, we show that Syk overexpression leads to increased tau accumulation and promotes tau hyperphosphorylation at multiple epitopes in human neuron-like SH-SY5Y cells, further supporting a role of Syk in the formation of tau pathogenic species. Collectively, our data show that Syk activation occurs following Aβ deposition and the formation of tau pathological species. Given that we have previously shown that Syk activation also promotes Aβ formation and tau hyperphosphorylation, our data suggest that AD pathological lesions may be self-propagating via a Syk dependent mechanism highlighting Syk as an attractive therapeutic target for the treatment of AD.

One fungus, one name promotes progressive plant pathology

NARCIS (Netherlands)

Wingfield, M.J.; De Beer, Z.W.; Slippers, B.; Wingfield, B.D.; Groenewald, J.Z.; Lombard, L.; Crous, P.W.

2011-01-01

The robust and reliable identification of fungi underpins virtually every element of plant pathology, from disease diagnosis to studies of biology, management/control, quarantine and, even more recently, comparative genomics. Most plant diseases are caused by fungi, typically pleomorphic organisms,

One fungus, one name promotes progressive plant pathology

NARCIS (Netherlands)

Wingfield, M.J.; Beer, de Z.W.; Slippers, B.; Wingfield, B.D.; Groenewald, J.Z.; Lombard, L.; Crous, P.W.

2012-01-01

The robust and reliable identification of fungi underpins virtually every element of plant pathology, from disease diagnosis to studies of biology, management/control, quarantine and, even more recently, comparative genomics. Most plant diseases are caused by fungi, typically pleomorphic organisms,

Molecular Neuropathology of TDP-43 Proteinopathies

Directory of Open Access Journals (Sweden)

Manuela Neumann

2009-01-01

Full Text Available The identification of TDP-43 as the major component of the pathologic inclusions in most forms of sporadic and familial frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U and amyotrophic lateral sclerosis (ALS resolved a long-standing enigma concerning the nature of the ubiquitinated disease protein under these conditions. Anti-TDP-43 immunohistochemistry and the recent development of novel tools, such as phosphorylation-specific TDP-43 antibodies, have increased our knowledge about the spectrum of pathological changes associated with FTLD-U and ALS and moreover, facilitated the neuropathological routine diagnosis of these conditions. This review summarizes the recent advances in our understanding on the molecular neuropathology and pathobiology of TDP-43 in FTLD and ALS.

Molecular and parametric imaging with iron oxides

International Nuclear Information System (INIS)

Matuszewski, L.; Bremer, C.; Tombach, B.; Heindel, W.

2007-01-01

Superparamagnetic iron oxide (SPIO) contrast agents, clinically established for high resolution magnetic resonance imaging of reticuloendothelial system containing anatomical structures, can additionally be exploited for the non-invasive characterization and quantification of pathology down to the molecular level. In this context, SPIOs can be applied for non-invasive cell tracking, quantification of tissue perfusion and target specific imaging, as well as for the detection of gene expression. This article provides an overview of new applications for clinically approved iron oxides as well of new, modified SPIO contrast agents for parametric and molecular imaging. (orig.) [de

Molecular Insights into Crimean-Congo Hemorrhagic Fever Virus

Directory of Open Access Journals (Sweden)

Marko Zivcec

2016-04-01

Full Text Available Crimean-Congo hemorrhagic fever virus (CCHFV is a tick-borne pathogen that causes high morbidity and mortality. Efficacy of vaccines and antivirals to treat human CCHFV infections remains limited and controversial. Research into pathology and underlying molecular mechanisms of CCHFV and other nairoviruses is limited. Significant progress has been made in our understanding of CCHFV replication and pathogenesis in the past decade. Here we review the most recent molecular advances in CCHFV-related research, and provide perspectives on future research.

CT and pathologic correlation acute miliary pulmonary tuberculosis

International Nuclear Information System (INIS)

Yang Jing; Ma Daqing; Zhang Yansong; Guan Yansheng; Yang Jun; Liu Weihua

2011-01-01

Objective: To elucidate the CT characteristics and pathology of acute miliary pulmonary tuberculosis (AMPT). Methods: The CT features of AMPT in 25 cases were analyzed retrospectively, and the CT features in HIV-seronegative and HIV-seropositive patients were compared by 2-sided exact probability Chi-square test. Two lung specimens were inflated and fixed by Heitzman's method. HRCT scans, gross specimen section (80-150 μm) and histologic section (5 μm) were performed on dry lung specimens and CT-pathologic correlation was conducted. The distribution of micronodules in the secondary lobule on HRCT and pathology in one specimen was evaluated by Chi-square test. Results: Twenty five patients with AMPT were included in this study, including 11 HIV-seropositive patients and 14 HIV- seronegative patients. HRCT showed diffuse micronodules randomly distributed throughout both lungs in 25 patients, and ground-glass opacity (17 patients) was the predominant complicated finding. Coalescence of nodules and consolidation in HIV-seropositive patients (5 and 6 patients) were markedly higher than that in HIV-seronegative patients (none). In lung specimens, most nodules located in the lung parenchyma between the central bronchovascular bundle and the perilobular structures (792 and 560 nodules), which located in the interlobular septum pathologically. The distribution of micronodules in the secondary lobule showed on HRCT (1060 nodules) and pathology (864 nodules) was not significantly difference (χ 2 =2.814, P>0.05) . HRCT showed ground-glass opacities when ARDS occurred, which were pulmonary edema, inflammation and hyaline membrane on alveolar wall pathologically. Conclusions: The HRCT characteristic of nodule distribution in AMPT is random. ARDS should be suspected when diffuse ground-glass opacities appear on HRCT. (authors)

Applications of flow cytometry in plant pathology for genome size determination, detection and physiological status.

Science.gov (United States)

D'Hondt, Liesbet; Höfte, Monica; Van Bockstaele, Erik; Leus, Leen

2011-10-01

Flow cytometers are probably the most multipurpose laboratory devices available. They can analyse a vast and very diverse range of cell parameters. This technique has left its mark on cancer, human immunodeficiency virus and immunology research, and is indispensable in routine clinical diagnostics. Flow cytometry (FCM) is also a well-known tool for the detection and physiological status assessment of microorganisms in drinking water, marine environments, food and fermentation processes. However, flow cytometers are seldom used in plant pathology, despite FCM's major advantages as both a detection method and a research tool. Potential uses of FCM include the characterization of genome sizes of fungal and oomycete populations, multiplexed pathogen detection and the monitoring of the viability, culturability and gene expression of plant pathogens, and many others. This review provides an overview of the history, advantages and disadvantages of FCM, and focuses on the current applications and future possibilities of FCM in plant pathology. © 2011 THE AUTHORS. MOLECULAR PLANT PATHOLOGY © 2011 BSPP AND BLACKWELL PUBLISHING LTD.

[Sociodemographic Traits and Comorbidities in Pathological Gamblers With a Suicide Attempt in Spain].

Science.gov (United States)

Verdura-Vizcaíno, Ernesto José; Fernández-Navarro, Pablo; Vian-Lains, Antonio; Ibañez, Ángela; Baca-García, Enrique

2015-01-01

Suicide is the first cause of non-natural death in Spain. Among addictive disorders, pathological gambling is one the most significant independent risk factors for suicidal behavior. The objective of this study is to describe and compare the sociodemographic traits, comorbidity and attempt characteristics, between suicide attempters who fulfill diagnostic criteria for pathological gambling and those who do not. A total of 345 patients admitted to the emergency department of a University Hospital in Madrid between 1999 and 2004 were interviewed for this study. To describe and compare the demographic characteristics, comorbidity and those related to attempted suicide, using logistic regression models adjusted for sex and age were used. Suicide attempters who fulfilled diagnostic criteria for pathological gambling were predominantly male, with a low education level, and had more offspring. Furthermore, these patients had more comorbidities, such as: global substance dependence, nicotine, cocaine and opioid dependence. The present study suggests that pathological gamblers represent a distinct subgroup among suicide attempters, with particular characteristics, similar to those found in pathological gamblers in the general population. Copyright © 2015 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Quality of pathology reports for advanced ovarian cancer

DEFF Research Database (Denmark)

Verleye, Leen; Ottevanger, Petronella B; Kristensen, Gunnar B

2011-01-01

To assess the quality of surgical pathology reports of advanced stage ovarian, fallopian tube and primary peritoneal cancer. This quality assurance project was performed within the EORTC-GCG 55971/NCIC-CTG OV13 study comparing primary debulking surgery followed by chemotherapy with neoadjuvant...

The Surgical Treatment and Outcome of Nonmetastatic Extremity Osteosarcoma with Pathological Fractures

Directory of Open Access Journals (Sweden)

Zhi-Ping Deng

2015-01-01

Conclusions: Our study suggests that surgically treated patients with pathologic fractures in osteosarcoma have adequate local control and do not have a poorer outcome compared to patients without a fracture. Though osteosarcoma with a pathologic fracture is not a contraindication for limb salvage, appropriate case selection is important when deciding local control options to ensure adequate oncologic clearance.

Down's Syndrome with Alzheimer's Disease-Like Pathology: What Can It Teach Us about the Amyloid Cascade Hypothesis?

Directory of Open Access Journals (Sweden)

Rania M. Bakkar

2010-01-01

Full Text Available Down's syndrome (DS, trisomy 21 represents a complex genetic abnormality that leads to pathology in later life that is similar to Alzheimer's disease (AD. We compared two cases of DS with APOE 3/3 genotypes, a similar age at death, and comparable amyloid-beta 42 peptide (A42 burdens in the brain but that differed markedly in the severity of AD-like pathology. One exhibited extensive neurofibrillary pathology whereas the other showed minimal features of this type. Comparable loads of A42 could relate to the cases' similar life-time accumulation of A due to trisomy 21-enhanced metabolism of amyloid precursor protein (APP. The cases' significant difference in AD-like pathology, however, suggests that parenchymal deposition of A42, even when extensive, may not inevitably trigger AD-like tau pathology (though it may be necessary. Thus, these observations of a natural experiment may contribute to understanding the nuances of the amyloid cascade hypothesis of AD pathogenesis.

Nanomedicine for the molecular diagnosis of cardiovascular pathologies

Energy Technology Data Exchange (ETDEWEB)

Juenet, Maya; Varna, Mariana; Aid-Launais, Rachida [Inserm, U1148, Cardiovascular Bio-Engineering, X. Bichat Hospital, 75018, Paris (France); Université Paris 13, Institut Galilée, Sorbonne Paris Cité, 75018, Paris (France); Chauvierre, Cédric, E-mail: cedric.chauvierre@inserm.fr [Inserm, U1148, Cardiovascular Bio-Engineering, X. Bichat Hospital, 75018, Paris (France); Université Paris 13, Institut Galilée, Sorbonne Paris Cité, 75018, Paris (France); Letourneur, Didier [Inserm, U1148, Cardiovascular Bio-Engineering, X. Bichat Hospital, 75018, Paris (France); Université Paris 13, Institut Galilée, Sorbonne Paris Cité, 75018, Paris (France)

2015-12-18

Predicting acute clinical events caused by atherosclerotic plaque rupture remains a clinical challenge. Anatomic mapping of the vascular tree provided by standard imaging technologies is not always sufficient for a robust diagnosis. Yet biological mechanisms leading to unstable plaques have been identified and corresponding biomarkers have been described. Nanosystems charged with contrast agents and targeted towards these specific biomarkers have been developed for several types of imaging modalities. The first systems that have reached the clinic are ultrasmall superparamagnetic iron oxides for Magnetic Resonance Imaging. Their potential relies on their passive accumulation by predominant physiological mechanisms in rupture-prone plaques. Active targeting strategies are under development to improve their specificity and set up other types of nanoplatforms. Preclinical results show a huge potential of nanomedicine for cardiovascular diagnosis, as long as the safety of these nanosystems in the body is studied in depth. - Highlights: • Ischemic stroke and myocardial infarction are the main causes of death in the world. • Their prevalence is related to late detection of high-risk atherosclerotic plaques. • Biomarkers of atherosclerosis evolution and potential ligands have been identified. • Nanosystems based on these ligands appear promising for early molecular diagnosis. • Preclinical and clinical nanosystems for common imaging modalities are described.

Nanomedicine for the molecular diagnosis of cardiovascular pathologies

International Nuclear Information System (INIS)

Juenet, Maya; Varna, Mariana; Aid-Launais, Rachida; Chauvierre, Cédric; Letourneur, Didier

2015-01-01

Predicting acute clinical events caused by atherosclerotic plaque rupture remains a clinical challenge. Anatomic mapping of the vascular tree provided by standard imaging technologies is not always sufficient for a robust diagnosis. Yet biological mechanisms leading to unstable plaques have been identified and corresponding biomarkers have been described. Nanosystems charged with contrast agents and targeted towards these specific biomarkers have been developed for several types of imaging modalities. The first systems that have reached the clinic are ultrasmall superparamagnetic iron oxides for Magnetic Resonance Imaging. Their potential relies on their passive accumulation by predominant physiological mechanisms in rupture-prone plaques. Active targeting strategies are under development to improve their specificity and set up other types of nanoplatforms. Preclinical results show a huge potential of nanomedicine for cardiovascular diagnosis, as long as the safety of these nanosystems in the body is studied in depth. - Highlights: • Ischemic stroke and myocardial infarction are the main causes of death in the world. • Their prevalence is related to late detection of high-risk atherosclerotic plaques. • Biomarkers of atherosclerosis evolution and potential ligands have been identified. • Nanosystems based on these ligands appear promising for early molecular diagnosis. • Preclinical and clinical nanosystems for common imaging modalities are described.

Variable ultrasonography findings of extremity lymphangioma: Pathologic correlation

International Nuclear Information System (INIS)

Oh, Jong Young; Nam, Kyung Jin; Lee, Ki Nam; Kim, Chan Sung; Lee, Jin Hwa; Kim, Dae Chul

2002-01-01

The great majority of lymphangiomas occur in the neck (75%) and axilla (20%), but extremity lymphangioma is rare. We correlate variable sonographic features of extremity lymphangioma with pathologic findings. We reviewed the sonographic findings of extremity lymphangioma in 14 patients (M:F=8:6). The all cases were histologically confirmed by operation. The variable sonographic features of extremity lymphangioma were compared to pathologic findings. The multilocular cystic mass with ill defined boundaries was distinctive sonographic appearance of extremity lymphangioma. But there were variable sonographic findings such as heterogeneous echogenic mass or homogeneous echogenic portion. The histologic section of echogenic lesion reveals clusters of abnormal

Feline panleukopenia virus revisited : molecular characteristics and pathological lesions associated with three recent isolates

Directory of Open Access Journals (Sweden)

M. Van Vuuren

2000-07-01

Full Text Available The low incidence of clinical signs or pathological lesions compatible with feline panleukopenia in cats has created the perception among practitioners that the disease has disappeared since the emergence of canine parvovirus type 2 in the late 1970s.Three parvoviruses that were recently isolated from a domestic cat and 2 cheetahs in cell culture or detected by means of the polymerase chain reaction were shown to be typical feline parvoviruses. Phylogenetic comparison with other FPV isolates did not reveal a particular African cluster.

Surgical Pathology Resident Rotation Restructuring at a Tertiary Care Academic Center.

Science.gov (United States)

Mehr, Chelsea R; Obstfeld, Amrom E; Barrett, Amanda C; Montone, Kathleen T; Schwartz, Lauren E

2017-01-01

Changes in the field of pathology and resident education necessitate ongoing evaluation of residency training. Evolutionary change is particularly important for surgical pathology rotations, which form the core of anatomic pathology training programs. In the past, we organized this rotation based on subjective insight. When faced with the recent need to restructure the rotation, we strove for a more evidence-based process. Our approach involved 2 primary sources of data. We quantified the number of cases and blocks submitted per case type to estimate workload and surveyed residents about the time required to gross specimens in all organ systems. A multidisciplinary committee including faculty, residents, and staff evaluated the results and used the data to model how various changes to the rotation would affect resident workload, turnaround time, and other variables. Finally, we identified rotation structures that equally distributed work and created a point-based system that capped grossing time for residents of different experience. Following implementation, we retrospectively compared turnaround time and duty hour violations before and after these changes and surveyed residents about their experiences with both systems. We evaluated the accuracy of the point-based system by examining grossing times and comparing them to the assigned point values. We found overall improvement in the rotation following the implementation. As there is essentially no literature on the subject of surgical pathology rotation organization, we hope that our experience will provide a road map to improve pathology resident education at other institutions.

Surgical Pathology Resident Rotation Restructuring at a Tertiary Care Academic Center

Directory of Open Access Journals (Sweden)

Chelsea R. Mehr MD

2017-11-01

Full Text Available Changes in the field of pathology and resident education necessitate ongoing evaluation of residency training. Evolutionary change is particularly important for surgical pathology rotations, which form the core of anatomic pathology training programs. In the past, we organized this rotation based on subjective insight. When faced with the recent need to restructure the rotation, we strove for a more evidence-based process. Our approach involved 2 primary sources of data. We quantified the number of cases and blocks submitted per case type to estimate workload and surveyed residents about the time required to gross specimens in all organ systems. A multidisciplinary committee including faculty, residents, and staff evaluated the results and used the data to model how various changes to the rotation would affect resident workload, turnaround time, and other variables. Finally, we identified rotation structures that equally distributed work and created a point-based system that capped grossing time for residents of different experience. Following implementation, we retrospectively compared turnaround time and duty hour violations before and after these changes and surveyed residents about their experiences with both systems. We evaluated the accuracy of the point-based system by examining grossing times and comparing them to the assigned point values. We found overall improvement in the rotation following the implementation. As there is essentially no literature on the subject of surgical pathology rotation organization, we hope that our experience will provide a road map to improve pathology resident education at other institutions.

Pitfall in quantum mechanical/molecular mechanical molecular dynamics simulation of small solutes in solution.

Science.gov (United States)

Hu, Hao; Liu, Haiyan

2013-05-30

Developments in computing hardware and algorithms have made direct molecular dynamics simulation with the combined quantum mechanical/molecular mechanical methods affordable for small solute molecules in solution, in which much improved accuracy can be obtained via the quantum mechanical treatment of the solute molecule and even sometimes water molecules in the first solvation shell. However, unlike the conventional molecular mechanical simulations of large molecules, e.g., proteins, in solutions, special care must be taken in the technical details of the simulation, including the thermostat of the solute/solvent system, so that the conformational space of the solute molecules can be properly sampled. We show here that the common setup for classical molecular mechanical molecular dynamics simulations, such as the Berendsen or single Nose-Hoover thermostat, and/or rigid water models could lead to pathological sampling of the solutes' conformation. In the extreme example of a methanol molecule in aqueous solution, improper and sluggish setups could generate two peaks in the distribution of the O-H bond length. We discuss the factors responsible for this somewhat unexpected result and evoke a simple and ancient technical fix-up to resolve this problem.

Transvaginal versus transabdominal sonography in the evaluation of pelvic pathology

International Nuclear Information System (INIS)

Qureshi, I.H.; Ullah, H.; Akram, M.H.; Ashfaq, S.; Nayyar, S.

2004-01-01

Objective: To find the accuracy of sonographic information provided by transvaginal sonography (TVS) in pelvic pathology as compared to transabdominal sonography (TAS). Materials and Methods: Hundred patients were included in the study from a total of 212 referred for pelvic sonography. Two radiologists independently performed transabdominal and transvaginal sonography of these patients. An independent observer compared the findings. TVS was graded as superior, equal or inferior to TAS depending on the score assigned by them. Results: TVS was considered superior in 63%, equal in 27% and inferior in 10% of the cases as compared to transabdominal sonography. It was graded inferior to TAS in cases with large pelvic masses and superior in majority of cases of ovarian follicle monitoring, polycystic ovaries, endometrial carcinoma and suspected ectopic pregnancy. Cases in which both techniques were considered equal included patients with no abnormal finding, some pelvic masses and advanced pelvic inflammatory disease. Conclusion: Transvagival sonography is superior to transabdominal sonography in most cases of pelvic pathology. However, TAS should still be the initial sonographic technique for routine evaluation of the female pelvis followed by TVS if indicated. In cases of ovarian follicle monitoring, suspected polycystic ovaries, endometrial pathology and suspected ectopic pregnancy, TVS may be used as the initial sonographic technique and can even replace TAS. (author)

Finding the unexpected: pathological examination of surgically resected femoral heads

Energy Technology Data Exchange (ETDEWEB)

Fornasier, V.L. [St. Michael' s Hospital, University of Toronto, Department of Laboratory Medicine and Pathobiology, Toronto, Ontario (Canada); Battaglia, D.M. [St. Michael' s Hospital, University of Toronto, Department of Laboratory Medicine and Pathobiology, Toronto, Ontario (Canada); St. Michael' s Hospital, University of Toronto, Division of Pathology, Toronto, Ontario (Canada)

2005-06-01

To study the clinically diagnosed disease process but also identify additional, clinically undetected pathologies in femoral heads resected for replacement arthroplasty. A retrospective review was carried out of the pathological findings in 460 surgically resected femoral heads. Serial sections were submitted to low-energy fine-detail radiography, then decalcified sections stained by the WHO method were examined. The preoperative clinical and imaging diagnoses were compared with the pathological findings and special interest was placed on assessing the clinical significance of any unexpected, clinically undetected findings. The most common findings included the presence of bone islands (solitary osteomas) and areas of avascular necrosis in addition to the primary joint disease for which the patient underwent surgery. The preoperative symptomatology did not distinguish between the known primary disease and the additional pathological findings. Some of the clinically unidentified lesions were of a size that fell below the ability of current clinical investigations to detect. However, the finding of lesions by tissue fine-detail radiography indicates that current, more sensitive clinical imaging techniques may identify them. Careful examination of surgically resected femoral heads is important to ensure that all pathologies are identified and assessed for clinical relevance. (orig.)

Finding the unexpected: pathological examination of surgically resected femoral heads

International Nuclear Information System (INIS)

Fornasier, V.L.; Battaglia, D.M.

2005-01-01

To study the clinically diagnosed disease process but also identify additional, clinically undetected pathologies in femoral heads resected for replacement arthroplasty. A retrospective review was carried out of the pathological findings in 460 surgically resected femoral heads. Serial sections were submitted to low-energy fine-detail radiography, then decalcified sections stained by the WHO method were examined. The preoperative clinical and imaging diagnoses were compared with the pathological findings and special interest was placed on assessing the clinical significance of any unexpected, clinically undetected findings. The most common findings included the presence of bone islands (solitary osteomas) and areas of avascular necrosis in addition to the primary joint disease for which the patient underwent surgery. The preoperative symptomatology did not distinguish between the known primary disease and the additional pathological findings. Some of the clinically unidentified lesions were of a size that fell below the ability of current clinical investigations to detect. However, the finding of lesions by tissue fine-detail radiography indicates that current, more sensitive clinical imaging techniques may identify them. Careful examination of surgically resected femoral heads is important to ensure that all pathologies are identified and assessed for clinical relevance. (orig.)

Pathological gambling: an impulse control disorder? Measurement of impulsivity using neurocognitive tests.

Science.gov (United States)

Dannon, Pinhas N; Shoenfeld, Netta; Rosenberg, Oded; Kertzman, Semion; Kotler, Moshe

2010-04-01

Pathological gambling is classified in the DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders) and in the ICD-10 (International Classification of Disease) as an impulse control disorder. The association between impulsivity and pathological gambling remains a matter of debate: some researchers find high levels of impulsivity within pathological gamblers, others report no difference compared to controls, and yet others even suggest that it is lower. In this review we examine the relationship between pathological gambling and impulsivity assessed by various neurocognitive tests. These tests--the Stroop task, the Stop Signal Task, the Matching Familiar Figures Task, the Iowa Gambling Task, the Wisconsin Card Sorting Test, the Tower of London test, and the Continuous Performance Test--demonstrated less impulsivity in gambling behavior. The differences in performance between pathological gamblers and healthy controls on the neurocognitive tasks could be due to addictive behavior features rather than impulsive behavior.

The Rise of Forensic Pathology in Human Medicine: Lessons for Veterinary Forensic Pathology.

Science.gov (United States)

Pollanen, M S

2016-09-01

The rise of forensic pathology in human medicine has greatly contributed to the administration of justice, public safety and security, and medical knowledge. However, the evolution of human forensic pathology has been challenging. Veterinary forensic pathologists can learn from some of the lessons that have informed the growth and development of human forensic pathology. Three main observations have emerged in the past decade. First, wrongful convictions tell us to use a truth-seeking stance rather than an a priori "think dirty" stance when investigating obscure death. Second, missed homicides and concealed homicides tell us that training and certification are the beginning of reliable forensic pathology. Third, failure of a sustainable institutional arrangement that fosters a combination of service, research, and teaching will lead to stagnation of knowledge. Forensic pathology of humans and animals will flourish, help protect society, and support justice if we embrace a modern biomedical scientific model for our practice. We must build training programs, contribute to the published literature, and forge strong collaborative institutions. © The Author(s) 2016.

Thermodynamic Molecular Switch in Sequence-Specific Hydrophobic Interaction: Two Computational Models Compared

Directory of Open Access Journals (Sweden)

Paul Chun

2003-01-01

Full Text Available We have shown in our published work the existence of a thermodynamic switch in biological systems wherein a change of sign in ΔCp°(Treaction leads to a true negative minimum in the Gibbs free energy change of reaction, and hence, a maximum in the related Keq. We have examined 35 pair-wise, sequence-specific hydrophobic interactions over the temperature range of 273–333 K, based on data reported by Nemethy and Scheraga in 1962. A closer look at a single example, the pair-wise hydrophobic interaction of leucine-isoleucine, will demonstrate the significant differences when the data are analyzed using the Nemethy-Scheraga model or treated by the Planck-Benzinger methodology which we have developed. The change in inherent chemical bond energy at 0 K, ΔH°(T0 is 7.53 kcal mol-1 compared with 2.4 kcal mol-1, while ‹ts› is 365 K as compared with 355 K, for the Nemethy-Scheraga and Planck-Benzinger model, respectively. At ‹tm›, the thermal agitation energy is about five times greater than ΔH°(T0 in the Planck-Benzinger model, that is 465 K compared to 497 K in the Nemethy-Scheraga model. The results imply that the negative Gibbs free energy minimum at a well-defined ‹ts›, where TΔS° = 0 at about 355 K, has its origin in the sequence-specific hydrophobic interactions, which are highly dependent on details of molecular structure. The Nemethy-Scheraga model shows no evidence of the thermodynamic molecular switch that we have found to be a universal feature of biological interactions. The Planck-Benzinger method is the best known for evaluating the innate temperature-invariant enthalpy, ΔH°(T0, and provides for better understanding of the heat of reaction for biological molecules.

Pilomatricomas in children: imaging characteristics with pathologic correlation

International Nuclear Information System (INIS)

Lim, Hyun Wook; Im, Soo Ah; Lim, Gye-Yeon; Park, Hyun Jin; Lee, Heejeong; Sung, Mi Sook; Kang, Bong Joo; Kim, Jee Young

2007-01-01

Although pilomatricoma commonly occurs in children, there is still a poor understanding of the imaging characteristics of pilomatricoma and lack of agreement regarding its imaging findings and histopathologic features. To characterize the radiologic appearance of pilomatricomas on US, CT, and MR and to correlate the imaging findings with histopathologic features. The imaging findings of 47 pilomatricomas on US (n = 17), CT (n = 31), and MR (n = 5) were retrospectively evaluated. Pathologic specimens of all cases were reviewed and compared with imaging findings. All lesions were well-circumscribed, subcutaneous nodules with partial attachment to the overlying skin. On US, the lesions were mostly hyperechoic with posterior acoustic shadowing and hypoechoic rim. On CT, they appeared as enhancing soft-tissue masses with varying amounts of calcification. MR findings were internal reticulations and patchy areas on T2-weighted images and contrast-enhanced T1-weighted images, corresponding to edematous stroma on pathology. Peritumoral inflammatory changes and connective capsule on pathology were well correlated with imaging findings. Pilomatricoma should be considered when US or CT shows a well-defined hyperechoic or calcific nodule in subcutaneous fat attached to the skin in children. MR images may be helpful in diagnosis. Pathologic findings are well correlated with imaging findings. (orig.)

Quality of pathology reporting is crucial for cancer care and registration: a baseline assessment for breast cancers diagnosed in Belgium in 2008.

Science.gov (United States)

De Schutter, H; Van Damme, N; Colpaert, C; Galant, C; Lambein, K; Cornelis, A; Neven, P; Van Eycken, E

2015-04-01

Given the crucial role of pathology reporting in the management of breast cancers, we aimed to investigate the quality and variability of breast cancer pathology reporting in Belgium. Detailed information on non-molecular and molecular parameters was retrieved from the pathology protocols available at the Belgian Cancer Registry for 10,007 breast cancers diagnosed in Belgium in 2008. Substantial underreporting was shown for several clinically relevant non-molecular parameters, such as lymphovascular invasion. High-volume laboratories performed only slightly better than others, and analyses at the individual laboratory level showed clear inter-laboratory variability in reporting for all volume categories. Information on ER/PR and HER2 IHC was mentioned in respectively 91.7% and 90.8% of evaluative cases. HER2 ISH data were available for 78.5% of the cases judged to be 2+ for HER2 IHC. For cases with different specimens analysed, discordance between these specimens was highest for HER2, followed by PR. For HER2, results obtained from different laboratories were even less concordant. In addition, inter-laboratory differences were noted in the used ER/PR scoring systems, the proportion of ER-/PR+ cases, and the relation between histological grade and ER/PR positivity. Data on Ki67 were only available for 43.8% of the investigated cases, and showed inconsistent use of cut-off values. Breast pathology reporting in Belgium in 2008 was suboptimal and showed considerable inter-laboratory variability. Synoptic reporting has been proposed as a facilitator towards increased reporting quality and harmonization, but the lack of aligned informatics remains a major hurdle in its concrete implementation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Echo-Patterns of SmaII HepatoceIlular Carcinoma : A Pathologic Correlation

International Nuclear Information System (INIS)

Shin, Gil Hyun; Lim, Joo Won; Lee, Dong Ho; Ko, Young Tae; Yoon, Yup; Kim, Yoon Wha

1995-01-01

To evaluate the relationship of echo-patterns with pathologic findings in small hepatocellular carcinoma(HCC). Sonographic and pathologic correlation was done retrospectively in l5 cases of small HCC (≤ 3cm). The echogenecity of the lesion was compared with that of the adjacent normal liver parenchyma and classified into hypoechogenicity, isoechogenicity, and hyperechogenicity. The resected lesions we reanalyzed regarding the presence of coagulation necrosis, hemorrhage, fatty change, interstitial fibrosis, and sinusoidal dilatation. Assuming that those features contributed to the echogenicity of the lesion, we counted the number of the pathologic features that were seen in the resected lesion. Nine lesions classified asisoechoic, four lesions as hypoechoic, and two lesions as hyperechoic. At pathologic examination of the resected lesion, interstitial fibrosis was seen in 5 cases (33%), sinusoidal dilatation in 4(27%), coagulation necrosis in 2(l3%), fatty change in 2(l3%), and hemorrhage in 1(7%). All hypoechoic lesions were composed of purely cellular component without evidence of the pathologic features described above. The average number of the pathologic features was 1 in iso echoic lesion and 2 in hyperechoic lesion. Echo-patterns of small hepatocellular carcinoma are considered to be related with pathologic findings. Coagulation necrosis, hemorrhage, fatty change,interstitial fibrosis, and sinusoidal dilatation contribute to the increased echogenicity of small HCC

Pathological game use in adults with and without Autism Spectrum Disorder

Directory of Open Access Journals (Sweden)

Christopher R. Engelhardt

2017-06-01

Full Text Available This study tested whether adults with autism spectrum disorder (ASD are at higher risk for pathological game use than typically developing (TD adults. Participants included 119 adults with and without ASD. Participants completed measures assessing daily hours of video game use, percent of free time spent playing video games, and symptoms of pathological game use. The results indicated that adults with ASD endorsed more symptoms of video game pathology than did TD adults. This relationship was strong, enjoying 300,000-to-1 odds in Bayesian model comparison. Results also showed that adults with ASD spent more daily hours playing video games and spent a higher percent of their free time playing video games than did TD adults. Even after adjustment for these differences in daily video game hours and proportion of free time spent on games, model comparisons found evidence for a difference in game pathology scores associated with ASD status. Additionally, escapism motives for playing video games was associated with game pathology scores in both ASD and TD adults, replicating and extending a previous report. In conclusion, the risk for pathological game use appears larger in adults with ASD compared with TD adults. These findings point to pathological game use as a potentially important focus of clinical attention in adults with ASD.

Structure and Pathology of Tau Protein in Alzheimer Disease

Directory of Open Access Journals (Sweden)

Michala Kolarova

2012-01-01

Full Text Available Alzheimer's disease (AD is the most common type of dementia. In connection with the global trend of prolonging human life and the increasing number of elderly in the population, the AD becomes one of the most serious health and socioeconomic problems of the present. Tau protein promotes assembly and stabilizes microtubules, which contributes to the proper function of neuron. Alterations in the amount or the structure of tau protein can affect its role as a stabilizer of microtubules as well as some of the processes in which it is implicated. The molecular mechanisms governing tau aggregation are mainly represented by several posttranslational modifications that alter its structure and conformational state. Hence, abnormal phosphorylation and truncation of tau protein have gained attention as key mechanisms that become tau protein in a pathological entity. Evidences about the clinicopathological significance of phosphorylated and truncated tau have been documented during the progression of AD as well as their capacity to exert cytotoxicity when expressed in cell and animal models. This paper describes the normal structure and function of tau protein and its major alterations during its pathological aggregation in AD.

MR imaging of renal cell carcinoma. Associations among signal intensity, tumor enhancement, and pathologic findings

Energy Technology Data Exchange (ETDEWEB)

Yabuki, Takayuki; Togami, Izumi; Kitagawa, Takahiro; Sasai, Nobuya; Tsushima, Tomoyasu; Shirasaki, Yoshinori; Hiraki, Yoshio [Okayama Univ. (Japan). Graduate School of Medicine and Dentistry

2003-08-01

The purpose of this study was to compare the MR characteristics of renal cell carcinomas against histologic findings and to assess the correlations among signal intensity, tumor enhancement, and pathologic findings. Fifty-four patients (56 lesions) were examined by MR imaging and then underwent partial or radical nephrectomy. The pathologic diagnosis of all lesions was renal cell carcinoma. All MR examinations were performed as dynamic studies using the same 1.5-T scanner. MR characteristics were compared against pathologic findings after resection, and the correlations among signal intensity, tumor enhancement, and pathologic findings were then assessed. A significant correlation was observed between tumor grade and tumor enhancement, with G3 lesions tending to show little enhancement. Regardless of the histologic classification, G3 tumors were found to contain highly heterotypic cancer cells and very few vessels by histopathologic examination. No significant correlations were noted between the other MR characteristics and pathologic findings. Renal cell carcinomas showing little enhancement tend to be highly malignant lesions based on the pathologic findings. Special consideration is required for these tumors with regard to the selection of surgical intervention and follow-up observation. (author)

MR imaging of renal cell carcinoma. Associations among signal intensity, tumor enhancement, and pathologic findings

International Nuclear Information System (INIS)

Yabuki, Takayuki; Togami, Izumi; Kitagawa, Takahiro; Sasai, Nobuya; Tsushima, Tomoyasu; Shirasaki, Yoshinori; Hiraki, Yoshio

2003-01-01

The purpose of this study was to compare the MR characteristics of renal cell carcinomas against histologic findings and to assess the correlations among signal intensity, tumor enhancement, and pathologic findings. Fifty-four patients (56 lesions) were examined by MR imaging and then underwent partial or radical nephrectomy. The pathologic diagnosis of all lesions was renal cell carcinoma. All MR examinations were performed as dynamic studies using the same 1.5-T scanner. MR characteristics were compared against pathologic findings after resection, and the correlations among signal intensity, tumor enhancement, and pathologic findings were then assessed. A significant correlation was observed between tumor grade and tumor enhancement, with G3 lesions tending to show little enhancement. Regardless of the histologic classification, G3 tumors were found to contain highly heterotypic cancer cells and very few vessels by histopathologic examination. No significant correlations were noted between the other MR characteristics and pathologic findings. Renal cell carcinomas showing little enhancement tend to be highly malignant lesions based on the pathologic findings. Special consideration is required for these tumors with regard to the selection of surgical intervention and follow-up observation. (author)

Infrared Spectroscopic Imaging for Prostate Pathology Practice

Science.gov (United States)

2011-04-01

Clinical Pathology, Chicago 3. Partin AW, Mangold LA, Lamm DM , Walsh PC, Epstein JI, Pearson JD (2001) Urology 58:843–848 4. De La Taille A, Viellefond...are used to seeing only in optical microscopy,” he recalls. “The crispness , the details were comparable.” In fact, the pixel size is only a half

Tumor Size on Abdominal MRI Versus Pathologic Specimen in Resected Pancreatic Adenocarcinoma: Implications for Radiation Treatment Planning

Energy Technology Data Exchange (ETDEWEB)

Hall, William A., E-mail: whall4@emory.edu [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Mikell, John L. [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Mittal, Pardeep [Department of Radiology, Emory University, Atlanta, Georgia (United States); Colbert, Lauren [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Prabhu, Roshan S. [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Kooby, David A. [Department of Surgery, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Nickleach, Dana [Biostatistics and Bioinformatics Shared Resource, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Hanley, Krisztina [Department of Pathology, Emory University, Atlanta, Georgia (United States); Sarmiento, Juan M. [Department of Surgery, Emory University, Atlanta, Georgia (United States); Ali, Arif N.; Landry, Jerome C. [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States)

2013-05-01

Purpose: We assessed the accuracy of abdominal magnetic resonance imaging (MRI) for determining tumor size by comparing the preoperative contrast-enhanced T1-weighted gradient echo (3-dimensional [3D] volumetric interpolated breath-hold [VIBE]) MRI tumor size with pathologic specimen size. Methods and Materials: The records of 92 patients who had both preoperative contrast-enhanced 3D VIBE MRI images and detailed pathologic specimen measurements were available for review. Primary tumor size from the MRI was independently measured by a single diagnostic radiologist (P.M.) who was blinded to the pathology reports. Pathologic tumor measurements from gross specimens were obtained from the pathology reports. The maximum dimensions of tumor measured in any plane on the MRI and the gross specimen were compared. The median difference between the pathology sample and the MRI measurements was calculated. A paired t test was conducted to test for differences between the MRI and pathology measurements. The Pearson correlation coefficient was used to measure the association of disparity between the MRI and pathology sizes with the pathology size. Disparities relative to pathology size were also examined and tested for significance using a 1-sample t test. Results: The median patient age was 64.5 years. The primary site was pancreatic head in 81 patients, body in 4, and tail in 7. Three patients were American Joint Commission on Cancer stage IA, 7 stage IB, 21 stage IIA, 58 stage IIB, and 3 stage III. The 3D VIBE MRI underestimated tumor size by a median difference of 4 mm (range, −34-22 mm). The median largest tumor dimensions on MRI and pathology specimen were 2.65 cm (range, 1.5-9.5 cm) and 3.2 cm (range, 1.3-10 cm), respectively. Conclusions: Contrast-enhanced 3D VIBE MRI underestimates tumor size by 4 mm when compared with pathologic specimen. Advanced abdominal MRI sequences warrant further investigation for radiation therapy planning in pancreatic adenocarcinoma before

Tumor Size on Abdominal MRI Versus Pathologic Specimen in Resected Pancreatic Adenocarcinoma: Implications for Radiation Treatment Planning

International Nuclear Information System (INIS)

Hall, William A.; Mikell, John L.; Mittal, Pardeep; Colbert, Lauren; Prabhu, Roshan S.; Kooby, David A.; Nickleach, Dana; Hanley, Krisztina; Sarmiento, Juan M.; Ali, Arif N.; Landry, Jerome C.

2013-01-01

Purpose: We assessed the accuracy of abdominal magnetic resonance imaging (MRI) for determining tumor size by comparing the preoperative contrast-enhanced T1-weighted gradient echo (3-dimensional [3D] volumetric interpolated breath-hold [VIBE]) MRI tumor size with pathologic specimen size. Methods and Materials: The records of 92 patients who had both preoperative contrast-enhanced 3D VIBE MRI images and detailed pathologic specimen measurements were available for review. Primary tumor size from the MRI was independently measured by a single diagnostic radiologist (P.M.) who was blinded to the pathology reports. Pathologic tumor measurements from gross specimens were obtained from the pathology reports. The maximum dimensions of tumor measured in any plane on the MRI and the gross specimen were compared. The median difference between the pathology sample and the MRI measurements was calculated. A paired t test was conducted to test for differences between the MRI and pathology measurements. The Pearson correlation coefficient was used to measure the association of disparity between the MRI and pathology sizes with the pathology size. Disparities relative to pathology size were also examined and tested for significance using a 1-sample t test. Results: The median patient age was 64.5 years. The primary site was pancreatic head in 81 patients, body in 4, and tail in 7. Three patients were American Joint Commission on Cancer stage IA, 7 stage IB, 21 stage IIA, 58 stage IIB, and 3 stage III. The 3D VIBE MRI underestimated tumor size by a median difference of 4 mm (range, −34-22 mm). The median largest tumor dimensions on MRI and pathology specimen were 2.65 cm (range, 1.5-9.5 cm) and 3.2 cm (range, 1.3-10 cm), respectively. Conclusions: Contrast-enhanced 3D VIBE MRI underestimates tumor size by 4 mm when compared with pathologic specimen. Advanced abdominal MRI sequences warrant further investigation for radiation therapy planning in pancreatic adenocarcinoma before

Stroop performance in pathological gamblers.

Science.gov (United States)

Kertzman, Semion; Lowengrub, Katherine; Aizer, Anat; Nahum, Zeev Ben; Kotler, Moshe; Dannon, Pinhas N

2006-05-30

Pathological gambling is a relatively prevalent psychiatric disorder that typically leads to severe family, social, legal, and occupational problems and is associated with a high rate of suicide attempts. Understanding the neurobiological basis of pathological gambling is a current focus of research, and emerging data have demonstrated that pathological gamblers may have impaired decision-making because of an inability to inhibit irrelevant information. In this study, we examined pathological gamblers by using the Stroop Color-Word Test, a neurocognitive task used to assess interference control. The "reverse" variant of the Stroop Color-Word Test was administered to a cohort of medication-free pathological gamblers (n=62) and a cohort of age-matched controls (n=83). In the reverse variant of the Stroop task, subjects are asked to read the meaning of the word rather than name the ink color. The reverse Stroop task was chosen because it highly discriminates ability to inhibit interference in a population of psychiatric patients. In our study, performance on the reverse Stroop task in the pathological gamblers was significantly slower and less accurate than in the healthy subjects. A new finding in our study was that for pathological gamblers, the average reaction time in the neutral condition (where the color names are displayed in black letters) was slower than the average reaction time in the incongruent condition (where the meaning of the color name and the color of the printed letters are different). This controlled study extends previous findings by showing that performance on the Stroop task is impaired in a sample of medication-free pathological gamblers.

Pathological rate matrices: from primates to pathogens

Directory of Open Access Journals (Sweden)

Knight Rob

2008-12-01

Full Text Available Abstract Background Continuous-time Markov models allow flexible, parametrically succinct descriptions of sequence divergence. Non-reversible forms of these models are more biologically realistic but are challenging to develop. The instantaneous rate matrices defined for these models are typically transformed into substitution probability matrices using a matrix exponentiation algorithm that employs eigendecomposition, but this algorithm has characteristic vulnerabilities that lead to significant errors when a rate matrix possesses certain 'pathological' properties. Here we tested whether pathological rate matrices exist in nature, and consider the suitability of different algorithms to their computation. Results We used concatenated protein coding gene alignments from microbial genomes, primate genomes and independent intron alignments from primate genomes. The Taylor series expansion and eigendecomposition matrix exponentiation algorithms were compared to the less widely employed, but more robust, Padé with scaling and squaring algorithm for nucleotide, dinucleotide, codon and trinucleotide rate matrices. Pathological dinucleotide and trinucleotide matrices were evident in the microbial data set, affecting the eigendecomposition and Taylor algorithms respectively. Even using a conservative estimate of matrix error (occurrence of an invalid probability, both Taylor and eigendecomposition algorithms exhibited substantial error rates: ~100% of all exonic trinucleotide matrices were pathological to the Taylor algorithm while ~10% of codon positions 1 and 2 dinucleotide matrices and intronic trinucleotide matrices, and ~30% of codon matrices were pathological to eigendecomposition. The majority of Taylor algorithm errors derived from occurrence of multiple unobserved states. A small number of negative probabilities were detected from the Pad�� algorithm on trinucleotide matrices that were attributable to machine precision. Although the Pad

Benchmarking Academic Anatomic Pathologists: The Association of Pathology Chairs Survey.

Science.gov (United States)

Ducatman, Barbara S; Parslow, Tristram

2016-01-01

The most common benchmarks for faculty productivity are derived from Medical Group Management Association (MGMA) or Vizient-AAMC Faculty Practice Solutions Center ® (FPSC) databases. The Association of Pathology Chairs has also collected similar survey data for several years. We examined the Association of Pathology Chairs annual faculty productivity data and compared it with MGMA and FPSC data to understand the value, inherent flaws, and limitations of benchmarking data. We hypothesized that the variability in calculated faculty productivity is due to the type of practice model and clinical effort allocation. Data from the Association of Pathology Chairs survey on 629 surgical pathologists and/or anatomic pathologists from 51 programs were analyzed. From review of service assignments, we were able to assign each pathologist to a specific practice model: general anatomic pathologists/surgical pathologists, 1 or more subspecialties, or a hybrid of the 2 models. There were statistically significant differences among academic ranks and practice types. When we analyzed our data using each organization's methods, the median results for the anatomic pathologists/surgical pathologists general practice model compared to MGMA and FPSC results for anatomic and/or surgical pathology were quite close. Both MGMA and FPSC data exclude a significant proportion of academic pathologists with clinical duties. We used the more inclusive FPSC definition of clinical "full-time faculty" (0.60 clinical full-time equivalent and above). The correlation between clinical full-time equivalent effort allocation, annual days on service, and annual work relative value unit productivity was poor. This study demonstrates that effort allocations are variable across academic departments of pathology and do not correlate well with either work relative value unit effort or reported days on service. Although the Association of Pathology Chairs-reported median work relative value unit productivity

Nuclear microprobe analysis of muscle biopsies: Applications in pathology and clinic

International Nuclear Information System (INIS)

Moretto, Ph.; Coquet, M.; Gherardi, R.K.; Stoedzel, P.

2000-01-01

The nuclear microprobe analysis of muscle biopsy sections has been recently applied to investigate different muscle disorders. This technique, employed as a complementary examination in the frame of pathological studies, permitted to confirm the diagnosis for a first pathology and to elucidate the cause of a second. In skeletal muscles of a young patient suffering from a slow progressive myopathy, calcium accumulations have been demonstrated in histologically abnormal fibers. These findings have been compared to histopathological characteristics previously described. On the other hand, we have evaluated muscle sections from two patients who presented symptoms of an inflammatory myopathy, a rare pathology that recently emerged in France. The chemical analyses permitted us to highlight local aluminium infiltration in muscles. The hypothesis of an unusual reaction to intramuscular aluminium accumulation has been advanced. These studies demonstrate the capability for ion beam microanalytical techniques to address acute problems in pathology

Musculoskeletal ultrasound including definitions for ultrasonographic pathology

DEFF Research Database (Denmark)

Wakefield, RJ; Balint, PV; Szkudlarek, Marcin

2005-01-01

Ultrasound (US) has great potential as an outcome in rheumatoid arthritis trials for detecting bone erosions, synovitis, tendon disease, and enthesopathy. It has a number of distinct advantages over magnetic resonance imaging, including good patient tolerability and ability to scan multiple joints...... in a short period of time. However, there are scarce data regarding its validity, reproducibility, and responsiveness to change, making interpretation and comparison of studies difficult. In particular, there are limited data describing standardized scanning methodology and standardized definitions of US...... pathologies. This article presents the first report from the OMERACT ultrasound special interest group, which has compared US against the criteria of the OMERACT filter. Also proposed for the first time are consensus US definitions for common pathological lesions seen in patients with inflammatory arthritis....

Molecular and cellular neurocardiology: development, and cellular and molecular adaptations to heart disease

Science.gov (United States)

Anderson, Mark E.; Birren, Susan J.; Fukuda, Keiichi; Herring, Neil; Hoover, Donald B.; Kanazawa, Hideaki; Paterson, David J.; Ripplinger, Crystal M.

2016-01-01

Abstract The nervous system and cardiovascular system develop in concert and are functionally interconnected in both health and disease. This white paper focuses on the cellular and molecular mechanisms that underlie neural–cardiac interactions during development, during normal physiological function in the mature system, and during pathological remodelling in cardiovascular disease. The content on each subject was contributed by experts, and we hope that this will provide a useful resource for newcomers to neurocardiology as well as aficionados. PMID:27060296

Physiological and molecular biochemical mechanisms of bile formation

Science.gov (United States)

Reshetnyak, Vasiliy Ivanovich

2013-01-01

This review considers the physiological and molecular biochemical mechanisms of bile formation. The composition of bile and structure of a bile canaliculus, biosynthesis and conjugation of bile acids, bile phospholipids, formation of bile micellar structures, and enterohepatic circulation of bile acids are described. In general, the review focuses on the molecular physiology of the transporting systems of the hepatocyte sinusoidal and apical membranes. Knowledge of physiological and biochemical basis of bile formation has implications for understanding the mechanisms of development of pathological processes, associated with diseases of the liver and biliary tract. PMID:24259965

Gambling pathology is associated with dampened cortisol response among men and women.

Science.gov (United States)

Paris, J J; Franco, C; Sodano, R; Frye, C A; Wulfert, E

2010-02-09

Pathological gambling has many similarities to pharmacological addiction. Notably, both pathological gambling and drug addiction are characterized by aberrations in hypothalamic-pituitary-adrenal (HPA) axis responding. As well, there are indications that gender differences may play a role in these processes. Whether gender and/or HPA response are associated with pathological gambling was of interest. Recreational and pathological gamblers (15 men and 6 women per group) had the HPA factor, cortisol, assessed in saliva before and after watching a video of their preferred mode of gambling (slot machines, horse race betting, scratch-off tickets, blackjack, video poker, craps, sports betting, online casino games, or lottery tickets), and a video of neutral stimuli (a rollercoaster ride). Basal levels of salivary cortisol did not significantly differ among recreational and pathological gamblers. However, recreational gamblers demonstrated significantly increased salivary cortisol levels after the gambling and rollercoaster videos, whereas pathological gamblers demonstrated no salivary cortisol increase in response to either video stimulus. There was also a non-significant trend for women to have a greater cortisol response to video stimuli compared to men. These data suggest that pathological gambling is associated with hypoactive HPA response to gambling stimuli, similar to chronic drug exposure, and gender may contribute to this effect. Published by Elsevier Inc.

[Establishing Individualized Medicine for Intractable Cancer Based on Clinical Molecular Pathogenesis].

Science.gov (United States)

Jono, Hirofumi

2018-01-01

　Although cancer treatment has dramatically improved with the development of molecular-targeted agents over the past decade, identifying eligible patients and predicting the therapeutic effects remain a major challenge. Because intratumoral heterogeneity represents genetic and molecular differences affecting patients' responses to these therapeutic agents, establishing individualized medicine based on precise molecular pathological analysis of tumors is urgently required. This review focuses on the pathogenesis of oral squamous cell carcinoma (OSCC), a common head and neck neoplasm, and introduces our approaches toward developing novel anticancer therapies particularly based on clinical molecular pathogenesis. Deeper understanding of more precise molecular pathogenesis in clinical settings may open up novel strategies for establishing individualized medicine for OSCC.

Molecular Mechanisms of Glutamine Synthetase Mutations that Lead to Clinically Relevant Pathologies.

Directory of Open Access Journals (Sweden)

Benedikt Frieg

2016-02-01

Full Text Available Glutamine synthetase (GS catalyzes ATP-dependent ligation of ammonia and glutamate to glutamine. Two mutations of human GS (R324C and R341C were connected to congenital glutamine deficiency with severe brain malformations resulting in neonatal death. Another GS mutation (R324S was identified in a neurologically compromised patient. However, the molecular mechanisms underlying the impairment of GS activity by these mutations have remained elusive. Molecular dynamics simulations, free energy calculations, and rigidity analyses suggest that all three mutations influence the first step of GS catalytic cycle. The R324S and R324C mutations deteriorate GS catalytic activity due to loss of direct interactions with ATP. As to R324S, indirect, water-mediated interactions reduce this effect, which may explain the suggested higher GS residual activity. The R341C mutation weakens ATP binding by destabilizing the interacting residue R340 in the apo state of GS. Additionally, the mutation is predicted to result in a significant destabilization of helix H8, which should negatively affect glutamate binding. This prediction was tested in HEK293 cells overexpressing GS by dot-blot analysis: Structural stability of H8 was impaired through mutation of amino acids interacting with R341, as indicated by a loss of masking of an epitope in the glutamate binding pocket for a monoclonal anti-GS antibody by L-methionine-S-sulfoximine; in contrast, cells transfected with wild type GS showed the masking. Our analyses reveal complex molecular effects underlying impaired GS catalytic activity in three clinically relevant mutants. Our findings could stimulate the development of ATP binding-enhancing molecules by which the R324S mutant can be repaired extrinsically.

Comparative characterization of molecular varieties of thyroxine-binding human globulin

International Nuclear Information System (INIS)

Ermolenko, M.N.; Sviridov, O.V.; Strel'chenok, O.A.

1986-01-01

Two molecular varieties of thyroxine-binding globulin (TBG) of human retroplacental blood, obtained as a result of fractionation of pure TBG on concanavalin A-Sepharose, were studied. It was shown that these varieties (TBG-1 and TBG-2) are immunologically identical; they have the same molecular weight and amino acid composition, exhibit the same affinity for thyroid hormones, and are indistinguishable in spectral characteristics. And yet, TBG-1 and TBG-2 have differences in charge, detectable in isoelectrofocusing, and a different monosaccharide composition. The existence of molecular varieties of TBG during pregnancy is apparently due to the peculiarities of the glycosylation of the polypeptide chain during TBG biosynthesis

MRI for transformation of preserved organs and their pathologies into digital formats for medical education and creation of a virtual pathology museum. A pilot study

International Nuclear Information System (INIS)

Venkatesh, S.K.; Wang, G.; Seet, J.E.; Teo, L.L.S.; Chong, V.F.H.

2013-01-01

Aim: To evaluate the feasibility of magnetic resonance imaging (MRI) for the transformation of preserved organs and their disease entities into digital formats for medical education and creation of a virtual museum. Materials and methods: MRI of selected 114 pathology specimen jars representing different organs and their diseases was performed using a 3 T MRI machine with two or more MRI sequences including three-dimensional (3D) T1-weighted (T1W), 3D-T2W, 3D-FLAIR (fluid attenuated inversion recovery), fat–water separation (DIXON), and gradient-recalled echo (GRE) sequences. Qualitative assessment of MRI for depiction of disease and internal anatomy was performed. Volume rendering was performed on commercially available workstations. The digital images, 3D models, and photographs of specimens were archived into a workstation serving as a virtual pathology museum. Results: MRI was successfully performed on all specimens. The 3D-T1W and 3D-T2W sequences demonstrated the best contrast between normal and pathological tissues. The digital material is a useful aid for understanding disease by giving insights into internal structural changes not apparent on visual inspection alone. Volume rendering produced vivid 3D models with better contrast between normal tissue and diseased tissue compared to real specimens or their photographs in some cases. The digital library provides good illustration material for radiological–pathological correlation by enhancing pathological anatomy and information on nature and signal characteristics of tissues. In some specimens, the MRI appearance may be different from corresponding organ and disease in vivo due to dead tissue and changes induced by prolonged contact with preservative fluid. Conclusions: MRI of pathology specimens is feasible and provides excellent images for education and creating a virtual pathology museum that can serve as permanent record of digital material for self-directed learning, improving teaching aids, and

Social cost of pathological gambling.

Science.gov (United States)

Ladouceur, R; Boisvert, J M; Pépin, M; Loranger, M; Sylvain, C

1994-12-01

Pathological gambling creates enormous problems for the afflicted individuals, their families, employers, and society, and has numerous disastrous financial consequences. The present study evaluates the financial burdens of pathological gambling by questioning pathological gamblers in treatment in Gamblers Anonymous (n=60; 56 males, 4 females; mean age = 40 years old) about personal debts, loss of productivity at work, illegal activities, medical costs and the presence of other dependencies. Results show that important debts, loss of productivity at work and legal problems are associated with pathological gambling. Discussion is formulated in terms of the social cost of adopting a liberal attitude toward the legalization of various gambling activities.

Systems pathology: a critical review.

Science.gov (United States)

Costa, Jose

2012-02-01

The technological advances of the last twenty years together with the dramatic increase in computational power have injected new life into systems-level thinking in Medicine. This review emphasizes the close relationship of Systems Pathology to Systems Biology and delineates the differences between Systems Pathology and Clinical Systems Pathology. It also suggests an algorithm to support the application of systems-level thinking to clinical research, proposes applying systems-level thinking to the health care systems and forecasts an acceleration of preventive medicine as a result of the coupling of personal genomics with systems pathology. Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Comparative molecular dynamics study of neuromyelitis optica-immunoglobulin G binding to aquaporin-4 extracellular domains.

Science.gov (United States)

Alberga, Domenico; Trisciuzzi, Daniela; Lattanzi, Gianluca; Bennett, Jeffrey L; Verkman, Alan S; Mangiatordi, Giuseppe Felice; Nicolotti, Orazio

2017-08-01

Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system in which most patients have serum autoantibodies (called NMO-IgG) that bind to astrocyte water channel aquaporin-4 (AQP4). A potential therapeutic strategy in NMO is to block the interaction of NMO-IgG with AQP4. Building on recent observation that some single-point and compound mutations of the AQP4 extracellular loop C prevent NMO-IgG binding, we carried out comparative Molecular Dynamics (MD) investigations on three AQP4 mutants, TP 137-138 AA, N 153 Q and V 150 G, whose 295-ns long trajectories were compared to that of wild type human AQP4. A robust conclusion of our modeling is that loop C mutations affect the conformation of neighboring extracellular loop A, thereby interfering with NMO-IgG binding. Analysis of individual mutations suggested specific hydrogen bonding and other molecular interactions involved in AQP4-IgG binding to AQP4. Copyright © 2017 Elsevier B.V. All rights reserved.

Molecular medicine of fragile X syndrome: based on known molecular mechanisms.

Science.gov (United States)

Luo, Shi-Yu; Wu, Ling-Qian; Duan, Ran-Hui

2016-02-01

Extensive research on fragile X mental retardation gene knockout mice and mutant Drosophila models has largely expanded our knowledge on mechanism-based treatment of fragile X syndrome (FXS). In light of these findings, several clinical trials are now underway for therapeutic translation to humans. Electronic literature searches were conducted using the PubMed database and ClinicalTrials.gov. The search terms included "fragile X syndrome", "FXS and medication", "FXS and therapeutics" and "FXS and treatment". Based on the publications identified in this search, we reviewed the neuroanatomical abnormalities in FXS patients and the potential pathogenic mechanisms to monitor the progress of FXS research, from basic studies to clinical trials. The pathological mechanisms of FXS were categorized on the basis of neuroanatomy, synaptic structure, synaptic transmission and fragile X mental retardation protein (FMRP) loss of function. The neuroanatomical abnormalities in FXS were described to motivate extensive research into the region-specific pathologies in the brain responsible for FXS behavioural manifestations. Mechanism-directed molecular medicines were classified according to their target pathological mechanisms, and the most recent progress in clinical trials was discussed. Current mechanism-based studies and clinical trials have greatly contributed to the development of FXS pharmacological therapeutics. Research examining the extent to which these treatments provided a rescue effect or FMRP compensation for the developmental impairments in FXS patients may help to improve the efficacy of treatments.

Contrasting Pathology of the Stress Granule Proteins TIA-1 and G3BP in Tauopathies

Science.gov (United States)

Vanderweyde, Tara; Yu, Haung; Varnum, Megan; Liu-Yesucevitz, Liqun; Citro, Allison; Ikezu, Tsuneya; Duff, Karen; Wolozin, Benjamin

2012-01-01

Stress induces aggregation of RNA-binding proteins to form inclusions, termed stress granules (SGs). Recent evidence suggests that SG proteins also colocalize with neuropathological structures, but whether this occurs in Alzheimer’s disease is unknown. We examined the relationship between SG proteins and neuropathology in brain tissue from P301L Tau transgenic mice, as well as in cases of Alzheimer’s disease and FTDP-17. The pattern of SG pathology differs dramatically based on the RNA-binding protein examined. SGs positive for T-cell intracellular antigen-1 (TIA-1) or tristetraprolin (TTP) initially do not colocalize with tau pathology, but then merge with tau inclusions as disease severity increases. In contrast, G3BP (ras GAP-binding protein) identifies a novel type of molecular pathology that shows increasing accumulation in neurons with increasing disease severity, but often is not associated with classic markers of tau pathology. TIA-1 and TTP both bind phospho-tau, and TIA-1 overexpression induces formation of inclusions containing phospho-tau. These data suggest that SG formation might stimulate tau pathophysiology. Thus, study of RNA-binding proteins and SG biology highlights novel pathways interacting with the pathophysiology of AD, providing potentially new avenues for identifying diseased neurons and potentially novel mechanisms regulating tau biology. PMID:22699908

HDR Pathological Image Enhancement Based on Improved Bias Field Correction and Guided Image Filter

Directory of Open Access Journals (Sweden)

Qingjiao Sun

2016-01-01

Full Text Available Pathological image enhancement is a significant topic in the field of pathological image processing. This paper proposes a high dynamic range (HDR pathological image enhancement method based on improved bias field correction and guided image filter (GIF. Firstly, a preprocessing including stain normalization and wavelet denoising is performed for Haematoxylin and Eosin (H and E stained pathological image. Then, an improved bias field correction model is developed to enhance the influence of light for high-frequency part in image and correct the intensity inhomogeneity and detail discontinuity of image. Next, HDR pathological image is generated based on least square method using low dynamic range (LDR image, H and E channel images. Finally, the fine enhanced image is acquired after the detail enhancement process. Experiments with 140 pathological images demonstrate the performance advantages of our proposed method as compared with related work.

Development of a curriculum in molecular diagnostics, genomics and personalized medicine for dermatology trainees.

Science.gov (United States)

Murphy, Michael J; Shahriari, Neda; Payette, Michael; Mnayer, Laila; Elaba, Zendee

2016-10-01

Results of molecular studies are redefining the diagnosis and management of a wide range of skin disorders. Dermatology training programs maintain a relative gap in relevant teaching. To develop a curriculum in molecular diagnostics, genomics and personalized medicine for dermatology trainees at our institution. The aim is to provide trainees with a specialty-appropriate, working knowledge in clinical molecular dermatology. The Departments of Dermatology and Pathology and Laboratory Medicine collaborated on the design and implementation of educational objectives and teaching modalities for the new curriculum. A multidisciplinary curriculum was developed. It comprises: (i) assigned reading from the medical literature and reference textbook; (ii) review of teaching sets; (iii) two 1 hour lectures; (iv) trainee presentations; (v) 1-week rotation in a clinical molecular pathology and cytogenetics laboratory; and (vi) assessments and feedback. Residents who participated in the curriculum to date have found the experience to be of value. Our curriculum provides a framework for other dermatology residency programs to develop their own specific approach to molecular diagnostics education. Such training will provide a foundation for lifelong learning as molecular testing evolves and becomes integral to the practice of dermatology. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The clinical pathologic research of invasive pituitary adenomas

International Nuclear Information System (INIS)

Guo Lingchuan; Zheng Yushuang; Wang Shouli; Hui Guozhen; Li Xiangdong

2012-01-01

Objective: To study the pathological morphologic characteristics of invasive pituitary tumor and the affect of vascularization to the tumor's invasion. Methods: One hundred and thirty cases of pituitary adenoma patients were divided into two groups, including invasive pituitary adenomas and non-invasive pituitary adenomas, and the clinical data of two groups were analysed and compared. Results : The difference was statistically significant between the invasive group and the non-invasive group in the incidence rate of pathological morphologic characteristics such as high nuclear cytoplasmic ratio, cell pleomorphism, nuclear atypia and nucleoli appearance (P<0.05); there were nuclear atypia and nucleolus margination in the invasive group through electron microscopy. And there was statistical significant difference in rate of MVD expression which was higher in the invasive group than that of noninvasive group (P<0.05). Conclusion: The pathological morphologic characteristics of pituitary tumor and the high expression of MVD are significantly reference valuable in tumor aggression diagnosis, which provides valuable indicators for early clinical diagnosis of tumor invasion. (authors)

Nonredundant functions of alphabeta and gammadelta T cells in acrolein-induced pulmonary pathology.

Science.gov (United States)

Borchers, Michael T; Wesselkamper, Scott C; Eppert, Bryan L; Motz, Gregory T; Sartor, Maureen A; Tomlinson, Craig R; Medvedovic, Mario; Tichelaar, Jay W

2008-09-01

Acrolein exposure represents a significant human health hazard. Repeated acrolein exposure causes the accumulation of monocytes/macrophages and lymphocytes, mucous cell metaplasia, and epithelial injury. Currently, the mechanisms that control these events are unclear, and the relative contribution of T-cell subsets to pulmonary pathologies following repeated exposures to irritants is unknown. To examine whether lymphocyte subpopulations regulate inflammation and epithelial cell pathology, we utilized a mouse model of pulmonary pathology induced by repeated acrolein exposures. The role of lymphocyte subsets was examined by utilizing transgenic mice genetically deficient in either alphabeta T cells or gammadelta T cells, and changes in cellular, molecular, and pathologic outcomes associated with repeated inhalation exposure to 2.0 and 0.5 ppm acrolein were measured. To examine the potential functions of lymphocyte subsets, we purified these cells from the lungs of mice repeatedly exposed to 2.0 ppm acrolein, isolated and amplified messenger RNA, and performed microarray analysis. Our data demonstrate that alphabeta T cells are required for macrophage accumulation, whereas gammadelta T cells are critical regulators of epithelial cell homeostasis, as identified by epithelial cell injury and apoptosis, following repeated acrolein exposure. This is supported by microarray analyses that indicated the T-cell subsets are unique in their gene expression profiles following acrolein exposures. Microarray analyses identified several genes that may contribute to phenotypes mediated by T-cell subpopulations including those involved in cytokine receptor signaling, chemotaxis, growth factor production, lymphocyte activation, and apoptosis. These data provide strong evidence that T-cell subpopulations in the lung are major determinants of pulmonary pathology and highlight the advantages of dissecting their effector functions in response to toxicant exposures.

Veterinary software application for comparison of thermograms for pathology evaluation

Science.gov (United States)

Pant, Gita; Umbaugh, Scott E.; Dahal, Rohini; Lama, Norsang; Marino, Dominic J.; Sackman, Joseph

2017-09-01

The bilateral symmetry property in mammals allows for the detection of pathology by comparison of opposing sides. For any pathological disorder, thermal patterns differ compared to the normal body part. A software application for veterinary clinics has been under development to input two thermograms of body parts on both sides, one normal and the other unknown, and the application compares them based on extracted features and appropriate similarity and difference measures and outputs the likelihood of pathology. Here thermographic image data from 19° C to 40° C was linearly remapped to create images with 256 gray level values. Features were extracted from these images, including histogram, texture and spectral features. The comparison metrics used are the vector inner product, Tanimoto, Euclidean, city block, Minkowski and maximum value metric. Previous research with the anterior cruciate ligament (ACL) pathology in dogs suggested any thermogram variation below a threshold of 40% of Euclidean distance is normal and above 40% is abnormal. Here the 40% threshold was applied to a new ACL image set and achieved a sensitivity of 75%, an improvement from the 55% sensitivity of the previous work. With the new data set it was determined that using a threshold of 20% provided a much improved 92% sensitivity metric. However, this will require further research to determine the corresponding specificity success rate. Additionally, it was found that the anterior view provided better results than the lateral view. It was also determined that better results were obtained with all three feature sets than with just the histogram and texture sets. Further experiments are ongoing with larger image datasets, and pathologies, new features and comparison metric evaluation for determination of more accurate threshold values to separate normal and abnormal images.

PathBot: A Radiology-Pathology Correlation Dashboard.

Science.gov (United States)

Kelahan, Linda C; Kalaria, Amit D; Filice, Ross W

2017-12-01

Pathology is considered the "gold standard" of diagnostic medicine. The importance of radiology-pathology correlation is seen in interdepartmental patient conferences such as "tumor boards" and by the tradition of radiology resident immersion in a radiologic-pathology course at the American Institute of Radiologic Pathology. In practice, consistent pathology follow-up can be difficult due to time constraints and cumbersome electronic medical records. We present a radiology-pathology correlation dashboard that presents radiologists with pathology reports matched to their dictations, for both diagnostic imaging and image-guided procedures. In creating our dashboard, we utilized the RadLex ontology and National Center for Biomedical Ontology (NCBO) Annotator to identify anatomic concepts in pathology reports that could subsequently be mapped to relevant radiology reports, providing an automated method to match related radiology and pathology reports. Radiology-pathology matches are presented to the radiologist on a web-based dashboard. We found that our algorithm was highly specific in detecting matches. Our sensitivity was slightly lower than expected and could be attributed to missing anatomy concepts in the RadLex ontology, as well as limitations in our parent term hierarchical mapping and synonym recognition algorithms. By automating radiology-pathology correlation and presenting matches in a user-friendly dashboard format, we hope to encourage pathology follow-up in clinical radiology practice for purposes of self-education and to augment peer review. We also hope to provide a tool to facilitate the production of quality teaching files, lectures, and publications. Diagnostic images have a richer educational value when they are backed up by the gold standard of pathology.

Molecular biomarkers in idiopathic pulmonary fibrosis

Science.gov (United States)

Ley, Brett; Brown, Kevin K.

2014-01-01

Molecular biomarkers are highly desired in idiopathic pulmonary fibrosis (IPF), where they hold the potential to elucidate underlying disease mechanisms, accelerated drug development, and advance clinical management. Currently, there are no molecular biomarkers in widespread clinical use for IPF, and the search for potential markers remains in its infancy. Proposed core mechanisms in the pathogenesis of IPF for which candidate markers have been offered include alveolar epithelial cell dysfunction, immune dysregulation, and fibrogenesis. Useful markers reflect important pathological pathways, are practically and accurately measured, have undergone extensive validation, and are an improvement upon the current approach for their intended use. The successful development of useful molecular biomarkers is a central challenge for the future of translational research in IPF and will require collaborative efforts among those parties invested in advancing the care of patients with IPF. PMID:25260757

Response monitoring of breast cancer patients receiving neoadjuvant chemotherapy using quantitative ultrasound, texture, and molecular features.

Directory of Open Access Journals (Sweden)

Lakshmanan Sannachi

Full Text Available Pathological response of breast cancer to chemotherapy is a prognostic indicator for long-term disease free and overall survival. Responses of locally advanced breast cancer in the neoadjuvant chemotherapy (NAC settings are often variable, and the prediction of response is imperfect. The purpose of this study was to detect primary tumor responses early after the start of neoadjuvant chemotherapy using quantitative ultrasound (QUS, textural analysis and molecular features in patients with locally advanced breast cancer.The study included ninety six patients treated with neoadjuvant chemotherapy. Breast tumors were scanned with a clinical ultrasound system prior to chemotherapy treatment, during the first, fourth and eighth week of treatment, and prior to surgery. Quantitative ultrasound parameters and scatterer-based features were calculated from ultrasound radio frequency (RF data within tumor regions of interest. Additionally, texture features were extracted from QUS parametric maps. Prior to therapy, all patients underwent a core needle biopsy and histological subtypes and biomarker ER, PR, and HER2 status were determined. Patients were classified into three treatment response groups based on combination of clinical and pathological analyses: complete responders (CR, partial responders (PR, and non-responders (NR. Response classifications from QUS parameters, receptors status and pathological were compared. Discriminant analysis was performed on extracted parameters using a support vector machine classifier to categorize subjects into CR, PR, and NR groups at all scan times.Of the 96 patients, the number of CR, PR and NR patients were 21, 52, and 23, respectively. The best prediction of treatment response was achieved with the combination mean QUS values, texture and molecular features with accuracies of 78%, 86% and 83% at weeks 1, 4, and 8, after treatment respectively. Mean QUS parameters or clinical receptors status alone predicted the

Slot Machine Response Frequency Predicts Pathological Gambling

DEFF Research Database (Denmark)

Linnet, Jakob; Rømer Thomsen, Kristine; Møller, Arne

2013-01-01

. This study tested the hypothesis that response frequency is associated with symptom severity in pathological gambling. We tested response frequency among twenty-two pathological gambling sufferers and twenty-one non-problem gamblers on a commercially available slot machine, and screened for pathological...... in individuals with exacerbated pathological gambling symptoms. These findings may have important implications for detecting behaviors underlying pathological gambling....

Molecular subtype classification of urothelial carcinoma in Lynch syndrome.

Science.gov (United States)

Therkildsen, Christina; Eriksson, Pontus; Höglund, Mattias; Jönsson, Mats; Sjödahl, Gottfrid; Nilbert, Mef; Liedberg, Fredrik

2018-05-23

Lynch syndrome confers an increased risk for urothelial carcinoma (UC). Molecular subtypes may be relevant to prognosis and therapeutic possibilities, but have to date not been defined in Lynch syndrome-associated urothelial cancer. We aimed to provide a molecular description of Lynch syndrome-associated UC. Thus, Lynch syndrome-associated UC of the upper urinary tract and the urinary bladder were identified in the Danish hereditary non-polyposis colorectal cancer (HNPCC) register and were transcriptionally and immunohistochemically profiled and further related to data from 307 sporadic urothelial carcinomas. Whole genome mRNA expression profiles of 41 tumors and immunohistochemical stainings against FGFR3, KRT5, CCNB1, RB1, and CDKN2A (p16) of 37 tumors from Lynch syndrome patients were generated. Pathological data, microsatellite instability, anatomic location, and overall survival data was analyzed and compared with sporadic bladder cancer. The 41 Lynch syndrome-associated UC developed at a mean age of 61 years with 59% women. mRNA expression profiling and immunostaining classified the majority of the Lynch syndrome-associated UC as Urothelial-like tumors with only 20% being Genomically Unstable, Basal/SCC-like or other subtypes. The subtypes were associated with stage, grade, and microsatellite instability. Comparison to larger data sets revealed that Lynch syndrome-associated UC share molecular similarities with sporadic UC. In conclusion, transcriptomic and immunohistochemical profiling identifies a predominance of the Urothelial-like molecular subtype in Lynch syndrome and reveals that the molecular subtypes of sporadic bladder cancer are relevant also within this hereditary, mismatch-repair defective subset. This article is protected by copyright. All rights reserved. Molecular Oncology (2018) © 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

Digital diffraction analysis enables low-cost molecular diagnostics on a smartphone.

Science.gov (United States)

Im, Hyungsoon; Castro, Cesar M; Shao, Huilin; Liong, Monty; Song, Jun; Pathania, Divya; Fexon, Lioubov; Min, Changwook; Avila-Wallace, Maria; Zurkiya, Omar; Rho, Junsung; Magaoay, Brady; Tambouret, Rosemary H; Pivovarov, Misha; Weissleder, Ralph; Lee, Hakho

2015-05-05

The widespread distribution of smartphones, with their integrated sensors and communication capabilities, makes them an ideal platform for point-of-care (POC) diagnosis, especially in resource-limited settings. Molecular diagnostics, however, have been difficult to implement in smartphones. We herein report a diffraction-based approach that enables molecular and cellular diagnostics. The D3 (digital diffraction diagnosis) system uses microbeads to generate unique diffraction patterns which can be acquired by smartphones and processed by a remote server. We applied the D3 platform to screen for precancerous or cancerous cells in cervical specimens and to detect human papillomavirus (HPV) DNA. The D3 assay generated readouts within 45 min and showed excellent agreement with gold-standard pathology or HPV testing, respectively. This approach could have favorable global health applications where medical access is limited or when pathology bottlenecks challenge prompt diagnostic readouts.

Molecular Classification and Correlates in Colorectal Cancer

OpenAIRE

Ogino, Shuji; Goel, Ajay

2008-01-01

Molecular classification of colorectal cancer is evolving. As our understanding of colorectal carcinogenesis improves, we are incorporating new knowledge into the classification system. In particular, global genomic status [microsatellite instability (MSI) status and chromosomal instability (CIN) status] and epigenomic status [CpG island methylator phenotype (CIMP) status] play a significant role in determining clinical, pathological and biological characteristics of colorectal cancer. In thi...

Pathology annual. Part 2

International Nuclear Information System (INIS)

Rosen, P.P.

1987-01-01

This book contains 11 selections. Some of the titles are: Applications of in situ DNA hybridization technology to diagnostic surgical pathology; Neoplasms associated with immune deficiencies; Chronic gastritis: The pathologists's role; Necrosis in lymph nodes; Pathologic changes of osteochondrodysplasia in infancy: A review; and Immunoglobulin light chain nephropathies

Association between distal ulnar morphology and extensor carpi ulnaris tendon pathology

International Nuclear Information System (INIS)

Chang, Connie Y.; Huang, Ambrose J.; Bredella, Miriam A.; Kattapuram, Susan V.; Torriani, Martin

2014-01-01

The purpose of this study was to evaluate the association between distal ulnar morphology and extensor carpi ulnaris (ECU) tendon pathology. We retrospectively reviewed 71 adult wrist MRI studies with ECU tendon pathology (tenosynovitis, tendinopathy, or tear), and/or ECU subluxation. Subjects did not have a history of trauma, surgery, infection, or inflammatory arthritis. MRI studies from 46 subjects without ECU tendon pathology or subluxation were used as controls. The following morphological parameters of the distal ulna were measured independently by two readers: ulnar variance relative to radius, ulnar styloid process length, ECU groove depth and length. Subjects and controls were compared using Student's t test. Inter-observer agreement (ICC) was calculated. There was a significant correlation between negative ulnar variance and ECU tendon pathology (reader 1 [R1], P = 0.01; reader 2 [R2], P 0.64 for all parameters. Distal ulnar morphology may be associated with ECU tendon abnormalities. (orig.)

Acceptance and Commitment Therapy versus Cognitive Therapy for the Treatment of Comorbid Eating Pathology

Science.gov (United States)

Juarascio, Adrienne S.; Forman, Evan M.; Herbert, James D.

2010-01-01

Previous research has indicated that although eating pathology is prevalent in college populations, both CBT and non-CBT-based therapies achieve only limited effectiveness. The current study examined several questions related to the treatment of eating pathology within the context of a larger randomized controlled trial that compared standard CBT…

Renal cell carcinoma: incidental detection and pathological staging.

Science.gov (United States)

Siow, W Y; Yip, S K; Ng, L G; Tan, P H; Cheng, W S; Foo, K T

2000-10-01

In developed countries, there has been increased incidental detection of renal cell carcinoma (RCC). The incidence, pathological stage and survival of incidentally detected carcinoma in a developing country in Asia where, from 1990 to 1998, 165 renal cell carcinomas were identified. The clinical presentation, diagnostic-imaging modality employed, pathological staging and patient survival was reviewed. Incidental renal cancers included those that were diagnosed through health screening or detected incidentally through imaging studies for other conditions. The survival between these incidentally detected lesions and their symptomatic counterparts (suspected group) was compared. Sixty-four patients (39%) had their tumours detected incidentally, including 39 who were entirely asymptomatic and 25 who presented with non-specific symptoms, not initially suggestive of RCC. For the entire group, computed tomography provided the definitive diagnosis in 81% of cases. The incidental detection group had significantly smaller size of tumour (5.9 cm c.f. 7.6 cm), lower stage and lower histological grading. In particular, 78% of patients with incidental RCC had stage I or II diseases (TNM stage classification), compared with 57% of patients with suspected tumour (p c.f. 66% at last follow up; p < 0.05; log-rank test) over a mean follow up period of 33 months (range 1-91). Regression analysis showed that stage of disease was the only independent variable predictive of clinical outcome. In conclusion, that significant numbers of RCC were detected incidentally. These tumours were of a lower clinical pathological stage and had a better prognosis.

Surgical treatment of limbic epilepsy associated with extrahippocampal lesions: the problem of dual pathology.

Science.gov (United States)

Lévesque, M F; Nakasato, N; Vinters, H V; Babb, T L

1991-09-01

The authors present their review of 178 patients who underwent en bloc temporal lobectomies as surgical treatment for intractable epilepsy. Hippocampal cell density was quantitatively analyzed and the histology of the anterior temporal lobe was reviewed. Fifty-four patients (30.3%) had evidence of extrahippocampal lesions in addition to neuronal cell loss within the hippocampus (the dual pathology group). The pattern of cell loss was analyzed in the remaining 124 cases (69.7%) with no extrahippocampal pathology, and compared with that of the dual pathology group and a control group of four nonepileptic patients. Hippocampal cell loss was found in almost all epileptic patients compared to the control group. Severe cell loss greater than 30% of control values was found in 88.7% of patients without extrahippocampal lesions, but in only 51.8% of patients with dual pathology. The difference between these two groups was statistically significant (p less than 0.001). In the dual pathology group, lesions of different pathology had a significant relationship with the degree of hippocampal cell loss: all 12 patients with glioma had mild cell loss, whereas all 13 patients with heterotopia were associated with severe cell loss. Severity of hippocampal cell loss was also analyzed in relation to seizure history: a prior severe head injury was associated with severe cell loss. Other factors such as seizure duration, secondary generalization, or family history of seizures were not associated with hippocampal damage. Dual pathology may produce a combination of neocortical and temporolimbic epilepsies that warrants a precise definition of the true epileptogenic area prior to surgical treatment.

Treatment outcome in patients with triple negative early stage breast cancers compared with other molecular subtypes

International Nuclear Information System (INIS)

Kim, Ja Young; Chang, Sei Kyung; Lee, Bo Mi; Shin, Hyun Soo; Park, Heily

2012-01-01

To determine whether triple negative (TN) early stage breast cancers have poorer survival rates compared with other molecular types. Between August 2000 and July 2006, patients diagnosed with stage I, II early stage breast cancers, in whom all three markers (estrogen receptor, progesterone receptor, and human epidermal growth factor receptor [HER]-2) were available and treated with modified radical mastectomy or breast conserving surgery followed by radiotherapy, were retrospectively reviewed. Of 446 patients, 94 (21.1%) were classified as TN, 57 (12.8%) as HER-2 type, and 295 (66.1%) as luminal. TN was more frequently associated with young patients younger than 35 years old (p = 0.002), higher histologic grade (p 0.05). We found that patients with TN early stage breast cancers had no difference in survival rates compared with other molecular subtypes. Prospective study in homogeneous treatment group will need for a prognosis of TN early stage breast cancer.

Chapter 24: the coming of molecular biology and its impact on clinical neurology.

Science.gov (United States)

Smith, Christopher U M

2010-01-01

Although the chemical study of the nervous system dates back well into the 19th century, molecular biology and especially molecular neurobiology only began to be established in the second half of the 20th century. This chapter reviews their impact on clinical neuroscience during the 50 years since Watson and Crick published their seminal paper. After a short review of the part played by F.O. Schmitt in establishing molecular neuroscience the chapter outlines work that led to a detailed understanding of the biochemical structure and function of nerve cell membranes and their embedded channel proteins, receptors, and other molecules. The chapter then turns to the numerous pathologies that result from disorders of these elements: the various channel and gap-junction pathologies. The chapter continues with a discussion of some of the diseases caused by defective DNA, especially the trinucleotide repeat expansion diseases (TREDs) and ends with a short account of the development of molecular approaches to prion diseases, myasthenia gravis, and the neurodegenerative diseases of old age. Francis Bacon said long ago that "knowledge is power." The hope is that increasing molecular knowledge will help cure some of the human suffering seen in the neurological ward and clinic.

Dopamine release in ventral striatum during Iowa Gambling Task performance is associated with increased excitement levels in pathological gambling

DEFF Research Database (Denmark)

Linnet, Jakob; Møller, Arne; Peterson, Ericka

2011-01-01

Aims Gambling excitement is believed to be associated with biological measures of pathological gambling. Here, we tested the hypothesis that dopamine release would be associated with increased excitement levels in Pathological Gamblers compared with Healthy Controls. Design Pathological Gamblers...... and Healthy Controlswere experimentally compared in a non-gambling (baseline) and gambling condition. Measurements We used Positron Emission Tomography (PET) with the tracer raclopride to measure dopamine D 2/3 receptor availability in the ventral striatum during a non-gambling and gambling condition...... of the Iowa GamblingTask (IGT). After each condition participants rated their excitement level. Setting Laboratory experiment. Participants 18 Pathological Gamblers and 16 Healthy Controls. Findings Pathological Gamblers with dopamine release in the ventral striatum had significantly higher excitement levels...

Comparative Circadian Metabolomics Reveal Differential Effects of Nutritional Challenge in the Serum and Liver.

Science.gov (United States)

Abbondante, Serena; Eckel-Mahan, Kristin L; Ceglia, Nicholas J; Baldi, Pierre; Sassone-Corsi, Paolo

2016-02-05

Diagnosis and therapeutic interventions in pathological conditions rely upon clinical monitoring of key metabolites in the serum. Recent studies show that a wide range of metabolic pathways are controlled by circadian rhythms whose oscillation is affected by nutritional challenges, underscoring the importance of assessing a temporal window for clinical testing and thereby questioning the accuracy of the reading of critical pathological markers in circulation. We have been interested in studying the communication between peripheral tissues under metabolic homeostasis perturbation. Here we present a comparative circadian metabolomic analysis on serum and liver in mice under high fat diet. Our data reveal that the nutritional challenge induces a loss of serum metabolite rhythmicity compared with liver, indicating a circadian misalignment between the tissues analyzed. Importantly, our results show that the levels of serum metabolites do not reflect the circadian liver metabolic signature or the effect of nutritional challenge. This notion reveals the possibility that misleading reads of metabolites in circulation may result in misdiagnosis and improper treatments. Our findings also demonstrate a tissue-specific and time-dependent disruption of metabolic homeostasis in response to altered nutrition. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Neurological soft signs in individuals with pathological gambling.

Directory of Open Access Journals (Sweden)

Igor Elman

Full Text Available Increased neurological soft signs (NSSs have been found in a number of neuropsychiatric syndromes, including chemical addiction. The present study examined NSSs related to perceptual-motor and visuospatial processing in a behavioral addiction viz., pathological gambling (PG. As compared to mentally healthy individuals, pathological gamblers displayed significantly poorer ability to copy two- and three-dimensional figures, to recognize objects against a background noise, and to orient in space on a road-map test. Results indicated that PG is associated with subtle cerebral cortical abnormalities. Further prospective clinical research is needed to address the NSSs' origin and chronology (e.g., predate or follow the development of PG as well as their response to therapeutic interventions and/or their ability to predict such a response.

Programmed necrosis and necroptosis – molecular mechanisms

Directory of Open Access Journals (Sweden)

Agata Giżycka

2015-12-01

Full Text Available Programmed necrosis has been proven vital for organism development and homeostasis maintenance. Its regulatory effects on functional activity of the immune system, as well as on pathways regulating the death mechanisms in cells with diminished apoptotic activity, including malignant cells, have been confirmed. There is also increasing evidence indicating necrosis involvement in many human pathologies. Contrary to previous beliefs, necrosis is not only a passive, pathological, gene-independent process. However, the current knowledge regarding molecular regulation of programmed necrosis is scarce. In part this is due to the multiplicity and complexity of signaling pathways involved in programmed necrosis, as well as the absence of specific cellular markers identifying this process, but also the ambiguous and imprecise international terminology. This review presents the current state of the art on molecular mechanisms of programmed necrosis. In particular, its specific and frequent form, necroptosis, is discussed. The role of RIP1 and RIP3 kinases in this process is presented, as well as the diverse pathways induced by ligation of tumor necrosis factor α, to its receptor, TNFR1, i.e. cell survival, apoptosis or necroptosis.

Breast MR biopsy: Pathological and radiological correlation

International Nuclear Information System (INIS)

Dratwa, Chloe; Chopier, Jocelyne; Jalaguier-Coudray, Aurelie; Thomassin-Piana, Jeanne; Gonin, Julie; Antoine, Martine; Trop, Isabelle; Darai, Emile; Thomassin-Naggara, Isabelle

2016-01-01

To identify pathological features for sample analysis of magnetic resonance imaging-guided vaccum-assisted breast biopsy (MRIgVaBB) to optimize radio pathological correlation and identify discordant benign result. Databases of two centres were queried to identify MRIgVaBB performed between January 2009 and February 2013. A cohort of 197 women (mean age: 54.5 years (24-77)) with 208 lesions was identified. We retrospectively analyzed all prebiopsy MRI examinations according to the new BI-RADS lexicon, and all biopsy samples to describe the lesion of interest, its interface with the surrounding breast tissue and other associated features. The malignancy rate was 26.0 % (54/208) with an underestimation rate of 15.67 % (5/32). A visible interface at pathology between a biopsied lesion and the surrounding breast tissue was more frequently identified in mass enhancement compared to NME or focus (p = 0.0003). Regional NME was correlated with a high degree of fibrosis (p = 0.001) and the presence of PASH (p = 0.0007). Linear or segmental NME was correlated with the presence of periductal mastitis (p = 0.0003). The description of a visible interface between the target lesion and the surrounding tissue is crucial to confirm the correct targeting of an MR mass or a NME. (orig.)

Wavelet-based compression of pathological images for telemedicine applications

Science.gov (United States)

Chen, Chang W.; Jiang, Jianfei; Zheng, Zhiyong; Wu, Xue G.; Yu, Lun

2000-05-01

In this paper, we present the performance evaluation of wavelet-based coding techniques as applied to the compression of pathological images for application in an Internet-based telemedicine system. We first study how well suited the wavelet-based coding is as it applies to the compression of pathological images, since these images often contain fine textures that are often critical to the diagnosis of potential diseases. We compare the wavelet-based compression with the DCT-based JPEG compression in the DICOM standard for medical imaging applications. Both objective and subjective measures have been studied in the evaluation of compression performance. These studies are performed in close collaboration with expert pathologists who have conducted the evaluation of the compressed pathological images and communication engineers and information scientists who designed the proposed telemedicine system. These performance evaluations have shown that the wavelet-based coding is suitable for the compression of various pathological images and can be integrated well with the Internet-based telemedicine systems. A prototype of the proposed telemedicine system has been developed in which the wavelet-based coding is adopted for the compression to achieve bandwidth efficient transmission and therefore speed up the communications between the remote terminal and the central server of the telemedicine system.

42 CFR 493.853 - Condition: Pathology.

Science.gov (United States)

2010-10-01

... 42 Public Health 5 2010-10-01 2010-10-01 false Condition: Pathology. 493.853 Section 493.853 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... These Tests § 493.853 Condition: Pathology. The specialty of pathology includes, for purposes of...

Molecular spectral imaging system for quantitative immunohistochemical analysis of early diabetic retinopathy.

Science.gov (United States)

Li, Qingli; Zhang, Jingfa; Wang, Yiting; Xu, Guoteng

2009-12-01

A molecular spectral imaging system has been developed based on microscopy and spectral imaging technology. The system is capable of acquiring molecular spectral images from 400 nm to 800 nm with 2 nm wavelength increments. The basic principles, instrumental systems, and system calibration method as well as its applications for the calculation of the stain-uptake by tissues are introduced. As a case study, the system is used for determining the pathogenesis of diabetic retinopathy and evaluating the therapeutic effects of erythropoietin. Some molecular spectral images of retinal sections of normal, diabetic, and treated rats were collected and analyzed. The typical transmittance curves of positive spots stained for albumin and advanced glycation end products are retrieved from molecular spectral data with the spectral response calibration algorithm. To explore and evaluate the protective effect of erythropoietin (EPO) on retinal albumin leakage of streptozotocin-induced diabetic rats, an algorithm based on Beer-Lambert's law is presented. The algorithm can assess the uptake by histologic retinal sections of stains used in quantitative pathology to label albumin leakage and advanced glycation end products formation. Experimental results show that the system is helpful for the ophthalmologist to reveal the pathogenesis of diabetic retinopathy and explore the protective effect of erythropoietin on retinal cells of diabetic rats. It also highlights the potential of molecular spectral imaging technology to provide more effective and reliable diagnostic criteria in pathology.

Improving Molecular Genetic Test Utilization through Order Restriction, Test Review, and Guidance.

Science.gov (United States)

Riley, Jacquelyn D; Procop, Gary W; Kottke-Marchant, Kandice; Wyllie, Robert; Lacbawan, Felicitas L

2015-05-01

The ordering of molecular genetic tests by health providers not well trained in genetics may have a variety of untoward effects. These include the selection of inappropriate tests, the ordering of panels when the assessment of individual or fewer genes would be more appropriate, inaccurate result interpretation and inappropriate patient guidance, and significant unwarranted cost expenditure. We sought to improve the utilization of molecular genetic tests by requiring providers without specialty training in genetics to use genetic counselors and molecular genetic pathologists to assist in test selection. We used a genetic and genomic test review process wherein the laboratory-based genetic counselor performed the preanalytic assessment of test orders and test triage. Test indication and clinical findings were evaluated against the test panel composition, methods, and test limitations under the supervision of the molecular genetic pathologist. These test utilization management efforts resulted in a decrease in genetic test ordering and a gross cost savings of $1,531,913 since the inception of these programs in September 2011 through December 2013. The combination of limiting the availability of complex genetic tests and providing guidance regarding appropriate test strategies is an effective way to improve genetic tests, contributing to judicious use of limited health care resources. Copyright © 2015 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Pathological fractures in children

Science.gov (United States)

De Mattos, C. B. R.; Binitie, O.; Dormans, J. P.

2012-01-01

Pathological fractures in children can occur as a result of a variety of conditions, ranging from metabolic diseases and infection to tumours. Fractures through benign and malignant bone tumours should be recognised and managed appropriately by the treating orthopaedic surgeon. The most common benign bone tumours that cause pathological fractures in children are unicameral bone cysts, aneurysmal bone cysts, non-ossifying fibromas and fibrous dysplasia. Although pathological fractures through a primary bone malignancy are rare, these should be recognised quickly in order to achieve better outcomes. A thorough history, physical examination and review of plain radiographs are crucial to determine the cause and guide treatment. In most benign cases the fracture will heal and the lesion can be addressed at the time of the fracture, or after the fracture is healed. A step-wise and multidisciplinary approach is necessary in caring for paediatric patients with malignancies. Pathological fractures do not have to be treated by amputation; these fractures can heal and limb salvage can be performed when indicated. PMID:23610658

The Nun Study: risk factors for pathology and clinical-pathologic correlations.

Science.gov (United States)

Mortimer, James A

2012-07-01

The Nun Study was the first cohort study to enroll and follow a large, well-defined population that included demented and non-demented participants, all of whom agreed to donate their brains for research. The inclusion of systematic neuropathologic analysis in this study has resulted in a greater understanding of the role of Alzheimer and vascular pathology in the expression of memory deficits and dementia and has provided data showing that biomarkers for the pathology may be evident many decades earlier in adult life. Findings related to neuropathology in this study have included the following: (1) Although clinical outcomes were strongly correlated with Alzheimer neuropathology, about one-third of the participants fulfilling criteria for neuropathologic Alzheimer's disease (AD) were not demented at the time of death. (2) Brain infarcts by themselves had little effect on cognitive status, but played an important role in increasing the risk of dementia associated with Alzheimer pathology. (3) Hippocampal volume was strongly correlated with Braak neurofibrillary stage even in participants with normal cognitive function. (4) A linguistic characteristic of essays written in early adult life, idea density, had a strong association with not only clinical outcomes in late life, but the severity of Alzheimer neuropathology as well. (5) The effect of apolipoprotein E-e4 on dementia was mediated through Alzheimer, but not vascular pathology.

CD147 expression predicts biochemical recurrence after prostatectomy independent of histologic and pathologic features.

Science.gov (United States)

Bauman, Tyler M; Ewald, Jonathan A; Huang, Wei; Ricke, William A

2015-07-25

CD147 is an MMP-inducing protein often implicated in cancer progression. The purpose of this study was to investigate the expression of CD147 in prostate cancer (PCa) progression and the prognostic ability of CD147 in predicting biochemical recurrence after prostatectomy. Plasma membrane-localized CD147 protein expression was quantified in patient samples using immunohistochemistry and multispectral imaging, and expression was compared to clinico-pathological features (pathologic stage, Gleason score, tumor volume, preoperative PSA, lymph node status, surgical margins, biochemical recurrence status). CD147 specificity and expression were confirmed with immunoblotting of prostate cell lines, and CD147 mRNA expression was evaluated in public expression microarray datasets of patient prostate tumors. Expression of CD147 protein was significantly decreased in localized tumors (pT2; p = 0.02) and aggressive PCa (≥pT3; p = 0.004), and metastases (p = 0.001) compared to benign prostatic tissue. Decreased CD147 was associated with advanced pathologic stage (p = 0.009) and high Gleason score (p = 0.02), and low CD147 expression predicted biochemical recurrence (HR 0.55; 95 % CI 0.31-0.97; p = 0.04) independent of clinico-pathologic features. Immunoblot bands were detected at 44 kDa and 66 kDa, representing non-glycosylated and glycosylated forms of CD147 protein, and CD147 expression was lower in tumorigenic T10 cells than non-tumorigenic BPH-1 cells (p = 0.02). Decreased CD147 mRNA expression was associated with increased Gleason score and pathologic stage in patient tumors but is not associated with recurrence status. Membrane-associated CD147 expression is significantly decreased in PCa compared to non-malignant prostate tissue and is associated with tumor progression, and low CD147 expression predicts biochemical recurrence after prostatectomy independent of pathologic stage, Gleason score, lymph node status, surgical margins, and tumor volume in multivariable

Communication skills in diagnostic pathology.

Science.gov (United States)

Lehr, Hans-Anton; Bosman, Fred T

2016-01-01

Communication is an essential element of good medical practice also in pathology. In contrast to technical or diagnostic skills, communication skills are not easy to define, teach, or assess. Rules almost do not exist. In this paper, which has a rather personal character and cannot be taken as a set of guidelines, important aspects of communication in pathology are explored. This includes what should be communicated to the pathologist on the pathology request form, communication between pathologists during internal (interpathologist) consultation, communication around frozen section diagnoses, modalities of communication of a final diagnosis, with whom and how critical and unexpected findings should be communicated, (in-)adequate routes of communication for pathology diagnoses, who will (or might) receive pathology reports, and what should be communicated and how in case of an error or a technical problem. An earlier more formal description of what the responsibilities are of a pathologist as communicator and as collaborator in a medical team is added in separate tables. The intention of the paper is to stimulate reflection and discussion rather than to formulate strict rules.

European and US publications in the 50 highest ranking pathology journals from 2000 to 2006.

Science.gov (United States)

Fritzsche, F R; Oelrich, B; Dietel, M; Jung, K; Kristiansen, G

2008-04-01

To analyse the contributions of the 15 primary member states of the European Union and selected non-European countries to pathological research between 2000 and 2006. Pathological journals were screened using ISI Web of Knowledge database. The number of publications and related impact factors were determined for each country. Relevant socioeconomic indicators were related to the scientific output. Subsequently, results were compared to publications in 10 of the leading biomedical journals. The research output remained generally stable. In Europe, the UK, Germany, France, Italy and Spain ranked top concerning contributions to publications and impact factors in the pathological and leading general biomedical journals. With regard to socioeconomic data, smaller, mainly northern European countries showed a relatively higher efficiency. Of the lager countries, the UK is the most efficient in that respect. The rising economic powers of China and India were consistently in the rear. Results mirror the leading role of the USA in pathology research but also show the relevance of European scientists. The scientometric approach in this study provides a new fundamental and comparative overview of pathology research in the European Union and the USA which could help to benchmark scientific output among countries.

Comparing 3 guidelines on the management of surgically removed pancreatic cysts with regard to pathological outcome.

Science.gov (United States)

Lekkerkerker, Selma J; Besselink, Marc G; Busch, Olivier R; Verheij, Joanne; Engelbrecht, Marc R; Rauws, Erik A; Fockens, Paul; van Hooft, Jeanin E

2017-05-01

Currently, 3 guidelines are available for the management of pancreatic cysts. These guidelines vary in their indication for resection of high-risk cysts. We retrospectively compared the final pathologic outcome of surgically removed pancreatic cysts with the indications for resection according to 3 different guidelines. Patients who underwent pancreatic resection were extracted from our prospective pancreatic cyst database (2006-present). The final histopathologic diagnosis was compared with the initial indication for surgery stated by the guidelines of the International Association of Pancreatology (IAP), European Study Group on Cystic tumors of the Pancreas and American Gastroenterological Association (AGA). We considered surgery in retrospect justified for malignancy, high-grade dysplasia, solid pseudopapillary neoplasms, neuroendocrine tumors or symptom improvement. Furthermore, we evaluated the patients with suspected intraductal papillary mucinous neoplasm (IPMN) separately. Overall, 115 patients underwent pancreatic resection. The preoperative diagnosis was correct in 83 of 115 patients (72%) and differentiation between benign and premalignant in 99 of 115 patients (86%). In retrospect, surgery was justified according to the aforementioned criteria in 52 of 115 patients (45%). For patients with suspected IPMN (n = 75) resection was justified in 36 of 67 (54%), 36 of 68 (53%), and 32 of 54 (59%) of patients who would have had surgery based on the IAP, European, or AGA guidelines, respectively. The AGA guideline would have avoided resection in 21 of 75 (28%) patients, versus 8 of 75 (11%) and 7 of 75 (9%) when the IAP or European guideline would have been applied strictly. Nevertheless, 4 of 33 patients (12%) with high-grade dysplasia or malignancy would have been missed with the AGA guidelines, compared with none with the IAP or European guidelines. Although fewer patients undergo unnecessary surgery based on the AGA guidelines, the risk of missing

Psychological therapies for pathological and problem gambling.

Science.gov (United States)

Cowlishaw, Sean; Merkouris, Stephanie; Dowling, Nicki; Anderson, Christopher; Jackson, Alun; Thomas, Shane

2012-11-14

following completion of treatment) and follow-up assessments (conducted from 9 to 12 months following completion of treatment), respectively, using the standardised mean difference (SMD) or risk ratio (RR). We synthesised results through random-effects meta-analysis. Fourteen studies (n = 1245) met the inclusion criteria. Eleven studies compared CBT with control and comparisons at 0 to 3 months post-treatment showed beneficial effects of therapy that ranged from medium (when defined by financial loss from gambling: SMD -0.52; 95% confidence interval (CI) -0.71 to -0.33, n = 505) to very large (for gambling symptom severity: SMD -1.82; 95% CI -2.61 to -1.02, n = 402). Only one study (n = 147) compared groups at 9 to 12 months follow-up and produced smaller effects that were not significant. Four studies of motivational interviewing therapy were identified and mainly considered samples demonstrating less severe gambling (relative to studies of pathological gamblers). Data suggested reduced financial loss from gambling following motivational interviewing therapy at 0 to 3 months post-treatment (SMD -0.41; 95% CI -0.75 to -0.07, n = 244), although comparisons on other outcomes were not significant. The effect approached zero when defined by gambling symptom severity (SMD -0.03; 95% CI -0.55 to 0.50, n = 163). Studies compared groups at 9 to 12 months follow-up and found a significant effect of motivational interviewing therapy in terms of frequency of gambling (SMD -0.53; 95% CI -1.04 to -0.02, n = 62), with comparisons on other outcomes that were not significant. Two studies of integrative therapies also considered samples demonstrating overall low gambling severity, and found no significant effects of therapy at 0 to 3 months post-treatment. Comparisons at 9 to 12 months follow-up suggested a medium effect from therapy in terms of gambling symptom severity, with no significant differences for other outcomes. One study (n = 18) considered another psychological therapy (i

Radiographic pathology for technologists

International Nuclear Information System (INIS)

Mace, J.D.; Kowalczyk, N.

1988-01-01

This book explains the fundamentals of disease mechanisms and relates this to the practice of radiologic science. Each chapter begins with a discussion of normal anatomy and physiology, then covers pathology and demonstrates how the pathology appears on film. Imaging modalities such as computed tomography, MRI, and ultrasound are also discussed. Clinical case studies are included

Crowdsourcing the General Public for Large Scale Molecular Pathology Studies in Cancer.

Science.gov (United States)

Candido Dos Reis, Francisco J; Lynn, Stuart; Ali, H Raza; Eccles, Diana; Hanby, Andrew; Provenzano, Elena; Caldas, Carlos; Howat, William J; McDuffus, Leigh-Anne; Liu, Bin; Daley, Frances; Coulson, Penny; Vyas, Rupesh J; Harris, Leslie M; Owens, Joanna M; Carton, Amy F M; McQuillan, Janette P; Paterson, Andy M; Hirji, Zohra; Christie, Sarah K; Holmes, Amber R; Schmidt, Marjanka K; Garcia-Closas, Montserrat; Easton, Douglas F; Bolla, Manjeet K; Wang, Qin; Benitez, Javier; Milne, Roger L; Mannermaa, Arto; Couch, Fergus; Devilee, Peter; Tollenaar, Robert A E M; Seynaeve, Caroline; Cox, Angela; Cross, Simon S; Blows, Fiona M; Sanders, Joyce; de Groot, Renate; Figueroa, Jonine; Sherman, Mark; Hooning, Maartje; Brenner, Hermann; Holleczek, Bernd; Stegmaier, Christa; Lintott, Chris; Pharoah, Paul D P

2015-07-01

Citizen science, scientific research conducted by non-specialists, has the potential to facilitate biomedical research using available large-scale data, however validating the results is challenging. The Cell Slider is a citizen science project that intends to share images from tumors with the general public, enabling them to score tumor markers independently through an internet-based interface. From October 2012 to June 2014, 98,293 Citizen Scientists accessed the Cell Slider web page and scored 180,172 sub-images derived from images of 12,326 tissue microarray cores labeled for estrogen receptor (ER). We evaluated the accuracy of Citizen Scientist's ER classification, and the association between ER status and prognosis by comparing their test performance against trained pathologists. The area under ROC curve was 0.95 (95% CI 0.94 to 0.96) for cancer cell identification and 0.97 (95% CI 0.96 to 0.97) for ER status. ER positive tumors scored by Citizen Scientists were associated with survival in a similar way to that scored by trained pathologists. Survival probability at 15 years were 0.78 (95% CI 0.76 to 0.80) for ER-positive and 0.72 (95% CI 0.68 to 0.77) for ER-negative tumors based on Citizen Scientists classification. Based on pathologist classification, survival probability was 0.79 (95% CI 0.77 to 0.81) for ER-positive and 0.71 (95% CI 0.67 to 0.74) for ER-negative tumors. The hazard ratio for death was 0.26 (95% CI 0.18 to 0.37) at diagnosis and became greater than one after 6.5 years of follow-up for ER scored by Citizen Scientists, and 0.24 (95% CI 0.18 to 0.33) at diagnosis increasing thereafter to one after 6.7 (95% CI 4.1 to 10.9) years of follow-up for ER scored by pathologists. Crowdsourcing of the general public to classify cancer pathology data for research is viable, engages the public and provides accurate ER data. Crowdsourced classification of research data may offer a valid solution to problems of throughput requiring human input.

Muscle biopsies from human muscle diseases with myopathic pathology reveal common alterations in mitochondrial function.

Science.gov (United States)

Sunitha, Balaraju; Gayathri, Narayanappa; Kumar, Manish; Keshava Prasad, Thottethodi Subrahmanya; Nalini, Atchayaram; Padmanabhan, Balasundaram; Srinivas Bharath, Muchukunte Mukunda

2016-07-01

Muscle diseases are clinically and genetically heterogeneous and manifest as dystrophic, inflammatory and myopathic pathologies, among others. Our previous study on the cardiotoxin mouse model of myodegeneration and inflammation linked muscle pathology with mitochondrial damage and oxidative stress. In this study, we investigated whether human muscle diseases display mitochondrial changes. Muscle biopsies from muscle disease patients, represented by dysferlinopathy (dysfy) (dystrophic pathology; n = 43), polymyositis (PM) (inflammatory pathology; n = 24), and distal myopathy with rimmed vacuoles (DMRV) (distal myopathy; n = 31) were analyzed. Mitochondrial damage (ragged blue and COX-deficient fibers) was revealed in dysfy, PM, and DMRV cases by enzyme histochemistry (SDH and COX-SDH), electron microscopy (vacuolation and altered cristae) and biochemical assays (significantly increased ADP/ATP ratio). Proteomic analysis of muscle mitochondria from all three muscle diseases by isobaric tag for relative and absolute quantitation labeling and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis demonstrated down-regulation of electron transport chain (ETC) complex subunits, assembly factors and Krebs cycle enzymes. Interestingly, 80 of the under-expressed proteins were common among the three pathologies. Assay of ETC and Krebs cycle enzyme activities validated the MS data. Mitochondrial proteins from muscle pathologies also displayed higher tryptophan (Trp) oxidation and the same was corroborated in the cardiotoxin model. Molecular modeling predicted Trp oxidation to alter the local structure of mitochondrial proteins. Our data highlight mitochondrial alterations in muscle pathologies, represented by morphological changes, altered mitochondrial proteome and protein oxidation, thereby establishing the role of mitochondrial damage in human muscle diseases. We investigated whether human muscle diseases display mitochondrial changes. Muscle biopsies

Usual interstitial pneumonia and nonspecific interstitial pneumonia: Correlation between CT findings at the site of biopsy with pathological diagnoses

Energy Technology Data Exchange (ETDEWEB)

Sumikawa, Hiromitsu, E-mail: h-sumikawa@radiol.med.osaka-u.ac.jp [Department of Radiology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0825 (Japan); Johkoh, Takeshi [Department of Radiology, Kinki Central Hospital of Mutual Aid Association of Public Health Teachers, 3-1 Kurumazuka, Itami, Hyougo 664-8533 (Japan); Fujimoto, Kiminori [Department of Radiology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011 (Japan); Ichikado, Kazuya [Division of Respiratory Medicine, Saiseikai Kumamoto Hospital, 5-3-1 Tikami, Kumamoto, 861-4193 (Japan); Colby, Thomas V. [Department of Pathology, Mayo Clinic, Scottsdale, AZ (United States); Fukuoka, Junya [Laboratory of Pathology, Toyama University Hospital, Toyama (Japan); Taniguchi, Hiroyuki; Kondoh, Yasuhiro; Kataoka, Kensuke [Department of Respiratory Medicine, Tosei General Hospital, 160 Nishioiwake-cho, Seto City, Aichi (Japan); Yanagawa, Masahiro; Koyama, Mitsuhiro; Honda, Osamu; Tomiyama, Noriyuki [Department of Radiology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0825 (Japan)

2012-10-15

Objectives: The aim of this study was to correlate high-resolution CT (HRCT) findings at the site of biopsy with the whole lung CT and pathologic diagnoses in usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP). Methods: The study included 35 patients (25 UIP and 10 NSIP) diagnosed both pathologically and clinically. 81 surgical biopsy specimens (54 UIP, and 27 NSIP) and extracted areas corresponding to biopsy sites on HRCT were analyzed. CT interpretations were compared with pathological diagnoses in both extracted images and the whole lung. Concordant and discordant cases in multiple extracted images were divided and analyzed. Then the whole cases were categorized by including or not at least one UIP diagnosis of extracted images and evaluated. Results: The diagnoses in extracted sites significantly correlated with pathological diagnoses (p = 0.047). There were significant differences in the concordances of extracted images compared with the diagnosis of whole lung and pathology (p = 0.008, 0.003, respectively). All 7 cases that were not concordant were diagnosed as radiological UIP with whole lung CT. The cases with at least one UIP diagnosis of extracted CT images were diagnosed as UIP in pathology more frequently (18 in 25) (p = 0.007). Conclusions: Radiological UIP in whole CT had more frequently discordant diagnoses from multiple extracted images than NSIP. And there were more cases in pathological UIP that included at least one UIP diagnosis of extracted images compared with pathological NSIP.

[Dual pathology].

Science.gov (United States)

Rougier, A

2008-05-01

Dual pathology is defined as the association of two potentially epileptogenic lesions, hippocampal (sclerosis, neuronal loss) and extrahippocampal (temporal or extratemporal). Epileptic activity may be generated by either lesion and the relative importance of every lesion's epileptogenicity conditions the surgical strategy adopted. Most frequently associated with hippocampal sclerosis are cortical dysplasias. The common physiopathology of the two lesions is not clearly established. Extrahippocampal lesions may be undetectable on MRI (microdysgenesis, for example) and ictal discharge patterns may vary among dual pathology patients. The surgical strategy depends on the location of the extrahippocampal lesion and its relative role in seizure generation; however, reported surgical results suggest that simultaneous resection of mesial temporal structures along with the extrahippocampal lesion should be performed.