WorldWideScience

Sample records for common complex diseases

  1. Endophenotype Network Models: Common Core of Complex Diseases

    Science.gov (United States)

    Ghiassian, Susan Dina; Menche, Jörg; Chasman, Daniel I.; Giulianini, Franco; Wang, Ruisheng; Ricchiuto, Piero; Aikawa, Masanori; Iwata, Hiroshi; Müller, Christian; Zeller, Tania; Sharma, Amitabh; Wild, Philipp; Lackner, Karl; Singh, Sasha; Ridker, Paul M.; Blankenberg, Stefan; Barabási, Albert-László; Loscalzo, Joseph

    2016-06-01

    Historically, human diseases have been differentiated and categorized based on the organ system in which they primarily manifest. Recently, an alternative view is emerging that emphasizes that different diseases often have common underlying mechanisms and shared intermediate pathophenotypes, or endo(pheno)types. Within this framework, a specific disease’s expression is a consequence of the interplay between the relevant endophenotypes and their local, organ-based environment. Important examples of such endophenotypes are inflammation, fibrosis, and thrombosis and their essential roles in many developing diseases. In this study, we construct endophenotype network models and explore their relation to different diseases in general and to cardiovascular diseases in particular. We identify the local neighborhoods (module) within the interconnected map of molecular components, i.e., the subnetworks of the human interactome that represent the inflammasome, thrombosome, and fibrosome. We find that these neighborhoods are highly overlapping and significantly enriched with disease-associated genes. In particular they are also enriched with differentially expressed genes linked to cardiovascular disease (risk). Finally, using proteomic data, we explore how macrophage activation contributes to our understanding of inflammatory processes and responses. The results of our analysis show that inflammatory responses initiate from within the cross-talk of the three identified endophenotypic modules.

  2. Contribution of rare and common variants determine complex diseases-Hirschsprung disease as a model.

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    Alves, Maria M; Sribudiani, Yunia; Brouwer, Rutger W W; Amiel, Jeanne; Antiñolo, Guillermo; Borrego, Salud; Ceccherini, Isabella; Chakravarti, Aravinda; Fernández, Raquel M; Garcia-Barcelo, Maria-Mercè; Griseri, Paola; Lyonnet, Stanislas; Tam, Paul K; van Ijcken, Wilfred F J; Eggen, Bart J L; te Meerman, Gerard J; Hofstra, Robert M W

    2013-10-01

    Finding genes for complex diseases has been the goal of many genetic studies. Most of these studies have been successful by searching for genes and mutations in rare familial cases, by screening candidate genes and by performing genome wide association studies. However, only a small fraction of the total genetic risk for these complex genetic diseases can be explained by the identified mutations and associated genetic loci. In this review we focus on Hirschsprung disease (HSCR) as an example of a complex genetic disorder. We describe the genes identified in this congenital malformation and postulate that both common 'low penetrant' variants in combination with rare or private 'high penetrant' variants determine the risk on HSCR, and likely, on other complex diseases. We also discuss how new technological advances can be used to gain further insights in the genetic background of complex diseases. Finally, we outline a few steps to develop functional assays in order to determine the involvement of these variants in disease development.

  3. Genome-wide association analysis of imputed rare variants: application to seven common complex diseases.

    Science.gov (United States)

    Mägi, Reedik; Asimit, Jennifer L; Day-Williams, Aaron G; Zeggini, Eleftheria; Morris, Andrew P

    2012-12-01

    Genome-wide association studies have been successful in identifying loci contributing effects to a range of complex human traits. The majority of reproducible associations within these loci are with common variants, each of modest effect, which together explain only a small proportion of heritability. It has been suggested that much of the unexplained genetic component of complex traits can thus be attributed to rare variation. However, genome-wide association study genotyping chips have been designed primarily to capture common variation, and thus are underpowered to detect the effects of rare variants. Nevertheless, we demonstrate here, by simulation, that imputation from an existing scaffold of genome-wide genotype data up to high-density reference panels has the potential to identify rare variant associations with complex traits, without the need for costly re-sequencing experiments. By application of this approach to genome-wide association studies of seven common complex diseases, imputed up to publicly available reference panels, we identify genome-wide significant evidence of rare variant association in PRDM10 with coronary artery disease and multiple genes in the major histocompatibility complex (MHC) with type 1 diabetes. The results of our analyses highlight that genome-wide association studies have the potential to offer an exciting opportunity for gene discovery through association with rare variants, conceivably leading to substantial advancements in our understanding of the genetic architecture underlying complex human traits.

  4. Rare and low-frequency variants in human common diseases and other complex traits.

    Science.gov (United States)

    Lettre, Guillaume

    2014-11-01

    In humans, most of the genetic variation is rare and often population-specific. Whereas the role of rare genetic variants in familial monogenic diseases is firmly established, we are only now starting to explore the contribution of this class of genetic variation to human common diseases and other complex traits. Such large-scale experiments are possible due to the development of next-generation DNA sequencing. Early findings suggested that rare and low-frequency coding variation might have a large effect on human phenotypes (eg, PCSK9 missense variants on low-density lipoprotein-cholesterol and coronary heart diseases). This observation sparked excitement in prognostic and diagnostic medicine, as well as in genetics-driven strategies to develop new drugs. In this review, I describe results and present initial conclusions regarding some of the recent rare and low-frequency variant discoveries. We can already assume that most phenotype-associated rare and low-frequency variants have modest-to-weak phenotypical effect. Thus, we will need large cohorts to identify them, as for common variants in genome-wide association studies. As we expand the list of associated rare and low-frequency variants, we can also better recognise the current limitations: we need to develop better statistical methods to optimally test association with rare variants, including non-coding variation, and to account for potential confounders such as population stratification.

  5. The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.

    Science.gov (United States)

    Astle, William J; Elding, Heather; Jiang, Tao; Allen, Dave; Ruklisa, Dace; Mann, Alice L; Mead, Daniel; Bouman, Heleen; Riveros-Mckay, Fernando; Kostadima, Myrto A; Lambourne, John J; Sivapalaratnam, Suthesh; Downes, Kate; Kundu, Kousik; Bomba, Lorenzo; Berentsen, Kim; Bradley, John R; Daugherty, Louise C; Delaneau, Olivier; Freson, Kathleen; Garner, Stephen F; Grassi, Luigi; Guerrero, Jose; Haimel, Matthias; Janssen-Megens, Eva M; Kaan, Anita; Kamat, Mihir; Kim, Bowon; Mandoli, Amit; Marchini, Jonathan; Martens, Joost H A; Meacham, Stuart; Megy, Karyn; O'Connell, Jared; Petersen, Romina; Sharifi, Nilofar; Sheard, Simon M; Staley, James R; Tuna, Salih; van der Ent, Martijn; Walter, Klaudia; Wang, Shuang-Yin; Wheeler, Eleanor; Wilder, Steven P; Iotchkova, Valentina; Moore, Carmel; Sambrook, Jennifer; Stunnenberg, Hendrik G; Di Angelantonio, Emanuele; Kaptoge, Stephen; Kuijpers, Taco W; Carrillo-de-Santa-Pau, Enrique; Juan, David; Rico, Daniel; Valencia, Alfonso; Chen, Lu; Ge, Bing; Vasquez, Louella; Kwan, Tony; Garrido-Martín, Diego; Watt, Stephen; Yang, Ying; Guigo, Roderic; Beck, Stephan; Paul, Dirk S; Pastinen, Tomi; Bujold, David; Bourque, Guillaume; Frontini, Mattia; Danesh, John; Roberts, David J; Ouwehand, Willem H; Butterworth, Adam S; Soranzo, Nicole

    2016-11-17

    Many common variants have been associated with hematological traits, but identification of causal genes and pathways has proven challenging. We performed a genome-wide association analysis in the UK Biobank and INTERVAL studies, testing 29.5 million genetic variants for association with 36 red cell, white cell, and platelet properties in 173,480 European-ancestry participants. This effort yielded hundreds of low frequency (<5%) and rare (<1%) variants with a strong impact on blood cell phenotypes. Our data highlight general properties of the allelic architecture of complex traits, including the proportion of the heritable component of each blood trait explained by the polygenic signal across different genome regulatory domains. Finally, through Mendelian randomization, we provide evidence of shared genetic pathways linking blood cell indices with complex pathologies, including autoimmune diseases, schizophrenia, and coronary heart disease and evidence suggesting previously reported population associations between blood cell indices and cardiovascular disease may be non-causal. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Differential virulence and disease progression following Mycobacterium tuberculosis complex infection of the common marmoset (Callithrix jacchus).

    Science.gov (United States)

    Via, Laura E; Weiner, Danielle M; Schimel, Daniel; Lin, Philana Ling; Dayao, Emmanuel; Tankersley, Sarah L; Cai, Ying; Coleman, M Teresa; Tomko, Jaime; Paripati, Praveen; Orandle, Marlene; Kastenmayer, Robin J; Tartakovsky, Michael; Rosenthal, Alexander; Portevin, Damien; Eum, Seok Yong; Lahouar, Saher; Gagneux, Sebastien; Young, Douglas B; Flynn, Joanne L; Barry, Clifton E

    2013-08-01

    Existing small-animal models of tuberculosis (TB) rarely develop cavitary disease, limiting their value for assessing the biology and dynamics of this highly important feature of human disease. To develop a smaller primate model with pathology similar to that seen in humans, we experimentally infected the common marmoset (Callithrix jacchus) with diverse strains of Mycobacterium tuberculosis of various pathogenic potentials. These included recent isolates of the modern Beijing lineage, the Euro-American X lineage, and M. africanum. All three strains produced fulminant disease in this animal with a spectrum of progression rates and clinical sequelae that could be monitored in real time using 2-deoxy-2-[(18)F]fluoro-d-glucose (FDG) positron emission tomography (PET)/computed tomography (CT). Lesion pathology at sacrifice revealed the entire spectrum of lesions observed in human TB patients. The three strains produced different rates of progression to disease, various extents of extrapulmonary dissemination, and various degrees of cavitation. The majority of live births in this species are twins, and comparison of results from siblings with different infecting strains allowed us to establish that the infection was highly reproducible and that the differential virulence of strains was not simply host variation. Quantitative assessment of disease burden by FDG-PET/CT provided an accurate reflection of the pathology findings at necropsy. These results suggest that the marmoset offers an attractive small-animal model of human disease that recapitulates both the complex pathology and spectrum of disease observed in humans infected with various M. tuberculosis strain clades.

  7. Differential Virulence and Disease Progression following Mycobacterium tuberculosis Complex Infection of the Common Marmoset (Callithrix jacchus)

    Science.gov (United States)

    Via, Laura E.; Weiner, Danielle M.; Schimel, Daniel; Lin, Philana Ling; Dayao, Emmanuel; Tankersley, Sarah L.; Cai, Ying; Coleman, M. Teresa; Tomko, Jaime; Paripati, Praveen; Orandle, Marlene; Kastenmayer, Robin J.; Tartakovsky, Michael; Rosenthal, Alexander; Portevin, Damien; Eum, Seok Yong; Lahouar, Saher; Gagneux, Sebastien; Young, Douglas B.; Flynn, JoAnne L.

    2013-01-01

    Existing small-animal models of tuberculosis (TB) rarely develop cavitary disease, limiting their value for assessing the biology and dynamics of this highly important feature of human disease. To develop a smaller primate model with pathology similar to that seen in humans, we experimentally infected the common marmoset (Callithrix jacchus) with diverse strains of Mycobacterium tuberculosis of various pathogenic potentials. These included recent isolates of the modern Beijing lineage, the Euro-American X lineage, and M. africanum. All three strains produced fulminant disease in this animal with a spectrum of progression rates and clinical sequelae that could be monitored in real time using 2-deoxy-2-[18F]fluoro-d-glucose (FDG) positron emission tomography (PET)/computed tomography (CT). Lesion pathology at sacrifice revealed the entire spectrum of lesions observed in human TB patients. The three strains produced different rates of progression to disease, various extents of extrapulmonary dissemination, and various degrees of cavitation. The majority of live births in this species are twins, and comparison of results from siblings with different infecting strains allowed us to establish that the infection was highly reproducible and that the differential virulence of strains was not simply host variation. Quantitative assessment of disease burden by FDG-PET/CT provided an accurate reflection of the pathology findings at necropsy. These results suggest that the marmoset offers an attractive small-animal model of human disease that recapitulates both the complex pathology and spectrum of disease observed in humans infected with various M. tuberculosis strain clades. PMID:23716617

  8. A robust GWSS method to simultaneously detect rare and common variants for complex disease.

    Directory of Open Access Journals (Sweden)

    Chung-Feng Kao

    Full Text Available The rapid advances in sequencing technologies and the resulting next-generation sequencing data provide the opportunity to detect disease-associated variants with a better solution, in particular for low-frequency variants. Although both common and rare variants might exert their independent effects on the risk for the trait of interest, previous methods to detect the association effects rarely consider them simultaneously. We proposed a class of test statistics, the generalized weighted-sum statistic (GWSS, to detect disease associations in the presence of common and rare variants with a case-control study design. Information of rare variants was aggregated using a weighted sum method, while signal directions and strength of the variants were considered at the same time. Permutations were performed to obtain the empirical p-values of the test statistics. Our simulation showed that, compared to the existing methods, the GWSS method had better performance in most of the scenarios. The GWSS (in particular VDWSS-t method is particularly robust for opposite association directions, association strength, and varying distributions of minor-allele frequencies. It is therefore promising for detecting disease-associated loci. For empirical data application, we also applied our GWSS method to the Genetic Analysis Workshop 17 data, and the results were consistent with the simulation, suggesting good performance of our method. As re-sequencing studies become more popular to identify putative disease loci, we recommend the use of this newly developed GWSS to detect associations with both common and rare variants.

  9. Genetics of complex diseases.

    Science.gov (United States)

    Motulsky, Arno G

    2006-02-01

    Approaches to the study of the genetic basis of common complex diseases and their clinical applications are considered. Monogenic Mendelian inheritance in such conditions is infrequent but its elucidation may help to detect pathogenic mechanisms in the more common variety of complex diseases. Involvement by multiple genes in complex diseases usually occurs but the isolation and identification of specific genes so far has been exceptional. The role of common polymorphisms as indicators of disease risk in various studies is discussed.

  10. Report: Genetics of complex diseases

    Institute of Scientific and Technical Information of China (English)

    MOTULSKY Arno G.

    2006-01-01

    Approaches to the study of the genetic basis of common complex diseases and their clinical applications are considered. Monogenic Mendelian inheritance in such conditions is infrequent but its elucidation may help to detect pathogenic mechanisms in the more common variety of complex diseases. Involvement by multiple genes in complex diseases usually occurs but the isolation and identification of specific genes so far has been exceptional. The role of common polymorphisms as indicators of disease risk in various studies is discussed.

  11. Bioenergetics in human evolution and disease: implications for the origins of biological complexity and the missing genetic variation of common diseases.

    Science.gov (United States)

    Wallace, Douglas C

    2013-07-19

    Two major inconsistencies exist in the current neo-Darwinian evolutionary theory that random chromosomal mutations acted on by natural selection generate new species. First, natural selection does not require the evolution of ever increasing complexity, yet this is the hallmark of biology. Second, human chromosomal DNA sequence variation is predominantly either neutral or deleterious and is insufficient to provide the variation required for speciation or for predilection to common diseases. Complexity is explained by the continuous flow of energy through the biosphere that drives the accumulation of nucleic acids and information. Information then encodes complex forms. In animals, energy flow is primarily mediated by mitochondria whose maternally inherited mitochondrial DNA (mtDNA) codes for key genes for energy metabolism. In mammals, the mtDNA has a very high mutation rate, but the deleterious mutations are removed by an ovarian selection system. Hence, new mutations that subtly alter energy metabolism are continuously introduced into the species, permitting adaptation to regional differences in energy environments. Therefore, the most phenotypically significant gene variants arise in the mtDNA, are regional, and permit animals to occupy peripheral energy environments where rarer nuclear DNA (nDNA) variants can accumulate, leading to speciation. The neutralist-selectionist debate is then a consequence of mammals having two different evolutionary strategies: a fast mtDNA strategy for intra-specific radiation and a slow nDNA strategy for speciation. Furthermore, the missing genetic variation for common human diseases is primarily mtDNA variation plus regional nDNA variants, both of which have been missed by large, inter-population association studies.

  12. Studying the Efficiency of “Bilator-6” Complex Preparation Against Fungoid Diseases of Garden Strawberry and Common Barberry

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    Fomichev Valeriy Tarasovich

    2014-04-01

    Full Text Available The article aims at studying the produced complex preparation “Bilator” characterized by multifunctional effect. Bilator is a nano-structured water solution of bischofite salts (MgCl2 subjected to electrochemical processing with the use of copper anode. In order to activate the efficiency of this solution at the level of a cellular membrane the authors propose the technology of its electrochemical processing as a result of which qualitative characteristics change: the solution turns heterogeneous where the substance is connected in the colloidal nanostructures (micelles representing neutral particles with the sizes of 20-250 nanometers. The colloidal (micellar form of solution structure eliminates coagulation processes, reduces the size of a gradient of osmotic pressure on border of a cell and, thereby, provides better delivery of active agents at cellular level. The structure of a cellular membrane, having the sizes of carrying-out channels of 30-40 nanometers, provides penetration into the cell only to those elements whose sizes do not exceed this range. It gives the chance to use each ingredient with maximum efficiency, facilitates their penetration and provides the synergism. The conducted research proved the efficiency of Bilator-6 preparation for protecting a common barberry and a garden strawberry from mealy dew. The data allowed to assume the positive influence of the preparation on intensity of blossoming of these plants.

  13. Eosinophil Count Is a Common Factor for Complex Metabolic and Pulmonary Traits and Diseases: The LifeLines Cohort Study

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    Bashirova, Dinara; Prins, Bram P.; Corpeleijn, Eva; Bruinenberg, Marcel; Franke, Lude; van der Harst, Pim; Navis, Gerjan; Wolffenbuttel, Bruce H. R.; Stolk, Ronald P.; Wijmenga, Cisca; Postma, Dirkje S.; Koppelman, Gerard H.; Boezen, H. Marike; Vonk, Judith; Snieder, Harold; Alizadeh, Behrooz Z.

    2016-01-01

    There is ongoing debate on the association between eosinophil count and diseases, as previous studies were inconsistent. We studied the relationship of eosinophil count with 22 complex metabolic, cardiac, and pulmonary traits and diseases. From the population-based LifeLines Cohort Study (N = 167,729), 13,301 individuals were included. We focused on relationship of eosinophil count with three classes of metabolic (7 traits, 2 diseases), cardiac (6 traits, 2 diseases), and pulmonary (2 traits, 2 diseases) outcomes. Regression analyses were applied in overall, women and men, while adjusted for age, sex, BMI and smoking. A p-value of <0.00076 was considered statistically significant. 58.2% of population were women (mean±SD 51.3±11.1 years old). In overall, one-SD higher of ln-eosinophil count was associated with a 0.04 (±SE ±0.002;p = 6.0×10−6) SD higher levels in ln-BMI, 0.06 (±0.007;p = 3.1×10−12) SD in ln-TG, 0.04 (±0.003;p = 7.0×10−6) SD in TC, 0.04 (±0.004;p = 6.3×10−7) SD in LDL, 0.04 (±0.006;p = 6.0×10−6) SD in HbA1c; and with a 0.05 (±0.004;p = 1.7×10−8) SD lower levels in HDL, 0.05 (±0.007;p = 3.4×10−23) SD in FEV1, and 0.09 (±0.001;p = 6.6×10−28) SD in FEV1/FVC. A higher ln-eosinophil count was associated with 1.18 (95%CI 1.09–1.28;p = 2.0×10−5) odds ratio of obesity, 1.29 (1.19–1.39;p = 1.1×10−10) of metabolic syndrome, 1.40 (1.25–1.56;p = 2.7×10−9) of COPD and 1.81 (1.61–2.03;p = 1.0×10−23) of asthma. Similar results were found in women. We found no association between ln-eosinophil count either with blood pressure indices in overall, women and men; or with BMI, LDL, HbA1c and obesity in men. In a large population based cohort, we confirmed eosinophil count as a potential factor implicated in metabolic and pulmonary outcomes. PMID:27978545

  14. Common errors in disease mapping

    Directory of Open Access Journals (Sweden)

    Ricardo Ocaña-Riola

    2010-05-01

    Full Text Available Many morbid-mortality atlases and small-area studies have been carried out over the last decade. However, the methods used to draw up such research, the interpretation of results and the conclusions published are often inaccurate. Often, the proliferation of this practice has led to inefficient decision-making, implementation of inappropriate health policies and negative impact on the advancement of scientific knowledge. This paper reviews the most frequent errors in the design, analysis and interpretation of small-area epidemiological studies and proposes a diagnostic evaluation test that should enable the scientific quality of published papers to be ascertained. Nine common mistakes in disease mapping methods are discussed. From this framework, and following the theory of diagnostic evaluation, a standardised test to evaluate the scientific quality of a small-area epidemiology study has been developed. Optimal quality is achieved with the maximum score (16 points, average with a score between 8 and 15 points, and low with a score of 7 or below. A systematic evaluation of scientific papers, together with an enhanced quality in future research, will contribute towards increased efficacy in epidemiological surveillance and in health planning based on the spatio-temporal analysis of ecological information.

  15. Genetics of complex diseases

    DEFF Research Database (Denmark)

    Mellerup, Erling; Møller, Gert Lykke; Koefoed, Pernille

    2012-01-01

    A complex disease with an inheritable component is polygenic, meaning that several different changes in DNA are the genetic basis for the disease. Such a disease may also be genetically heterogeneous, meaning that independent changes in DNA, i.e. various genotypes, can be the genetic basis...... for the disease. Each of these genotypes may be characterized by specific combinations of key genetic changes. It is suggested that even if all key changes are found in genes related to the biology of a certain disease, the number of combinations may be so large that the number of different genotypes may be close...

  16. How important are rare variants in common disease?

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    Saint Pierre, Aude; Génin, Emmanuelle

    2014-09-01

    Genome-wide association studies have uncovered hundreds of common genetic variants involved in complex diseases. However, for most complex diseases, these common genetic variants only marginally contribute to disease susceptibility. It is now argued that rare variants located in different genes could in fact play a more important role in disease susceptibility than common variants. These rare genetic variants were not captured by genome-wide association studies using single nucleotide polymorphism-chips but with the advent of next-generation sequencing technologies, they have become detectable. It is now possible to study their contribution to common disease by resequencing samples of cases and controls or by using new genotyping exome arrays that cover rare alleles. In this review, we address the question of the contribution of rare variants in common disease by taking the examples of different diseases for which some resequencing studies have already been performed, and by summarizing the results of simulation studies conducted so far to investigate the genetic architecture of complex traits in human. So far, empirical data have not allowed the exclusion of many models except the most extreme ones involving only a small number of rare variants with large effects contributing to complex disease. To unravel the genetic architecture of complex disease, case-control data will not be sufficient, and alternative study designs need to be proposed together with methodological developments.

  17. Insights into the pathogenic character of a common NUBPL branch-site mutation associated with mitochondrial disease and complex I deficiency using a yeast model

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    Mateusz M. Wydro

    2013-09-01

    Complex I deficiencies are the most common causes of mitochondrial disorders. They can result from mutations not only in the structural subunits but also in a growing number of known assembly factors. A branch-site mutation in the human gene encoding assembly factor NUBPL has recently been associated with mitochondrial encephalopathy and complex I deficiency in seven independent cases. Moreover, the mutation is present in 1.2% of European haplotypes. To investigate its pathogenicity, we have reconstructed the altered C-terminus that results from the branch-site mutation and frameshift in the homologous Ind1 protein in the respiratory yeast Yarrowia lipolytica. We demonstrate that the altered sequence did not affect IND1 mRNA stability, yet it led to a decrease in Ind1 protein level. The instability of mutant Ind1 resulted in a strong decrease in complex I activity and caused slow growth, resembling the phenotype of the deletion strain of IND1. The presented data confirms the deleterious impact of the altered C-terminus resulting from the branch-site mutation. Furthermore, our approach demonstrates the great potential of Y. lipolytica as a model to investigate complex I deficiencies, especially in cases with genetic complexity.

  18. Hypertriglyceridemia, a common dyslipidemia of complex definition

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    Chiara Trenti

    2013-04-01

    Full Text Available Background: Hypertriglyceridemia is a common biochemical finding. Depending on the triglyceride levels it can be associated with increased risk of acute pancreatitis and of cardiovascular disease. The most severe forms have a genetic basis. Clinical case: We report a case of a 60-year-old woman with very high triglycerides (800- 3,000 mg/dL and normal cholesterol levels. The patient is a non smoker, on hypolipemic diet, non alcoholic consumer, and on regular physical exercise. Her blood pressure is normal, BMI is 20, waist circumference is 78 cm. Thyroid, renal and hepatic function are normal. She has never had acute pancreatitis or cardiovascular disease. Discussion: The diagnostic and therapeutic management of this case is discussed. Causes of primary (genetic and secondary hypertriglyceridemia are also reviewed, together with clinical features and management on every day practice. We focused on severe hypertriglyceridemia.

  19. Transcriptome analysis of a rotenone model of parkinsonism reveals complex I-tied and -untied toxicity mechanisms common to neurodegenerative diseases.

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    Yofre Cabeza-Arvelaiz

    Full Text Available The pesticide rotenone, a neurotoxin that inhibits the mitochondrial complex I, and destabilizes microtubules (MT has been linked to Parkinson disease (PD etiology and is often used to model this neurodegenerative disease (ND. Many of the mechanisms of action of rotenone are posited mechanisms of neurodegeneration; however, they are not fully understood. Therefore, the study of rotenone-affected functional pathways is pertinent to the understanding of NDs pathogenesis. This report describes the transcriptome analysis of a neuroblastoma (NB cell line chronically exposed to marginally toxic and moderately toxic doses of rotenone. The results revealed a complex pleiotropic response to rotenone that impacts a variety of cellular events, including cell cycle, DNA damage response, proliferation, differentiation, senescence and cell death, which could lead to survival or neurodegeneration depending on the dose and time of exposure and cell phenotype. The response encompasses an array of physiological pathways, modulated by transcriptional and epigenetic regulatory networks, likely activated by homeostatic alterations. Pathways that incorporate the contribution of MT destabilization to rotenone toxicity are suggested to explain complex I-independent rotenone-induced alterations of metabolism and redox homeostasis. The postulated mechanisms involve the blockage of mitochondrial voltage-dependent anions channels (VDACs by tubulin, which coupled with other rotenone-induced organelle dysfunctions may underlie many presumed neurodegeneration mechanisms associated with pathophysiological aspects of various NDs including PD, AD and their variant forms. Thus, further investigation of such pathways may help identify novel therapeutic paths for these NDs.

  20. Common acquired kidney diseases in children

    African Journals Online (AJOL)

    5. Common acquired kidney diseases in children. Examination of the urine is probably the most ... rheumatic fever and APSGN should not ... remains unknown. ... Volume overload may also cause ..... systematic review of observational studies.

  1. Lipedema: A Relatively Common Disease with Extremely Common Misconceptions

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    Herbst, Karen L.

    2016-01-01

    Lipedema, or adiposis dolorosa, is a common adipose tissue disorder that is believed to affect nearly 11% of adult women worldwide. It is characterized most commonly by disproportionate adipocyte hypertrophy of the lower extremities, significant tenderness to palpation, and a failure to respond to extreme weight loss modalities. Women with lipedema report a rapid growth of the lipedema subcutaneous adipose tissue in the setting of stress, surgery, and/or hormonal changes. Women with later stages of lipedema have a classic “column leg” appearance, with masses of nodular fat, easy bruising, and pain. Despite this relatively common disease, there are few physicians who are aware of it. As a result, patients are often misdiagnosed with lifestyle-induced obesity, and/or lymphedema, and subjected to unnecessary medical interventions and fat-shaming. Diagnosis is largely clinical and based on criteria initially established in 1951. Treatment of lipedema is effective and includes lymphatic support, such as complete decongestive therapy, and specialized suction lipectomy to spare injury to lymphatic channels and remove the diseased lipedema fat. With an incidence that may affect nearly 1 in 9 adult women, it is important to generate appropriate awareness, conduct additional research, and identify better diagnostic and treatment modalities for lipedema so these women can obtain the care that they need and deserve.

  2. Neurodegenerative diseases: a common etiology and a common therapy.

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    Pierpaoli, Walter

    2005-12-01

    The variety of names of neurodegenerative diseases (NDDs) does not indicate that there is a wide variety of causes and a multiple number of cures. In fact NDDs derive from a common and repetitive, almost monotonous multicausal origin. NDDs are initiated invariably by a sudden or silent insidious decrease in immunologic resistance of the T cell-dependent or delayed type, produced by a large variety of psychological-emotional and/or environmental "stressors" (e.g., social, family-domestic, economic, alimentary, traumatic, and professional). These stressors increase the vulnerability of tissues (in this case, a section of the central or peripheral nervous system) to attack by a common virus (e.g., adenoviruses and herpesviruses). This attack creates a vicious circle leading to emergence of virus-generated tissue autoantigens and then to formation of autoantibodies. Use of corticosteroids and immunosuppressive drugs dramatically worsen and "eternalize" the diseases with further immunosuppression. Invariably, onset of NDDs is anticipated by a clear-cut alteration of the hormonal cyclicity, which closely controls immunity. My experience with patients in the last five years indicates a new approach to prevent and cure NDDs, based on a system totally divergent from present therapies. In fact "resetting the hormonal cyclicity clock" results in restoration of hormone-dependent antiviral immunity, arrest of disease progression, and at least partial recovery of neural functions, whatever the origin, anatomic location, and course of pathology.

  3. Polymylagia rheumatica: common disease, elusive diagnosis.

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    Mager, Diana R

    2015-03-01

    Polymyalgia rheumatica (PMR) is a common inflammatory rheumatic disease with little known about its etiology or incidence. Frequently found in older adult women, this disease can be debilitating, painful, and dangerous. Diagnosing PMR can be elusive due to lack of specific laboratory tests, and treatment with use of long-term glucocorticoids can be difficult due to side effects. The following article describes the pathophysiology, diagnosis, signs and symptoms, and treatment of PMR, as well as implications for home healthcare.

  4. Canine immune complex diseases.

    Science.gov (United States)

    Plechner, A J

    1976-11-01

    Though not conclusive, our primary findings indicate that a feature common to many of our tumor and ICD patients is depressed cortisol production. Additionally, the response to ACTH adrenal cortex stimulation tests, at 2-hour intervals between rest and stimulation, have ranged from negative to substantially less than would be expected in normal subjects. Peripheral plasma cortisol values for dogs, at rest and 2 hours after ACTH stimulation, respectively, have been reported as 2-10 and 25-30 mug/dl, 3-8 and 7.5-18 mug/dl, and 1-12.5 and 9.5-22 mug/dl. For representative patients, our resting values have been 1.2-5.2 mug/dl, vs 1.2-7.6 mug after ACTH stimulation (Table 2). Altogether we have studied 42 cases in detail, and we feel that a post-ACTH level of 8.0 mug/dl or less is a conservative indication of adrenocortical insufficiency; all levels have been between 1 and 8 mug/dl. We believe these low cortisol levels indicate either a genetically-induced adrenal cortical insufficiency (evident at 2 months to 1 year of age) or an immune complex adrenal cortical suppression (occurring after 1 year of age in association with other immunodeficiency disorders). Our studies demonstrate a need for biphasic therapy. We have found it necessary to not only initiate cortisone acetate therapy to support the deficient adrenal cortical secretion, but also use other immunosuppressive drugs to control the ICD. If the target organ has been suppressed or destroyed, the need for supplementation is obvious. However, other immune-injury moieties must be suppressed also, eg, ANA, anti-IgG antibodies, etc.

  5. Common ground, complex problems and decision making

    NARCIS (Netherlands)

    Beers, P.J.; Boshuizen, H.P.A.; Kirschner, P.A.; Gijselaers, W.H.

    2006-01-01

    Organisations increasingly have to deal with complex problems. They often use multidisciplinary teams to cope with such problems where different team members have different perspectives on the problem, different individual knowledge and skills, and different approaches on how to solve the problem. I

  6. Common diseases as determinants of menopausal age.

    Science.gov (United States)

    Li, Jingmei; Eriksson, Mikael; Czene, Kamila; Hall, Per; Rodriguez-Wallberg, Kenny A

    2016-12-01

    Can the diagnosis of common diseases before menopause influence age at natural menopause (ANM) onset? Polycystic ovary syndrome (PCOS) and depression were observed to delay menopause. It has been observed that women who undergo early menopause experience a higher burden of health problems related to metabolic syndromes, heart disease and depression, but whether ANM can be influenced by common adult diseases has not been studied extensively. All women attending mammography screening or clinical mammography at four hospitals in Sweden were invited to participate in the Karolinska Mammography Project for Risk Prediction of Breast Cancer (KARMA) study. Between January 2011 and March 2013, 70 877 women were recruited. Information from the baseline questionnaire filled out upon enrollment was used in this cross-sectional analysis on predictors of ANM onset. We limited our analyses to 61 936 women with complete data on ANM and covariates and a follow-up time (from birth to menopause or censoring) of at least 35 years. Premenopausal diagnoses of depression, anorexia, bulimia, PCOS, ovarian cyst, heart failure, myocardial infarction, angina pectoris, stroke, preeclampsia, diabetes, hypertension and hyperlipidemia were examined as time-dependent variables in multivariable Cox regression analyses, adjusting for reproductive factors (age at menarche, menstrual cycle regularity in adult life, number of children and premenopausal oral contraceptive use) and risk factors of common diseases (education, physical activity at 18 years and information at the time of questionnaire including BMI, ever smoking and alcohol consumption). Women with PCOS and depression were independently associated with later menopause (hazard ratio (95% CI): 0.44 (0.28-0.71) and 0.95 (0.91-1.00), respectively), compared to women with no such histories. The associations remained significant in a subset of women who had never received gynecological surgery or hormone treatment (n = 32313, 0.21 (0

  7. Down syndrome and Alzheimer's disease: Common pathways, common goals.

    Science.gov (United States)

    Hartley, Dean; Blumenthal, Thomas; Carrillo, Maria; DiPaolo, Gilbert; Esralew, Lucille; Gardiner, Katheleen; Granholm, Ann-Charlotte; Iqbal, Khalid; Krams, Michael; Lemere, Cynthia; Lott, Ira; Mobley, William; Ness, Seth; Nixon, Ralph; Potter, Huntington; Reeves, Roger; Sabbagh, Marwan; Silverman, Wayne; Tycko, Benjamin; Whitten, Michelle; Wisniewski, Thomas

    2015-06-01

    In the United States, estimates indicate there are between 250,000 and 400,000 individuals with Down syndrome (DS), and nearly all will develop Alzheimer's disease (AD) pathology starting in their 30s. With the current lifespan being 55 to 60 years, approximately 70% will develop dementia, and if their life expectancy continues to increase, the number of individuals developing AD will concomitantly increase. Pathogenic and mechanistic links between DS and Alzheimer's prompted the Alzheimer's Association to partner with the Linda Crnic Institute for Down Syndrome and the Global Down Syndrome Foundation at a workshop of AD and DS experts to discuss similarities and differences, challenges, and future directions for this field. The workshop articulated a set of research priorities: (1) target identification and drug development, (2) clinical and pathological staging, (3) cognitive assessment and clinical trials, and (4) partnerships and collaborations with the ultimate goal to deliver effective disease-modifying treatments. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  8. New IBD genetics: common pathways with other diseases.

    Science.gov (United States)

    Lees, C W; Barrett, J C; Parkes, M; Satsangi, J

    2011-12-01

    Complex disease genetics has been revolutionised in recent years by the advent of genome-wide association (GWA) studies. The chronic inflammatory bowel diseases (IBDs), Crohn's disease and ulcerative colitis have seen notable successes culminating in the discovery of 99 published susceptibility loci/genes (71 Crohn's disease; 47 ulcerative colitis) to date. Approximately one-third of loci described confer susceptibility to both Crohn's disease and ulcerative colitis. Amongst these are multiple genes involved in IL23/Th17 signalling (IL23R, IL12B, JAK2, TYK2 and STAT3), IL10, IL1R2, REL, CARD9, NKX2.3, ICOSLG, PRDM1, SMAD3 and ORMDL3. The evolving genetic architecture of IBD has furthered our understanding of disease pathogenesis. For Crohn's disease, defective processing of intracellular bacteria has become a central theme, following gene discoveries in autophagy and innate immunity (associations with NOD2, IRGM, ATG16L1 are specific to Crohn's disease). Genetic evidence has also demonstrated the importance of barrier function to the development of ulcerative colitis (HNF4A, LAMB1, CDH1 and GNA12). However, when the data are analysed in more detail, deeper themes emerge including the shared susceptibility seen with other diseases. Many immune-mediated diseases overlap in this respect, paralleling the reported epidemiological evidence. However, in several cases the reported shared susceptibility appears at odds with the clinical picture. Examples include both type 1 and type 2 diabetes mellitus. In this review we will detail the presently available data on the genetic overlap between IBD and other diseases. The discussion will be informed by the epidemiological data in the published literature and the implications for pathogenesis and therapy will be outlined. This arena will move forwards very quickly in the next few years. Ultimately, we anticipate that these genetic insights will transform the landscape of common complex diseases such as IBD.

  9. Governing the Commons for two decades: a complex story

    NARCIS (Netherlands)

    Berge, E.; Laerhoven, F.S.J. van

    2011-01-01

    In complex systems, the elements are interrelated in ways that ensure that one element cannot be studied without accounting for the others. We take as a fact that the world over time has become more and more complex. The story of Elinor Ostrom’s Governing the Commons is among other things a story wi

  10. Common lung conditions: chronic obstructive pulmonary disease.

    Science.gov (United States)

    Delzell, John E

    2013-06-01

    The etiology of chronic obstructive pulmonary disease (COPD) is chronic lung inflammation. In the United States, this inflammation most commonly is caused by smoking. COPD is diagnosed when an at-risk patient presents with respiratory symptoms and has irreversible airway obstruction indicated by a forced expiratory volume in 1 second/forced vital capacity ratio of less than 0.7. Management goals for COPD include smoking cessation, symptom reduction, exacerbation reduction, hospitalization avoidance, and improvement of quality of life. Stable patients with COPD who remain symptomatic despite using short-acting bronchodilators should start inhaled maintenance drugs to reduce symptoms and exacerbations, avoid hospitalizations, and improve quality of life. A long-acting anticholinergic or a long-acting beta2-agonist (LABA) can be used for initial therapy; these drugs have fewer adverse effects than inhaled corticosteroids (ICS). If patients remain symptomatic despite monotherapy, dual therapy with a long-acting anticholinergic and a LABA, or a LABA and an ICS, may be beneficial. Triple therapy (ie, a long-acting anticholinergic, a LABA, and an ICS) also is used, but it is unclear if triple therapy is superior to dual therapy. Roflumilast, an oral selective inhibitor of phosphodiesterase 4, is used to manage moderate to severe COPD. Continuous oxygen therapy is indicated for patients with COPD who have severe hypoxemia (ie, PaO2 less than 55 mm Hg or an oxygen saturation less than 88% on room air). Nonpharmacologic strategies also are useful to improve patient outcomes. Pulmonary rehabilitation improves dyspnea and quality of life. Pulmonary rehabilitation after an acute exacerbation reduces hospitalizations and mortality, and improves quality of life and exercise capacity. Smoking cessation is the most effective management strategy for reducing morbidity and mortality in patients with COPD. Lung volume reduction surgery, bullectomy, and lung transplantation are

  11. Common Periodontal Diseases of Children and Adolescents

    OpenAIRE

    Hayat Al-Ghutaimel; Hisham Riba; Salem Al-Kahtani; Saad Al-Duhaimi

    2014-01-01

    Background. Since 2000, studies, experiments, and clinical observations revealed high prevalence of periodontal diseases among children and adolescents. Therefore, this paper was designed to provide an update for dental practitioners on epidemiology, microbiology, pathology, prevention, diagnosis, and treatment of periodontal diseases in children and adolescents. Methods. This paper reviews the current literature concerning periodontal diseases in pediatric dentistry. It includes MEDLINE data...

  12. Exome localization of complex disease association signals

    Directory of Open Access Journals (Sweden)

    Lewis Cathryn M

    2011-02-01

    Full Text Available Abstract Background Genome-wide association studies (GWAS of common diseases have had a tremendous impact on genetic research over the last five years; the field is now moving from microarray-based technology towards next-generation sequencing. To evaluate the potential of association studies for complex diseases based on exome sequencing we analysed the distribution of association signal with respect to protein-coding genes based on GWAS data for seven diseases from the Wellcome Trust Case Control Consortium. Results We find significant concentration of association signal in exons and genes for Crohn's Disease, Type 1 Diabetes and Bipolar Disorder, but also observe enrichment from up to 40 kilobases upstream to 40 kilobases downstream of protein-coding genes for Crohn's Disease and Type 1 Diabetes; the exact extent of the distribution is disease dependent. Conclusions Our work suggests that exome sequencing may be a feasible approach to find genetic variation associated with complex disease. Extending the exome sequencing to include flanking regions therefore promises further improvement of covering disease-relevant variants.

  13. Bronchiectasis: Phenotyping a Complex Disease.

    Science.gov (United States)

    Chalmers, James D

    2017-03-15

    Bronchiectasis is a long-neglected disease currently experiencing a surge in interest. It is a highly complex condition with numerous aetiologies, co-morbidities and a heterogeneous disease presentation and clinical course. The past few years have seen major advances in our understanding of the disease, primarily through large real-life cohort studies. The main outcomes of interest in bronchiectasis are symptoms, exacerbations, treatment response, disease progression and death. We are now more able to identify clearly the radiological, clinical, microbiological and inflammatory contributors to these outcomes. Over the past couple of years, multidimensional scoring systems such as the Bronchiectasis Severity Index have been introduced to predict disease severity and mortality. Although there are currently no licensed therapies for bronchiectasis, an increasing number of clinical trials are planned or ongoing. While this emerging evidence is awaited, bronchiectasis guidelines will continue to be informed largely by real-life evidence from observational studies and patient registries. Key developments in the bronchiectasis field include the establishment of international disease registries and characterisation of disease phenotypes using cluster analysis and biological data.

  14. Common Periodontal Diseases of Children and Adolescents

    Directory of Open Access Journals (Sweden)

    Hayat Al-Ghutaimel

    2014-01-01

    “microbiology of periodontal diseases,” “classification of periodontal diseases,” “epidemiology of periodontal diseases,” and “treatment of periodontal diseases.” Articles were evaluated by title and/or abstract and relevance to pediatric dentistry. Sixty-five citations were selected by this method and by the references within the chosen articles. A review of the comprehensive textbooks on pediatric dentistry and periodontology was done. Some recommendations were based on the opinions of experienced researchers and clinicians, when data were inconclusive.

  15. Common DNA sequence variation and psychiatric disease

    NARCIS (Netherlands)

    Ripke, S.

    2014-01-01

    In a genome-wide association study (GWAS), a large number of SNPs are genotyped in a large number of cases (with disease) and controls (without disease) using commercially available high-throughput genotyping platforms. In a GWAS, the genotype data collected in cases and unaffected, population-match

  16. Nutrition and genetic susceptibility to common diseases.

    Science.gov (United States)

    Motulsky, A G

    1992-06-01

    Genetic factors play a role in chronic disease and conditions such as coronary heart disease, hypertension, and obesity. Individual responses to nutritional factors involved in such conditions vary depending upon a person's genetic make-up. The role of individual genes is best understood for the hyperlipidemias that predispose to coronary heart disease. Until more and better information on gene-nutritional interactions is available, general population-wide recommendations regarding a prudent diet appear reasonable. At the same time, high risk screening for certain conditions such as the hyperlipidemias is appropriate.

  17. Diabetic Myonecrosis: Uncommon Complications in Common Diseases

    Directory of Open Access Journals (Sweden)

    Sisira Sran

    2014-01-01

    Full Text Available We report a case of sudden thigh pain from spontaneous quadriceps necrosis, also known as diabetic myonecrosis, in a 28-year-old patient with poorly controlled diabetes mellitus. Diabetic muscle infarction is a rare end-organ complication seen in patients with poor glycemic control and advanced chronic microvascular complications. Proposed mechanisms involve atherosclerotic microvascular occlusion, ischemia-reperfusion related injury, vasculitis with microthrombi formation, and an acquired antiphospholipid syndrome. Diabetic myonecrosis most commonly presents as sudden thigh pain with swelling and should be considered in any patient who has poorly controlled diabetes mellitus.

  18. Pathogenesis: common pathways between hidradenitis suppurativa and Crohn disease.

    Science.gov (United States)

    García Martínez, F J; Menchén, L

    2016-09-01

    Both hidradenitis suppurativa and Crohn disease are considered chronic inflammatory diseases due to immune dysregulation. The high prevalence of Crohn disease patients diagnosed with hidradenitis suppurativa suggests the existence of common pathogenic links. The present literature review analyses the similarities and differences in the pathogenesis of the two diseases, in the search for new research and knowledge targets.

  19. Drug Induced Steatohepatitis: An Uncommon Culprit of a Common Disease

    Directory of Open Access Journals (Sweden)

    Liane Rabinowich

    2015-01-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is a leading cause of liver disease in developed countries. Its frequency is increasing in the general population mostly due to the widespread occurrence of obesity and the metabolic syndrome. Although drugs and dietary supplements are viewed as a major cause of acute liver injury, drug induced steatosis and steatohepatitis are considered a rare form of drug induced liver injury (DILI. The complex mechanism leading to hepatic steatosis caused by commonly used drugs such as amiodarone, methotrexate, tamoxifen, valproic acid, glucocorticoids, and others is not fully understood. It relates not only to induction of the metabolic syndrome by some drugs but also to their impact on important molecular pathways including increased hepatocytes lipogenesis, decreased secretion of fatty acids, and interruption of mitochondrial β-oxidation as well as altered expression of genes responsible for drug metabolism. Better familiarity with this type of liver injury is important for early recognition of drug hepatotoxicity and crucial for preventing severe forms of liver injury and cirrhosis. Moreover, understanding the mechanisms leading to drug induced hepatic steatosis may provide much needed clues to the mechanism and potential prevention of the more common form of metabolic steatohepatitis.

  20. Common Diseases and Some Demographic Characteristics among Saudi Women

    Science.gov (United States)

    Al-Haramlah, Ahmed Abdulrahman; Al-Bakr, Fawziah; Merza, Haniah

    2015-01-01

    This study aimed to detect the common diseases among Saudi women and their relationship with the level of physical activity and some variables. This study was applied to 1233 Saudi woman in different regions of the Kingdom, and adopted to explore the common diseases: obesity, hypertension, diabetes, cholesterol and asthma. The study results showed…

  1. Different Polycomb group complexes regulate common target genes in Arabidopsis.

    Science.gov (United States)

    Makarevich, Grigory; Leroy, Olivier; Akinci, Umut; Schubert, Daniel; Clarenz, Oliver; Goodrich, Justin; Grossniklaus, Ueli; Köhler, Claudia

    2006-09-01

    Polycomb group (PcG) proteins convey epigenetic inheritance of repressed transcriptional states. Although the mechanism of the action of PcG is not completely understood, methylation of histone H3 lysine 27 (H3K27) is important in establishing PcG-mediated transcriptional repression. We show that the plant PcG target gene PHERES1 is regulated by histone trimethylation on H3K27 residues mediated by at least two different PcG complexes in plants, containing the SET domain proteins MEDEA or CURLY LEAF/SWINGER. Furthermore, we identify FUSCA3 as a potential PcG target gene and show that FUSCA3 is regulated by MEDEA and CURLY LEAF/SWINGER. We propose that different PcG complexes regulate a common set of target genes during the different stages of plant development.

  2. Can Protein in Common Skin Bacteria Offer Disease Protection?

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_162192.html Can Protein in Common Skin Bacteria Offer Disease Protection? RoxP ... Swedish researchers report that Propionibacterium acnes secretes a protein called RoxP that protects against bacteria that are ...

  3. Common Occupational Health Problems In Disease Control In Nigeria

    African Journals Online (AJOL)

    Common Occupational Health Problems In Disease Control In Nigeria. ... laboratories, hazardous gases like ethylene oxide and nitrous oxides; physical agents like ... When duely exposed, health workers are at high risk of health problems like ...

  4. Common neighbour structure and similarity intensity in complex networks

    Science.gov (United States)

    Hou, Lei; Liu, Kecheng

    2017-10-01

    Complex systems as networks always exhibit strong regularities, implying underlying mechanisms governing their evolution. In addition to the degree preference, the similarity has been argued to be another driver for networks. Assuming a network is randomly organised without similarity preference, the present paper studies the expected number of common neighbours between vertices. A symmetrical similarity index is accordingly developed by removing such expected number from the observed common neighbours. The developed index can not only describe the similarities between vertices, but also the dissimilarities. We further apply the proposed index to measure of the influence of similarity on the wring patterns of networks. Fifteen empirical networks as well as artificial networks are examined in terms of similarity intensity and degree heterogeneity. Results on real networks indicate that, social networks are strongly governed by the similarity as well as the degree preference, while the biological networks and infrastructure networks show no apparent similarity governance. Particularly, classical network models, such as the Barabási-Albert model, the Erdös-Rényi model and the Ring Lattice, cannot well describe the social networks in terms of the degree heterogeneity and similarity intensity. The findings may shed some light on the modelling and link prediction of different classes of networks.

  5. Complexation of buffer constituents with neutral complexation agents: part I. Impact on common buffer properties.

    Science.gov (United States)

    Riesová, Martina; Svobodová, Jana; Tošner, Zdeněk; Beneš, Martin; Tesařová, Eva; Gaš, Bohuslav

    2013-09-17

    The complexation of buffer constituents with the complexation agent present in the solution can very significantly influence the buffer properties, such as pH, ionic strength, or conductivity. These parameters are often crucial for selection of the separation conditions in capillary electrophoresis or high-pressure liquid chromatography (HPLC) and can significantly affect results of separation, particularly for capillary electrophoresis as shown in Part II of this paper series (Beneš, M.; Riesová, M.; Svobodová, J.; Tesařová, E.; Dubský, P.; Gaš, B. Anal. Chem. 2013, DOI: 10.1021/ac401381d). In this paper, the impact of complexation of buffer constituents with a neutral complexation agent is demonstrated theoretically as well as experimentally for the model buffer system composed of benzoic acid/LiOH or common buffers (e.g., CHES/LiOH, TAPS/LiOH, Tricine/LiOH, MOPS/LiOH, MES/LiOH, and acetic acid/LiOH). Cyclodextrins as common chiral selectors were used as model complexation agents. We were not only able to demonstrate substantial changes of pH but also to predict the general complexation characteristics of selected compounds. Because of the zwitterion character of the common buffer constituents, their charged forms complex stronger with cyclodextrins than the neutral ones do. This was fully proven by NMR measurements. Additionally complexation constants of both forms of selected compounds were determined by NMR and affinity capillary electrophoresis with a very good agreement of obtained values. These data were advantageously used for the theoretical descriptions of variations in pH, depending on the composition and concentration of the buffer. Theoretical predictions were shown to be a useful tool for deriving some general rules and laws for complexing systems.

  6. The complexity of epigenetic diseases.

    Science.gov (United States)

    Brazel, Ailbhe Jane; Vernimmen, Douglas

    2016-01-01

    Over the past 30 years, a plethora of pathogenic mutations affecting enhancer regions and epigenetic regulators have been identified. Coupled with more recent genome-wide association studies (GWAS) and epigenome-wide association studies (EWAS) implicating major roles for regulatory mutations in disease, it is clear that epigenetic mechanisms represent important biomarkers for disease development and perhaps even therapeutic targets. Here, we discuss the diversity of disease-causing mutations in enhancers and epigenetic regulators, with a particular focus on cancer.

  7. Genetics in Common Liver Diseases: From Pathophysiology to Precise Treatment.

    Science.gov (United States)

    Lammert, Frank

    In the past 2 decades, advances in genetics have improved our understanding of liver disease and physiology. Firstly, developments in genomic technologies drove the identification of genes responsible for monogenic (Mendelian) liver diseases. Over the last decade, genome-wide association studies allowed for the dissection of the genetic susceptibility to complex liver diseases such as fatty liver disease and drug-induced liver injury, in which environmental co-factors play critical roles. The findings have allowed the identification and elaboration of pathophysiological processes, have indicated the need for reclassification of liver diseases and risk factors and have already pointed to new disease treatments. This is illustrated by the interaction of alcohol, overnutrition and the PNPLA3 gene, which represents an 'infernal triangle' for the liver. In the future, genetics will allow further stratification of liver diseases and contribute to personalized (precision) medicine, offering novel opportunities for translational research and clinical care of our patients. © 2016 S. Karger AG, Basel.

  8. The Link Between Lysosomal Storage Disorders and More Common Diseases

    Directory of Open Access Journals (Sweden)

    Michael Beck MD

    2016-12-01

    Full Text Available In the last decades, it has become more and more evident that lysosomal storage disorders and common neurodegenerative diseases such as Alzheimer and Parkinson diseases have clinical, neuropathological, and genetic features in common, including lysosomal dysfunction and impaired autophagy. Patients with Gaucher and even carriers of Gaucher disease have an increased risk to develop Parkinson disease. Likewise, individuals who are heterozygous for a mutation of a gene that causes an adult form of neuronal ceroid lipofuscinosis are more likely to be affected by a form of frontotemporal dementia in their later life. A further example is the gene NAGLU encoding the enzyme α- N -acetylglucosaminidase, which is deficient in patients with mucopolysaccharidosis type IIIB. Mutations of the NAGLU gene have been observed in patients affected by an axonal neuropathy. An interesting unexpected finding was the link between stuttering and genes that are essential for the function of all lysosomal enzymes. This review will present some example of the association of lysosomal storage disorders and neurodegenerative disease and discuss possible pathogenic mechanisms that are common to both conditions. The understanding of the pathophysiology of the endosomal–lysosomal–autophagic system may help to develop drugs, which might provide benefit not only for patients with rare lysosomal storage disorders but also for individuals affected by more common diseases.

  9. The Link Between Lysosomal Storage Disorders and More Common Diseases

    Directory of Open Access Journals (Sweden)

    Michael Beck MD

    2016-12-01

    Full Text Available In the last decades, it has become more and more evident that lysosomal storage disorders and common neurodegenerative diseases such as Alzheimer and Parkinson diseases have clinical, neuropathological, and genetic features in common, including lysosomal dysfunction and impaired autophagy. Patients with Gaucher and even carriers of Gaucher disease have an increased risk to develop Parkinson disease. Likewise, individuals who are heterozygous for a mutation of a gene that causes an adult form of neuronal ceroid lipofuscinosis are more likely to be affected by a form of frontotemporal dementia in their later life. A further example is the gene NAGLU encoding the enzyme α-N-acetylglucosaminidase, which is deficient in patients with mucopolysaccharidosis type IIIB. Mutations of the NAGLU gene have been observed in patients affected by an axonal neuropathy. An interesting unexpected finding was the link between stuttering and genes that are essential for the function of all lysosomal enzymes. This review will present some example of the association of lysosomal storage disorders and neurodegenerative disease and discuss possible pathogenic mechanisms that are common to both conditions. The understanding of the pathophysiology of the endosomal–lysosomal–autophagic system may help to develop drugs, which might provide benefit not only for patients with rare lysosomal storage disorders but also for individuals affected by more common diseases.

  10. Childhood Obesity & Dental Disease: Common Causes, Common Solutions. Oral Health & Obesity Policy Brief

    Science.gov (United States)

    Children Now, 2011

    2011-01-01

    Too many California children suffer from high rates of preventable chronic conditions associated with childhood obesity and dental disease. The state is experiencing a crisis in both areas. Fortunately, common factors that contribute to both conditions--including the rates of breastfeeding, access to healthy food and the consumption of…

  11. OVERVIEWS OF THE TREATMENT AND CONTROL OF COMMON FISH DISEASES

    Directory of Open Access Journals (Sweden)

    Madhuri Sharma

    2012-07-01

    Full Text Available Similar to other animals, fish can also suffer from different diseases. All fish carry pathogens and parasites. Disease is a prime agent affecting fish mortality, especially when fish are young. Pathogens which can cause fish diseases comprise: viral infections, bacterial infections, fungal infections, protozoan infections, water mould infection, etc. Fish are also exposed from different environmental pollutants, including drugs and chemicals. The most common fish diseases, particularly in freshwater aquaria, include columnaris, gill disease, ick (ich, dropsy, tail and fin-rot, fungal infections, white spot disease, pop-eye, cloudy eye, swim bladder disease, lice and nematode worms infestation, water quality induced diseases, constipation, anorexia, chilodonella, ergasilus, tuberculosis, glugea, henneguya, hexamita, hole-in-the-head disease, injuries, leeches in aquaria, lymphocystis, marine velvet, and neon-tetra disease, etc. Antibiotics are frequently used to control fish diseases caused by bacteria, but there is an increasing risk of developing antibiotic resistant strains of bacteria. The non-specific immune functions such as bacteriolytic activity and leukocyte function of fish have been improved by some herbs. Plants have been used as traditional medicine since time immemorial to control bacterial, viral, fungal and other diseases.

  12. Inflammation: The Common Pathway of Stress-Related Diseases

    Science.gov (United States)

    Liu, Yun-Zi; Wang, Yun-Xia; Jiang, Chun-Lei

    2017-01-01

    While modernization has dramatically increased lifespan, it has also witnessed that the nature of stress has changed dramatically. Chronic stress result failures of homeostasis thus lead to various diseases such as atherosclerosis, non-alcoholic fatty liver disease (NAFLD) and depression. However, while 75%–90% of human diseases is related to the activation of stress system, the common pathways between stress exposure and pathophysiological processes underlying disease is still debatable. Chronic inflammation is an essential component of chronic diseases. Additionally, accumulating evidence suggested that excessive inflammation plays critical roles in the pathophysiology of the stress-related diseases, yet the basis for this connection is not fully understood. Here we discuss the role of inflammation in stress-induced diseases and suggest a common pathway for stress-related diseases that is based on chronic mild inflammation. This framework highlights the fundamental impact of inflammation mechanisms and provides a new perspective on the prevention and treatment of stress-related diseases. PMID:28676747

  13. [Development of expert diagnostic system for common respiratory diseases].

    Science.gov (United States)

    Xu, Wei-hua; Chen, You-ling; Yan, Zheng

    2014-03-01

    To develop an internet-based expert diagnostic system for common respiratory diseases. SaaS system was used to build architecture; pattern of forward reasoning was applied for inference engine design; ASP.NET with C# from the tool pack of Microsoft Visual Studio 2005 was used for website-interview medical expert system.The database of the system was constructed with Microsoft SQL Server 2005. The developed expert system contained large data memory and high efficient function of data interview and data analysis for diagnosis of various diseases.The users were able to perform this system to obtain diagnosis for common respiratory diseases via internet. The developed expert system may be used for internet-based diagnosis of various respiratory diseases,particularly in telemedicine setting.

  14. Common themes in changing vector-borne disease scenarios.

    Science.gov (United States)

    Molyneux, David H

    2003-01-01

    The impact of climate change on disease patterns is controversial. However, global burden of disease studies suggest that infectious diseases will contribute a proportionately smaller burden of disease over the next 2 decades as non-communicable diseases emerge as public health problems. However, infectious diseases contribute proportionately more in the poorest quintile of the population. Notwithstanding the different views of the impact of global warming on vector-borne infections this paper reviews the conditions which drive the changing epidemiology of these infections and suggests that such change is linked by common themes including interactions of generalist vectors and reservoir hosts at interfaces with humans, reduced biodiversity associated with anthropogenic environmental changes, increases in Plasmodium falciparum: P. vivax ratios and well-described land use changes such as hydrological, urbanization, agricultural, mining and forest-associated impacts (extractive activities, road building, deforestation and migration) which are seen on a global scale.

  15. Advanced Role of Neutrophils in Common Respiratory Diseases

    Directory of Open Access Journals (Sweden)

    Jinping Liu

    2017-01-01

    Full Text Available Respiratory diseases, always being a threat towards the health of people all over the world, are most tightly associated with immune system. Neutrophils serve as an important component of immune defense barrier linking innate and adaptive immunity. They participate in the clearance of exogenous pathogens and endogenous cell debris and play an essential role in the pathogenesis of many respiratory diseases. However, the pathological mechanism of neutrophils remains complex and obscure. The traditional roles of neutrophils in severe asthma, chronic obstructive pulmonary diseases (COPD, pneumonia, lung cancer, pulmonary fibrosis, bronchitis, and bronchiolitis had already been reviewed. With the development of scientific research, the involvement of neutrophils in respiratory diseases is being brought to light with emerging data on neutrophil subsets, trafficking, and cell death mechanism (e.g., NETosis, apoptosis in diseases. We reviewed all these recent studies here to provide you with the latest advances about the role of neutrophils in respiratory diseases.

  16. Distilling pathophysiology from complex disease genetics.

    Science.gov (United States)

    Chakravarti, Aravinda; Clark, Andrew G; Mootha, Vamsi K

    2013-09-26

    Technologies for genome-wide sequence interrogation have dramatically improved our ability to identify loci associated with complex human disease. However, a chasm remains between correlations and causality that stems, in part, from a limiting theoretical framework derived from Mendelian genetics and an incomplete understanding of disease physiology. Here we propose a set of criteria, akin to Koch's postulates for infectious disease, for assigning causality between genetic variants and human disease phenotypes. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Effects of Common Equine Endocrine Diseases on Reproduction.

    Science.gov (United States)

    Burns, Teresa A

    2016-12-01

    Endocrine diseases, such as equine metabolic syndrome and pituitary pars intermedia dysfunction, are common in domesticated horse populations, and the frequency with which these diseases are encountered and managed by equine veterinary practitioners is expected to increase as the population ages. As clinicians learn more about the effects of these diseases on equine reproductive physiology and efficiency (including effects on reproductive seasonality, ovulation efficiency, implantation, early pregnancy loss, duration of pregnancy, and lactation), strategies and guidelines for improving fertility in affected animals continue to evolve. It is hoped that further research will establish these recommendations more firmly.

  18. Genetics of Common Endocrine Disease: The Present and the Future.

    Science.gov (United States)

    Goodarzi, Mark O

    2016-03-01

    In honor of the 75th issue of the Journal of Clinical Endocrinology and Metabolism, the author was invited to present his perspectives on genetics in human endocrinology. This paper reviews what the field has achieved in the genetics of common endocrine disease, and offers predictions on where the field will move in the future and its impact on endocrine clinical practice. The October 2015 data release of the National Human Genome Research Institute-European Bioinformatics Institute (NHGRI-EBI) Catalog of Published Genome-wide Association Studies was queried regarding endocrinologic diseases and traits. PubMed searches were focused on genetic prediction of disease, genetic findings and drug targets, functional interrogation of genetic loci, use of genetics to subtype disease, missing heritability, systems genomics, and higher order chromatin structures as regulators of gene function. Nearly a quarter of genome wide association study findings concern endocrinologic diseases and traits. While these findings have not yet dramatically altered clinical care, genetics will have a major impact by providing the drug targets of tomorrow, facilitated by experimental and bioinformatic advances that will shorten the time from gene discovery to drug development. Use of genetic findings to subtype common endocrine disease will allow more precise prevention and treatment efforts. Future advances will allow us to move away from the common view of DNA as a string of letters, allowing exploration of higher order structure that likely explains much "missing heritability." The future will see a greater role of genetics at the bedside, with genetic epidemiologic discoveries leading not only to new treatments of endocrine disease, but also helping us prescribe the right drug to the right patients by allowing subclassification of common heterogeneous endocrine conditions. Future technological breakthroughs will reveal the heritable mysteries hidden in chromatin structure, leading to a

  19. Common mechanisms of autoimmune diseases (the autoimmune tautology).

    Science.gov (United States)

    Anaya, Juan-Manuel

    2012-09-01

    The fact that autoimmune diseases share subphenotypes, physiopathological mechanisms and genetic factors has been called autoimmune tautology, and indicates that they have a common origin. The autoimmune phenotypes vary depending on the target cell and the affected organ, gender, ancestry, trigger factors and age at onset. Ten shared characteristics supporting this logical theory are herein reviewed.

  20. Disease transmission by cannibalism: rare event or common occurrence?

    Science.gov (United States)

    Rudolf, Volker H W; Antonovics, Janis

    2007-05-07

    Cannibalism has been documented as a possible disease transmission route in several species, including humans. However, the dynamics resulting from this type of disease transmission are not well understood. Using a theoretical model, we explore how cannibalism (i.e. killing and consumption of dead conspecifics) and intraspecific necrophagy (i.e. consumption of dead conspecifics) affect host-pathogen dynamics. We show that group cannibalism, i.e. shared consumption of victims, is a necessary condition for disease spread by cannibalism in the absence of alternative transmission modes. Thus, endemic diseases transmitted predominantly by cannibalism are likely to be rare, except in social organisms that share conspecific prey. These results are consistent with a review of the literature showing that diseases transmitted by cannibalism are infrequent in animals, even though both cannibalism and trophic transmission are very common.

  1. Common mechanisms of onset of cancer and neurodegenerative diseases.

    Science.gov (United States)

    Ariga, Hiroyoshi

    2015-01-01

    Onset of cancer and neurodegenerative disease occurs by abnormal cell growth and neuronal cell death, respectively, and the number of patients with both diseases has been increasing in parallel with an increase in mean lifetime, especially in developed countries. Although both diseases are sporadic, about 10% of the diseases are genetically inherited, and analyses of such familial forms of gene products have contributed to an understanding of the molecular mechanisms underlying the onset and pathogenesis of these diseases. I have been working on c-myc, a protooncogene, for a long time and identified various c-Myc-binding proteins that play roles in c-Myc-derived tumorigenesis. Among these proteins, some proteins have been found to be also responsible for the onset of neurodegenerative diseases, including Parkinson's disease, retinitis pigmentosa and cerebellar atrophy. In this review, I summarize our findings indicating the common mechanisms of onset between cancer and neurodegenerative diseases, with a focus on genes such as DJ-1 and Myc-Modulator 1 (MM-1) and signaling pathways that contribute to the onset and pathogenesis of cancer and neurodegenerative diseases.

  2. Common Agency and Computational Complexity : Theory and Experimental Evidence

    NARCIS (Netherlands)

    Kirchsteiger, G.; Prat, A.

    1999-01-01

    In a common agency game, several principals try to influence the behavior of an agent. Common agency games typically have multiple equilibria. One class of equilibria, called truthful, has been identified by Bernheim and Whinston and has found widespread use in the political economy literature. In t

  3. Epigenetic Epidemiology of Complex Diseases Using Twins

    DEFF Research Database (Denmark)

    Tan, Qihua

    2013-01-01

    through multiple epigenetic mechanisms. This paper reviews the new developments in using twins to study disease-related epigenetic alterations, links them to lifetime environmental exposure with a focus on the discordant twin design and proposes novel data-analytical approaches with the aim of promoting...... a more efficient use of twins in epigenetic studies of complex human diseases....

  4. Expanded complexity of unstable repeat diseases

    OpenAIRE

    Polak, Urszula; McIvor, Elizabeth; Dent, Sharon Y.R.; Wells, Robert D.; Napierala, Marek.

    2012-01-01

    Unstable Repeat Diseases (URDs) share a common mutational phenomenon of changes in the copy number of short, tandemly repeated DNA sequences. More than 20 human neurological diseases are caused by instability, predominantly expansion, of microsatellite sequences. Changes in the repeat size initiate a cascade of pathological processes, frequently characteristic of a unique disease or a small subgroup of the URDs. Understanding of both the mechanism of repeat instability and molecular consequen...

  5. Age at Onset in Two Common Neurodegenerative Diseases Is Genetically Controlled

    Science.gov (United States)

    Li, Yi-Ju; Scott, William K.; Hedges, Dale J.; Zhang, Fengyu; Gaskell, P. Craig; Nance, Martha A.; Watts, Ray L.; Hubble, Jean P.; Koller, William C.; Pahwa, Rajesh; Stern, Matthew B.; Hiner, Bradley C.; Jankovic, Joseph; Allen, Jr., Fred H.; Goetz, Christopher G.; Mastaglia, Frank; Stajich, Jeffrey M.; Gibson, Rachel A.; Middleton, Lefkos T.; Saunders, Ann M.; Scott, Burton L.; Small, Gary W.; Nicodemus, Kristin K.; Reed, Allison D.; Schmechel, Donald E.; Welsh-Bohmer, Kathleen A.; Conneally, P. Michael; Roses, Allen D.; Gilbert, John R.; Vance, Jeffery M.; Haines, Jonathan L.; Pericak-Vance, Margaret A.

    2002-01-01

    To identify genes influencing age at onset (AAO) in two common neurodegenerative diseases, a genomic screen was performed for AAO in families with Alzheimer disease (AD; n=449) and Parkinson disease (PD; n=174). Heritabilities between 40%–60% were found in both the AD and PD data sets. For PD, significant evidence for linkage to AAO was found on chromosome 1p (LOD = 3.41). For AD, the AAO effect of APOE (LOD = 3.28) was confirmed. In addition, evidence for AAO linkage on chromosomes 6 and 10 was identified independently in both the AD and PD data sets. Subsequent unified analyses of these regions identified a single peak on chromosome 10q between D10S1239 and D10S1237, with a maximum LOD score of 2.62. These data suggest that a common gene affects AAO in these two common complex neurodegenerative diseases. PMID:11875758

  6. Common variation in ISL1 confers genetic susceptibility for human congenital heart disease.

    Directory of Open Access Journals (Sweden)

    Kristen N Stevens

    Full Text Available Congenital heart disease (CHD is the most common birth abnormality and the etiology is unknown in the overwhelming majority of cases. ISLET1 (ISL1 is a transcription factor that marks cardiac progenitor cells and generates diverse multipotent cardiovascular cell lineages. The fundamental role of ISL1 in cardiac morphogenesis makes this an exceptional candidate gene to consider as a cause of complex congenital heart disease. We evaluated whether genetic variation in ISL1 fits the common variant-common disease hypothesis. A 2-stage case-control study examined 27 polymorphisms mapping to the ISL1 locus in 300 patients with complex congenital heart disease and 2,201 healthy pediatric controls. Eight genic and flanking ISL1 SNPs were significantly associated with complex congenital heart disease. A replication study analyzed these candidate SNPs in 1,044 new cases and 3,934 independent controls and confirmed that genetic variation in ISL1 is associated with risk of non-syndromic congenital heart disease. Our results demonstrate that two different ISL1 haplotypes contribute to risk of CHD in white and black/African American populations.

  7. Epigenetic Epidemiology of Complex Diseases Using Twins

    DEFF Research Database (Denmark)

    Tan, Qihua

    2013-01-01

    In the past decades, studies on twins have had a great impact on dissecting the genetic and environmental contributions to human diseases and complex traits. In the era of functional genomics, the valuable samples of twins help to bridge the gap between gene activity and environmental conditions...... through multiple epigenetic mechanisms. This paper reviews the new developments in using twins to study disease-related epigenetic alterations, links them to lifetime environmental exposure with a focus on the discordant twin design and proposes novel data-analytical approaches with the aim of promoting...... a more efficient use of twins in epigenetic studies of complex human diseases....

  8. Breast cancer. Part 1: Awareness and common benign diseases.

    Science.gov (United States)

    Harmer, Victoria

    Breast cancer is the most common cancer for women in the United Kingdom and topic on which there is much information. This article discusses the principles behind breast awareness and breast health, detailing common benign breast diseases that cause disproportionate anxiety. The NHS Breast Screening Programme is celebrating 20 years of screening this year, and in all randomized controlled trials of women aged 50 and over, mortality from breast cancer is reduced in those offered screening compared with unscreened controls (although the reduction is not statistically significant in all trials). Once a breast cancer is diagnosed, the different characteristics and stage of the disease can be identified through histopathology and scans. These factors will be discussed later in this article, including illustrating if a cancer is hormone sensitive or HER-2 positive, for example. These factors enable clinicians to recommend a treatment pathway suitable for each individual.

  9. Is there a Common Genetic Basis for Autoimmune Diseases?

    Directory of Open Access Journals (Sweden)

    Juan-Manuel Anaya

    2006-01-01

    Full Text Available Autoimmune diseases (ADs represent a diverse collection of diseases in terms of their demographic profile and primary clinical manifestations. The commonality between them however, is the damage to tissues and organs that arises from the response to self-antigens. The presence of shared pathophysiological mechanisms within ADs has stimulated searches for common genetic roots to these diseases. Two approaches have been undertaken to sustain the “common genetic origin” theory of ADs. Firstly, a clinical genetic analysis showed that autoimmunity aggregates within families of probands diagnosed with primary Sjögren's (pSS syndrome or type 1 diabetes mellitus (T1D. A literature review supported the establishment of a familiar cluster of ADs depending upon the proband's disease phenotype. Secondly, in a same and well-defined population, a large genetic association study indicated that a number of polymorphic genes (i.e. HLA-DRB1, TNF and PTPN22 influence the susceptibility for acquiring different ADs. Likewise, association and linkage studies in different populations have revealed that several susceptibility loci overlap in ADs, and clinical studies have shown that frequent clustering of several ADs occurs. Thus, the genetic factors for ADs consist of two types: those which are common to many ADs (acting in epistatic pleitropy and those that are specific to a given disorder. Their identification and functional characterization will allow us to predict their effect as well as to indicate potential new therapeutic interventions. Both autoimmunity family history and the co-occurrence of ADs in affected probands should be considered when performing genetic association and linkage studies.

  10. Detection of Common Dental Diseases by Dental Hygiene-Therapists

    OpenAIRE

    Macey, Richard John

    2016-01-01

    Thesis submitted to the University of Manchester by Richard Macey for the Degree of Doctor of Philosophy entitled “Detection of Common Dental Diseases by Dental Hygiene-Therapists”, February 2016.Many adult patients that attend NHS dental practices on a regular basis are asymptomatic and do not need any further treatment other than a routine dental examination (“check-up”). As the oral health of the adult population is predicted to improve further, using the General Dental Practitioner to und...

  11. The most common otorhinolaryngologic manifestations of granulomatous diseases

    Directory of Open Access Journals (Sweden)

    Heshiki, Rosana Emiko

    2008-09-01

    Full Text Available Introduction: Granulomatous diseases result from immunopathologic processes in which there is a failure in the fagocitosis of intracellular organisms. They can cause oral, nasal and pharyngeal mucosa ulcers, vocal cords lesions, otorrhoea and oropharyngeal vegetant lesions. Objective: Describing the most frequent otorhinolaryngologic manifestations in common granulomatous diseases: hanseniasis, paracoccidioidomycosis, leishmaniasis. Method: A retrospective study has been carried out from records of patients diagnosed with the abovementioned diseases between January 1, 2005 and October 31, 2007 in an infectology ambulatory of a tertiary hospital. Results: 142 patients were evaluated; 93 with leishmaniasis, 39 with paracoccidioidomycosis and 10 with hanseniasis. In 93 cases of leishmaniasis, 16 (17.2% had mucosal affection, and the most common signs were septum perforation and nasal mucosal ulcers, both with 8 cases. In paracoccidioidomycosis, oropharyngeal ulcer was the most frequent, with 15 cases (38,4%. Conclusion: Head and neck signs and symptoms are common in patients with leishmaniasis and paracoccidioidomycosis. Nasal manifestations prevail in leishmaniasis and oropharyngeal ones in paracoccidioidomycosis.

  12. Network properties of complex human disease genes identified through genome-wide association studies.

    Directory of Open Access Journals (Sweden)

    Fredrik Barrenas

    Full Text Available BACKGROUND: Previous studies of network properties of human disease genes have mainly focused on monogenic diseases or cancers and have suffered from discovery bias. Here we investigated the network properties of complex disease genes identified by genome-wide association studies (GWAs, thereby eliminating discovery bias. PRINCIPAL FINDINGS: We derived a network of complex diseases (n = 54 and complex disease genes (n = 349 to explore the shared genetic architecture of complex diseases. We evaluated the centrality measures of complex disease genes in comparison with essential and monogenic disease genes in the human interactome. The complex disease network showed that diseases belonging to the same disease class do not always share common disease genes. A possible explanation could be that the variants with higher minor allele frequency and larger effect size identified using GWAs constitute disjoint parts of the allelic spectra of similar complex diseases. The complex disease gene network showed high modularity with the size of the largest component being smaller than expected from a randomized null-model. This is consistent with limited sharing of genes between diseases. Complex disease genes are less central than the essential and monogenic disease genes in the human interactome. Genes associated with the same disease, compared to genes associated with different diseases, more often tend to share a protein-protein interaction and a Gene Ontology Biological Process. CONCLUSIONS: This indicates that network neighbors of known disease genes form an important class of candidates for identifying novel genes for the same disease.

  13. Network properties of complex human disease genes identified through genome-wide association studies.

    Science.gov (United States)

    Barrenas, Fredrik; Chavali, Sreenivas; Holme, Petter; Mobini, Reza; Benson, Mikael

    2009-11-30

    Previous studies of network properties of human disease genes have mainly focused on monogenic diseases or cancers and have suffered from discovery bias. Here we investigated the network properties of complex disease genes identified by genome-wide association studies (GWAs), thereby eliminating discovery bias. We derived a network of complex diseases (n = 54) and complex disease genes (n = 349) to explore the shared genetic architecture of complex diseases. We evaluated the centrality measures of complex disease genes in comparison with essential and monogenic disease genes in the human interactome. The complex disease network showed that diseases belonging to the same disease class do not always share common disease genes. A possible explanation could be that the variants with higher minor allele frequency and larger effect size identified using GWAs constitute disjoint parts of the allelic spectra of similar complex diseases. The complex disease gene network showed high modularity with the size of the largest component being smaller than expected from a randomized null-model. This is consistent with limited sharing of genes between diseases. Complex disease genes are less central than the essential and monogenic disease genes in the human interactome. Genes associated with the same disease, compared to genes associated with different diseases, more often tend to share a protein-protein interaction and a Gene Ontology Biological Process. This indicates that network neighbors of known disease genes form an important class of candidates for identifying novel genes for the same disease.

  14. [Complex diseases: the importance of genetics].

    Science.gov (United States)

    Libioulle, C; Bours, V

    2012-01-01

    Complex diseases usually harbour hereditary factors linked with multiple susceptibility genes. The additive effects of genetic and environmental factors are responsible for the pathology. The impact of heredity has been demonstrated through family studies, but also, and mostly, through the study of adopted people and twins. Recently, genome wide association studies (GWAS) allowed the identification of many susceptibility genes for most complex diseases. However, a large part of the heritability is still missing, probably because of insufficient exploration of rare genetic variants and/or epigenetic factors. The ultimate goal of these genetic studies is the definition of an individual risk leading to specific preventive measures (model "predict and prevent"), but this purpose remains very remote for the majority of complex diseases.

  15. Shared genetic variants suggest common pathways in allergy and autoimmune diseases

    DEFF Research Database (Denmark)

    Kreiner-Møller, Eskil; Waage, Johannes; Standl, Marie

    2016-01-01

    Background: The relationship between allergy and autoimmune disorders is complex and poorly understood. Objective: To investigate commonalities in genetic loci and pathways between allergy and autoimmune diseases to elucidate shared disease mechanisms. Methods: We meta-analyzed two GWAS on self......-reported allergy and sensitization comprising a total of 62,330 individuals. These results were used to calculate enrichment for SNPs previously associated with autoimmune diseases. Furthermore, we probed for enrichment within genetic pathways and of transcription factor binding sites, and characterized...... commonalities in the variant burden on tissue-specific regulatory sites by calculating the enrichment of allergy SNPs falling in gene regulatory regions in various cells using Encode Roadmap DHS data, and compared the allergy data with all known diseases. Conclusion: Among 290 loci previously associated with 16...

  16. Partitioning Heritability of Regulatory and Cell-Type-Specific Variants across 11 Common Diseases

    DEFF Research Database (Denmark)

    Gusev, Alexander; Lee, S Hong; Trynka, Gosia

    2014-01-01

    Regulatory and coding variants are known to be enriched with associations identified by genome-wide association studies (GWASs) of complex disease, but their contributions to trait heritability are currently unknown. We applied variance-component methods to imputed genotype data for 11 common...... diseases to partition the heritability explained by genotyped SNPs (hg(2)) across functional categories (while accounting for shared variance due to linkage disequilibrium). Extensive simulations showed that in contrast to current estimates from GWAS summary statistics, the variance-component approach...... partitions heritability accurately under a wide range of complex-disease architectures. Across the 11 diseases DNaseI hypersensitivity sites (DHSs) from 217 cell types spanned 16% of imputed SNPs (and 24% of genotyped SNPs) but explained an average of 79% (SE = 8%) of hg(2) from imputed SNPs (5.1× enrichment...

  17. Common Eye Diseases in Children in Saudi Arabia (Jazan)

    Science.gov (United States)

    Darraj, Abdulrahman; Barakat, Walid; Kenani, Mona; Shajry, Reem; Khawaji, Abdullah; Bakri, Sultan; Makin, Abdulrahman; Mohanna, Azza; Yassin, Abu Obaida

    2016-01-01

    BACKGROUND The rise in childhood eye diseases has become a matter of concern in Saudi Arabia, and hence a study has been conducted on the residents of Jazan. The aim of the research was to find out the root cause of such issues and provide a solution to prevent such circumstances for it may affect the vision of children. In this study, therefore, we aimed to determine the types of childhood eye diseases in Jazan and to discuss the best ways to prevent them or prevent their effect on the vision of our children. Our institutions are working toward the longevity and welfare of the residents, and healthcare is one of the important aspects in such a field. METHODS This is a retrospective review of all patients less than 18 years of age who presented to the pediatric ophthalmology clinic of Prince Mohammed Bin Nasser Hospital, Jazan, between October 2014 and October 2015. The data, collected on 385 cases, included the age at first presentation, sex, clinical diagnosis, refractive error (RE) if present, and whether the child had amblyopia. If the child did not undergo complete ophthalmic examination with cycloplegic refraction, he/she was excluded. All data were collected and analyzed using the software SPSS. A P-value sex among children with REs and squint. Trauma was seen more commonly among males and in the group aged 12–18 years. CONCLUSION In this retrospective study, the focus was on the common childhood eye diseases that were considerably high. Hypermetropia was the predominant RE, which is in contrast to other studies where myopia was more common. However, it is important to promote public education on the significance of early detection of strabismus, REs, and amblyopia and have periodic screening in schools. The discussion of the various issues is aimed at increasing the awareness and building a support for the cause by creating the knowledge base to treat things on time and acknowledging the severity of the issues. PMID:27679531

  18. Eukaryotic enhancers: common features, regulation, and participation in diseases.

    Science.gov (United States)

    Erokhin, Maksim; Vassetzky, Yegor; Georgiev, Pavel; Chetverina, Darya

    2015-06-01

    Enhancers are positive DNA regulatory sequences controlling temporal and tissue-specific gene expression. These elements act independently of their orientation and distance relative to the promoters of target genes. Enhancers act through a variety of transcription factors that ensure their correct match with target promoters and consequent gene activation. There is a growing body of evidence on association of enhancers with transcription factors, co-activators, histone chromatin marks, and lncRNAs. Alterations in enhancers lead to misregulation of gene expression, causing a number of human diseases. In this review, we focus on the common characteristics of enhancers required for transcription stimulation.

  19. Common variants in CASP3 confer susceptibility to Kawasaki disease.

    Science.gov (United States)

    Onouchi, Yoshihiro; Ozaki, Kouichi; Buns, Jane C; Shimizu, Chisato; Hamada, Hiromichi; Honda, Takafumi; Terai, Masaru; Honda, Akihito; Takeuchi, Takashi; Shibuta, Shoichi; Suenaga, Tomohiro; Suzuki, Hiroyuki; Higashi, Kouji; Yasukawa, Kumi; Suzuki, Yoichi; Sasago, Kumiko; Kemmotsu, Yasushi; Takatsuki, Shinichi; Saji, Tsutomu; Yoshikawa, Tetsushi; Nagai, Toshiro; Hamamoto, Kunihiro; Kishi, Fumio; Ouchi, Kazunobu; Sato, Yoshitake; Newburger, Jane W; Baker, Annette L; Shulman, Stanford T; Rowley, Anne H; Yashiro, Mayumi; Nakamura, Yoshikazu; Wakui, Keiko; Fukushima, Yoshimitsu; Fujino, Akihiro; Tsunoda, Tatsuhiko; Kawasaki, Tomisaku; Hata, Akira; Nakamura, Yusuke; Tanaka, Toshihiro

    2010-07-15

    Kawasaki disease (KD; OMIM 611775) is an acute vasculitis syndrome which predominantly affects small- and medium-sized arteries of infants and children. Epidemiological data suggest that host genetics underlie the disease pathogenesis. Here we report that multiple variants in the caspase-3 gene (CASP3) that are in linkage disequilibrium confer susceptibility to KD in both Japanese and US subjects of European ancestry. We found that a G to A substitution of one commonly associated SNP located in the 5' untranslated region of CASP3 (rs72689236; P = 4.2 x 10(-8) in the Japanese and P = 3.7 x 10(-3) in the European Americans) abolished binding of nuclear factor of activated T cells to the DNA sequence surrounding the SNP. Our findings suggest that altered CASP3 expression in immune effecter cells influences susceptibility to KD.

  20. 602 Cvid: A Common but Still Underdiagnosed Disease

    Science.gov (United States)

    Gallego, Claudia; González-Díaz, Sandra; del Carmen Zarate, Maria; Arias-Cruz, Alfredo; Garcia-Calderin, Diego; Yanneth Mejia Salas, Karla; Calva, Maricruz; Alfredo Dominguez Sansores, Luis

    2012-01-01

    Background Among the more than 150 different forms of Primary Immunodeficiency Diseases (PID) the CVID is the most common symptomatic primary immunodeficiency, present mainly in adults. There is a failure of B cells to develop and differentiate into plasma cells; at consequent a reduction of the production of one or more isotypes of antibody can also affected Cell-mediated immunity. Common manifestations included recurrent bacterial infections, that typically involve the upper and lower respiratory tract. Some patients are highly prone to autoimmune manifestations, lymphoid hyperplasia, and tumors. Methods We presented 3 cases of CVID with a variety of clinical presentation, evolution and complications related to delayed diagnosis. Results A 34 year old male presented chronic diarrhea, weight loss, malnutrition and recurrent upper respiratory infections; digestive tract endoscopy and biopsy was reported with villous atrophy, chronic inflammation and low grade non-Hodgkin's lymphoma B cell. Unfortunately this patient refused the use of gamma globulin treatment, had a high morbidity, and finally the patient died. The case of a nurse with clinical manifestation of recurrent rinosinusitis and pneumonia, which was diagnosed as IDCV 17 years later, after she developed pulmonary bronchiectasis. Fortunately the disease is under control and she is actually under treatment with intravenous immunoglobulin. Finally, the case of a 44 year old female, who suffered from recurrent upper respiratory infections, additionally had a thyroid gland tumor associated which affecting the thyroid function. Conclusions In the 3 cases had low levels of all immunoglobulin as a hallmark. The clinician must be suspecting this condition in all adults with recurrent infectious disease who have gastrointestinal symptoms or who are detected a malignant disease. Early diagnosis and correct treatment are critical in preventing tissue damage, long-term sequelae and death. Replacement with intravenous

  1. Treatment and Prevention of Common Complications of Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Sheikh Salahuddin Ahmed

    2014-01-01

    Full Text Available Chronic kidney disease (CKD is a worldwide public health problem with an increasing incidence and prevalence. Outcomes of CKD include not only complications of decreased kidney function and cardiovascular disease but also kidney failure causing increased morbidity and mortality. Unfortunately, CKD is often undetected and undertreated because of its insidious onset, variable progression, and length of time to overt kidney failure. Diabetes is now the leading cause of CKD requiring renal replacement therapy in many parts of the world, and its prevalence is increasing disproportionately in the developing countries. This review article outlines the current recommendations from various clinical guidelines and research studies for treatment, prevention and delaying the progression of both CKD and its common complications such as hypertension, anemia, renal osteodystrophy, electrolyte and acid-base imbalance, and hyperlipidemia. Recommendations for nutrition in CKD and measures adopted for early diabetic kidney disease to prevent further progression have also been reviewed. There is strong evidence that early detection and management of CKD can prevent or reduce disease progression, decrease complications and improve outcomes. Evidence supports that achieving optimal glucose control, blood pressure, reduction in albuminuria with a multifactorial intervention slows the progression of CKD. Angiotensin-converting enzyme inhibitors and angiotensin-II receptor antagonists are most effective because of their unique ability to decrease proteinuria, a factor important for the progression of CKD.

  2. Molecular paleontology and complexity in the last eukaryotic common ancestor.

    Science.gov (United States)

    Koumandou, V Lila; Wickstead, Bill; Ginger, Michael L; van der Giezen, Mark; Dacks, Joel B; Field, Mark C

    2013-01-01

    Eukaryogenesis, the origin of the eukaryotic cell, represents one of the fundamental evolutionary transitions in the history of life on earth. This event, which is estimated to have occurred over one billion years ago, remains rather poorly understood. While some well-validated examples of fossil microbial eukaryotes for this time frame have been described, these can provide only basic morphology and the molecular machinery present in these organisms has remained unknown. Complete and partial genomic information has begun to fill this gap, and is being used to trace proteins and cellular traits to their roots and to provide unprecedented levels of resolution of structures, metabolic pathways and capabilities of organisms at these earliest points within the eukaryotic lineage. This is essentially allowing a molecular paleontology. What has emerged from these studies is spectacular cellular complexity prior to expansion of the eukaryotic lineages. Multiple reconstructed cellular systems indicate a very sophisticated biology, which by implication arose following the initial eukaryogenesis event but prior to eukaryotic radiation and provides a challenge in terms of explaining how these early eukaryotes arose and in understanding how they lived. Here, we provide brief overviews of several cellular systems and the major emerging conclusions, together with predictions for subsequent directions in evolution leading to extant taxa. We also consider what these reconstructions suggest about the life styles and capabilities of these earliest eukaryotes and the period of evolution between the radiation of eukaryotes and the eukaryogenesis event itself.

  3. Molecular paleontology and complexity in the last eukaryotic common ancestor

    Science.gov (United States)

    Koumandou, V. Lila; Wickstead, Bill; Ginger, Michael L.; van der Giezen, Mark; Dacks, Joel B.

    2013-01-01

    Eukaryogenesis, the origin of the eukaryotic cell, represents one of the fundamental evolutionary transitions in the history of life on earth. This event, which is estimated to have occurred over one billion years ago, remains rather poorly understood. While some well-validated examples of fossil microbial eukaryotes for this time frame have been described, these can provide only basic morphology and the molecular machinery present in these organisms has remained unknown. Complete and partial genomic information has begun to fill this gap, and is being used to trace proteins and cellular traits to their roots and to provide unprecedented levels of resolution of structures, metabolic pathways and capabilities of organisms at these earliest points within the eukaryotic lineage. This is essentially allowing a molecular paleontology. What has emerged from these studies is spectacular cellular complexity prior to expansion of the eukaryotic lineages. Multiple reconstructed cellular systems indicate a very sophisticated biology, which by implication arose following the initial eukaryogenesis event but prior to eukaryotic radiation and provides a challenge in terms of explaining how these early eukaryotes arose and in understanding how they lived. Here, we provide brief overviews of several cellular systems and the major emerging conclusions, together with predictions for subsequent directions in evolution leading to extant taxa. We also consider what these reconstructions suggest about the life styles and capabilities of these earliest eukaryotes and the period of evolution between the radiation of eukaryotes and the eukaryogenesis event itself. PMID:23895660

  4. Prevalence of common disease-associated variants in Asian Indians

    Directory of Open Access Journals (Sweden)

    Allayee Hooman

    2008-02-01

    Full Text Available Abstract Background Asian Indians display a high prevalence of diseases linked to changes in diet and environment that have arisen as their lifestyle has become more westernized. Using 1200 genome-wide polymorphisms in 432 individuals from 15 Indian language groups, we have recently shown that: (i Indians constitute a distinct population-genetic cluster, and (ii despite the geographic and linguistic diversity of the groups they exhibit a relatively low level of genetic heterogeneity. Results We investigated the prevalence of common polymorphisms that have been associated with diseases, such as atherosclerosis (ALOX5, hypertension (CYP3A5, AGT, GNB3, diabetes (CAPN10, TCF7L2, PTPN22, prostate cancer (DG8S737, rs1447295, Hirschsprung disease (RET, and age-related macular degeneration (CFH, LOC387715. In addition, we examined polymorphisms associated with skin pigmentation (SLC24A5 and with the ability to taste phenylthiocarbamide (TAS2R38. All polymorphisms were studied in a cohort of 576 India-born Asian Indians sampled in the United States. This sample consisted of individuals whose mother tongue is one of 14 of the 22 "official" languages recognized in India as well as individuals whose mother tongue is Parsi, a cultural group that has resided in India for over 1000 years. Analysis of the data revealed that allele frequency differences between the different Indian language groups were small, and interestingly the variant alleles of ALOX5 g.8322G>A and g.50778G>A, and PTPN22 g.36677C>T were present only in a subset of the Indian language groups. Furthermore, a latitudinal cline was identified both for the allele frequencies of the SNPs associated with hypertension (CYP3A5, AGT, GNB3, as well as for those associated with the ability to taste phenylthiocarbamide (TAS2R38. Conclusion Although caution is warranted due to the fact that this US-sampled Indian cohort may not represent a random sample from India, our results will hopefully assist in the

  5. Analysis of the human diseasome using phenotype similarity between common, genetic, and infectious diseases

    Science.gov (United States)

    Hoehndorf, Robert; Schofield, Paul N.; Gkoutos, Georgios V.

    2015-06-01

    Phenotypes are the observable characteristics of an organism arising from its response to the environment. Phenotypes associated with engineered and natural genetic variation are widely recorded using phenotype ontologies in model organisms, as are signs and symptoms of human Mendelian diseases in databases such as OMIM and Orphanet. Exploiting these resources, several computational methods have been developed for integration and analysis of phenotype data to identify the genetic etiology of diseases or suggest plausible interventions. A similar resource would be highly useful not only for rare and Mendelian diseases, but also for common, complex and infectious diseases. We apply a semantic text-mining approach to identify the phenotypes (signs and symptoms) associated with over 6,000 diseases. We evaluate our text-mined phenotypes by demonstrating that they can correctly identify known disease-associated genes in mice and humans with high accuracy. Using a phenotypic similarity measure, we generate a human disease network in which diseases that have similar signs and symptoms cluster together, and we use this network to identify closely related diseases based on common etiological, anatomical as well as physiological underpinnings.

  6. Analysis of the human diseasome using phenotype similarity between common, genetic, and infectious diseases

    KAUST Repository

    Hoehndorf, Robert

    2015-06-08

    Phenotypes are the observable characteristics of an organism arising from its response to the environment. Phenotypes associated with engineered and natural genetic variation are widely recorded using phenotype ontologies in model organisms, as are signs and symptoms of human Mendelian diseases in databases such as OMIM and Orphanet. Exploiting these resources, several computational methods have been developed for integration and analysis of phenotype data to identify the genetic etiology of diseases or suggest plausible interventions. A similar resource would be highly useful not only for rare and Mendelian diseases, but also for common, complex and infectious diseases. We apply a semantic text-mining approach to identify the phenotypes (signs and symptoms) associated with over 6,000 diseases. We evaluate our text-mined phenotypes by demonstrating that they can correctly identify known disease-associated genes in mice and humans with high accuracy. Using a phenotypic similarity measure, we generate a human disease network in which diseases that have similar signs and symptoms cluster together, and we use this network to identify closely related diseases based on common etiological, anatomical as well as physiological underpinnings.

  7. Salmonella Hepatitis: An Uncommon Complication of a Common Disease

    Directory of Open Access Journals (Sweden)

    Ritu Karoli

    2012-01-01

    Full Text Available Typhoid fever is a very common infectious disease of tropics, associated with high morbidity and mortality. Typhoid fever is often associated with hepatomegaly and mildly deranged liver functions; a clinical picture of acute hepatitis is a rare complication. We report a young patient who presented with fever and jaundice and was found to have acute hepatitis secondary to typhoid fever. Recognition of Salmonella hepatitis is of clinical importance as it can mimic acute viral hepatitis. Early institution of specific therapy can improve the prognosis in these patients.Typhoid fever is a very common infectious disease of tropics, associated with high morbidity and mortality. Typhoid fever is often associated with hepatomegaly and mildly deranged liver functions; a clinical picture of acute hepatitis is a rare complication. We report a young patient who presented with fever and jaundice and was found to have acute hepatitis secondary to typhoid fever. Recognition of Salmonella hepatitis is of clinical importance as it can mimic acute viral hepatitis. Early institution of specific therapy can improve the prognosis in these patients.

  8. Common pathophysiological mechanisms of chronic kidney disease: therapeutic perspectives.

    Science.gov (United States)

    López-Novoa, José M; Martínez-Salgado, Carlos; Rodríguez-Peña, Ana B; López-Hernández, Francisco J

    2010-10-01

    It is estimated that over 10% of the adult population in developed countries have some degree of chronic kidney disease (CKD). CKD is a progressive and irreversible deterioration of the renal excretory function that results in implementation of renal replacement therapy in the form of dialysis or renal transplant, which may also lead to death. CKD poses a growing problem to society as the incidence of the disease increases at an annual rate of 8%, and consumes up to 2% of the global health expenditure. CKD is caused by a variety of factors including diabetes, hypertension, infection, reduced blood supply to the kidneys, obstruction of the urinary tract and genetic alterations. The nephropathies associated with some of these conditions have been modeled in animals, this being crucial to understanding their pathophysiological mechanism and assessing prospective treatments at the preclinical level. This article reviews and updates the pathophysiological knowledge acquired primarily from experimental models and human studies of CKD. It also highlights the common mechanism(s) underlying the most relevant chronic nephropathies which lead to the appearance of a progressive, common renal phenotype regardless of aetiology. Based on this knowledge, a therapeutic horizon for the treatment of CKD is described. Present therapy primarily based upon renin-angiotensin inhibition, future diagnostics and therapeutic perspectives based upon anti-inflammatory, anti-fibrotic and hemodynamic approaches, new drugs targeting specific signaling pathways, and advances in gene and cell therapies, are all elaborated.

  9. Chapter 5: Network biology approach to complex diseases.

    Directory of Open Access Journals (Sweden)

    Dong-Yeon Cho

    Full Text Available Complex diseases are caused by a combination of genetic and environmental factors. Uncovering the molecular pathways through which genetic factors affect a phenotype is always difficult, but in the case of complex diseases this is further complicated since genetic factors in affected individuals might be different. In recent years, systems biology approaches and, more specifically, network based approaches emerged as powerful tools for studying complex diseases. These approaches are often built on the knowledge of physical or functional interactions between molecules which are usually represented as an interaction network. An interaction network not only reports the binary relationships between individual nodes but also encodes hidden higher level organization of cellular communication. Computational biologists were challenged with the task of uncovering this organization and utilizing it for the understanding of disease complexity, which prompted rich and diverse algorithmic approaches to be proposed. We start this chapter with a description of the general characteristics of complex diseases followed by a brief introduction to physical and functional networks. Next we will show how these networks are used to leverage genotype, gene expression, and other types of data to identify dysregulated pathways, infer the relationships between genotype and phenotype, and explain disease heterogeneity. We group the methods by common underlying principles and first provide a high level description of the principles followed by more specific examples. We hope that this chapter will give readers an appreciation for the wealth of algorithmic techniques that have been developed for the purpose of studying complex diseases as well as insight into their strengths and limitations.

  10. Systems genetics view of endometriosis: a common complex disorder.

    Science.gov (United States)

    Baranov, Vladislav S; Ivaschenko, Tatyana E; Liehr, Thomas; Yarmolinskaya, Maria I

    2015-02-01

    epigenetic influences, which result in many different clinical forms of the disease.

  11. Common immunologic mechanisms in inflammatory bowel disease and spondylarthropathies

    Institute of Scientific and Technical Information of China (English)

    Massimo C Fantini; Francesco Pallone; Giovanni Monteleone

    2009-01-01

    Spondyloarthropathies (SpA) are commonly observed extra-intestinal manifestations of both Crohn's disease (CD) and ulcerative colitis (UC), the two major forms of inflammatory bowel diseases (IBD). However, the immunological link between these two clinical entities is still poorly understood. Several lines of evidence indicate that SpA may originate from the relocation to the joints of the immune process primarily induced in the gut. The transfer of the intestinal inflammatory process into the joints implicates that immune cells activated in the gut-draining lymph nodes can localize, at a certain point of the intestinal disease, either into the gut or into the joints. This is indicated by the overlapping expression of adhesion molecules observed on the surface of intestinal and synovial endothelial cells during inflammation. Moreover bacterial antigens and HLA-B27 expression may be implicated in the reactivation of T cells at the articular level. Finally, accumulating evidence indicates that a T helper 17 cell-mediated immune response may contribute to IBD and IBD-related SpA with a crucial role played by tumor necrosis factor-α in CD and to a lesser extent in UC.

  12. Epidemiology of the most common oral mucosal diseases in children.

    Science.gov (United States)

    Rioboo-Crespo, Maria del Rosario; Planells-del Pozo, Paloma; Rioboo-García, Rafael

    2005-01-01

    Dentists who treat children must be alert to the possibility of finding diseases of the oral mucosa, especially in younger children. The present study aimed to review the most updated information and the experience of our group in order to yield epidemiological data that assist diagnosis of the most common diseases of the oral mucosa in children. Recent epidemiologic studies have shown a wide variability in the prevalence of oral mucosal lesions in different regions of the world and have led researchers to draw disparate conclusions. Moreover, studies have not been designed using standard criteria, further explaining the wide variability in the percentage of different groups of children with oral lesions, which ranges from 4.1 to 52.6%. The lesions most frequently considered by authors and that most often appear in the different studies are: recurrent aphthous stomatitis (0.9-10.8%), labial herpes (0.78-5.2%), fissured tongue (1.49-23%), geographic tongue (0.60-9.8%), oral candidiasis (0.01-37%) and traumatic injury (0.09%-22.15%). Dentists must be able to detect any of the numerous possible disorders and perform the correct differential diagnosis, key to the treatment plan. The aim of this paper, based on a review of the different national and international studies, is to contribute data on the most important oral mucosal diseases in the paediatric population in terms of prevalence and differential diagnosis.

  13. Genetics of diabetic nephropathy: are there clues to the understanding of common kidney diseases?

    Science.gov (United States)

    Conway, B R; Maxwell, A P

    2009-01-01

    Diabetic nephropathy is the most common cause of end-stage renal disease in the Western world. There is evidence for a genetic susceptibility to diabetic kidney disease, but despite intensive research efforts it has proved difficult to identify the causative genes. Improvements in genotyping technologies have made genome-wide association studies (GWAS), employing hundreds of thousands of single nucleotide polymorphisms, affordable. Recently, such scans have advanced understanding of the genetics of common complex diseases, finding more than 100 novel susceptibility variants for diverse disorders including type 1 and 2 diabetes, coronary heart disease, Crohn's disease and rheumatoid arthritis. In this review, type 2 diabetes is highlighted to illustrate how genome-wide association studies have been used to study the genetics of complex multifactorial conditions; in addition, diabetic nephropathy will be used to demonstrate how similar scans could be employed to detect genetic factors predisposing to kidney disease. The identification of such variants would permit early identification of atrisk patients, enabling targeting of therapy and a move towards primary prevention. In addition, these powerful research methodologies may identify genes that were not previously known to predispose to nephropathy, thereby enhancing our understanding of the pathophysiology of renal disorders and potentially leading to novel therapeutic approaches.

  14. Common Variants in Mendelian Kidney Disease Genes and Their Association with Renal Function

    Science.gov (United States)

    Fuchsberger, Christian; Köttgen, Anna; O’Seaghdha, Conall M.; Pattaro, Cristian; de Andrade, Mariza; Chasman, Daniel I.; Teumer, Alexander; Endlich, Karlhans; Olden, Matthias; Chen, Ming-Huei; Tin, Adrienne; Kim, Young J.; Taliun, Daniel; Li, Man; Feitosa, Mary; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C.; Glazer, Nicole; Isaacs, Aaron; Rao, Madhumathi; Smith, Albert V.; O’Connell, Jeffrey R.; Struchalin, Maksim; Tanaka, Toshiko; Li, Guo; Hwang, Shih-Jen; Atkinson, Elizabeth J.; Lohman, Kurt; Cornelis, Marilyn C.; Johansson, Åsa; Tönjes, Anke; Dehghan, Abbas; Couraki, Vincent; Holliday, Elizabeth G.; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tõnu; Deshmukh, Harshal; Ulivi, Sheila; Chu, Audrey Y.; Murgia, Federico; Trompet, Stella; Imboden, Medea; Kollerits, Barbara; Pistis, Giorgio; Harris, Tamara B.; Launer, Lenore J.; Aspelund, Thor; Eiriksdottir, Gudny; Mitchell, Braxton D.; Boerwinkle, Eric; Schmidt, Helena; Hofer, Edith; Hu, Frank; Demirkan, Ayse; Oostra, Ben A.; Turner, Stephen T.; Ding, Jingzhong; Andrews, Jeanette S.; Freedman, Barry I.; Giulianini, Franco; Koenig, Wolfgang; Illig, Thomas; Döring, Angela; Wichmann, H.-Erich; Zgaga, Lina; Zemunik, Tatijana; Boban, Mladen; Minelli, Cosetta; Wheeler, Heather E.; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H.; Wright, Alan F.; Campbell, Harry; Ellinghaus, David; Nöthlings, Ute; Jacobs, Gunnar; Biffar, Reiner; Ernst, Florian; Homuth, Georg; Kroemer, Heyo K.; Nauck, Matthias; Stracke, Sylvia; Völker, Uwe; Völzke, Henry; Kovacs, Peter; Stumvoll, Michael; Mägi, Reedik; Hofman, Albert; Uitterlinden, Andre G.; Rivadeneira, Fernando; Aulchenko, Yurii S.; Polasek, Ozren; Hastie, Nick; Vitart, Veronique; Helmer, Catherine; Wang, Jie Jin; Stengel, Bénédicte; Ruggiero, Daniela; Bergmann, Sven; Kähönen, Mika; Viikari, Jorma; Nikopensius, Tiit; Province, Michael; Colhoun, Helen; Doney, Alex; Robino, Antonietta; Krämer, Bernhard K.; Portas, Laura; Ford, Ian; Buckley, Brendan M.; Adam, Martin; Thun, Gian-Andri; Paulweber, Bernhard; Haun, Margot; Sala, Cinzia; Mitchell, Paul; Ciullo, Marina; Vollenweider, Peter; Raitakari, Olli; Metspalu, Andres; Palmer, Colin; Gasparini, Paolo; Pirastu, Mario; Jukema, J. Wouter; Probst-Hensch, Nicole M.; Kronenberg, Florian; Toniolo, Daniela; Gudnason, Vilmundur; Shuldiner, Alan R.; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; van Duijn, Cornelia M.; Borecki, Ingrid; Kardia, Sharon L.R.; Liu, Yongmei; Curhan, Gary C.; Rudan, Igor; Gyllensten, Ulf; Wilson, James F.; Franke, Andre; Pramstaller, Peter P.; Rettig, Rainer; Prokopenko, Inga; Witteman, Jacqueline; Hayward, Caroline; Ridker, Paul M.; Bochud, Murielle; Heid, Iris M.; Siscovick, David S.; Fox, Caroline S.; Kao, W. Linda; Böger, Carsten A.

    2013-01-01

    Many common genetic variants identified by genome-wide association studies for complex traits map to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2 meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research. PMID:24029420

  15. Genetic Testing for Complex Diseases: a Simulation Study Perspective

    CERN Document Server

    Vinh, Nguyen Xuan

    2011-01-01

    It is widely recognized nowadays that complex diseases are caused by, amongst the others, multiple genetic factors. The recent advent of genome-wide association study (GWA) has triggered a wave of research aimed at discovering genetic factors underlying common complex diseases. While the number of reported susceptible genetic variants is increasing steadily, the application of such findings into diseases prognosis for the general population is still unclear, and there are doubts about whether the size of the contribution by such factors is significant. In this respect, some recent simulation-based studies have shed more light to the prospect of genetic tests. In this report, we discuss several aspects of simulation-based studies: their parameters, their assumptions, and the information they provide.

  16. Recent mitochondrial DNA mutations increase the risk of developing common late-onset human diseases.

    Directory of Open Access Journals (Sweden)

    Gavin Hudson

    2014-05-01

    Full Text Available Mitochondrial DNA (mtDNA is highly polymorphic at the population level, and specific mtDNA variants affect mitochondrial function. With emerging evidence that mitochondrial mechanisms are central to common human diseases, it is plausible that mtDNA variants contribute to the "missing heritability" of several complex traits. Given the central role of mtDNA genes in oxidative phosphorylation, the same genetic variants would be expected to alter the risk of developing several different disorders, but this has not been shown to date. Here we studied 38,638 individuals with 11 major diseases, and 17,483 healthy controls. Imputing missing variants from 7,729 complete mitochondrial genomes, we captured 40.41% of European mtDNA variation. We show that mtDNA variants modifying the risk of developing one disease also modify the risk of developing other diseases, thus providing independent replication of a disease association in different case and control cohorts. High-risk alleles were more common than protective alleles, indicating that mtDNA is not at equilibrium in the human population, and that recent mutations interact with nuclear loci to modify the risk of developing multiple common diseases.

  17. Erectile Dysfunction ia a common problem in Interstitial Lung Disease

    DEFF Research Database (Denmark)

    Fløe, Andreas; Hilberg, Ole; Wijsenbeek, Marlies

    .6%) had co-morbid heart disease and/or manifest atherosclerosis, and 6 (11.8%) had diabetes mellitus (DM). 39 (76.5%) had fibrosing ILD on high-resolution CT-scan or lung biopsy (IPF n=24, Fibrosing NSIP n=7, unclassifiable ILD with fibrosis n=8). 35 ILD patients (70%) had ED, and 22 (44%) hereof had...... severe ED. Having a co-morbidity was not associated with increased risk of ED (OR 0,94, P=0,74).  Conclusion: Our data clearly demonstrate that ED is a common problem in ILD. Almost half of all patients in this study had severe ED. This is, to our knowledge, the first study to report on the occurrence...... of sexual problems among male patients with ILD. The rate of ED was comparable to that found among COPD patients in prior studies. Further research is needed in order to identify specific risk factors for ED among ILD patients....

  18. Understanding rare and common diseases in the context of human evolution.

    Science.gov (United States)

    Quintana-Murci, Lluis

    2016-11-07

    The wealth of available genetic information is allowing the reconstruction of human demographic and adaptive history. Demography and purifying selection affect the purge of rare, deleterious mutations from the human population, whereas positive and balancing selection can increase the frequency of advantageous variants, improving survival and reproduction in specific environmental conditions. In this review, I discuss how theoretical and empirical population genetics studies, using both modern and ancient DNA data, are a powerful tool for obtaining new insight into the genetic basis of severe disorders and complex disease phenotypes, rare and common, focusing particularly on infectious disease risk.

  19. A nondegenerate code of deleterious variants in Mendelian loci contributes to complex disease risk.

    Science.gov (United States)

    Blair, David R; Lyttle, Christopher S; Mortensen, Jonathan M; Bearden, Charles F; Jensen, Anders Boeck; Khiabanian, Hossein; Melamed, Rachel; Rabadan, Raul; Bernstam, Elmer V; Brunak, Søren; Jensen, Lars Juhl; Nicolae, Dan; Shah, Nigam H; Grossman, Robert L; Cox, Nancy J; White, Kevin P; Rzhetsky, Andrey

    2013-09-26

    Although countless highly penetrant variants have been associated with Mendelian disorders, the genetic etiologies underlying complex diseases remain largely unresolved. By mining the medical records of over 110 million patients, we examine the extent to which Mendelian variation contributes to complex disease risk. We detect thousands of associations between Mendelian and complex diseases, revealing a nondegenerate, phenotypic code that links each complex disorder to a unique collection of Mendelian loci. Using genome-wide association results, we demonstrate that common variants associated with complex diseases are enriched in the genes indicated by this "Mendelian code." Finally, we detect hundreds of comorbidity associations among Mendelian disorders, and we use probabilistic genetic modeling to demonstrate that Mendelian variants likely contribute nonadditively to the risk for a subset of complex diseases. Overall, this study illustrates a complementary approach for mapping complex disease loci and provides unique predictions concerning the etiologies of specific diseases. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. A Non-Degenerate Code of Deleterious Variants in Mendelian Loci Contributes to Complex Disease Risk

    Science.gov (United States)

    Blair, David R.; Lyttle, Christopher S.; Mortensen, Jonathan M.; Bearden, Charles F.; Jensen, Anders Boeck; Khiabanian, Hossein; Melamed, Rachel; Rabadan, Raul; Bernstam, Elmer V.; Brunak, Søren; Jensen, Lars Juhl; Nicolae, Dan; Shah, Nigam H.; Grossman, Robert L.; Cox, Nancy J.; White, Kevin P.; Rzhetsky, Andrey

    2013-01-01

    Summary Whereas countless highly penetrant variants have been associated with Mendelian disorders, the genetic etiologies underlying complex diseases remain largely unresolved. Here, we examine the extent to which Mendelian variation contributes to complex disease risk by mining the medical records of over 110 million patients. We detect thousands of associations between Mendelian and complex diseases, revealing a non-degenerate, phenotypic code that links each complex disorder to a unique collection of Mendelian loci. Using genome-wide association results, we demonstrate that common variants associated with complex diseases are enriched in the genes indicated by this “Mendelian code.” Finally, we detect hundreds of comorbidity associations among Mendelian disorders, and we use probabilistic genetic modeling to demonstrate that Mendelian variants likely contribute non-additively to the risk for a subset of complex diseases. Overall, this study illustrates a complementary approach for mapping complex disease loci and provides unique predictions concerning the etiologies of specific diseases. PMID:24074861

  1. The exocyst complex in health and disease

    Directory of Open Access Journals (Sweden)

    Magdanela eMartin-Urdiroz

    2016-04-01

    Full Text Available Exocytosis involves the fusion of intracellular secretory vesicles with the PM, thereby delivering integral membrane proteins to the cell surface and releasing material into the extracellular space. Importantly, exocytosis also provides a source of lipid moieties for membrane extension. The tethering of the secretory vesicle before docking and fusion with the PM is mediated by the exocyst complex, an evolutionary conserved octameric complex of proteins. Recent findings indicate that the exocyst complex also takes part in other intra-cellular processes besides secretion. These various functions seem to converge towards defining a direction of membrane growth in a range of systems from fungi to plants and from neurons to cilia. In this review we summarise the current knowledge of exocyst function in cell polarity, signalling and cell-cell communication and discuss implications for plant and animal health and disease.

  2. Phenotypic commonalities in familial and sporadic Parkinson disease.

    Science.gov (United States)

    Baba, Yasuhiko; Markopoulou, Katerina; Putzke, John D; Whaley, Nathaniel R; Farrer, Matthew J; Wszolek, Zbigniew K; Uitti, Ryan J

    2006-04-01

    Parkinson disease (PD) is a clinically well-documented neurodegenerative disorder. However, the mechanism or mechanisms of its phenotypic expressions are still unknown. To compare phenotypes by examining demographic and clinical features of patients with familial PD and sporadic PD and with or without a family history of PD. Historical review of patients with sporadic PD in clinic-based samples and individual patients diagnosed with PD from families whose linkage to mutations or loci has been identified. Movement disorder clinic in a referral center. A total of 1277 patients with sporadic PD and 40 patients with familial PD. Clinical features, including distribution by sex, initial motor symptom, location of initial motor symptom, and frequency of asymmetric motor symptoms. Despite different etiologic backgrounds, both familial and sporadic PD exhibited several interesting commonalities, including a higher incidence in men, tremor as the initial motor symptom (predominantly involving the upper extremities), and asymmetric parkinsonism during disease course. The increased incidence of parkinsonism in men with familial PD suggests that the sex disparity is more likely the result of a protective effect against development of PD in women than of an increased risk in men that is associated with environmental factors. Phenotypic similarity among familial and sporadic PD indicates that a similar topographic distribution of the nigrostriatal lesion exists in patients with either form of PD regardless of apparent genetic influence.

  3. Partitioning Heritability of Regulatory and Cell-Type-Specific Variants across 11 Common Diseases

    Science.gov (United States)

    Gusev, Alexander; Lee, S. Hong; Trynka, Gosia; Finucane, Hilary; Vilhjálmsson, Bjarni J.; Xu, Han; Zang, Chongzhi; Ripke, Stephan; Bulik-Sullivan, Brendan; Stahl, Eli; Ripke, Stephan; Neale, Benjamin M.; Corvin, Aiden; Walters, James T.R.; Farh, Kai-How; Holmans, Peter A.; Lee, Phil; Bulik-Sullivan, Brendan; Collier, David A.; Huang, Hailiang; Pers, Tune H.; Agartz, Ingrid; Agerbo, Esben; Albus, Margot; Alexander, Madeline; Amin, Farooq; Bacanu, Silviu A.; Begemann, Martin; Belliveau, Richard A.; Bene, Judit; Bergen, Sarah E.; Bevilacqua, Elizabeth; Bigdeli, Tim B.; Black, Donald W.; Børglum, Anders D.; Bruggeman, Richard; Buccola, Nancy G.; Buckner, Randy L.; Byerley, William; Cahn, Wiepke; Cai, Guiqing; Campion, Dominique; Cantor, Rita M.; Carr, Vaughan J.; Carrera, Noa; Catts, Stanley V.; Chambert, Kimberly D.; Chan, Raymond C.K.; Chen, Ronald Y.L.; Chen, Eric Y.H.; Cheng, Wei; Cheung, Eric F.C.; Chong, Siow Ann; Cloninger, C. Robert; Cohen, David; Cohen, Nadine; Cormican, Paul; Craddock, Nick; Crowley, James J.; Curtis, David; Davidson, Michael; Davis, Kenneth L.; Degenhardt, Franziska; Del Favero, Jurgen; DeLisi, Lynn E.; Demontis, Ditte; Dikeos, Dimitris; Dinan, Timothy; Djurovic, Srdjan; Donohoe, Gary; Drapeau, Elodie; Duan, Jubao; Dudbridge, Frank; Durmishi, Naser; Eichhammer, Peter; Eriksson, Johan; Escott-Price, Valentina; Essioux, Laurent; Fanous, Ayman H.; Farrell, Martilias S.; Frank, Josef; Franke, Lude; Freedman, Robert; Freimer, Nelson B.; Friedl, Marion; Friedman, Joseph I.; Fromer, Menachem; Genovese, Giulio; Georgieva, Lyudmila; Gershon, Elliot S.; Giegling, Ina; Giusti-Rodrguez, Paola; Godard, Stephanie; Goldstein, Jacqueline I.; Golimbet, Vera; Gopal, Srihari; Gratten, Jacob; Grove, Jakob; de Haan, Lieuwe; Hammer, Christian; Hamshere, Marian L.; Hansen, Mark; Hansen, Thomas; Haroutunian, Vahram; Hartmann, Annette M.; Henskens, Frans A.; Herms, Stefan; Hirschhorn, Joel N.; Hoffmann, Per; Hofman, Andrea; Hollegaard, Mads V.; Hougaard, David M.; Ikeda, Masashi; Joa, Inge; Julià, Antonio; Kahn, René S.; Kalaydjieva, Luba; Karachanak-Yankova, Sena; Karjalainen, Juha; Kavanagh, David; Keller, Matthew C.; Kelly, Brian J.; Kennedy, James L.; Khrunin, Andrey; Kim, Yunjung; Klovins, Janis; Knowles, James A.; Konte, Bettina; Kucinskas, Vaidutis; Kucinskiene, Zita Ausrele; Kuzelova-Ptackova, Hana; Kähler, Anna K.; Laurent, Claudine; Keong, Jimmy Lee Chee; Lee, S. Hong; Legge, Sophie E.; Lerer, Bernard; Li, Miaoxin; Li, Tao; Liang, Kung-Yee; Lieberman, Jeffrey; Limborska, Svetlana; Loughland, Carmel M.; Lubinski, Jan; Lnnqvist, Jouko; Macek, Milan; Magnusson, Patrik K.E.; Maher, Brion S.; Maier, Wolfgang; Mallet, Jacques; Marsal, Sara; Mattheisen, Manuel; Mattingsdal, Morten; McCarley, Robert W.; McDonald, Colm; McIntosh, Andrew M.; Meier, Sandra; Meijer, Carin J.; Melegh, Bela; Melle, Ingrid; Mesholam-Gately, Raquelle I.; Metspalu, Andres; Michie, Patricia T.; Milani, Lili; Milanova, Vihra; Mokrab, Younes; Morris, Derek W.; Mors, Ole; Mortensen, Preben B.; Murphy, Kieran C.; Murray, Robin M.; Myin-Germeys, Inez; Mller-Myhsok, Bertram; Nelis, Mari; Nenadic, Igor; Nertney, Deborah A.; Nestadt, Gerald; Nicodemus, Kristin K.; Nikitina-Zake, Liene; Nisenbaum, Laura; Nordin, Annelie; O’Callaghan, Eadbhard; O’Dushlaine, Colm; O’Neill, F. Anthony; Oh, Sang-Yun; Olincy, Ann; Olsen, Line; Van Os, Jim; Pantelis, Christos; Papadimitriou, George N.; Papiol, Sergi; Parkhomenko, Elena; Pato, Michele T.; Paunio, Tiina; Pejovic-Milovancevic, Milica; Perkins, Diana O.; Pietilinen, Olli; Pimm, Jonathan; Pocklington, Andrew J.; Powell, John; Price, Alkes; Pulver, Ann E.; Purcell, Shaun M.; Quested, Digby; Rasmussen, Henrik B.; Reichenberg, Abraham; Reimers, Mark A.; Richards, Alexander L.; Roffman, Joshua L.; Roussos, Panos; Ruderfer, Douglas M.; Salomaa, Veikko; Sanders, Alan R.; Schall, Ulrich; Schubert, Christian R.; Schulze, Thomas G.; Schwab, Sibylle G.; Scolnick, Edward M.; Scott, Rodney J.; Seidman, Larry J.; Shi, Jianxin; Sigurdsson, Engilbert; Silagadze, Teimuraz; Silverman, Jeremy M.; Sim, Kang; Slominsky, Petr; Smoller, Jordan W.; So, Hon-Cheong; Spencer, Chris C.A.; Stahl, Eli A.; Stefansson, Hreinn; Steinberg, Stacy; Stogmann, Elisabeth; Straub, Richard E.; Strengman, Eric; Strohmaier, Jana; Stroup, T. Scott; Subramaniam, Mythily; Suvisaari, Jaana; Svrakic, Dragan M.; Szatkiewicz, Jin P.; Sderman, Erik; Thirumalai, Srinivas; Toncheva, Draga; Tooney, Paul A.; Tosato, Sarah; Veijola, Juha

    2014-01-01

    Regulatory and coding variants are known to be enriched with associations identified by genome-wide association studies (GWASs) of complex disease, but their contributions to trait heritability are currently unknown. We applied variance-component methods to imputed genotype data for 11 common diseases to partition the heritability explained by genotyped SNPs (hg2) across functional categories (while accounting for shared variance due to linkage disequilibrium). Extensive simulations showed that in contrast to current estimates from GWAS summary statistics, the variance-component approach partitions heritability accurately under a wide range of complex-disease architectures. Across the 11 diseases DNaseI hypersensitivity sites (DHSs) from 217 cell types spanned 16% of imputed SNPs (and 24% of genotyped SNPs) but explained an average of 79% (SE = 8%) of hg2 from imputed SNPs (5.1× enrichment; p = 3.7 × 10−17) and 38% (SE = 4%) of hg2 from genotyped SNPs (1.6× enrichment, p = 1.0 × 10−4). Further enrichment was observed at enhancer DHSs and cell-type-specific DHSs. In contrast, coding variants, which span 1% of the genome, explained <10% of hg2 despite having the highest enrichment. We replicated these findings but found no significant contribution from rare coding variants in independent schizophrenia cohorts genotyped on GWAS and exome chips. Our results highlight the value of analyzing components of heritability to unravel the functional architecture of common disease. PMID:25439723

  4. A genomic pathway approach to a complex disease: axon guidance and Parkinson disease.

    Science.gov (United States)

    Lesnick, Timothy G; Papapetropoulos, Spiridon; Mash, Deborah C; Ffrench-Mullen, Jarlath; Shehadeh, Lina; de Andrade, Mariza; Henley, John R; Rocca, Walter A; Ahlskog, J Eric; Maraganore, Demetrius M

    2007-06-01

    While major inroads have been made in identifying the genetic causes of rare Mendelian disorders, little progress has been made in the discovery of common gene variations that predispose to complex diseases. The single gene variants that have been shown to associate reproducibly with complex diseases typically have small effect sizes or attributable risks. However, the joint actions of common gene variants within pathways may play a major role in predisposing to complex diseases (the paradigm of complex genetics). The goal of this study was to determine whether polymorphism in a candidate pathway (axon guidance) predisposed to a complex disease (Parkinson disease [PD]). We mined a whole-genome association dataset and identified single nucleotide polymorphisms (SNPs) that were within axon-guidance pathway genes. We then constructed models of axon-guidance pathway SNPs that predicted three outcomes: PD susceptibility (odds ratio = 90.8, p = 4.64 x 10(-38)), survival free of PD (hazards ratio = 19.0, p = 5.43 x 10(-48)), and PD age at onset (R(2) = 0.68, p = 1.68 x 10(-51)). By contrast, models constructed from thousands of random selections of genomic SNPs predicted the three PD outcomes poorly. Mining of a second whole-genome association dataset and mining of an expression profiling dataset also supported a role for many axon-guidance pathway genes in PD. These findings could have important implications regarding the pathogenesis of PD. This genomic pathway approach may also offer insights into other complex diseases such as Alzheimer disease, diabetes mellitus, nicotine and alcohol dependence, and several cancers.

  5. A genomic pathway approach to a complex disease: axon guidance and Parkinson disease.

    Directory of Open Access Journals (Sweden)

    Timothy G Lesnick

    2007-06-01

    Full Text Available While major inroads have been made in identifying the genetic causes of rare Mendelian disorders, little progress has been made in the discovery of common gene variations that predispose to complex diseases. The single gene variants that have been shown to associate reproducibly with complex diseases typically have small effect sizes or attributable risks. However, the joint actions of common gene variants within pathways may play a major role in predisposing to complex diseases (the paradigm of complex genetics. The goal of this study was to determine whether polymorphism in a candidate pathway (axon guidance predisposed to a complex disease (Parkinson disease [PD]. We mined a whole-genome association dataset and identified single nucleotide polymorphisms (SNPs that were within axon-guidance pathway genes. We then constructed models of axon-guidance pathway SNPs that predicted three outcomes: PD susceptibility (odds ratio = 90.8, p = 4.64 x 10(-38, survival free of PD (hazards ratio = 19.0, p = 5.43 x 10(-48, and PD age at onset (R(2 = 0.68, p = 1.68 x 10(-51. By contrast, models constructed from thousands of random selections of genomic SNPs predicted the three PD outcomes poorly. Mining of a second whole-genome association dataset and mining of an expression profiling dataset also supported a role for many axon-guidance pathway genes in PD. These findings could have important implications regarding the pathogenesis of PD. This genomic pathway approach may also offer insights into other complex diseases such as Alzheimer disease, diabetes mellitus, nicotine and alcohol dependence, and several cancers.

  6. [Neuroimmunological diseases associated with VGKC complex antibodies].

    Science.gov (United States)

    Watanabe, Osamu

    2013-05-01

    Antibodies to voltage-gated potassium channels(VGKC) were first identified by radioimmunoassay of radioisotope labeled alpha-dendrotoxin-VGKCs solubilized from rabbit brain. These antibodies were found only in a proportion of patients with acquired neuromyotonia (Isaacs' syndrome). VGKC antibodies were also detected in Morvan's syndrome and in a form of autoimmune limbic encephalitis. Recent studies indicated that the "VGKC" antibodies are mainly directed toward associated proteins(for example LGI-1, Caspr-2) that complex with the VGKCs themselves. The "VGKC" antibodies are now usually known as VGKC-complex antibodies. In general, LGI-1 antibodies are most common in limbic encephalitis with SIADH. Caspr-2 antibodies are present in the majority of patients with Morvan's syndrome. These patients develop combinations of CNS symptoms, autonomic dysfunction, and peripheral nerve hyperexcitability.

  7. Association studies in common endocrine diseases (review article

    Directory of Open Access Journals (Sweden)

    Akrami SM

    2007-05-01

    Full Text Available Our understanding of the pathogenesis of endocrine disorders increase rapidly by genetic studies at the molecular level. Common endocrine disorders such as diabetes mellitus, obesity, osteoporosis, dyslipidemia and cancer follow the multifactorial model in the genetic aspect. This review tries to clarify the approach in molecular studies of such diseases for clinicians in different specialties. How to evaluate a possible association between a single nucleotide polymorphism and an endocrinopathy or its complication is the main concern of this review. Two approaches for gene mapping will be discussed as well as main challenges regarding each approach. All such genetic studies ideally include some test of the association between genome sequence variation and the phenotype of interest such as the trait itself, the presence of a given complication, or measures of some endocrinopathy-related intermediate trait. Despite different advances in this analysis, there are major concerns regarding the overall performance and robustness of genetic association studies. By using powerful new high-throughput methods, further insights to molecular basis of such endocrine disorders can be expected. Close correlation between geneticists and clinicians can effectively bridge between basic sciences and clinical investigations.

  8. Sporadic Parkinson disease and amyotrophic lateral sclerosis complex (Brait-Fahn-Schwartz disease).

    Science.gov (United States)

    Manno, Concetta; Lipari, Alessio; Bono, Valeria; Taiello, Alfonsa Claudia; La Bella, Vincenzo

    2013-03-15

    Clinical evidence for parkinsonism may accompany Amyotrophic Lateral Sclerosis with a frequency ranging from 5% to 17%. The concurrence of Amyotrophic Lateral Sclerosis and Parkinson's disease, outside the known Guam and Kii Peninsula foci, is instead rare, but this raises the possibility of a common pathogenesis. Clinically this complex presents with a levodopa-responsive parkinsonism and Amyotrophic Lateral Sclerosis and has been termed Brait-Fahn-Schwartz disease. Here we describe two patients with this uncommon neurodegenerative complex. Both presented with Parkinson disease and progressed to a full blown Amyotrophic Lateral Sclerosis. We further suggest that the association of Parkinson disease and Amyotrophic Lateral Sclerosis represents a distinct nosological entity, which should be kept separated from extrapyramidal signs and symptoms that may occur in Amyotrophic Lateral Sclerosis.

  9. Rare disease relations through common genes and protein interactions.

    Science.gov (United States)

    Fernandez-Novo, Sara; Pazos, Florencio; Chagoyen, Monica

    2016-06-01

    ODCs (Orphan Disease Connections), available at http://csbg.cnb.csic.es/odcs, is a novel resource to explore potential molecular relations between rare diseases. These molecular relations have been established through the integration of disease susceptibility genes and human protein-protein interactions. The database currently contains 54,941 relations between 3032 diseases.

  10. Common misconceptions about 5-aminosalicylates and thiopurines in inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Javier P Gisbert; María Chaparro; Fernando Gomollón

    2011-01-01

    Misconceptions are common in the care of patients with inflammatory bowel disease (IBD). In this paper, we state the most commonly found misconceptions in clinical practice and deal with the use of 5-aminosalicylates and thiopurines, to review the related scientific evidence, and make appropriate recommendations. Prevention of errors needs knowledge to avoid making such errors through ignorance. However, the amount of knowledge is increasing so quickly that one new danger is an overabundance of information. IBD is a model of a very complex disease and our goal with this review is to summarize the key evidence for the most common daily clinical problems. With regard to the use of 5-aminosalicylates, the best practice may to be consider abandoning the use of these drugs in patients with small bowel Crohn' s disease. The combined approach with oral plus topical 5-aminosalicylates should be the first-line therapy in patients with active ulcerative colitis; once-daily treatment should be offered as a first choice regimen due to its better compliance and higher efficacy. With regard to thiopurines, they seem to be as effective in ulcerative colitis as in Crohn' s disease. Underdosing of thiopurines is a form of undertreatment. Thiopurines should probably be continued indefinitely because their withdrawal is associated with a high risk of relapse. Mercaptopurine is a safe alternative in patients with digestive intolerance or hepatotoxicity due to azathioprine. Finally, thiopurine methyltransferase (TPMT) screening cannot substitute for regular monitoring because the majority of cases of myelotoxicity are not TPMT-related.

  11. Risk prediction for complex diseases: application to Parkinson disease.

    Science.gov (United States)

    Hall, Taryn O; Wan, Jia Y; Mata, Ignacio F; Kerr, Kathleen F; Snapinn, Katherine W; Samii, Ali; Roberts, John W; Agarwal, Pinky; Zabetian, Cyrus P; Edwards, Karen L

    2013-05-01

    The aim of this study was to evaluate the risk of Parkinson disease using clinical and demographic data alone and when combined with information from genes associated with Parkinson disease. A total of 1,967 participants in the dbGAP NeuroGenetics Research Consortium data set were included. Single-nucleotide polymorphisms associated with Parkinson disease at a genome-wide significance level in previous genome-wide association studies were included in risk prediction. Risk allele scores were calculated as the weighted count of the minor alleles. Five models were constructed. Discriminatory capability was evaluated using the area under the curve. Both family history and genetic risk scores increased risk for Parkinson disease. Although the fullest model, which included both family history and genetic risk information, resulted in the highest area under the curve, there were no significant differences between models using family history alone and those using genetic information alone. Adding genome-wide association study-derived genotypes, family history information, or both to standard demographic risk factors for Parkinson disease resulted in an improvement in discriminatory capacity. In the full model, the contributions of genotype data and family history information to discriminatory capacity were similar, and both were statistically significant. This suggests that there is limited overlap between genetic risk factors identified through genome-wide association study and unmeasured susceptibility variants captured by family history. Our results are similar to those of studies of other complex diseases and indicate that genetic risk prediction for Parkinson disease requires identification of additional genetic risk factors and/or better methods for risk prediction in order to achieve a degree of risk prediction that is clinically useful.Genet Med 2013:15(5):361-367.

  12. Decoding the role of regulatory element polymorphisms in complex disease.

    Science.gov (United States)

    Vockley, Christopher M; Barrera, Alejandro; Reddy, Timothy E

    2017-04-01

    Genetic variation in gene regulatory elements contributes to diverse human diseases, ranging from rare and severe developmental defects to common and complex diseases such as obesity and diabetes. Early examples of regulatory mechanisms of human diseases involve large chromosomal rearrangements that change the regulatory connections within the genome. Single nucleotide variants in regulatory elements can also contribute to disease, potentially via demonstrated associations with changes in transcription factor binding, enhancer activity, post-translational histone modifications, long-range enhancer-promoter interactions, or RNA polymerase recruitment. Establishing causality between non-coding genetic variants, gene regulation, and disease has recently become more feasible with advances in genome-editing and epigenome-editing technologies. As establishing causal regulatory mechanisms of diseases becomes routine, functional annotation of target genes is likely to emerge as a major bottleneck for translation into patient benefits. In this review, we discuss the history and recent advances in understanding the regulatory mechanisms of human disease, and new challenges likely to be encountered once establishing those mechanisms becomes rote. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Challenging the Research Base of the Common Core State Standards: A Historical Reanalysis of Text Complexity

    Science.gov (United States)

    Gamson, David A.; Lu, Xiaofei; Eckert, Sarah Anne

    2013-01-01

    The widely adopted Common Core State Standards (CCSS) call for raising the level of text complexity in textbooks and reading materials used by students across all grade levels in the United States; the authors of the English Language Arts component of the CCSS build their case for higher complexity in part upon a research base they say shows a…

  14. Does song complexity matter in an intra-sexual context in common blackbirds

    DEFF Research Database (Denmark)

    Hesler, Nana; Sacher, Thomas; Coppack, Timothy;

    Bird song is thought to be subject of both inter- and intra-sexual selection and song complexity a signal of male quality. One aspect of song complexity, repertoire size, correlates with estimates of male quality in several passerine species.  The Common Blackbird (Turdus merula) has a large...

  15. Common Membrane Trafficking Defects of Disease Associated Dynamin 2 Mutations

    OpenAIRE

    Liu, Ya-Wen; Lukiyanchuk, Vasyl; Schmid, Sandra L.

    2011-01-01

    Dynamin (Dyn) is a multidomain and multifunctional GTPase best known for its essential role in clathrin-mediated endocytosis (CME). Dyn2 mutations have been linked to two human diseases, Centronuclear Myopathy (CNM) and Charcot-Marie-Tooth (CMT) disease. Paradoxically, although Dyn2 is ubiquitously expressed and essential for embryonic development, the disease-associated Dyn2 mutants are autosomal dominant, but result in slowly progressing and tissue-specific diseases. Thus, although the cell...

  16. Disease Surveillance on Complex Social Networks.

    Directory of Open Access Journals (Sweden)

    Jose L Herrera

    2016-07-01

    Full Text Available As infectious disease surveillance systems expand to include digital, crowd-sourced, and social network data, public health agencies are gaining unprecedented access to high-resolution data and have an opportunity to selectively monitor informative individuals. Contact networks, which are the webs of interaction through which diseases spread, determine whether and when individuals become infected, and thus who might serve as early and accurate surveillance sensors. Here, we evaluate three strategies for selecting sensors-sampling the most connected, random, and friends of random individuals-in three complex social networks-a simple scale-free network, an empirical Venezuelan college student network, and an empirical Montreal wireless hotspot usage network. Across five different surveillance goals-early and accurate detection of epidemic emergence and peak, and general situational awareness-we find that the optimal choice of sensors depends on the public health goal, the underlying network and the reproduction number of the disease (R0. For diseases with a low R0, the most connected individuals provide the earliest and most accurate information about both the onset and peak of an outbreak. However, identifying network hubs is often impractical, and they can be misleading if monitored for general situational awareness, if the underlying network has significant community structure, or if R0 is high or unknown. Taking a theoretical approach, we also derive the optimal surveillance system for early outbreak detection but find that real-world identification of such sensors would be nearly impossible. By contrast, the friends-of-random strategy offers a more practical and robust alternative. It can be readily implemented without prior knowledge of the network, and by identifying sensors with higher than average, but not the highest, epidemiological risk, it provides reasonably early and accurate information.

  17. Stroke, complex regional pain syndrome and phantom limb pain: can commonalities direct future management?

    Science.gov (United States)

    Acerra, Nicole E; Souvlis, Tina; Moseley, G Lorimer

    2007-03-01

    Despite being different conditions, complex regional pain syndrome type 1, phantom limb pain and stroke share some potentially important similarities. This report examines experimental and clinical findings from each patient population. It identifies common aspects of symptomatic presentation, sensory phenomena and patterns of cortical reorganization. Based on these common findings, we argue that established principles of stroke rehabilitation are also applicable to rehabilitation of complex regional pain syndrome type 1 and phantom limb pain. In addition, we contend that promising treatment approaches for complex regional pain syndrome type 1 and phantom limb pain may be helpful in stroke rehabilitation. Examples of emerging supportive evidence for these hypotheses are provided and discussed.

  18. Role of Th17 cells in common liver diseases

    Directory of Open Access Journals (Sweden)

    WEI Linlin

    2013-06-01

    Full Text Available In recent years, it has been found that T helper type 17 (Th17 cells are a new subset of CD4+ Th cells. Th17 cells play an important role in the onset and development of many liver diseases and have become the research focus in immunology. This paper summarizes the studies on the relationship between Th17 cells and various liver diseases in order to provide a new idea for the study and treatment of liver diseases.

  19. MicroRNAs in common diseases and potential therapeutic applications.

    Science.gov (United States)

    Tsai, Louis M; Yu, Di

    2010-01-01

    1. Evidence gathered in recent years has revealed microRNAs (miRNAs) fine-tune gene expression and play an important role in various cellular processes, including cell growth, differentiation, proliferation and apoptosis. 2. The present review summarizes current knowledge of miRNA pathways in the pathogenesis of cancer, cardiac diseases, neurodegenerative diseases, diabetes, autoimmune/inflammatory diseases and infection. 3. There is considerable potential to target miRNAs as a novel approach in the treatment of human diseases. Currently, miRNA-based therapies are being examined in both animal models and human clinical trials.

  20. Rice Sheath Rot: An Emerging Ubiquitous Destructive Disease Complex.

    Science.gov (United States)

    Bigirimana, Vincent de P; Hua, Gia K H; Nyamangyoku, Obedi I; Höfte, Monica

    2015-01-01

    Around one century ago, a rice disease characterized mainly by rotting of sheaths was reported in Taiwan. The causal agent was identified as Acrocylindrium oryzae, later known as Sarocladium oryzae. Since then it has become clear that various other organisms can cause similar disease symptoms, including Fusarium sp. and fluorescent pseudomonads. These organisms have in common that they produce a range of phytotoxins that induce necrosis in plants. The same agents also cause grain discoloration, chaffiness, and sterility and are all seed-transmitted. Rice sheath rot disease symptoms are found in all rice-growing areas of the world. The disease is now getting momentum and is considered as an important emerging rice production threat. The disease can lead to variable yield losses, which can be as high as 85%. This review aims at improving our understanding of the disease etiology of rice sheath rot and mainly deals with the three most reported rice sheath rot pathogens: S. oryzae, the Fusarium fujikuroi complex, and Pseudomonas fuscovaginae. Causal agents, pathogenicity determinants, interactions among the various pathogens, epidemiology, geographical distribution, and control options will be discussed.

  1. Keeping the noise down: common random numbers for disease simulation modeling.

    Science.gov (United States)

    Stout, Natasha K; Goldie, Sue J

    2008-12-01

    Disease simulation models are used to conduct decision analyses of the comparative benefits and risks associated with preventive and treatment strategies. To address increasing model complexity and computational intensity, modelers use variance reduction techniques to reduce stochastic noise and improve computational efficiency. One technique, common random numbers, further allows modelers to conduct counterfactual-like analyses with direct computation of statistics at the individual level. This technique uses synchronized random numbers across model runs to induce correlation in model output thereby making differences easier to distinguish as well as simulating identical individuals across model runs. We provide a tutorial introduction and demonstrate the application of common random numbers in an individual-level simulation model of the epidemiology of breast cancer.

  2. Major histocompatibility (MH) class II ß gene polymorphism influences disease resistance of common carp (Cyprinus carpio L.)

    NARCIS (Netherlands)

    Rakus, K.L.; Wiegertjes, G.F.; Jurecka, P.M.; Walker, P.D.; Pilarczyk, A.; Irnazarow, I.

    2009-01-01

    Genes of the major histocompatibility complex (MHC) are crucial elements of adaptive immunity. High polymorphism renders the MHC genes highly suitable for studies on association with disease resistance. In common carp (Cyprinus carpio L.), there are two paralogous groups of MH class II B genes, Cyca

  3. Common sources of bias in gene-lifestyle interaction studies of cardiometabolic disease

    DEFF Research Database (Denmark)

    Oskari Kilpeläinen, Tuomas

    2013-01-01

    The role of gene x lifestyle interactions in the development of cardiometabolic diseases is often highlighted, but very few robustly replicated examples of interactions exist in the literature. The slow pace of discoveries may largely be due to interaction effects being generally small in magnitude...... and/or more complex than initially thought. However, the progress may also be hindered by the poor accuracy in large-scale epidemiological studies to estimate the true interaction effect sizes. Often, this bias tends to underestimate the interaction effect, leading to inadequate statistical power...... to detect the interaction. In this review, I will discuss the most common sources of bias in the estimation of gene x lifestyle interactions, and will discuss how such factors could be addressed in the future to enhance our potential to identify and replicate interactions for cardiometabolic diseases....

  4. Human DNA methylomes of neurodegenerative diseases show common epigenomic patterns

    Science.gov (United States)

    Sanchez-Mut, J V; Heyn, H; Vidal, E; Moran, S; Sayols, S; Delgado-Morales, R; Schultz, M D; Ansoleaga, B; Garcia-Esparcia, P; Pons-Espinal, M; de Lagran, M M; Dopazo, J; Rabano, A; Avila, J; Dierssen, M; Lott, I; Ferrer, I; Ecker, J R; Esteller, M

    2016-01-01

    Different neurodegenerative disorders often show similar lesions, such as the presence of amyloid plaques, TAU-neurotangles and synuclein inclusions. The genetically inherited forms are rare, so we wondered whether shared epigenetic aberrations, such as those affecting DNA methylation, might also exist. The studied samples were gray matter samples from the prefrontal cortex of control and neurodegenerative disease-associated cases. We performed the DNA methylation analyses of Alzheimer's disease, dementia with Lewy bodies, Parkinson's disease and Alzheimer-like neurodegenerative profile associated with Down's syndrome samples. The DNA methylation landscapes obtained show that neurodegenerative diseases share similar aberrant CpG methylation shifts targeting a defined gene set. Our findings suggest that neurodegenerative disorders might have similar pathogenetic mechanisms that subsequently evolve into different clinical entities. The identified aberrant DNA methylation changes can be used as biomarkers of the disorders and as potential new targets for the development of new therapies. PMID:26784972

  5. Common fish diseases and parasites affecting wild and farmed

    African Journals Online (AJOL)

    ACSS

    Current control strategies to control aquatic pathogens include use of chemo- therapeutants and ... Diagnosis and control of diseases and parasites in aquaculture production systems requires adoption of a ..... plan with enforceable regulatory.

  6. Disease transmission by cannibalism: rare event or common occurrence?

    OpenAIRE

    Rudolf, Volker H.W.; Antonovics, Janis

    2007-01-01

    Cannibalism has been documented as a possible disease transmission route in several species, including humans. However, the dynamics resulting from this type of disease transmission are not well understood. Using a theoretical model, we explore how cannibalism (i.e. killing and consumption of dead conspecifics) and intraspecific necrophagy (i.e. consumption of dead conspecifics) affect host–pathogen dynamics. We show that group cannibalism, i.e. shared consumption of victims, is a necessary c...

  7. Disseminated Abdominal Hydatidosis: A Rare Presentation of Common Infectious Disease

    Directory of Open Access Journals (Sweden)

    Abdulrahman Almalik

    2014-01-01

    Full Text Available Hydatid disease is one of the most geographically widespread zoonoses with substantial disease burden. In this report we are discussing an unusual case of intra-abdominal HD that was ongoing for 22 years despite two surgical interventions. Significant symptomatic relief was achieved within the first two months of combination therapy with albendazole and praziquantel. HD is still of public health concern in the Middle East that needs optimized care.

  8. Disseminated Abdominal Hydatidosis: A Rare Presentation of Common Infectious Disease

    Science.gov (United States)

    Almalik, Abdulrahman; Alsharidi, Aynaa; Al-Sheef, Mohammed; Enani, Mushirah

    2014-01-01

    Hydatid disease is one of the most geographically widespread zoonoses with substantial disease burden. In this report we are discussing an unusual case of intra-abdominal HD that was ongoing for 22 years despite two surgical interventions. Significant symptomatic relief was achieved within the first two months of combination therapy with albendazole and praziquantel. HD is still of public health concern in the Middle East that needs optimized care. PMID:25114815

  9. Eosinophilic cholecystitis with common bile duct stricture: a rare disease.

    Science.gov (United States)

    Mehanna, Daniel; Naseem, Zainab; Mustaev, Muslim

    2016-05-24

    Although the most common cause of cholecystitis is gallstones, other conditions may present as acute cholecystitis. We describe a case of eosinophilic cholecystitis with common bile duct stricture. A 36-year-old woman initially had generalised abdominal pain and peripheral eosinophilia. Diagnostic laparoscopy showed eosinophilic ascites and necrotic nodules on the posterior abdominal wall. She was treated with anthelminthics on presumption of toxacara infection based on borderline positivity of serological tests. She later presented with acute cholecystitis and had a cholecystectomy and choledocotomy. Day 9 T-tube cholangiogram showed irregular narrowing of the distal common bile duct. The patient's symptoms were improved with steroids and the T-tube was subsequently removed.

  10. [Virus disease complexes: transmissible pathological entities in invertebrates].

    Science.gov (United States)

    Odier, F; Vago, M C

    1975-05-21

    Virus disease complexes of Galleria mellonella L. due respectively to a Parvovirus with a Baculovirus and a Parovirus with an Iridovirus have been transmitted to healthy larvae by ingestion of corpses of larvae affected by these disease complexes. The histological and cytological injuries observed are identical to those noted during the study of the initial complexes.

  11. 9 CFR 381.82 - Diseases of the leukosis complex.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Diseases of the leukosis complex. 381... Carcasses and Parts § 381.82 Diseases of the leukosis complex. Carcasses of poultry affected with any one or more of the several forms of the avian leukosis complex shall be condemned....

  12. Network analysis identifies common genes associated with obesity in six obesity-related diseases*

    OpenAIRE

    Su, Li-ning; Wang, Yan-bing; Wnag, Chun-guang; Wei, Hui-ping

    2017-01-01

    Obesity has been reported to be associated with many diseases. However, common obesity-induced biological processes have not been evaluated across these diseases. We identified genes associated with obesity and obesity-related diseases, and used them to construct protein‒protein interaction networks. We also analyzed gene ontology (GO) in those genes overlapping between obesity and disease. Our work identifies gene modules common to obesity and obesity-related diseases, which can provide a ba...

  13. A Nomadic Subtelomeric Disease Resistance Gene Cluster in Common Bean

    Science.gov (United States)

    The B4 resistance (R)-gene cluster, located in subtelomeric region of chromosome 4, is one of the largest clusters known in common bean (Phaseolus vulgaris, Pv). We sequenced 650 kb spanning this locus and annotated 97 genes, 26 of which correspond to Coiled-coil-Nucleotide-Binding-Site-Leucine-Rich...

  14. Kullback-Leibler divergence for detection of rare haplotype common disease association.

    Science.gov (United States)

    Lin, Shili

    2015-11-01

    Rare haplotypes may tag rare causal variants of common diseases; hence, detection of such rare haplotypes may also contribute to our understanding of complex disease etiology. Because rare haplotypes frequently result from common single-nucleotide polymorphisms (SNPs), focusing on rare haplotypes is much more economical compared with using rare single-nucleotide variants (SNVs) from sequencing, as SNPs are available and 'free' from already amassed genome-wide studies. Further, associated haplotypes may shed light on the underlying disease causal mechanism, a feat unmatched by SNV-based collapsing methods. In recent years, data mining approaches have been adapted to detect rare haplotype association. However, as they rely on an assumed underlying disease model and require the specification of a null haplotype, results can be erroneous if such assumptions are violated. In this paper, we present a haplotype association method based on Kullback-Leibler divergence (hapKL) for case-control samples. The idea is to compare haplotype frequencies for the cases versus the controls by computing symmetrical divergence measures. An important property of such measures is that both the frequencies and logarithms of the frequencies contribute in parallel, thus balancing the contributions from rare and common, and accommodating both deleterious and protective, haplotypes. A simulation study under various scenarios shows that hapKL has well-controlled type I error rates and good power compared with existing data mining methods. Application of hapKL to age-related macular degeneration (AMD) shows a strong association of the complement factor H (CFH) gene with AMD, identifying several individual rare haplotypes with strong signals.

  15. Syphilitic hepatitis: an uncommon manifestation of a common disease.

    Science.gov (United States)

    Baveja, Sukriti; Garg, Shilpa; Rajdeo, Amol

    2014-03-01

    Hepatitis being first manifestation of secondary syphilis is rare. Here in we report a case of 39 years old male who was being treated for hepatitis and presented to us subsequently with itchy maculopapular rash. Venereal disease research laboratory (VDRL) titre was 1:16. Treponema pallidum hemagglutination assay (TPHA) was positive. He was treated with intramuscular Benzathine Penicillin. His hepatitis improved rapidly.

  16. Multiple common variants for celiac disease influencing immune gene expression

    NARCIS (Netherlands)

    Dubois, Patrick C. A.; Trynka, Gosia; Franke, Lude; Hunt, Karen A.; Romanos, Jihane; Curtotti, Alessandra; Zhernakova, Alexandra; Heap, Graham A. R.; Adany, Roza; Aromaa, Arpo; Bardella, Maria Teresa; van den Berg, Leonard H.; Bockett, Nicholas A.; de la Concha, Emilio G.; Dema, Barbara; Fehrmann, Rudolf S. N.; Fernandez-Arquero, Miguel; Fiatal, Szilvia; Grandone, Elvira; Green, Peter M.; Groen, Harry J. M.; Gwilliam, Rhian; Houwen, Roderick H. J.; Hunt, Sarah E.; Kaukinen, Katri; Kelleher, Dermot; Korponay-Szabo, Ilma; Kurppa, Kalle; MacMathuna, Padraic; Maki, Markku; Mazzilli, Maria Cristina; McCann, Owen T.; Mearin, M. Luisa; Mein, Charles A.; Mirza, Muddassar M.; Mistry, Vanisha; Mora, Barbara; Morley, Katherine I.; Mulder, Chris J.; Murray, Joseph A.; Nunez, Concepcion; Oosterom, Elvira; Ophoff, Roel A.; Polanco, Isabel; Peltonen, Leena; Platteel, Mathieu; Rybak, Anna; Salomaa, Veikko; Schweizer, Joachim J.; Sperandeo, Maria Pia; Tack, Greetje J.; Turner, Graham; Veldink, Jan H.; Verbeek, Wieke H. M.; Weersma, Rinse K.; Wolters, Victorien M.; Urcelay, Elena; Cukrowska, Bozena; Greco, Luigi; Neuhausen, Susan L.; McManus, Ross; Barisani, Donatella; Deloukas, Panos; Barrett, Jeffrey C.; Saavalainen, Paivi; Wijmenga, Cisca; van Heel, David A.

    2010-01-01

    We performed a second-generation genome-wide association study of 4,533 individuals with celiac disease (cases) and 10,750 control subjects. We genotyped 113 selected SNPs with P(GWAS) <10(-4) and 18 SNPs from 14 known loci in a further 4,918 cases and 5,684 controls. Variants from 13 new regions re

  17. Multiple common variants for celiac disease influencing immune gene expression

    NARCIS (Netherlands)

    Dubois, Patrick C. A.; Trynka, Gosia; Franke, Lude; Hunt, Karen A.; Romanos, Jihane; Curtotti, Alessandra; Zhernakova, Alexandra; Heap, Graham A. R.; Adany, Roza; Aromaa, Arpo; Bardella, Maria Teresa; van den Berg, Leonard H.; Bockett, Nicholas A.; de la Concha, Emilio G.; Dema, Barbara; Fehrmann, Rudolf S. N.; Fernandez-Arquero, Miguel; Fiatal, Szilvia; Grandone, Elvira; Green, Peter M.; Groen, Harry J. M.; Gwilliam, Rhian; Houwen, Roderick H. J.; Hunt, Sarah E.; Kaukinen, Katri; Kelleher, Dermot; Korponay-Szabo, Ilma; Kurppa, Kalle; MacMathuna, Padraic; Maki, Markku; Mazzilli, Maria Cristina; McCann, Owen T.; Mearin, M. Luisa; Mein, Charles A.; Mirza, Muddassar M.; Mistry, Vanisha; Mora, Barbara; Morley, Katherine I.; Mulder, Chris J.; Murray, Joseph A.; Nunez, Concepcion; Oosterom, Elvira; Ophoff, Roel A.; Polanco, Isabel; Peltonen, Leena; Platteel, Mathieu; Rybak, Anna; Salomaa, Veikko; Schweizer, Joachim J.; Sperandeo, Maria Pia; Tack, Greetje J.; Turner, Graham; Veldink, Jan H.; Verbeek, Wieke H. M.; Weersma, Rinse K.; Wolters, Victorien M.; Urcelay, Elena; Cukrowska, Bozena; Greco, Luigi; Neuhausen, Susan L.; McManus, Ross; Barisani, Donatella; Deloukas, Panos; Barrett, Jeffrey C.; Saavalainen, Paivi; Wijmenga, Cisca; van Heel, David A.

    We performed a second-generation genome-wide association study of 4,533 individuals with celiac disease (cases) and 10,750 control subjects. We genotyped 113 selected SNPs with P(GWAS) <10(-4) and 18 SNPs from 14 known loci in a further 4,918 cases and 5,684 controls. Variants from 13 new regions

  18. Congenital labial mucocele: rare presentation of a common disease.

    Science.gov (United States)

    Silva, Igor Henrique; Cardoso, Samantha; Carvalho, Camila Nunes; Carvalho, Alessandra Albuquerque Tavares; Leão, Jair Carneiro; Gueiros, Luiz Alcino

    2016-01-01

    Oral mucoceles are common lesions characterized by accumulation of mucus following rupture of a minor salivary gland duct. However, congenital mucoceles are a rare and distinctive oral condition observed in newborns. This case report details the features of a congenital labial nodule diagnosed as congenital mucocele. These lesions are rare in the oral cavity and should be diagnosed in the delivery room, but many cases are referred for further evaluation. Management is simple, and recurrence is not expected.

  19. Neuronal network disintegration: common pathways linking neurodegenerative diseases

    Science.gov (United States)

    Ahmed, Rebekah M; Devenney, Emma M; Irish, Muireann; Ittner, Arne; Naismith, Sharon; Ittner, Lars M; Rohrer, Jonathan D; Halliday, Glenda M; Eisen, Andrew; Hodges, John R; Kiernan, Matthew C

    2016-01-01

    Neurodegeneration refers to a heterogeneous group of brain disorders that progressively evolve. It has been increasingly appreciated that many neurodegenerative conditions overlap at multiple levels and therefore traditional clinicopathological correlation approaches to better classify a disease have met with limited success. Neuronal network disintegration is fundamental to neurodegeneration, and concepts based around such a concept may better explain the overlap between their clinical and pathological phenotypes. In this Review, promoters of overlap in neurodegeneration incorporating behavioural, cognitive, metabolic, motor, and extrapyramidal presentations will be critically appraised. In addition, evidence that may support the existence of large-scale networks that might be contributing to phenotypic differentiation will be considered across a neurodegenerative spectrum. Disintegration of neuronal networks through different pathological processes, such as prion-like spread, may provide a better paradigm of disease and thereby facilitate the identification of novel therapies for neurodegeneration. PMID:27172939

  20. Iron Deficiency Anemia: A Common and Curable Disease

    Science.gov (United States)

    Miller, Jeffery L.

    2013-01-01

    Iron deficiency anemia arises when the balance of iron intake, iron stores, and the body's loss of iron are insufficient to fully support production of erythrocytes. Iron deficiency anemia rarely causes death, but the impact on human health is significant. In the developed world, this disease is easily identified and treated, but frequently overlooked by physicians. In contrast, it is a health problem that affects major portions of the population in underdeveloped countries. Overall, the prevention and successful treatment for iron deficiency anemia remains woefully insufficient worldwide, especially among underprivileged women and children. Here, clinical and laboratory features of the disease are discussed, and then focus is placed on relevant economic, environmental, infectious, and genetic factors that converge among global populations. PMID:23613366

  1. Common Virus May Be Linked to Heart Disease, Diabetes in Some Women

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_163761.html Common Virus May Be Linked to Heart Disease, Diabetes in ... THURSDAY, Feb. 23, 2017 (HealthDay News) -- A common virus may make some women more susceptible to both ...

  2. Developmental Origins of Common Disease: Epigenetic Contributions to Obesity.

    Science.gov (United States)

    Kappil, Maya; Wright, Robert O; Sanders, Alison P

    2016-08-31

    The perinatal period is a window of susceptibility for later life disease. Recent epigenetic findings are beginning to increase our understanding of the molecular mechanisms that may contribute to the programming of obesity. This review summarizes recent evidence that supports the role of epigenetically mediated early life programming in the later onset of obesity. Establishing such links between environmental exposures and modifiable molecular changes ultimately holds promise to inform interventional efforts toward alleviating the environmentally mediated onset of obesity.

  3. Syphilitic hepatitis: An uncommon manifestation of a common disease

    Directory of Open Access Journals (Sweden)

    Sukriti Baveja

    2014-01-01

    Full Text Available Hepatitis being first manifestation of secondary syphilis is rare. Here in we report a case of 39 years old male who was being treated for hepatitis and presented to us subsequently with itchy maculopapular rash. Venereal disease research laboratory (VDRL titre was 1:16. Treponema pallidum hemagglutination assay (TPHA was positive. He was treated with intramuscular Benzathine Penicillin. His hepatitis improved rapidly.

  4. Cognitive impairments in common and rare somatic diseases

    Directory of Open Access Journals (Sweden)

    Natalia Vyacheslavovna Pizova

    2015-01-01

    Full Text Available The paper gives an update on the pathogenesis, clinical presentation, and pathomorphology of cognitive impairments (CIs in different autoimmune, endocrine, and infectious diseases, such as systemic lupus erythematosus, Sjögren's syndrome, BehНet's disease, primary angiitis of the central nervous system, polyarteritis nodosa, cryoglobulinemic vasculitis, hypothyroidism, herpetic lesion, and neurosyphilis. These patients are observed to have ischemic-hypoxic brain damage, the causes of which are free radical-induced cell injury, oxidative stress, excitation toxicity, cell necrosis and/or apoptosis, inflammation and immune disease, molecular sequestration, and cell death. There is enhanced imbalance in the pro-oxidant and antioxidant systems as cerebrovascular insufficiency progresses; as this takes place, the nerve cells are most susceptible to the induction of free radical reactions. In these cases, antioxidants that block the effects of free radicals and may potentially improve brain perfusion, by assisting the coupling of neurons and vessels, are first-choice drugs. To improve the cognitive status and to prevent the progression of CIs, it is important to build a cognitive reserve in a patient; this is largely favored by the preservation of a proactive approach to life and social bonds, as well as intellectual work.

  5. Major histocompatibility complex genes in the common carp (Cyprinus carpio L.).

    NARCIS (Netherlands)

    Erp, van S.H.M.

    1996-01-01

    This thesis describes a study of the major histocompatibility complex (Mhc) genes of the common carp (Cyprinus carpio L.). The molecules encoded by Mhc genes play an essential role in the specific immune response, by presenting antigens to T lymphocytes. Knowledge of the Mhc of carp, therefore, cont

  6. Activities for Challenging Gifted Learners by Increasing Complexity in the Common Core

    Science.gov (United States)

    McKeone, Alyssa; Caruso, Lenora; Bettle, Kailyn; Chase, Ashley; Bryson, Bridget; Schneider, Jean S.; Rule, Audrey C.

    2015-01-01

    Gifted learners need opportunities for critical and creative thinking to stretch their minds and imaginations. Strategies for increasing complexity in the four core areas of language arts, mathematics, science, and social studies were addressed using the Common Core and Iowa Core Standards through several methods. Descriptive adjective object…

  7. Clinical correlates of common corneal neovascular diseases: a literature review

    Institute of Scientific and Technical Information of China (English)

    Nizar; Saleh; Abdelfattah; Mohamed; Amgad; Amira; A; Zayed; Hamdy; Salem; Ahmed; E; Elkhanany; Heba; Hussein; Nawal; Abd; El-Baky

    2015-01-01

    A large subset of corneal pathologies involves the formation of new vessels(neovascularization), leading to compromised visual acuity. This article aims to review the clinical causes and presentations of corneal neovascularization(CNV) by examining the mechanisms behind common CNV-related corneal pathologies, with a particular focus on herpes simplex stromal keratitis,contact lenses-induced keratitis and CNV secondary to keratoplasty. Moreover, we reviewed CNV in the context of different types of corneal transplantation and keratoprosthesis, and summarized the most relevant treatment available so far.

  8. Extrinsic allergic alveolitis: a disease commoner in non-smokers.

    Science.gov (United States)

    Warren, C P

    1977-01-01

    The smoking habits of 18 patients with extrinsic allergic alveolitis, 22 with cryptogenic fibrosing alveolitis, and 75 patients with sarcoidosis were compared with the smoking habits of the normal population of the Prairie Region for 1973. The patients were diagnosed at the same two hospitals over the four-year period November 1971--75 and were of comparable age. Non-smoking was significantly associated with allergic alveolitis in men and the three cases in women were all non-smokers. For the other two diseases, smoking habits were similar to those of the local population. PMID:594937

  9. Penile herpes zoster: an unusual location for a common disease

    Directory of Open Access Journals (Sweden)

    Milan Bjekic

    2011-12-01

    Full Text Available Herpes zoster is a common dermatological condition which affects up to 20% of the population, most frequently involving the thoracic and facial dermatomes with sacral lesions occurring rarely and only a few reported cases of penile shingles. Case report: We report two cases of unusual penile clinical presentations of varicella zoster virus infection in immunocompetent men. The patients presented with grouped clusters of vesicles and erythema on the left side of penile shaft and posterior aspect of the left thigh and buttock, involving s2-s4 dermatomes. The lesions resolved quickly upon administration of oral antiviral therapy. Conclusion: Penile herpes zoster should not be overlooked in patients with unilateral vesicular rash.

  10. Penile herpes zoster: an unusual location for a common disease

    Directory of Open Access Journals (Sweden)

    Milan Bjekic

    Full Text Available Herpes zoster is a common dermatological condition which affects up to 20% of the population, most frequently involving the thoracic and facial dermatomes with sacral lesions occurring rarely and only a few reported cases of penile shingles. Case report: We report two cases of unusual penile clinical presentations of varicella zoster virus infection in immunocompetent men. The patients presented with grouped clusters of vesicles and erythema on the left side of penile shaft and posterior aspect of the left thigh and buttock, involving s2-s4 dermatomes. The lesions resolved quickly upon administration of oral antiviral therapy. Conclusion: Penile herpes zoster should not be overlooked in patients with unilateral vesicular rash.

  11. The small abnormal parathyroid gland is increasingly common and heralds operative complexity.

    Science.gov (United States)

    McCoy, Kelly L; Chen, Naomi H; Armstrong, Michaele J; Howell, Gina M; Stang, Michael T; Yip, Linwah; Carty, Sally E

    2014-06-01

    Over decades, improvements in presymptomatic screening and awareness of surgical benefits have changed the presentation and management of primary hyperparathyroidism (PHPT). Unrecognized multiglandular disease (MGD) remains a major cause of operative failure. We hypothesized that during parathyroid surgery the initial finding of a mildly enlarged gland is now frequent and predicts both MGD and failure. A prospective database was queried to examine the outcomes of initial exploration for sporadic PHPT using intraoperative PTH monitoring (IOPTH) over 15 years. All patients had follow-up ≥6 months (mean = 1.8 years). Cure was defined by normocalcemia at 6 months and microadenoma by resected weight of <200 mg. Of the 1,150 patients, 98.9 % were cured and 15 % had MGD. The highest preoperative calcium level decreased over time (p < 0.001) and varied directly with adenoma weight (p < 0.001). Over time, single adenoma weight dropped by half (p = 0.002) and microadenoma was increasingly common (p < 0.01). MGD risk varied inversely with weight of first resected abnormal gland. Microadenoma required bilateral exploration more often than macroadenoma (48 vs. 18 %, p < 0.01). When at exploration the first resected gland was <200 mg, the rates of MGD (40 vs. 11 %, p = 0.001), inadequate initial IOPTH drop (67 vs. 79 %, p = 0.002), operative failure (6.6 vs. 0.7 %, p < 0.001), and long-term recurrence (1.6 vs. 0.3 %, p = 0.007) were higher. Single parathyroid adenomas are smaller than in the past and require more complex pre- and intraoperative management. During exploration for sporadic PHPT, a first abnormal gland <200 mg should heighten suspicion of MGD and presages a tenfold higher failure rate.

  12. Network medicine approaches to the genetics of complex diseases.

    Science.gov (United States)

    Silverman, Edwin K; Loscalzo, Joseph

    2012-08-01

    Complex diseases are caused by perturbations of biological networks. Genetic analysis approaches focused on individual genetic determinants are unlikely to characterize the network architecture of complex diseases comprehensively. Network medicine, which applies systems biology and network science to complex molecular networks underlying human disease, focuses on identifying the interacting genes and proteins which lead to disease pathogenesis. The long biological path between a genetic risk variant and development of a complex disease involves a range of biochemical intermediates, including coding and non-coding RNA, proteins, and metabolites. Transcriptomics, proteomics, metabolomics, and other -omics technologies have the potential to provide insights into complex disease pathogenesis, especially if they are applied within a network biology framework. Most previous efforts to relate genetics to -omics data have focused on a single -omics platform; the next generation of complex disease genetics studies will require integration of multiple types of -omics data sets in a network context. Network medicine may also provide insight into complex disease heterogeneity, serve as the basis for new disease classifications that reflect underlying disease pathogenesis, and guide rational therapeutic and preventive strategies.

  13. A Nondegenerate Code of Deleterious Variants in Mendelian Loci Contributes to Complex Disease Risk

    DEFF Research Database (Denmark)

    Blair, David R.; Lyttle, Christopher S.; Mortensen, Jonathan M.

    2013-01-01

    with complex diseases are enriched in the genes indicated by this ‘‘Mendelian code.’’ Finally, we detect hundreds of comorbidity associations among Mendelian disorders, and we use probabilistic genetic modeling to demonstrate that Mendelian variants likely contribute nonadditively to the risk for a subset......Although countless highly penetrant variants have been associated with Mendelian disorders, the genetic etiologies underlying complex diseases remain largely unresolved. By mining the medical records of over 110 million patients, we examine the extent to which Mendelian variation contributes...... to complex disease risk. We detect thousands of associations between Mendelian and complex diseases, revealing a nondegenerate, phenotypic code that links each complex disorder to a unique collection of Mendelian loci. Using genome-wide association results, we demonstrate that common variants associated...

  14. Premature birth and diseases in premature infants: common genetic background?

    Science.gov (United States)

    Hallman, Mikko

    2012-04-01

    It has been proposed that during human evolution, development of obligate bipedalism, narrow birth canal cross-sectional area and the large brain have forced an adjustment in duration of pregnancy (scaling of gestational age; Plunkett 2011). Children compared to other mammals are born with proportionally small brains (compared to adult brains), suggesting shortening of pregnancy duration during recent evolution. Prevalence of both obstructed delivery and premature birth is still exceptionally high. In near term infants, functional maturity and viability is high, and gene variants predisposing to respiratory distress syndrome (RDS) are rare. Advanced antenatal and neonatal treatment practices during the new era of medicine allowed survival of also very preterm infants (gestation premature birth. Specific genes associating with diseases in preterm infants may also contribute to the susceptibility to preterm birth. Understanding and applying the knowledge of genetic interactions in normal and abnormal perinatal-neonatal development requires large, well-structured population cohorts, studies involving the whole genome and international interdisciplinary collaboration.

  15. Complex Regional Pain Syndrome: An inflammatory disease

    NARCIS (Netherlands)

    M. Dirckx (Maaike)

    2015-01-01

    markdownabstractThe pathophysiology of Complex Regional Pain Syndrome (CRPS) is complex and still not completely understood. In addition to a convincing role of inflammation, there are a number of arguments why an involvement of the immune system has been suggested in the pathophysiology of CRPS. Th

  16. Pituitary hyperplasia: an uncommon presentation of a common disease

    Science.gov (United States)

    Massolt, E T; Peeters, R P; Neggers, S J; de Herder, W W

    2015-01-01

    Summary A 21-year-old woman presented with amenorrhea, bilateral galactorrhea and fatigue. Visual acuity and visual fields were normal. Laboratory examination demonstrated hyperprolactinemia. Magnetic resonance imaging (MRI) of the pituitary showed a 19×17×12-mm sellar mass with supra- and parasellar extension, causing compression of the pituitary stalk and optic chiasm. Further examinations confirmed mild hyperprolactinemia, strongly elevated TSH (>500 mU/l), low free thyroxine (FT4), hypogonadotropic hypogonadism and secondary adrenal insufficiency. Hydrocortisone and l-T4 replacement therapy was started. Three months later, the galactorrhea had disappeared, thyroid function was normalized and MRI revealed regression of the pituitary enlargement, confirming the diagnosis of pituitary hyperplasia (PH) due to primary hypothyroidism. Subsequently, the menstrual cycle returned and the hypocortisolism normalized. This case demonstrates that severe primary hypothyroidism may have an unusual presentation and should be considered in the differential diagnosis of pituitary enlargement associated with moderate hyperprolactinemia. Learning points One should always try to find one etiology as the common cause of all the clinical findings in a pathologic process.Amenorrhea, galactorrhea and fatigue may be the only presenting clinical manifestations of primary hypothyroidism.Not every patient with galactorrhea, hyperprolactinemia and a pituitary mass has a prolactinoma.Primary hypothyroidism should always be considered in the differential diagnosis of hyperprolactinemia associated with pituitary enlargement and pituitary hormone(s) deficiency(ies).When PH due to primary hypothyroidism is suspected, thyroid hormone replacement should be started and only regression of pituitary enlargement on MRI follow-up can confirm the diagnosis.Examination of thyroid function in patients with a pituitary mass may avoid unnecessary surgery. PMID:26279852

  17. Mitochondrial complex I-linked disease.

    Science.gov (United States)

    Rodenburg, Richard J

    2016-07-01

    Complex I deficiency is the most frequently encountered single mitochondrial single enzyme deficiency in patients with a mitochondrial disorder. Although specific genotype-phenotype correlations are very difficult to identify, the majority of patients present with symptoms caused by leukodystrophy. The poor genotype-phenotype correlations can make establishing a diagnosis a challenge. The classical way to establish a complex I deficiency in patients is by performing spectrophotometric measurements of the enzyme in a muscle biopsy or other patient-derived material (liver or heart biopsy, cultured skin fibroblasts). Complex I is encoded by both the mtDNA and nuclear DNA and pathogenic mutations have been identified in the majority of the 44 genes encoding the structural subunits of complex I. In recent years, the increasing possibilities for diagnostic molecular genetic tests of large gene panels, exomes, and even entire genomes has led to the identification of many novel genetic defects causing complex I deficiency. Complex I mutations not only result in a reduced enzyme activity but also induce secondary effects at the cellular level, such as elevated reactive oxygen species production, altered membrane potential and mitochondrial morphology. At this moment there is no cure for complex I deficiency and the treatment options for complex I patients are restricted to symptomatic treatment. Recent developments, amongst others based on the treatment of the secondary effects of complex I deficiency, have shown to be promising as new therapeutic strategies in vitro and have entered clinical trials. This article is part of a Special Issue entitled Respiratory complex I, edited by Volker Zickermann and Ulrich Brandt.

  18. Complex Politics: A Quantitative Semantic and Topological Analysis of UK House of Commons Debates

    CERN Document Server

    Gurciullo, Stefano; Pereda, María; Battiston, Federico; Patania, Alice; Poledna, Sebastian; Hedblom, Daniel; Oztan, Bahattin Tolga; Herzog, Alexander; John, Peter; Mikhaylov, Slava

    2015-01-01

    This study is a first, exploratory attempt to use quantitative semantics techniques and topological analysis to analyze systemic patterns arising in a complex political system. In particular, we use a rich data set covering all speeches and debates in the UK House of Commons between 1975 and 2014. By the use of dynamic topic modeling (DTM) and topological data analysis (TDA) we show that both members and parties feature specific roles within the system, consistent over time, and extract global patterns indicating levels of political cohesion. Our results provide a wide array of novel hypotheses about the complex dynamics of political systems, with valuable policy applications.

  19. Common clinical practice versus new PRIM score in predicting coronary heart disease risk

    DEFF Research Database (Denmark)

    Frikke-Schmidt, Ruth; Tybjærg-Hansen, Anne; Schnohr, Peter;

    2010-01-01

    To compare the new Patient Rule Induction Method (PRIM) Score and common clinical practice with the Framingham Point Score for classification of individuals with respect to coronary heart disease (CHD) risk.......To compare the new Patient Rule Induction Method (PRIM) Score and common clinical practice with the Framingham Point Score for classification of individuals with respect to coronary heart disease (CHD) risk....

  20. Surgical treatment of complex small bowel Crohn disease.

    Science.gov (United States)

    Michelassi, Fabrizio; Sultan, Samuel

    2014-08-01

    The clinical presentations of Crohn disease of the small bowel vary from low to high complexity. Understanding the complexity of Crohn disease of the small bowel is important for the surgeon and the gastroenterologist caring for the patient and may be relevant for clinical research as a way to compare outcomes. Here, we present a categorization of complex small bowel Crohn disease and review its surgical treatment as a potential initial step toward the establishment of a definition of complex disease. The complexity of small bowel Crohn disease can be sorted into several categories: technical challenges, namely, fistulae, abscesses, bowel or ureteral obstruction, hemorrhage, cancer and thickened mesentery; extensive disease; the presence of short gut; a history of prolonged use of medications, particularly steroids, immunomodulators, and biological agents; and a high risk of recurrence. Although the principles of modern surgical treatment of Crohn disease have evolved to bowel conservation such as strictureplasty techniques and limited resection margins, such practices by themselves are often not sufficient for the management of complex small bowel Crohn disease. This manuscript reviews each category of complex small bowel Crohn disease, with special emphasis on appropriate surgical strategy.

  1. Application of R to investigate common gene regulatory network pathway among bipolar disorder and associate diseases

    Directory of Open Access Journals (Sweden)

    Nahida Habib

    2016-12-01

    Full Text Available Depression, Major Depression or mental disorder creates severe diseases. Mental illness such as Unipolar Major Depression, Bipolar Disorder, Dysthymia, Schizophrenia, Cardiovascular Diseases (Hypertension, Coronary Heart Disease, Stroke etc., are known as Major Depression. Several studies have revealed the possibilities about the association among Bipolar Disorder, Schizophrenia, Coronary Heart Diseases and Stroke with each other. The current study aimed to investigate the relationships between genetic variants in the above four diseases and to create a common pathway or PPI network. The associated genes of each disease are collected from different gene database with verification using R. After performing some preprocessing, mining and operations using R on collected genes, seven (7 common associated genes are discovered on selected four diseases (SZ, BD, CHD and Stroke. In each of the iteration, the numbers of collected genes are reduced up to 51%, 36%, 10%, 2% and finally less than 1% respectively. Moreover, common pathway on selected diseases has been investigated in this research.

  2. High Throughput Screening for Neurodegeneration and Complex Disease Phenotypes

    OpenAIRE

    Varma, Hemant; Lo, Donald C.; Stockwell, Brent R.

    2008-01-01

    High throughput screening (HTS) for complex diseases is challenging. This stems from the fact that complex phenotypes are difficult to adapt to rapid, high throughput assays. We describe the recent development of high throughput and high-content screens (HCS) for neurodegenerative diseases, with a focus on inherited neurodegenerative disorders, such as Huntington's disease. We describe, among others, HTS assays based on protein aggregation, neuronal death, caspase activation and mutant protei...

  3. Antibodies as predictors of complex autoimmune diseases.

    Science.gov (United States)

    Vojdani, A

    2008-01-01

    Emerging evidence has suggested environmental factors such as infections and xenobiotics and some dietary proteins and peptides in the pathogenesis of many autoimmune diseases. Considering the fact that autoantibodies can often be detected prior to the onset of a disease, in this study an enzyme immunoassay was used for measurement of antibodies against different highly purified antigens or synthetic peptides originating not only from human tissue, but also from cross-reactive epitopes of infectious agents, dietary proteins and xenobiotics. The measurement of antibodies against a panel of antigens allows for identification of patterns or antibody signatures, rather than just one or two markers of autoimmunity, thus establishing the premise for increased sensitivity and specificity of prediction, as well as positive predictive values. This panel of different autoantibodies was applied to 420 patients with different autoimmune diseases, including pernicious anemia, celiac disease, thyroiditis, lupus, rheumatoid arthritis, osteoarthritis, Addison's disease, type 1 diabetes, cardiovascular disease and autoimmunity, which are presented in this article. In all cases, the levels of these antibodies were significantly elevated in patients versus controls. Antibody patterns related to neuroautoimmune disorders, cancer, and patients with somatic hypermutation will be shown in a subsequent article. We believe that this novel 96 antigen-specific autoantibody or predictive antibody screen should be studied for its incorporation into routine medical examinations. Clinicians should be aware that the detection of antibodies should not automatically mean that a patient will definitely become ill, but would rather give a percentage of risk for autoimmune disease over subsequent months or years.

  4. Bovine rhinitis viruses are common in U.S. cattle with bovine respiratory disease.

    Science.gov (United States)

    Hause, Ben M; Collin, Emily A; Anderson, Joe; Hesse, Richard A; Anderson, Gary

    2015-01-01

    Bovine rhinitis viruses (BRV) are established etiological agents of bovine respiratory disease complex however little research into their epidemiology and ecology has been published for several decades. In the U.S., only bovine rhinitis A virus 1 (BRAV1) has been identified while bovine rhinitis A virus 2 (BRAV2) and bovine rhinitis B virus (BRBV) were previously only identified in England and Japan, respectively. Metagenomic sequencing of a nasal swab from a bovine respiratory disease (BRD) diagnostic submission from Kansas identified contigs with approximately 90% nucleotide similarity to BRAV2 and BRBV. A combination of de novo and templated assemblies using reference genomes yielded near complete BRAV2 and BRBV genomes. The near complete genome of bovine rhinitis A virus 1 (BRAV1) was also determined from a historical isolate to enable further molecular epidemiological studies. A 5'-nuclease reverse transcription PCR assay targeting the 3D polymerase gene was designed and used to screen 204 archived BRD clinical specimens. Thirteen (6.4%) were positive. Metagenomic sequencing of six positive samples identified mixed BRAV1/BRAV2, BRAV1/BRBV and BRAV2/BRBV infections for five samples. One sample showed infection only with BRAV1. Seroprevalence studies using a cell culture adapted BRBV found immunofluorescence assay-reactive antibodies were common in the herds analyzed. Altogether, these results demonstrate that BRV infections are common in cattle with respiratory disease and that BRAV1, BRAV2 and BRBV co-circulate in U.S. cattle and have high similarity to viruses isolated more than 30 years ago from diverse locations.

  5. Bovine rhinitis viruses are common in U.S. cattle with bovine respiratory disease.

    Directory of Open Access Journals (Sweden)

    Ben M Hause

    Full Text Available Bovine rhinitis viruses (BRV are established etiological agents of bovine respiratory disease complex however little research into their epidemiology and ecology has been published for several decades. In the U.S., only bovine rhinitis A virus 1 (BRAV1 has been identified while bovine rhinitis A virus 2 (BRAV2 and bovine rhinitis B virus (BRBV were previously only identified in England and Japan, respectively. Metagenomic sequencing of a nasal swab from a bovine respiratory disease (BRD diagnostic submission from Kansas identified contigs with approximately 90% nucleotide similarity to BRAV2 and BRBV. A combination of de novo and templated assemblies using reference genomes yielded near complete BRAV2 and BRBV genomes. The near complete genome of bovine rhinitis A virus 1 (BRAV1 was also determined from a historical isolate to enable further molecular epidemiological studies. A 5'-nuclease reverse transcription PCR assay targeting the 3D polymerase gene was designed and used to screen 204 archived BRD clinical specimens. Thirteen (6.4% were positive. Metagenomic sequencing of six positive samples identified mixed BRAV1/BRAV2, BRAV1/BRBV and BRAV2/BRBV infections for five samples. One sample showed infection only with BRAV1. Seroprevalence studies using a cell culture adapted BRBV found immunofluorescence assay-reactive antibodies were common in the herds analyzed. Altogether, these results demonstrate that BRV infections are common in cattle with respiratory disease and that BRAV1, BRAV2 and BRBV co-circulate in U.S. cattle and have high similarity to viruses isolated more than 30 years ago from diverse locations.

  6. 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

  7. Molecular diagnostics for the Sigatoka disease complex of banana

    NARCIS (Netherlands)

    Arzanlou, M.; Abeln, E.C.A.; Kema, G.H.J.; Waalwijk, C.; Carlier, J.; Crous, P.W.

    2007-01-01

    The Sigatoka disease complex of banana involves three related ascomycetous fungi, Mycosphaerella fijiensis, M. musicola, and M. eumusae. The exact distribution of these three species and their disease epidemiology remain unclear, because their symptoms and life cycles are rather similar. Disease

  8. Molecular diagnostics for the Sigatoka disease complex of banana

    NARCIS (Netherlands)

    Arzanlou, M.; Abeln, E.C.A.; Kema, G.H.J.; Waalwijk, C.; Carlier, J.; Crous, P.W.

    2007-01-01

    The Sigatoka disease complex of banana involves three related ascomycetous fungi, Mycosphaerella fijiensis, M. musicola, and M. eumusae. The exact distribution of these three species and their disease epidemiology remain unclear, because their symptoms and life cycles are rather similar. Disease dia

  9. Asthma in childhood: a complex, heterogeneous disease

    OpenAIRE

    2011-01-01

    Asthma in childhood is a heterogeneous disease with different phenotypes and variable clinical manifestations, which depend on the age, gender, genetic background, and environmental influences of the patients. Several longitudinal studies have been conducted to classify the phenotypes of childhood asthma, on the basis of the symptoms, triggers of wheezing illness, or pathophysiological features of the disease. These studies have provided us with important information about the different wheez...

  10. Components of coated vesicles and nuclear pore complexes share a common molecular architecture.

    Directory of Open Access Journals (Sweden)

    Damien Devos

    2004-12-01

    Full Text Available Numerous features distinguish prokaryotes from eukaryotes, chief among which are the distinctive internal membrane systems of eukaryotic cells. These membrane systems form elaborate compartments and vesicular trafficking pathways, and sequester the chromatin within the nuclear envelope. The nuclear pore complex is the portal that specifically mediates macromolecular trafficking across the nuclear envelope. Although it is generally understood that these internal membrane systems evolved from specialized invaginations of the prokaryotic plasma membrane, it is not clear how the nuclear pore complex could have evolved from organisms with no analogous transport system. Here we use computational and biochemical methods to perform a structural analysis of the seven proteins comprising the yNup84/vNup107-160 subcomplex, a core building block of the nuclear pore complex. Our analysis indicates that all seven proteins contain either a beta-propeller fold, an alpha-solenoid fold, or a distinctive arrangement of both, revealing close similarities between the structures comprising the yNup84/vNup107-160 subcomplex and those comprising the major types of vesicle coating complexes that maintain vesicular trafficking pathways. These similarities suggest a common evolutionary origin for nuclear pore complexes and coated vesicles in an early membrane-curving module that led to the formation of the internal membrane systems in modern eukaryotes.

  11. metabolicMine: an integrated genomics, genetics and proteomics data warehouse for common metabolic disease research.

    Science.gov (United States)

    Lyne, Mike; Smith, Richard N; Lyne, Rachel; Aleksic, Jelena; Hu, Fengyuan; Kalderimis, Alex; Stepan, Radek; Micklem, Gos

    2013-01-01

    Common metabolic and endocrine diseases such as diabetes affect millions of people worldwide and have a major health impact, frequently leading to complications and mortality. In a search for better prevention and treatment, there is ongoing research into the underlying molecular and genetic bases of these complex human diseases, as well as into the links with risk factors such as obesity. Although an increasing number of relevant genomic and proteomic data sets have become available, the quantity and diversity of the data make their efficient exploitation challenging. Here, we present metabolicMine, a data warehouse with a specific focus on the genomics, genetics and proteomics of common metabolic diseases. Developed in collaboration with leading UK metabolic disease groups, metabolicMine integrates data sets from a range of experiments and model organisms alongside tools for exploring them. The current version brings together information covering genes, proteins, orthologues, interactions, gene expression, pathways, ontologies, diseases, genome-wide association studies and single nucleotide polymorphisms. Although the emphasis is on human data, key data sets from mouse and rat are included. These are complemented by interoperation with the RatMine rat genomics database, with a corresponding mouse version under development by the Mouse Genome Informatics (MGI) group. The web interface contains a number of features including keyword search, a library of Search Forms, the QueryBuilder and list analysis tools. This provides researchers with many different ways to analyse, view and flexibly export data. Programming interfaces and automatic code generation in several languages are supported, and many of the features of the web interface are available through web services. The combination of diverse data sets integrated with analysis tools and a powerful query system makes metabolicMine a valuable research resource. The web interface makes it accessible to first

  12. [Role of environment in complex diseases: air pollution and food contaminants].

    Science.gov (United States)

    Scheen, A J; Giet, D

    2012-01-01

    Our polluted environment exposes human beings, along their life, to various toxic compounds that could trigger and aggravate different complex diseases. Such a phenomenon is well recognized for cardiovascular diseases, respiratory diseases and cancers, but other chronic inflammatory disorders may also been implicated. The most common factors, but also the most toxic, and thereby the most extensively investigated, are air pollutants (both indoor and outdoor pollution) and various contaminants present in drinking water and food (organic compounds, chemical products, heavy metals, ...). The complex interrelationships between food and pollutants, on the one hand, and between gene and environmental pollutants, including the influence of epigenetics, on the other hand, deserve further careful studies.

  13. The Human Phenotype Ontology: Semantic Unification of Common and Rare Disease

    Science.gov (United States)

    Groza, Tudor; Köhler, Sebastian; Moldenhauer, Dawid; Vasilevsky, Nicole; Baynam, Gareth; Zemojtel, Tomasz; Schriml, Lynn Marie; Kibbe, Warren Alden; Schofield, Paul N.; Beck, Tim; Vasant, Drashtti; Brookes, Anthony J.; Zankl, Andreas; Washington, Nicole L.; Mungall, Christopher J.; Lewis, Suzanna E.; Haendel, Melissa A.; Parkinson, Helen; Robinson, Peter N.

    2015-01-01

    The Human Phenotype Ontology (HPO) is widely used in the rare disease community for differential diagnostics, phenotype-driven analysis of next-generation sequence-variation data, and translational research, but a comparable resource has not been available for common disease. Here, we have developed a concept-recognition procedure that analyzes the frequencies of HPO disease annotations as identified in over five million PubMed abstracts by employing an iterative procedure to optimize precision and recall of the identified terms. We derived disease models for 3,145 common human diseases comprising a total of 132,006 HPO annotations. The HPO now comprises over 250,000 phenotypic annotations for over 10,000 rare and common diseases and can be used for examining the phenotypic overlap among common diseases that share risk alleles, as well as between Mendelian diseases and common diseases linked by genomic location. The annotations, as well as the HPO itself, are freely available. PMID:26119816

  14. Network biology concepts in complex disease comorbidities

    DEFF Research Database (Denmark)

    Hu, Jessica Xin; Thomas, Cecilia Engel; Brunak, Søren

    2016-01-01

    The co-occurrence of diseases can inform the underlying network biology of shared and multifunctional genes and pathways. In addition, comorbidities help to elucidate the effects of external exposures, such as diet, lifestyle and patient care. With worldwide health transaction data now often being...

  15. Common genetic variants associated with thyroid function may be risk alleles for Hashimoto's disease and Graves' disease.

    Science.gov (United States)

    Campbell, Purdey; Brix, Thomas H; Wilson, Scott G; Ward, Lynley C; Hui, Jennie; Beilby, John P; Hegedüs, Laszlo; Walsh, John P

    2015-02-14

    Recent studies have identified common genetic variants associated with TSH, free T4 and thyroid peroxidase antibodies, but it is unclear whether these differ between patients with Hashimoto's disease and Graves' disease. To examine whether 11 common genetic variants differ between Graves' disease and Hashimoto's disease. We genotyped 11 common variants in a discovery cohort of 203 Australian patients with autoimmune thyroid disease (AITD). Two variants with significant or suggestive associations were analysed in a replication cohort of 384 Danish patients. For rs753760 (PDE10A), the minor allele frequency in Graves' disease and Hashimoto's disease was 0·38 vs. 0·23, respectively, (P = 6·42 × 10(-4) ) in the discovery cohort, 0·29 vs. 0·24 (P = 0·147) in the replication cohort and 0·32 vs. 0·24 in combined analysis (P = 0·0021; all analyses adjusted for sex). In healthy controls from Busselton, the frequency was 0·29, significantly different from Hashimoto's disease but not Graves' disease. For rs4889009 (MAF gene region), the frequency of the minor G-allele in Graves' disease and Hashimoto's disease was 0·48 vs. 0·36 (P = 0·0156) in the discovery cohort, 0·48 vs. 0·34 (P = 1·83 × 10(-4) ) in the replication cohort and 0·48 vs. 0·35 in the combined analysis (P = 7·53 × 10(-6) ); in controls, the frequency was 0·38, significantly different from Graves' disease but not Hashimoto's disease. After further adjustment for smoking, associations with rs4889009 remained significant, whereas those with rs753760 were not. Common variants in PDE10A and MAF gene regions may influence whether patients with AITD develop Graves' disease or Hashimoto's disease. © 2015 John Wiley & Sons Ltd.

  16. Asthma in childhood: a complex, heterogeneous disease

    Directory of Open Access Journals (Sweden)

    Hai Lee Chung

    2011-01-01

    Full Text Available Asthma in childhood is a heterogeneous disease with different phenotypes and variable clinical manifestations, which depend on the age, gender, genetic background, and environmental influences of the patients. Several longitudinal studies have been conducted to classify the phenotypes of childhood asthma, on the basis of the symptoms, triggers of wheezing illness, or pathophysiological features of the disease. These studies have provided us with important information about the different wheezing phenotypes in young children and about potential mechanisms and risk factors for the development of chronic asthma. The goal of these studies was to provide a better insight into the causes and natural course of childhood asthma. It is well-known that complicated interactions between genes and environmental factors contribute to the development of asthma. Because childhood is a period of rapid growth in both the lungs and the immune system, developmental factors should be considered in the pathogenesis of childhood asthma. The pulmonary system continues to grow and develop until linear growth is completed. Longitudinal studies have reported significant age-related immune development during postnatal early life. These observations suggest that the phenotypes of childhood asthma vary among children and also in an individual child over time. Improved classification of heterogeneous conditions of the disease will help determine novel strategies for primary and secondary prevention and for the development of individualized treatment for childhood asthma.

  17. Patient access to complex chronic disease records on the Internet

    Directory of Open Access Journals (Sweden)

    Bartlett Cherry

    2012-08-01

    Full Text Available Abstract Background Access to medical records on the Internet has been reported to be acceptable and popular with patients, although most published evaluations have been of primary care or office-based practice. We tested the feasibility and acceptability of making unscreened results and data from a complex chronic disease pathway (renal medicine available to patients over the Internet in a project involving more than half of renal units in the UK. Methods Content and presentation of the Renal PatientView (RPV system was developed with patient groups. It was designed to receive information from multiple local information systems and to require minimal extra work in units. After piloting in 4 centres in 2005 it was made available more widely. Opinions were sought from both patients who enrolled and from those who did not in a paper survey, and from staff in an electronic survey. Anonymous data on enrolments and usage were extracted from the webserver. Results By mid 2011 over 17,000 patients from 47 of the 75 renal units in the UK had registered. Users had a wide age range (90 yrs but were younger and had more years of education than non-users. They were enthusiastic about the concept, found it easy to use, and 80% felt it gave them a better understanding of their disease. The most common reason for not enrolling was being unaware of the system. A minority of patients had security concerns, and these were reduced after enrolling. Staff responses were also strongly positive. They reported that it aided patient concordance and disease management, and increased the quality of consultations with a neutral effect on consultation length. Neither patient nor staff responses suggested that RPV led to an overall increase in patient anxiety or to an increased burden on renal units beyond the time required to enrol each patient. Conclusions Patient Internet access to secondary care records concerning a complex chronic disease is feasible and popular

  18. Severity of angular leaf spot and rust diseases on common beans in ...

    African Journals Online (AJOL)

    ACSS

    the incidence and severity of ALS in five bean agro-ecologies within Uganda was ... Key words: Common beans, disease management, Phaseolus vulgaris, ... plants has been shown to reduce pest and ... plant nutrition through organic soil.

  19. Common variants associated with plasma triglycerides and risk for coronary artery disease

    NARCIS (Netherlands)

    Do, Ron; Willer, Cristen J; Schmidt, Ellen M; Sengupta, Sebanti; Gao, Chi; Peloso, Gina M; Gustafsson, Stefan; Kanoni, Stavroula; Ganna, Andrea; Chen, Jin; Buchkovich, Martin L; Mora, Samia; Beckmann, Jacques S; Bragg-Gresham, Jennifer L; Chang, Hsing-Yi; Demirkan, Ayşe; Den Hertog, Heleen M; Donnelly, Louise A; Ehret, Georg B; Esko, Tõnu; Feitosa, Mary F; Ferreira, Teresa; Fischer, Krista; Fontanillas, Pierre; Fraser, Ross M; Freitag, Daniel F; Gurdasani, Deepti; Heikkilä, Kauko; Hyppönen, Elina; Isaacs, Aaron; Jackson, Anne U; Johansson, Asa; Johnson, Toby; Kaakinen, Marika; Kettunen, Johannes; Kleber, Marcus E; Li, Xiaohui; Luan, Jian'an; Lyytikäinen, Leo-Pekka; Magnusson, Patrik K E; Mangino, Massimo; Mihailov, Evelin; Montasser, May E; Müller-Nurasyid, Martina; Nolte, Ilja M; O'Connell, Jeffrey R; Palmer, Cameron D; Perola, Markus; Petersen, Ann-Kristin; Sanna, Serena; Saxena, Richa; Service, Susan K; Shah, Sonia; Shungin, Dmitry; Sidore, Carlo; Song, Ci; Strawbridge, Rona J; Surakka, Ida; Tanaka, Toshiko; Teslovich, Tanya M; Thorleifsson, Gudmar; Van den Herik, Evita G; Voight, Benjamin F; Volcik, Kelly A; Waite, Lindsay L; Wong, Andrew; Wu, Ying; Zhang, Weihua; Absher, Devin; Asiki, Gershim; Barroso, Inês; Been, Latonya F; Bolton, Jennifer L; Bonnycastle, Lori L; Brambilla, Paolo; Burnett, Mary S; Cesana, Giancarlo; Dimitriou, Maria; Doney, Alex S F; Döring, Angela; Elliott, Paul; Epstein, Stephen E; Eyjolfsson, Gudmundur Ingi; Gigante, Bruna; Goodarzi, Mark O; Grallert, Harald; Gravito, Martha L; Groves, Christopher J; Hallmans, Göran; Hartikainen, Anna-Liisa; Hayward, Caroline; Hernandez, Dena; Hicks, Andrew A; Holm, Hilma; Hung, Yi-Jen; Illig, Thomas; Jones, Michelle R; Kaleebu, Pontiano; Kastelein, John J P; Khaw, Kay-Tee; Kim, Eric; Klopp, Norman; Komulainen, Pirjo; Kumari, Meena; Langenberg, Claudia; Lehtimäki, Terho; Lin, Shih-Yi; Lindström, Jaana; Loos, Ruth J F; Mach, François; McArdle, Wendy L; Meisinger, Christa; Mitchell, Braxton D; Müller, Gabrielle; Nagaraja, Ramaiah; Narisu, Narisu; Nieminen, Tuomo V M; Nsubuga, Rebecca N; Olafsson, Isleifur; Ong, Ken K; Palotie, Aarno; Papamarkou, Theodore; Pomilla, Cristina; Pouta, Anneli; Rader, Daniel J; Reilly, Muredach P; Ridker, Paul M; Rivadeneira, Fernando; Rudan, Igor; Ruokonen, Aimo; Samani, Nilesh; Scharnagl, Hubert; Seeley, Janet; Silander, Kaisa; Stančáková, Alena; Stirrups, Kathleen; Swift, Amy J; Tiret, Laurence; Uitterlinden, Andre G; van Pelt, L Joost; Vedantam, Sailaja; Wainwright, Nicholas; Wijmenga, Cisca; Wild, Sarah H; Willemsen, Gonneke; Wilsgaard, Tom; Wilson, James F; Young, Elizabeth H; Zhao, Jing Hua; Adair, Linda S; Arveiler, Dominique; Assimes, Themistocles L; Bandinelli, Stefania; Bennett, Franklyn; Bochud, Murielle; Boehm, Bernhard O; Boomsma, Dorret I; Borecki, Ingrid B; Bornstein, Stefan R; Bovet, Pascal; Burnier, Michel; Campbell, Harry; Chakravarti, Aravinda; Chambers, John C; Chen, Yii-Der Ida; Collins, Francis S; Cooper, Richard S; Danesh, John; Dedoussis, George; de Faire, Ulf; Feranil, Alan B; Ferrières, Jean; Ferrucci, Luigi; Freimer, Nelson B; Gieger, Christian; Groop, Leif C; Gudnason, Vilmundur; Gyllensten, Ulf; Hamsten, Anders; Harris, Tamara B; Hingorani, Aroon; Hirschhorn, Joel N; Hofman, Albert; Hovingh, G Kees; Hsiung, Chao Agnes; Humphries, Steve E; Hunt, Steven C; Hveem, Kristian; Iribarren, Carlos; Järvelin, Marjo-Riitta; Jula, Antti; Kähönen, Mika; Kaprio, Jaakko; Kesäniemi, Antero; Kivimaki, Mika; Kooner, Jaspal S; Koudstaal, Peter J; Krauss, Ronald M; Kuh, Diana; Kuusisto, Johanna; Kyvik, Kirsten O; Laakso, Markku; Lakka, Timo A; Lind, Lars; Lindgren, Cecilia M; Martin, Nicholas G; März, Winfried; McCarthy, Mark I; McKenzie, Colin A; Meneton, Pierre; Metspalu, Andres; Moilanen, Leena; Morris, Andrew D; Munroe, Patricia B; Njølstad, Inger; Pedersen, Nancy L; Power, Chris; Pramstaller, Peter P; Price, Jackie F; Psaty, Bruce M; Quertermous, Thomas; Rauramaa, Rainer; Saleheen, Danish; Salomaa, Veikko; Sanghera, Dharambir K; Saramies, Jouko; Schwarz, Peter E H; Sheu, Wayne H-H; Shuldiner, Alan R; Siegbahn, Agneta; Spector, Tim D; Stefansson, Kari; Strachan, David P; Tayo, Bamidele O; Tremoli, Elena; Tuomilehto, Jaakko; Uusitupa, Matti; van Duijn, Cornelia M; Vollenweider, Peter; Wallentin, Lars; Wareham, Nicholas J; Whitfield, John B; Wolffenbuttel, Bruce H R; Altshuler, David; Ordovas, Jose M; Boerwinkle, Eric; Palmer, Colin N A; Thorsteinsdottir, Unnur; Chasman, Daniel I; Rotter, Jerome I; Franks, Paul W; Ripatti, Samuli; Cupples, L Adrienne; Sandhu, Manjinder S; Rich, Stephen S; Boehnke, Michael; Deloukas, Panos; Mohlke, Karen L; Ingelsson, Erik; Abecasis, Goncalo R; Daly, Mark J; Neale, Benjamin M; Kathiresan, Sekar

    2013-01-01

    Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common

  20. Common variants associated with plasma triglycerides and risk for coronary artery disease

    DEFF Research Database (Denmark)

    Do, R.; Willer, C. J.; Schmidt, E. M.

    2013-01-01

    Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common...

  1. From quantitative protein complex analysis to disease mechanism.

    Science.gov (United States)

    Texier, Y; Kinkl, N; Boldt, K; Ueffing, M

    2012-12-15

    Interest in the field of cilia biology and cilia-associated diseases - ciliopathies - has strongly increased over the last few years. Proteomic technologies, especially protein complex analysis by affinity purification-based methods, have been used to decipher various basic but also disease-associated mechanisms. This review focusses on some selected recent studies using affinity purification-based protein complex analysis, thereby exemplifying the great possibilities this technology offers.

  2. Comprehension of Complex Discourse in Different Stages of Huntington's Disease

    Science.gov (United States)

    Saldert, Charlotta; Fors, Angelika; Stroberg, Sofia; Hartelius, Lena

    2010-01-01

    Background: Huntington's disease not only affects motor speech control, but also may have an impact on the ability to produce and understand language in communication. Aims: The ability to comprehend basic and complex discourse was investigated in three different stages of Huntington's disease. Methods & Procedures: In this experimental group…

  3. Bacterial pathogens of acute sinusitis in the osteomeatal complex during common colds and wellness.

    Science.gov (United States)

    Han, Joseph K; Hendley, J Owen; Winther, Birgit

    2011-01-01

    Pathogenic bacteria have been cultured from the osteomeatal complex (OMC) in one-third of adults with apparent acute bacterial sinusitis; however, it is not known whether bacteria are present in the OMC during uncomplicated viral colds in adults. Adult volunteers were recruited for a study during wellness and at the time of acute common cold. Swab cultures were obtained from the OMC and from the nasopharynx by 2 routes (through the nose and through the mouth). Swab eluates were inoculated on selective agars to detect S. pneumoniae, H. influenzae, and M. catarrhalis. Bacterial pathogens were detected in the OMC more frequently during common colds than during wellness (31% vs 8%, p OMC were always present in the nasopharynx of the subject. Bacterial pathogens are present in the OMC in a subgroup of adult patients with uncomplicated upper respiratory illness/common cold. The nasopharynx appears to be the reservoir for bacterial pathogens in the OMC. Copyright © 2011 American Rhinologic Society-American Academy of Otolaryngic Allergy, LLC.

  4. Women with heart disease: can the common-sense model of illness help?

    Science.gov (United States)

    Shifren, Kim

    2003-04-01

    Noncompliance with cardiac rehabilitation programs is a major concern for female coronary heart disease patients. In this article I argue for the use of the common-sense model of illness in developing interventions to increase compliance with cardiac rehabilitation programs among women with heart disease. First, the common-sense model of illness is discussed. Second, a personal narrative technique that addresses the key components of the common-sense model of illness is presented. I recommend that a modified version of the personal narrative technique be used to increase women's compliance with cardiac rehabilitation programs because this technique is well suited for women's health issues.

  5. User self-governance in a complex policy design for managing water commons in Japan

    Science.gov (United States)

    Sarker, Ashutosh; Itoh, Tadao; Kada, Ryohei; Abe, Takaki; Nakashima, Masahiro; Herath, Gamini

    2014-03-01

    Studies have typically emphasized one of three major policy alternatives-government (state) ownership, privatization, or user self-governance-to address overuse of “the commons” as a natural resource shared by many competing users. Studies tend to focus on each alternative separately. Government ownership or privatization is usually understood to undermine user self-governing institutional arrangements, while user self-governance has proved to be a very powerful policy alternative in managing the commons in many cases. An important research question arises as to whether a complex policy design can strengthen the competence of user self-governing institutional arrangements. This article defines a complex policy design as one that involves a mix of flexible policy alternatives rather than a rigid alternative to address overuse issues. Drawing on Japan's irrigation water management experience, this study demonstrates that when a complex policy design is tailored to facilitate user autonomy, it further strengthens user self-governance. The study provides scholars with insight into how self-governing institutional arrangements-which were primarily developed in the existing literature with the government's role assumed as absent or implicit-could be enhanced when the role is strategically explicit.

  6. Associating genes and protein complexes with disease via network propagation.

    Directory of Open Access Journals (Sweden)

    Oron Vanunu

    2010-01-01

    Full Text Available A fundamental challenge in human health is the identification of disease-causing genes. Recently, several studies have tackled this challenge via a network-based approach, motivated by the observation that genes causing the same or similar diseases tend to lie close to one another in a network of protein-protein or functional interactions. However, most of these approaches use only local network information in the inference process and are restricted to inferring single gene associations. Here, we provide a global, network-based method for prioritizing disease genes and inferring protein complex associations, which we call PRINCE. The method is based on formulating constraints on the prioritization function that relate to its smoothness over the network and usage of prior information. We exploit this function to predict not only genes but also protein complex associations with a disease of interest. We test our method on gene-disease association data, evaluating both the prioritization achieved and the protein complexes inferred. We show that our method outperforms extant approaches in both tasks. Using data on 1,369 diseases from the OMIM knowledgebase, our method is able (in a cross validation setting to rank the true causal gene first for 34% of the diseases, and infer 139 disease-related complexes that are highly coherent in terms of the function, expression and conservation of their member proteins. Importantly, we apply our method to study three multi-factorial diseases for which some causal genes have been found already: prostate cancer, alzheimer and type 2 diabetes mellitus. PRINCE's predictions for these diseases highly match the known literature, suggesting several novel causal genes and protein complexes for further investigation.

  7. Inferring drug-disease associations based on known protein complexes.

    Science.gov (United States)

    Yu, Liang; Huang, Jianbin; Ma, Zhixin; Zhang, Jing; Zou, Yapeng; Gao, Lin

    2015-01-01

    Inferring drug-disease associations is critical in unveiling disease mechanisms, as well as discovering novel functions of available drugs, or drug repositioning. Previous work is primarily based on drug-gene-disease relationship, which throws away many important information since genes execute their functions through interacting others. To overcome this issue, we propose a novel methodology that discover the drug-disease association based on protein complexes. Firstly, the integrated heterogeneous network consisting of drugs, protein complexes, and disease are constructed, where we assign weights to the drug-disease association by using probability. Then, from the tripartite network, we get the indirect weighted relationships between drugs and diseases. The larger the weight, the higher the reliability of the correlation. We apply our method to mental disorders and hypertension, and validate the result by using comparative toxicogenomics database. Our ranked results can be directly reinforced by existing biomedical literature, suggesting that our proposed method obtains higher specificity and sensitivity. The proposed method offers new insight into drug-disease discovery. Our method is publicly available at http://1.complexdrug.sinaapp.com/Drug_Complex_Disease/Data_Download.html.

  8. Communicable diseases in complex emergencies: impact and challenges.

    Science.gov (United States)

    Connolly, Máire A; Gayer, Michelle; Ryan, Michael J; Salama, Peter; Spiegel, Paul; Heymann, David L

    Communicable diseases, alone or in combination with malnutrition, account for most deaths in complex emergencies. Factors promoting disease transmission interact synergistically leading to high incidence rates of diarrhoea, respiratory infection, malaria, and measles. This excess morbidity and mortality is avoidable as effective interventions are available. Adequate shelter, water, food, and sanitation linked to effective case management, immunisation, health education, and disease surveillance are crucial. However, delivery mechanisms are often compromised by loss of health staff, damage to infrastructure, insecurity, and poor co-ordination. Although progress has been made in the control of specific communicable diseases in camp settings, complex emergencies affecting large geographical areas or entire countries pose a greater challenge. Available interventions need to be implemented more systematically in complex emergencies with higher levels of coordination between governments, UN agencies, and non-governmental organisations. In addition, further research is needed to adapt and simplify interventions, and to explore novel diagnostics, vaccines, and therapies.

  9. Complex disease and phenotype mapping in the domestic dog.

    Science.gov (United States)

    Hayward, Jessica J; Castelhano, Marta G; Oliveira, Kyle C; Corey, Elizabeth; Balkman, Cheryl; Baxter, Tara L; Casal, Margret L; Center, Sharon A; Fang, Meiying; Garrison, Susan J; Kalla, Sara E; Korniliev, Pavel; Kotlikoff, Michael I; Moise, N S; Shannon, Laura M; Simpson, Kenneth W; Sutter, Nathan B; Todhunter, Rory J; Boyko, Adam R

    2016-01-22

    The domestic dog is becoming an increasingly valuable model species in medical genetics, showing particular promise to advance our understanding of cancer and orthopaedic disease. Here we undertake the largest canine genome-wide association study to date, with a panel of over 4,200 dogs genotyped at 180,000 markers, to accelerate mapping efforts. For complex diseases, we identify loci significantly associated with hip dysplasia, elbow dysplasia, idiopathic epilepsy, lymphoma, mast cell tumour and granulomatous colitis; for morphological traits, we report three novel quantitative trait loci that influence body size and one that influences fur length and shedding. Using simulation studies, we show that modestly larger sample sizes and denser marker sets will be sufficient to identify most moderate- to large-effect complex disease loci. This proposed design will enable efficient mapping of canine complex diseases, most of which have human homologues, using far fewer samples than required in human studies.

  10. Integrated Analyses of Gene Expression Profiles Digs out Common Markers for Rheumatic Diseases.

    Directory of Open Access Journals (Sweden)

    Lan Wang

    Full Text Available Rheumatic diseases have some common symptoms. Extensive gene expression studies, accumulated thus far, have successfully identified signature molecules for each rheumatic disease, individually. However, whether there exist shared factors across rheumatic diseases has yet to be tested.We collected and utilized 6 public microarray datasets covering 4 types of representative rheumatic diseases including rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, and osteoarthritis. Then we detected overlaps of differentially expressed genes across datasets and performed a meta-analysis aiming at identifying common differentially expressed genes that discriminate between pathological cases and normal controls. To further gain insights into the functions of the identified common differentially expressed genes, we conducted gene ontology enrichment analysis and protein-protein interaction analysis.We identified a total of eight differentially expressed genes (TNFSF10, CX3CR1, LY96, TLR5, TXN, TIA1, PRKCH, PRF1, each associated with at least 3 of the 4 studied rheumatic diseases. Meta-analysis warranted the significance of the eight genes and highlighted the general significance of four genes (CX3CR1, LY96, TLR5, and PRF1. Protein-protein interaction and gene ontology enrichment analyses indicated that the eight genes interact with each other to exert functions related to immune response and immune regulation.The findings support that there exist common factors underlying rheumatic diseases. For rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis and osteoarthritis diseases, those common factors include TNFSF10, CX3CR1, LY96, TLR5, TXN, TIA1, PRKCH, and PRF1. In-depth studies on these common factors may provide keys to understanding the pathogenesis and developing intervention strategies for rheumatic diseases.

  11. Common underlying diseases do not contribute in determining the causes of sudden unexplained death

    Institute of Scientific and Technical Information of China (English)

    TIAN Zhao-xing; L(U) Yan-yu; Chetan Rai Nugessur; YAN Wei; ZHAO Wen-kui; KONG Li-li; ZHENG Ya-an

    2013-01-01

    Background Underlying diseases have a statistically significant positive correlation to sudden death.However,sudden unexplained death (SUD) is different from sudden death,as there is no clinical evidence to support the sudden death due to the original underlying disease,nor a lethal pathological basis to be found during autopsy.In addition,SUD are more common in young,previously healthy individuals,usually without any signs of disease,with no positive lesions found after autopsy.Therefore,a causal relationship between SUD and the underlying disease needs to be further explored.This study aimed to explore the role that common underlying diseases play in patients with SUD and to reveal the correlation between them.Methods The medical records,history and case information of 208 patients with SUD were collected for the survey.All these SUD occurred in the emergency room of Peking University Third Hospital from January 2006 to December 2009.The patients were stratified by with and without common underlying diseases.To examine possible associations between the underlying diseases and the cause of unexplained sudden death,the chi-squared and Fisher's exact tests were used.Results Among the 208 patients,65 were diagnosed with common underlying diseases while 143 were not.Within these two groups,there were 45 patients for whom the clear cause of death was determined.However,there were no statistically significant differences or strong associations (x2=1.238,P >0.05) between the 11 patients with (16.90%) and 34 without (23.78%) common underlying disease among these 45 patients.We also found that occurrence of the common underlying diseases,such as neurological system,cardiovascular and pulmonary system diseases,are not statistically significant (P >0.05) in the diagnosis of the SUD.Conclusion Common underlying diseases make no obvious contributions to SUD and are not useful in diagnosing the underlying reasons for death.

  12. Long Non-Coding RNAs and Complex Human Diseases

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    Changning Liu

    2013-09-01

    Full Text Available Long non-coding RNAs (lncRNAs are a heterogeneous class of RNAs that are generally defined as non-protein-coding transcripts longer than 200 nucleotides. Recently, an increasing number of studies have shown that lncRNAs can be involved in various critical biological processes, such as chromatin remodeling, gene transcription, and protein transport and trafficking. Moreover, lncRNAs are dysregulated in a number of complex human diseases, including coronary artery diseases, autoimmune diseases, neurological disorders, and various cancers, which indicates their important roles in these diseases. Here, we reviewed the current understanding of lncRNAs, including their definition and subclassification, regulatory functions, and potential roles in different types of complex human diseases.

  13. Spreading dynamics and synchronization behavior of periodic diseases on complex networks

    Science.gov (United States)

    Xu, Degang; Xu, Xiyang; Yang, Chunhua; Gui, Weihua

    2017-01-01

    A new discrete-susceptible-infected-recovered-susceptible (DSIRS) model is introduced in this paper to investigate the disease spreading dynamics and synchronization behavior on complex networks. In the model, every node is considered independently rather than as a part of one group that has a common node state in complex networks. The synchronization phenomenon of epidemic spreading based on the model in random networks and scale-free networks is analyzed. Synchronization is affected by the infection duration, the complete cycle duration and the topological network structure, which affects the immune strategy. Accordingly, immune strategies including the maximum degree immune strategy and the nearest immune strategy are proposed to prevent disease propagating.

  14. Systematic localization of common disease-associated variation in regulatory DNA.

    Science.gov (United States)

    Maurano, Matthew T; Humbert, Richard; Rynes, Eric; Thurman, Robert E; Haugen, Eric; Wang, Hao; Reynolds, Alex P; Sandstrom, Richard; Qu, Hongzhu; Brody, Jennifer; Shafer, Anthony; Neri, Fidencio; Lee, Kristen; Kutyavin, Tanya; Stehling-Sun, Sandra; Johnson, Audra K; Canfield, Theresa K; Giste, Erika; Diegel, Morgan; Bates, Daniel; Hansen, R Scott; Neph, Shane; Sabo, Peter J; Heimfeld, Shelly; Raubitschek, Antony; Ziegler, Steven; Cotsapas, Chris; Sotoodehnia, Nona; Glass, Ian; Sunyaev, Shamil R; Kaul, Rajinder; Stamatoyannopoulos, John A

    2012-09-07

    Genome-wide association studies have identified many noncoding variants associated with common diseases and traits. We show that these variants are concentrated in regulatory DNA marked by deoxyribonuclease I (DNase I) hypersensitive sites (DHSs). Eighty-eight percent of such DHSs are active during fetal development and are enriched in variants associated with gestational exposure-related phenotypes. We identified distant gene targets for hundreds of variant-containing DHSs that may explain phenotype associations. Disease-associated variants systematically perturb transcription factor recognition sequences, frequently alter allelic chromatin states, and form regulatory networks. We also demonstrated tissue-selective enrichment of more weakly disease-associated variants within DHSs and the de novo identification of pathogenic cell types for Crohn's disease, multiple sclerosis, and an electrocardiogram trait, without prior knowledge of physiological mechanisms. Our results suggest pervasive involvement of regulatory DNA variation in common human disease and provide pathogenic insights into diverse disorders.

  15. Understanding Parkinson Disease: A Complex and Multifaceted Illness.

    Science.gov (United States)

    Gopalakrishna, Apoorva; Alexander, Sheila A

    2015-12-01

    Parkinson disease is an incredibly complex and multifaceted illness affecting millions of people in the United States. Parkinson disease is characterized by progressive dopaminergic neuronal dysfunction and loss, leading to debilitating motor, cognitive, and behavioral symptoms. Parkinson disease is an enigmatic illness that is still extensively researched today to search for a better understanding of the disease, develop therapeutic interventions to halt or slow progression of the disease, and optimize patient outcomes. This article aims to examine in detail the normal function of the basal ganglia and dopaminergic neurons in the central nervous system, the etiology and pathophysiology of Parkinson disease, related signs and symptoms, current treatment, and finally, the profound impact of understanding the disease on nursing care.

  16. Genetic basis of common diseases: the general theory of Mendelian recessive genetics.

    Science.gov (United States)

    Hutchinson, Michael; Spanaki, Cleanthe; Lebedev, Sergey; Plaitakis, Andreas

    2005-01-01

    Common diseases tend to appear sporadically, i.e., they appear in an individual who has no first or second degree relatives with the disease. Yet diseases are often associated with a slight but definite increase in risk to the children of an affected individual. This weak pattern of inheritability cannot be explained by conventional interpretations of Mendelian genetics, and it is therefore commonly held that there is "incomplete penetrance" of a gene, or that there are polygenic, or multifactorial modes of inheritance. However, such arguments are heuristic and lack predictive power. Here, we explore the possibility that "incomplete penetrance" means the existence of a second, disease-related, gene. By examining in detail a specific common condition, Parkinson's disease (PD), we show that the sporadic form of the disease can be fully explained by a compact fully penetrant genotype involving an interaction between two, and only two, genes. In this model, therefore PD is fundamentally genetic. Our digenic model is complementary to Mendelian recessive genetics, but taken together with the latter forms a complete description for recessive genetics on one chromosome. It explains the slight increase in risk to the children if one parent has sporadic PD, and makes strict predictions where both parents coincidentally have sporadic PD. These predictions were verified in two large and carefully selected kindred, where the data also argue against other genetic models, including oligogenic and polygenic schemes. Since the inheritance patterns of sporadic PD are reminiscent of what is seen in many common diseases, it is plausible that similar genetic forms could apply to other diseases. Seen in this light, diseases wash in and out of every family, so that in a sense, over time every human family is equally at risk for most diseases.

  17. Conceptual Foundations of Systems Biology Explaining Complex Cardiac Diseases.

    Science.gov (United States)

    Louridas, George E; Lourida, Katerina G

    2017-02-21

    Systems biology is an important concept that connects molecular biology and genomics with computing science, mathematics and engineering. An endeavor is made in this paper to associate basic conceptual ideas of systems biology with clinical medicine. Complex cardiac diseases are clinical phenotypes generated by integration of genetic, molecular and environmental factors. Basic concepts of systems biology like network construction, modular thinking, biological constraints (downward biological direction) and emergence (upward biological direction) could be applied to clinical medicine. Especially, in the field of cardiology, these concepts can be used to explain complex clinical cardiac phenotypes like chronic heart failure and coronary artery disease. Cardiac diseases are biological complex entities which like other biological phenomena can be explained by a systems biology approach. The above powerful biological tools of systems biology can explain robustness growth and stability during disease process from modulation to phenotype. The purpose of the present review paper is to implement systems biology strategy and incorporate some conceptual issues raised by this approach into the clinical field of complex cardiac diseases. Cardiac disease process and progression can be addressed by the holistic realistic approach of systems biology in order to define in better terms earlier diagnosis and more effective therapy.

  18. Conceptual Foundations of Systems Biology Explaining Complex Cardiac Diseases

    Directory of Open Access Journals (Sweden)

    George E. Louridas

    2017-02-01

    Full Text Available Systems biology is an important concept that connects molecular biology and genomics with computing science, mathematics and engineering. An endeavor is made in this paper to associate basic conceptual ideas of systems biology with clinical medicine. Complex cardiac diseases are clinical phenotypes generated by integration of genetic, molecular and environmental factors. Basic concepts of systems biology like network construction, modular thinking, biological constraints (downward biological direction and emergence (upward biological direction could be applied to clinical medicine. Especially, in the field of cardiology, these concepts can be used to explain complex clinical cardiac phenotypes like chronic heart failure and coronary artery disease. Cardiac diseases are biological complex entities which like other biological phenomena can be explained by a systems biology approach. The above powerful biological tools of systems biology can explain robustness growth and stability during disease process from modulation to phenotype. The purpose of the present review paper is to implement systems biology strategy and incorporate some conceptual issues raised by this approach into the clinical field of complex cardiac diseases. Cardiac disease process and progression can be addressed by the holistic realistic approach of systems biology in order to define in better terms earlier diagnosis and more effective therapy.

  19. Conceptual Foundations of Systems Biology Explaining Complex Cardiac Diseases

    Science.gov (United States)

    Louridas, George E.; Lourida, Katerina G.

    2017-01-01

    Systems biology is an important concept that connects molecular biology and genomics with computing science, mathematics and engineering. An endeavor is made in this paper to associate basic conceptual ideas of systems biology with clinical medicine. Complex cardiac diseases are clinical phenotypes generated by integration of genetic, molecular and environmental factors. Basic concepts of systems biology like network construction, modular thinking, biological constraints (downward biological direction) and emergence (upward biological direction) could be applied to clinical medicine. Especially, in the field of cardiology, these concepts can be used to explain complex clinical cardiac phenotypes like chronic heart failure and coronary artery disease. Cardiac diseases are biological complex entities which like other biological phenomena can be explained by a systems biology approach. The above powerful biological tools of systems biology can explain robustness growth and stability during disease process from modulation to phenotype. The purpose of the present review paper is to implement systems biology strategy and incorporate some conceptual issues raised by this approach into the clinical field of complex cardiac diseases. Cardiac disease process and progression can be addressed by the holistic realistic approach of systems biology in order to define in better terms earlier diagnosis and more effective therapy. PMID:28230815

  20. Advances in the genetically-complex autoinflammatory diseases

    Science.gov (United States)

    Ombrello, Michael J.

    2015-01-01

    Monogenic diseases usually demonstrate Mendelian inheritance and are caused by highly penetrant genetic variants of a single gene. In contrast, genetically-complex diseases arise from a combination of multiple genetic and environmental factors. The concept of autoinflammation originally emerged from the identification of individual, activating lesions of the innate immune system as the molecular basis of the hereditary periodic fever syndromes. In addition to these rare, monogenic forms of autoinflammation, genetically-complex autoinflammatory diseases like the periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome, chronic recurrent multifocal osteomyelitis (CRMO), Behçet’s disease, and systemic arthritis also fulfill the definition of autoinflammatory diseases - namely the development of apparently unprovoked episodes of inflammation without identifiable exogenous triggers and in the absence of autoimmunity. Interestingly, investigations of these genetically-complex autoinflammatory diseases have implicated both innate and adaptive immune abnormalities, blurring the line between autoinflammation and autoimmunity. This reinforces the paradigm of concerted innate and adaptive immune dysfunction leading to genetically-complex autoinflammatory phenotypes. PMID:26077134

  1. Infection Sources of a Common Non-tuberculous Mycobacterial Pathogen, Mycobacterium avium Complex

    Science.gov (United States)

    Nishiuchi, Yukiko; Iwamoto, Tomotada; Maruyama, Fumito

    2017-01-01

    Numerous studies have revealed a continuous increase in the worldwide incidence and prevalence of non-tuberculous mycobacteria (NTM) diseases, especially pulmonary Mycobacterium avium complex (MAC) diseases. Although it is not clear why NTM diseases have been increasing, one possibility is an increase of mycobacterial infection sources in the environment. Thus, in this review, we focused on the infection sources of pathogenic NTM, especially MAC. The environmental niches for MAC include water, soil, and dust. The formation of aerosols containing NTM arising from shower water, soil, and pool water implies that these niches can be infection sources. Furthermore, genotyping has shown that clinical isolates are identical to environmental ones from household tap water, bathrooms, potting soil, and garden soil. Therefore, to prevent and treat MAC diseases, it is essential to identify the infection sources for these organisms, because patients with these diseases often suffer from reinfections and recurrent infections with them. In the environmental sources, MAC and other NTM organisms can form biofilms, survive within amoebae, and exist in a free-living state. Mycobacterial communities are also likely to occur in these infection sources in households. Water distribution systems are a transmission route from natural water reservoirs to household tap water. Other infection sources include areas with frequent human contact, such as soil and bathrooms, indicating that individuals may carry NTM organisms that concomitantly attach to their household belongings. To explore the mechanisms associated with the global spread of infection and MAC transmission routes, an epidemiological population-wide genotyping survey would be very useful. A good example of the power of genotyping comes from M. avium subsp. hominissuis, where close genetic relatedness was found between isolates of it from European patients and pigs in Japan and Europe, implying global transmission of this bacterium

  2. Imaging of complex basin structures with the common reflection surface (CRS) stack method

    Science.gov (United States)

    Menyoli, Elive; Gajewski, Dirk; Hübscher, Christian

    2004-06-01

    Common reflection surface (CRS) stack technology is applied to seismic data from certain areas of the Donbas Foldbelt, Ukraine, after conventional seismic methods gave unsatisfactory results. On the conventionally processed post-stack migrated section the areas of interest already showed clear features of the basin structure, but reflector continuity and image quality were poor. It was our objective to improve the image quality in these areas to better support the geological interpretation and the model building. In contrast to the standard common mid-point (CMP) stack, in which a stacking trajectory is used, the CRS method transforms pre-processed multicoverage data into a zero-offset section by summing along stacking surfaces. The stacking operator is an approximation of the reflection response of a curved interface in an inhomogeneous medium. The primary advantage of the data-driven CRS stack method is its model independence and the enhancement of the signal-to-noise ratio of the stacked sections through a stacking reflection response along traces from more than one CMP gather. The presented results show that the multifold strength of the CRS stack is of particular advantage in the case of complex inverted features of Devonian-Carboniferous sediments in the Donbas Foldbelt data. We observe that in these areas where the confidence level for picking and interpretation of the stacking velocity model is low, imaging without a macrovelocity model gives improved results, because errors due to wrong or poor stacking velocity models are avoided.

  3. Locomotor activity in common spiny mice (Acomys cahirinuse: The effect of light and environmental complexity

    Directory of Open Access Journals (Sweden)

    Eilam David

    2004-11-01

    Full Text Available Abstract Background Rodents typically avoid illuminated and open areas, favoring dark or sheltered environments for activity. While previous studies focused on the effect of these environmental attributes on the level of activity, the present study tested whether the spatio-temporal structure of activity was also modified in illuminated compared with dark and complex compared with open arenas. For this, we tested common spiny mice (Acomys cahirinus in empty or stone-containing arenas with lights on or lights off. Results In an illuminated or open arena, spiny mice moved in less frequent but longer trips with relatively long distances between consecutive stops. In contrast, in either a dark arena or an arena with stones, the animals took shorter and more frequent trips, with more stops per trip and shorter inter-stop distances. In illuminated arenas spiny mice remained mainly along the walls, whereas locomotion in the center was more prevalent in dark empty arenas, and was carried out along convoluted paths. Increasing environmental complexity by adding stones to either illuminated or dark arenas increased locomotion along straight trajectories and away from walls. Conclusions Earlier findings of reduced activity in illuminated or open areas have been extended in the present study by demonstrating changes in the spatio-temporal structure of locomotor behavior. In the more complex arenas (with stones spiny mice traveled along short straight segments whereas in the open their trips were longer and took the shape of a zigzag path which is more effective against fast or nearby predators. Alternatively, the zigzag path may reflect a difficulty in navigation.

  4. Genetic evidence for common pathways in human age-related diseases.

    Science.gov (United States)

    Johnson, Simon C; Dong, Xiao; Vijg, Jan; Suh, Yousin

    2015-10-01

    Aging is the single largest risk factor for chronic disease. Studies in model organisms have identified conserved pathways that modulate aging rate and the onset and progression of multiple age-related diseases, suggesting that common pathways of aging may influence age-related diseases in humans as well. To determine whether there is genetic evidence supporting the notion of common pathways underlying age-related diseases, we analyzed the genes and pathways found to be associated with five major categories of age-related disease using a total of 410 genomewide association studies (GWAS). While only a small number of genes are shared among all five disease categories, those found in at least three of the five major age-related disease categories are highly enriched for apoliprotein metabolism genes. We found that a more substantial number of gene ontology (GO) terms are shared among the 5 age-related disease categories and shared GO terms include canonical aging pathways identified in model organisms, such as nutrient-sensing signaling, translation, proteostasis, stress responses, and genome maintenance. Taking advantage of the vast amount of genetic data from the GWAS, our findings provide the first direct evidence that conserved pathways of aging simultaneously influence multiple age-related diseases in humans as has been demonstrated in model organisms. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  5. Role of the Retromer Complex in Neurodegenerative Diseases.

    Science.gov (United States)

    Li, Chaosi; Shah, Syed Zahid Ali; Zhao, Deming; Yang, Lifeng

    2016-01-01

    The retromer complex is a protein complex that plays a central role in endosomal trafficking. Retromer dysfunction has been linked to a growing number of neurological disorders. The process of intracellular trafficking and recycling is crucial for maintaining normal intracellular homeostasis, which is partly achieved through the activity of the retromer complex. The retromer complex plays a primary role in sorting endosomal cargo back to the cell surface for reuse, to the trans-Golgi network (TGN), or alternatively to specialized endomembrane compartments, in which the cargo is not subjected to lysosomal-mediated degradation. In most cases, the retromer acts as a core that interacts with associated proteins, including sorting nexin family member 27 (SNX27), members of the vacuolar protein sorting 10 (VPS10) receptor family, the major endosomal actin polymerization-promoting complex known as Wiskott-Aldrich syndrome protein and scar homolog (WASH), and other proteins. Some of the molecules carried by the retromer complex are risk factors for neurodegenerative diseases. Defects such as haplo-insufficiency or mutations in one or several units of the retromer complex lead to various pathologies. Here, we summarize the molecular architecture of the retromer complex and the roles of this system in intracellular trafficking related the pathogenesis of neurodegenerative diseases.

  6. Synergisms between microbial pathogens in plant disease complexes: a growing trend

    Directory of Open Access Journals (Sweden)

    Jay Ram eLamichhane

    2015-05-01

    Full Text Available Plant diseases are often thought to be caused by one species or even by a specific strain. Microbes in nature however mostly occur as part of complex communities and this has been noted since the time of van Leeuwenhoek. Interestingly, most laboratory studies focus on single microbial strains grown in pure culture; we were therefore unaware of possible interspecies and/or inter-kingdom interactions of pathogenic microbes in the wild. In human and animal infections, it is now being recognized that many diseases are the result of multispecies synergistic interactions. This increases the complexity of the disease and has to be taken into consideration in the development of more effective control measures. On the other hand, there are only a few reports of synergistic pathogen-pathogen interactions in plant diseases and the mechanisms of interactions are currently unknown. Here we review some of these reports of synergism between different plant pathogens and their possible implications in crop health. Finally, we briefly highlight the recent technological advances in diagnostics as these are beginning to provide important insights into the microbial communities associated with complex plant diseases. These examples of synergistic interactions of plant pathogens that lead to disease complexes might prove to be more common than expected and understanding the underlying mechanisms might have important implications in plant disease epidemiology and management.

  7. Review: quantifying mitochondrial dysfunction in complex diseases of aging.

    Science.gov (United States)

    Horan, Martin P; Pichaud, Nicolas; Ballard, J William O

    2012-10-01

    There is accumulating evidence that mitochondrial respiratory malfunction is associated with aging-associated complex diseases. However, progress in our understanding of these diseases has been hampered by the sensitivity and throughput of systems employed to quantify dysfunction and inherent limitations of the biological systems studied. In this review, we describe and contrast two methodologies that have been developed for measuring mitochondrial function to address the need for improved sensitivity and increased throughput. We then consider the utility of each methodology in studying three biological systems: isolated mitochondria, cultured cells, and cell fibers and tissues. Finally, we discuss the application of each methodology in the study of mitochondrial dysfunction in Alzheimer's disease, type 2 diabetes mellitus, and aging-associated autophagy impairment and mitochondrial malfunction. We conclude that the methodologies are complementary, and researchers may need to examine multiple biological systems to unravel complex diseases of aging.

  8. Coupled disease-behavior dynamics on complex networks: A review

    Science.gov (United States)

    Wang, Zhen; Andrews, Michael A.; Wu, Zhi-Xi; Wang, Lin; Bauch, Chris T.

    2015-12-01

    It is increasingly recognized that a key component of successful infection control efforts is understanding the complex, two-way interaction between disease dynamics and human behavioral and social dynamics. Human behavior such as contact precautions and social distancing clearly influence disease prevalence, but disease prevalence can in turn alter human behavior, forming a coupled, nonlinear system. Moreover, in many cases, the spatial structure of the population cannot be ignored, such that social and behavioral processes and/or transmission of infection must be represented with complex networks. Research on studying coupled disease-behavior dynamics in complex networks in particular is growing rapidly, and frequently makes use of analysis methods and concepts from statistical physics. Here, we review some of the growing literature in this area. We contrast network-based approaches to homogeneous-mixing approaches, point out how their predictions differ, and describe the rich and often surprising behavior of disease-behavior dynamics on complex networks, and compare them to processes in statistical physics. We discuss how these models can capture the dynamics that characterize many real-world scenarios, thereby suggesting ways that policy makers can better design effective prevention strategies. We also describe the growing sources of digital data that are facilitating research in this area. Finally, we suggest pitfalls which might be faced by researchers in the field, and we suggest several ways in which the field could move forward in the coming years.

  9. Statistical Colocalization of Genetic Risk Variants for Related Autoimmune Diseases in the Context of Common Controls

    Science.gov (United States)

    Fortune, Mary D.; Guo, Hui; Burren, Oliver; Schofield, Ellen; Walker, Neil M.; Ban, Maria; Sawcer, Stephen J.; Bowes, John; Worthington, Jane; Barton, Ann; Eyre, Steve; Todd, John A.; Wallace, Chris

    2015-01-01

    Identifying whether potential causal variants for related diseases are shared can identify overlapping etiologies of multifactorial disorders. Colocalization methods disentangle shared and distinct causal variants. However, existing approaches require independent datasets. Here we extend two colocalization methods to allow for the shared control design commonly used in comparison of genome-wide association study results across diseases. Our analysis of four autoimmune diseases, type 1 diabetes (T1D), rheumatoid arthritis, celiac disease and multiple sclerosis, revealed 90 regions that were associated with at least one disease, 33 (37%) of which with two or more disorders. Nevertheless, for 14 of these 33 shared regions there was evidence that causal variants differed. We identified novel disease associations in 11 regions previously associated with one or more of the other three disorders. Four of eight T1D-specific regions contained known type 2 diabetes candidate genes: COBL, GLIS3, RNLS and BCAR1, suggesting a shared cellular etiology. PMID:26053495

  10. Rice Sheath Rot: An Emerging Ubiquitous Destructive Disease Complex

    OpenAIRE

    Vincent de Paul Bigirimana; Khuong Hoang Gia Hua; Obedi Ishibwela Nyamangyoku; Monica eHöfte

    2015-01-01

    Around one century ago, a rice disease characterized mainly by rotting of sheaths was reported in Taiwan. The causal agent was identified as Acrocylindrium oryzae, later known as Sarocladium oryzae. Since then it has become clear that various other organisms can cause similar disease symptoms, including Fusarium spp. and fluorescent pseudomonads. These organisms have in common that they produce a range of phytotoxins that induce necrosis in plants. The same agents also cause grain discolorati...

  11. The suggestion of common cause of disease, characteristics of human body, and medical treatment

    Directory of Open Access Journals (Sweden)

    Byung-Jun Cho

    2011-06-01

    Full Text Available Objectives & Methods: This suggestion was attempted to be elevated the recognition of common characteristics in disease. So, we performed to analyze the correlation of common cause of disease, characteristics of human body, and medical treatment. And the results are as follows. Results: 1. The cause of disease is consist of genetic factor, aging, habit, food of not good in health, weather, environment, deficit of the physical activity, stress and so on. 2. Generally, human has common and individual weakness. Individual weakness is appeared similar to the occurrence of volcano and lapse. 3. The correlation of disease and medical treatments is possible to explain using the quotation of the law of motion made by Isaac Newton, the great physicist. 4. When the process of the medical treatment was not progressed, the prognosis is determined by the correlation of the homeostasis(H' in human body and the homeostasis(H of disease. 5. The prognosis of disease is determined by the relationship between the energy of disease(F and medical treatment(F'. 6. The exact diagnosis is possible to predict the treatment sequence, and the facts that homeostasis in human body and disease, relationship between the energy of disease(F and medical treatment(F', action and reaction are important to determine the prognosis. 7. The careful observation of improving response and worsening action of disease becomes available for exact prognosis. Conclusion: The above described contents may be useful in clinical studies, and the concrete clinical reports about this will be made afterward.

  12. Complex disease and phenotype mapping in the domestic dog

    OpenAIRE

    2016-01-01

    The domestic dog is becoming an increasingly valuable model species in medical genetics, showing particular promise to advance our understanding of cancer and orthopaedic disease. Here we undertake the largest canine genome-wide association study to date, with a panel of over 4,200 dogs genotyped at 180,000 markers, to accelerate mapping efforts. For complex diseases, we identify loci significantly associated with hip dysplasia, elbow dysplasia, idiopathic epilepsy, lymphoma, mast cell tumour...

  13. Headache and attention deficit and hyperactivity disorder in children: common condition with complex relation and disabling consequences.

    Science.gov (United States)

    Parisi, Pasquale; Verrotti, Alberto; Paolino, Maria Chiara; Ferretti, Alessandro; Raucci, Umberto; Moavero, Romina; Villa, Maria Pia; Curatolo, Paolo

    2014-03-01

    The aim of this review was to analyze literature data on the complex association between headache and attention deficit and hyperactivity disorder (ADHD) in children, in order to explore its possible consequences on child neurological development. Headache and ADHD are two common conditions in the pediatric population. They both are disabling diseases that impact the child's quality of life and are associated with severe cognitive, emotional, and behavioral impairments. To assess and analyze literature data about the association of ADHD and headache in children and possible physiopathogenesis relationships, we searched for the following terms: headache, migraine, tension-type headache, ADHD, and children (MESH or text words). We found different studies that assess the clinical, epidemiological, and physiopathogenetic overlap between these two diseases, with contrasting results and unresolved questions. Structural and functional abnormalities in brain networks have been found to be central in both headache and ADHD pathophysiology. It will be crucial to gain a better understanding of how subcortical-cortical and corticocortical network development is altered during the onset of the disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Increased Transcript Complexity in Genes Associated with Chronic Obstructive Pulmonary Disease

    Science.gov (United States)

    Lackey, Lela; McArthur, Evonne; Laederach, Alain

    2015-01-01

    Genome-wide association studies aim to correlate genotype with phenotype. Many common diseases including Type II diabetes, Alzheimer’s, Parkinson’s and Chronic Obstructive Pulmonary Disease (COPD) are complex genetic traits with hundreds of different loci that are associated with varied disease risk. Identifying common features in the genes associated with each disease remains a challenge. Furthermore, the role of post-transcriptional regulation, and in particular alternative splicing, is still poorly understood in most multigenic diseases. We therefore compiled comprehensive lists of genes associated with Type II diabetes, Alzheimer’s, Parkinson’s and COPD in an attempt to identify common features of their corresponding mRNA transcripts within each gene set. The SERPINA1 gene is a well-recognized genetic risk factor of COPD and it produces 11 transcript variants, which is exceptional for a human gene. This led us to hypothesize that other genes associated with COPD, and complex disorders in general, are highly transcriptionally diverse. We found that COPD-associated genes have a statistically significant enrichment in transcript complexity stemming from a disproportionately high level of alternative splicing, however, Type II Diabetes, Alzheimer’s and Parkinson’s disease genes were not significantly enriched. We also identified a subset of transcriptionally complex COPD-associated genes (~40%) that are differentially expressed between mild, moderate and severe COPD. Although the genes associated with other lung diseases are not extensively documented, we found preliminary data that idiopathic pulmonary disease genes, but not cystic fibrosis modulators, are also more transcriptionally complex. Interestingly, complex COPD transcripts are more often the product of alternative acceptor site usage. To verify the biological importance of these alternative transcripts, we used RNA-sequencing analyses to determine that COPD-associated genes are frequently

  15. Synaptic Dysfunction in Alzheimer’s Disease and Glaucoma: From Common Degenerative Mechanisms Toward Neuroprotection

    Science.gov (United States)

    Criscuolo, Chiara; Fabiani, Carlotta; Cerri, Elisa; Domenici, Luciano

    2017-01-01

    Alzheimer’s disease (AD) and glaucoma are two distinct multifactorial neurodegenerative diseases, primarily affecting the elderly. Common pathophysiological mechanisms have been elucidated in the past decades. First of all both diseases are progressive, with AD leading to dementia and glaucoma inducing blindness. Pathologically, they all feature synaptic dysfunction with changes of neuronal circuitry, progressive accumulation of protein aggregates such as the beta amyloid (Aβ) and intracellular microtubule inclusions containing hyperphosphorylated tau, which belongs to microtubule associated protein family. During an early phase of degeneration, both diseases are characterized by synaptic dysfunction and changes of mitogen-activated protein kinases (MAPK). Common degenerative mechanisms underlying both diseases are discussed here, along with recent results on the potential use of the visual system as a biomarker for diagnosis and progression of AD. Common neuropathological changes and mechanisms in AD and glaucoma have facilitated the transfer of therapeutic strategies between diseases. In particular, we discuss past and present evidence for neuroprotective effects of brain-derived neurotrophic factor (BDNF).

  16. How genetics research in Parkinson's disease is enhancing understanding of the common idiopathic forms of the disease.

    Science.gov (United States)

    Cookson, Mark R; Xiromerisiou, Georgia; Singleton, Andrew

    2005-12-01

    Rapid progress in genetics has meant that there are now five genes identified for 'Parkinson's disease'. The detailed phenotypes vary, but generally the dominant genes cause a Lewy body disease spectrum whereas recessive genes cause a milder parkinsonism with variable inclusion body pathology. The subject of this review is to highlight these discoveries and to discuss their relationships to idiopathic Parkinson's disease. In January 2004, mutations in PINK1, coding for a mitochondrial kinase, were found to be causal for recessive parkinsonism. Subsequently, several studies have found additional mutations associated with early onset parkinsonism. Some cases have been described with a phenotype much closer to idiopathic Parkinson's disease, but it does not appear that PINK1 is a major risk factor for the sporadic disease. Later in the same year, the LRRK2 gene was shown to cause a dominant disease with a broader phenotype. The protein product was named dardarin and contains GTPase and kinase domains. Lewy bodies have been reported in LRRK2 cases, potentially linking this gene with sporadic Parkinson's disease. One mutation, G2019S, is found in a significant percentage of cases, including sporadic Parkinson's disease. Mutations in these two genes, along with previously described Mendelian variants, are beginning to yield important information about loss of specific neuronal groups or to protein inclusion pathology. How this relates to sporadic Parkinson's disease, however, is not yet fully defined. There are clear phenotypic overlaps with genetic and sporadic Parkinson's disease, especially for the dominant genes, suggesting that common facets of pathogenesis may exist.

  17. Common prognostic factors of work disability among employees with a chronic somatic disease: a systematic review of cohort studies.

    NARCIS (Netherlands)

    Detaille, S.I.; Heerkens, Y.F.; Engels, J.A.; Gulden, J.W.J. van der; Dijk, F.J. van

    2009-01-01

    OBJECTIVE: Based on prospective and retrospective disease cohort studies, the aim of this review was to determine common prognostic factors for work disability among employees with rheumatoid arthritis, asthma, chronic obstructive pulmonary disease, diabetes mellitus, and ischemic heart disease (IHD

  18. Common prognostic factors of work disability among employees with a chronic somatic disease: a systematic review of cohort studies

    NARCIS (Netherlands)

    S.I. Detaille; Y.F. Heerkens; J.A. Engels; J.W.J. van der Gulden; F.J.H. van Dijk

    2009-01-01

    Objective Based on prospective and retrospective disease cohort studies, the aim of this review was to determine common prognostic factors for work disability among employees with rheumatoid arthritis, asthma, chronic obstructive pulmonary disease, diabetes mellitus, and ischemic heart disease (IHD)

  19. Common prognostic factors of work disability among employees with a chronic somatic disease: a systematic review of cohort studies.

    NARCIS (Netherlands)

    Detaille, S.I.; Heerkens, Y.F.; Engels, J.A.; Gulden, J.W.J. van der; Dijk, F.J. van

    2009-01-01

    OBJECTIVE: Based on prospective and retrospective disease cohort studies, the aim of this review was to determine common prognostic factors for work disability among employees with rheumatoid arthritis, asthma, chronic obstructive pulmonary disease, diabetes mellitus, and ischemic heart disease

  20. Toxic and nontoxic components of botulinum neurotoxin complex are evolved from a common ancestral zinc protein

    Energy Technology Data Exchange (ETDEWEB)

    Inui, Ken [Department of Food and Cosmetic Science, Faculty of Bioindustry, Tokyo University of Agriculture, 196 Yasaka, Abashiri 099-2493 (Japan); Japan Society for the Promotion of Science, 1-8 Chiyoda-ku, Tokyo 102-8472 (Japan); Sagane, Yoshimasa [Department of Food and Cosmetic Science, Faculty of Bioindustry, Tokyo University of Agriculture, 196 Yasaka, Abashiri 099-2493 (Japan); Miyata, Keita [Department of Food and Cosmetic Science, Faculty of Bioindustry, Tokyo University of Agriculture, 196 Yasaka, Abashiri 099-2493 (Japan); Japan Society for the Promotion of Science, 1-8 Chiyoda-ku, Tokyo 102-8472 (Japan); Miyashita, Shin-Ichiro [Department of Food and Cosmetic Science, Faculty of Bioindustry, Tokyo University of Agriculture, 196 Yasaka, Abashiri 099-2493 (Japan); Suzuki, Tomonori [Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 (Japan); Shikamori, Yasuyuki [Agilent Technologies International Japan, Ltd. Takaura-cho 9-1, Hachioji-shi, Tokyo 192-0033 (Japan); Ohyama, Tohru; Niwa, Koichi [Department of Food and Cosmetic Science, Faculty of Bioindustry, Tokyo University of Agriculture, 196 Yasaka, Abashiri 099-2493 (Japan); Watanabe, Toshihiro, E-mail: t-watana@bioindustry.nodai.ac.jp [Department of Food and Cosmetic Science, Faculty of Bioindustry, Tokyo University of Agriculture, 196 Yasaka, Abashiri 099-2493 (Japan)

    2012-03-16

    Highlights: Black-Right-Pointing-Pointer BoNT and NTNHA proteins share a similar protein architecture. Black-Right-Pointing-Pointer NTNHA and BoNT were both identified as zinc-binding proteins. Black-Right-Pointing-Pointer NTNHA does not have a classical HEXXH zinc-coordinating motif similar to that found in all serotypes of BoNT. Black-Right-Pointing-Pointer Homology modeling implied probable key residues involved in zinc coordination. -- Abstract: Zinc atoms play an essential role in a number of enzymes. Botulinum neurotoxin (BoNT), the most potent toxin known in nature, is a zinc-dependent endopeptidase. Here we identify the nontoxic nonhemagglutinin (NTNHA), one of the BoNT-complex constituents, as a zinc-binding protein, along with BoNT. A protein structure classification database search indicated that BoNT and NTNHA share a similar domain architecture, comprising a zinc-dependent metalloproteinase-like, BoNT coiled-coil motif and concanavalin A-like domains. Inductively coupled plasma-mass spectrometry analysis demonstrated that every single NTNHA molecule contains a single zinc atom. This is the first demonstration of a zinc atom in this protein, as far as we know. However, the NTNHA molecule does not possess any known zinc-coordinating motif, whereas all BoNT serotypes possess the classical HEXXH motif. Homology modeling of the NTNHA structure implied that a consensus K-C-L-I-K-X{sub 35}-D sequence common among all NTNHA serotype molecules appears to coordinate a single zinc atom. These findings lead us to propose that NTNHA and BoNT may have evolved distinct functional specializations following their branching out from a common ancestral zinc protein.

  1. TOPIC DECONGESTANTS IN COMPLEX THERAPY OF UPPER AIRWAYS DISEASES

    Directory of Open Access Journals (Sweden)

    G.D. Tarasova

    2006-01-01

    Full Text Available In the complex treatment of the inflammatory diseases of ENT-organs (rhinitis, sinusitis, tubootitis and otitis media vasoconstrictors (topic decongestants are locally applied. Besides, they're used in diagnosing of nasal cavity diseases. Topic decongestants are produced as nasal drops and nasal sprays. Peculiarities of application of pharmaceuticals in children are dependent on inherent properties, particularly the duration of effect. These drugs each have proper dosage conditions that should be followed carefully in pediatric practice. Moreover, the physician must choose the efficient way of vasoconstrictor introduction into nasal cavity.Key words: edema, topic decongestants, ENT-organs diseases, rebound syndrome, children.

  2. Pathway-based analysis tools for complex diseases: a review.

    Science.gov (United States)

    Jin, Lv; Zuo, Xiao-Yu; Su, Wei-Yang; Zhao, Xiao-Lei; Yuan, Man-Qiong; Han, Li-Zhen; Zhao, Xiang; Chen, Ye-Da; Rao, Shao-Qi

    2014-10-01

    Genetic studies are traditionally based on single-gene analysis. The use of these analyses can pose tremendous challenges for elucidating complicated genetic interplays involved in complex human diseases. Modern pathway-based analysis provides a technique, which allows a comprehensive understanding of the molecular mechanisms underlying complex diseases. Extensive studies utilizing the methods and applications for pathway-based analysis have significantly advanced our capacity to explore large-scale omics data, which has rapidly accumulated in biomedical fields. This article is a comprehensive review of the pathway-based analysis methods-the powerful methods with the potential to uncover the biological depths of the complex diseases. The general concepts and procedures for the pathway-based analysis methods are introduced and then, a comprehensive review of the major approaches for this analysis is presented. In addition, a list of available pathway-based analysis software and databases is provided. Finally, future directions and challenges for the methodological development and applications of pathway-based analysis techniques are discussed. This review will provide a useful guide to dissect complex diseases.

  3. Episode resembling immune complex disease after cholera vaccination

    OpenAIRE

    Mall, Thomas; Gyr, Klaus

    2017-01-01

    The case of a 25-year-old patient is reported who suffered from a syndrome similar to immune complex disease following cholera revaccination. The clinical picture included fever, muscle, joint and abdominal pain, vomiting, serositis, hepatitis, suspected myocarditis, anaemia and thrombocytopenia. Clinical symptoms subsided spontaneously within two weeks. This case illustrates a hazard of cholera vaccination so far not reported in the literature

  4. Genetic variability for tuber yield, quality, and virus disease complex ...

    African Journals Online (AJOL)

    Genetic variability for tuber yield, quality, and virus disease complex traits in Uganda ... Silk and Sowola which showed high flowering ability failed to fertilise and set ... Up to five genes may be involved in â-carotene synthesis and probably in ...

  5. Complex social contagion makes networks more vulnerable to disease outbreaks

    CERN Document Server

    Campbell, Ellsworth

    2012-01-01

    Social network analysis is now widely used to investigate the dynamics of infectious disease spread from person to person. Vaccination dramatically disrupts the disease transmission process on a contact network, and indeed, sufficiently high vaccination rates can disrupt the process to such an extent that disease transmission on the network is effectively halted. Here, we build on mounting evidence that health behaviors - such as vaccination, and refusal thereof - can spread through social networks through a process of complex contagion that requires social reinforcement. Using network simulations that model both the health behavior and the infectious disease spread, we find that under otherwise identical conditions, the process by which the health behavior spreads has a very strong effect on disease outbreak dynamics. This variability in dynamics results from differences in the topology within susceptible communities that arise during the health behavior spreading process, which in turn depends on the topolo...

  6. Human copy number variation and complex genetic disease.

    Science.gov (United States)

    Girirajan, Santhosh; Campbell, Catarina D; Eichler, Evan E

    2011-01-01

    Copy number variants (CNVs) play an important role in human disease and population diversity. Advancements in technology have allowed for the analysis of CNVs in thousands of individuals with disease in addition to thousands of controls. These studies have identified rare CNVs associated with neuropsychiatric diseases such as autism, schizophrenia, and intellectual disability. In addition, copy number polymorphisms (CNPs) are present at higher frequencies in the population, show high diversity in copy number, sequence, and structure, and have been associated with multiple phenotypes, primarily related to immune or environmental response. However, the landscape of copy number variation still remains largely unexplored, especially for smaller CNVs and those embedded within complex regions of the human genome. An integrated approach including characterization of single nucleotide variants and CNVs in a large number of individuals with disease and normal genomes holds the promise of thoroughly elucidating the genetic basis of human disease and diversity.

  7. Areca nut chewing and systemic inflammation : evidence of a common pathway for systemic diseases

    NARCIS (Netherlands)

    Shafique, Kashif; Mirza, Saira Saeed; Vart, Priya; Memon, Abdul Rauf; Arain, Moin Islam; Tareen, Muhammad Farooq; Haq, Zia Ul

    2012-01-01

    Background: Areca nut, the seed of fruit of an oriental palm, known as Areca catechu, is commonly chewed in many countries. Diabetes, hypertension, cardiovascular diseases, oropharyngeal and oesophageal cancers have been associated with areca nut chewing and the mechanism by which areca nut chewing

  8. Areca nut chewing and systemic inflammation : evidence of a common pathway for systemic diseases

    NARCIS (Netherlands)

    Shafique, Kashif; Mirza, Saira Saeed; Vart, Priya; Memon, Abdul Rauf; Arain, Moin Islam; Tareen, Muhammad Farooq; Haq, Zia Ul

    2012-01-01

    Background: Areca nut, the seed of fruit of an oriental palm, known as Areca catechu, is commonly chewed in many countries. Diabetes, hypertension, cardiovascular diseases, oropharyngeal and oesophageal cancers have been associated with areca nut chewing and the mechanism by which areca nut chewing

  9. NOD2/CARD15 genotype and common gastrointestinal diseases in 43 600 individuals

    DEFF Research Database (Denmark)

    Yazdanyar, S.; Nordestgaard, B.G.

    2010-01-01

    associate with risk of nine common gastrointestinal diseases. Design and setting. We genotyped 43 596 white individuals from the Danish general population followed for 31 years, during which time 782 developed oesophagitis and reflux, 1395 ulcus ventriculi and duodeni, 1384 gastritis and dyspepsia, 1407...

  10. Spaces of genomics : exploring the innovation journey of genomics in research on common disease

    NARCIS (Netherlands)

    Bitsch, L.

    2013-01-01

    Genomics was introduced with big promises and expectations of its future contribution to our society. Medical genomics was introduced as that which would lay the foundation for a revolution in our management of common diseases. Genomics would lead the way towards a future of personalised medicine.

  11. Common variants associated with plasma triglycerides and risk for coronary artery disease

    NARCIS (Netherlands)

    Do, Ron; Willer, Cristen J; Schmidt, Ellen M; Sengupta, Sebanti; Gao, Chi; Peloso, Gina M; Gustafsson, Stefan; Kanoni, Stavroula; Ganna, Andrea; Chen, Jin; Buchkovich, Martin L; Mora, Samia; Beckmann, Jacques S; Bragg-Gresham, Jennifer L; Chang, Hsing-Yi; Demirkan, Ayşe; Den Hertog, Heleen M; Donnelly, Louise A; Ehret, Georg B; Esko, Tõnu; Feitosa, Mary F; Ferreira, Teresa; Fischer, Krista; Fontanillas, Pierre; Fraser, Ross M; Freitag, Daniel F; Gurdasani, Deepti; Heikkilä, Kauko; Hyppönen, Elina; Isaacs, Aaron; Jackson, Anne U; Johansson, Asa; Johnson, Toby; Kaakinen, Marika; Kettunen, Johannes; Kleber, Marcus E; Li, Xiaohui; Luan, Jian'an; Lyytikäinen, Leo-Pekka; Magnusson, Patrik K E; Mangino, Massimo; Mihailov, Evelin; Montasser, May E; Müller-Nurasyid, Martina; Nolte, Ilja M; O'Connell, Jeffrey R; Palmer, Cameron D; Perola, Markus; Petersen, Ann-Kristin; Sanna, Serena; Saxena, Richa; Service, Susan K; Shah, Sonia; Shungin, Dmitry; Sidore, Carlo; Song, Ci; Strawbridge, Rona J; Surakka, Ida; Tanaka, Toshiko; Teslovich, Tanya M; Thorleifsson, Gudmar; Van den Herik, Evita G; Voight, Benjamin F; Volcik, Kelly A; Waite, Lindsay L; Wong, Andrew; Wu, Ying; Zhang, Weihua; Absher, Devin; Asiki, Gershim; Barroso, Inês; Been, Latonya F; Bolton, Jennifer L; Bonnycastle, Lori L; Brambilla, Paolo; Burnett, Mary S; Cesana, Giancarlo; Dimitriou, Maria; Doney, Alex S F; Döring, Angela; Elliott, Paul; Epstein, Stephen E; Eyjolfsson, Gudmundur Ingi; Gigante, Bruna; Goodarzi, Mark O; Grallert, Harald; Gravito, Martha L; Groves, Christopher J; Hallmans, Göran; Hartikainen, Anna-Liisa; Hayward, Caroline; Hernandez, Dena; Hicks, Andrew A; Holm, Hilma; Hung, Yi-Jen; Illig, Thomas; Jones, Michelle R; Kaleebu, Pontiano; Kastelein, John J P; Khaw, Kay-Tee; Kim, Eric; Klopp, Norman; Komulainen, Pirjo; Kumari, Meena; Langenberg, Claudia; Lehtimäki, Terho; Lin, Shih-Yi; Lindström, Jaana; Loos, Ruth J F; Mach, François; McArdle, Wendy L; Meisinger, Christa; Mitchell, Braxton D; Müller, Gabrielle; Nagaraja, Ramaiah; Narisu, Narisu; Nieminen, Tuomo V M; Nsubuga, Rebecca N; Olafsson, Isleifur; Ong, Ken K; Palotie, Aarno; Papamarkou, Theodore; Pomilla, Cristina; Pouta, Anneli; Rader, Daniel J; Reilly, Muredach P; Ridker, Paul M; Rivadeneira, Fernando; Rudan, Igor; Ruokonen, Aimo; Samani, Nilesh; Scharnagl, Hubert; Seeley, Janet; Silander, Kaisa; Stančáková, Alena; Stirrups, Kathleen; Swift, Amy J; Tiret, Laurence; Uitterlinden, Andre G; van Pelt, L Joost; Vedantam, Sailaja; Wainwright, Nicholas; Wijmenga, Cisca; Wild, Sarah H; Willemsen, Gonneke; Wilsgaard, Tom; Wilson, James F; Young, Elizabeth H; Zhao, Jing Hua; Adair, Linda S; Arveiler, Dominique; Assimes, Themistocles L; Bandinelli, Stefania; Bennett, Franklyn; Bochud, Murielle; Boehm, Bernhard O; Boomsma, Dorret I; Borecki, Ingrid B; Bornstein, Stefan R; Bovet, Pascal; Burnier, Michel; Campbell, Harry; Chakravarti, Aravinda; Chambers, John C; Chen, Yii-Der Ida; Collins, Francis S; Cooper, Richard S; Danesh, John; Dedoussis, George; de Faire, Ulf; Feranil, Alan B; Ferrières, Jean; Ferrucci, Luigi; Freimer, Nelson B; Gieger, Christian; Groop, Leif C; Gudnason, Vilmundur; Gyllensten, Ulf; Hamsten, Anders; Harris, Tamara B; Hingorani, Aroon; Hirschhorn, Joel N; Hofman, Albert; Hovingh, G Kees; Hsiung, Chao Agnes; Humphries, Steve E; Hunt, Steven C; Hveem, Kristian; Iribarren, Carlos; Järvelin, Marjo-Riitta; Jula, Antti; Kähönen, Mika; Kaprio, Jaakko; Kesäniemi, Antero; Kivimaki, Mika; Kooner, Jaspal S; Koudstaal, Peter J; Krauss, Ronald M; Kuh, Diana; Kuusisto, Johanna; Kyvik, Kirsten O; Laakso, Markku; Lakka, Timo A; Lind, Lars; Lindgren, Cecilia M; Martin, Nicholas G; März, Winfried; McCarthy, Mark I; McKenzie, Colin A; Meneton, Pierre; Metspalu, Andres; Moilanen, Leena; Morris, Andrew D; Munroe, Patricia B; Njølstad, Inger; Pedersen, Nancy L; Power, Chris; Pramstaller, Peter P; Price, Jackie F; Psaty, Bruce M; Quertermous, Thomas; Rauramaa, Rainer; Saleheen, Danish; Salomaa, Veikko; Sanghera, Dharambir K; Saramies, Jouko; Schwarz, Peter E H; Sheu, Wayne H-H; Shuldiner, Alan R; Siegbahn, Agneta; Spector, Tim D; Stefansson, Kari; Strachan, David P; Tayo, Bamidele O; Tremoli, Elena; Tuomilehto, Jaakko; Uusitupa, Matti; van Duijn, Cornelia M; Vollenweider, Peter; Wallentin, Lars; Wareham, Nicholas J; Whitfield, John B; Wolffenbuttel, Bruce H R; Altshuler, David; Ordovas, Jose M; Boerwinkle, Eric; Palmer, Colin N A; Thorsteinsdottir, Unnur; Chasman, Daniel I; Rotter, Jerome I; Franks, Paul W; Ripatti, Samuli; Cupples, L Adrienne; Sandhu, Manjinder S; Rich, Stephen S; Boehnke, Michael; Deloukas, Panos; Mohlke, Karen L; Ingelsson, Erik; Abecasis, Goncalo R; Daly, Mark J; Neale, Benjamin M; Kathiresan, Sekar

    2013-01-01

    Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common va

  12. Common variants associated with plasma triglycerides and risk for coronary artery disease

    Science.gov (United States)

    Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common va...

  13. Trypsin inhibition: a potential cause of cobalamin deficiency common to the pathogenesis of Alzheimer-type dementia and AIDS dementia complex?

    Science.gov (United States)

    McCaddon, A; Regland, B; Fear, C F

    1995-08-01

    There is increasing evidence for an association between Alzheimer-type dementia (AD) and nutritionally independent cobalamin deficiency. Furthermore, low serum cobalamin values occur in a kindred with familial Alzheimer's disease (FAD) and histopathological confirmation of AD neuropathology. The Cobalamin deficiency could be either a consequence or cause of amyloidogenesis. Cobalamin deficiency is also associated with the acquired immunodeficiency syndrome (AIDS). A common pathogenic mechanism may exist for AIDS dementia complex (ADC) and AD, but there is no explanation at present for these associations. This paper presents the hypothesis that protease inhibition is a common factor in AD and ADC resulting in protein-bound cobalamin malabsorption and disrupted cobalamin metabolism.

  14. Impact of Air Pollutants on Oxidative Stress in Common Autophagy-Mediated Aging Diseases

    Directory of Open Access Journals (Sweden)

    Mohamed Saber Numan

    2015-02-01

    Full Text Available Atmospheric pollution-induced cellular oxidative stress is probably one of the pathogenic mechanisms involved in most of the common autophagy-mediated aging diseases, including neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS, Alzheimer’s, disease, as well as Paget’s disease of bone with or without frontotemporal dementia and inclusion body myopathy. Oxidative stress has serious damaging effects on the cellular contents: DNA, RNA, cellular proteins, and cellular organelles. Autophagy has a pivotal role in recycling these damaged non-functional organelles and misfolded or unfolded proteins. In this paper, we highlight, through a narrative review of the literature, that when autophagy processes are impaired during aging, in presence of cumulative air pollution-induced cellular oxidative stress and due to a direct effect on air pollutant, autophagy-mediated aging diseases may occur.

  15. Neuronal Complexity in Subthalamic Nucleus is Reduced in Parkinson's Disease.

    Science.gov (United States)

    Vyas, Saurabh; Huang, He; Gale, John T; Sarma, Sridevi V; Montgomery, Erwin B

    2016-01-01

    Several theories posit increased Subthalamic Nucleus (STN) activity is causal to Parkinsonism, yet in our previous study we showed that activity from 113 STN neurons from two epilepsy patients and 103 neurons from nine Parkinson's disease (PD) patients demonstrated no significant differences in frequencies or in the coefficients of variation of mean discharge frequencies per 1-s epochs. We continued our analysis using point process modeling to capture higher order temporal dynamics; in particular, bursting, beta-band oscillations, excitatory and inhibitory ensemble interactions, and neuronal complexity. We used this analysis as input to a logistic regression classifier and were able to differentiate between PD and epilepsy neurons with an accuracy of 92%. We also found neuronal complexity, i.e., the number of states in a neuron's point process model, and inhibitory ensemble dynamics, which can be interpreted as a reduction in complexity, to be the most important features with respect to classification accuracy. Even in a dataset with no significant differences in firing rate, we observed differences between PD and epilepsy for other single-neuron measures. Our results suggest PD comes with a reduction in neuronal "complexity," which translates to a neuron's ability to encode information; the more complexity, the more information the neuron can encode. This is also consistent with studies correlating disease to loss of variability in neuronal activity, as the lower the complexity, the less variability.

  16. Literature-Related Discovery: Common Factors for Parkinson’s Disease and Crohn’s Disease

    Science.gov (United States)

    2010-01-01

    between documents, analogous to Salton‘s cosine measure. Most relevant to the present paper are approaches that combine bibliographic coupling...prostaglandins and related analogs . Innate immunity and toll-like receptors: clinical implications of basic science research. Ways of dying: multiple...intakes. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. Effects of cocoa powder and dark chocolate on LDL oxidative

  17. Genetics and Genomics of Single-Gene Cardiovascular Diseases: Common Hereditary Cardiomyopathies as Prototypes of Single-Gene Disorders.

    Science.gov (United States)

    Marian, Ali J; van Rooij, Eva; Roberts, Robert

    2016-12-27

    This is the first of 2 review papers on genetics and genomics appearing as part of the series on "omics." Genomics pertains to all components of an organism's genes, whereas genetics involves analysis of a specific gene or genes in the context of heredity. The paper provides introductory comments, describes the basis of human genetic diversity, and addresses the phenotypic consequences of genetic variants. Rare variants with large effect sizes are responsible for single-gene disorders, whereas complex polygenic diseases are typically due to multiple genetic variants, each exerting a modest effect size. To illustrate the clinical implications of genetic variants with large effect sizes, 3 common forms of hereditary cardiomyopathies are discussed as prototypic examples of single-gene disorders, including their genetics, clinical manifestations, pathogenesis, and treatment. The genetic basis of complex traits is discussed in a separate paper. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  18. Forward-time simulations of human populations with complex diseases.

    Directory of Open Access Journals (Sweden)

    Bo Peng

    2007-03-01

    Full Text Available Due to the increasing power of personal computers, as well as the availability of flexible forward-time simulation programs like simuPOP, it is now possible to simulate the evolution of complex human diseases using a forward-time approach. This approach is potentially more powerful than the coalescent approach since it allows simulations of more than one disease susceptibility locus using almost arbitrary genetic and demographic models. However, the application of such simulations has been deterred by the lack of a suitable simulation framework. For example, it is not clear when and how to introduce disease mutants-especially those under purifying selection-to an evolving population, and how to control the disease allele frequencies at the last generation. In this paper, we introduce a forward-time simulation framework that allows us to generate large multi-generation populations with complex diseases caused by unlinked disease susceptibility loci, according to specified demographic and evolutionary properties. Unrelated individuals, small or large pedigrees can be drawn from the resulting population and provide samples for a wide range of study designs and ascertainment methods. We demonstrate our simulation framework using three examples that map genes associated with affection status, a quantitative trait, and the age of onset of a hypothetical cancer, respectively. Nonadditive fitness models, population structure, and gene-gene interactions are simulated. Case-control, sibpair, and large pedigree samples are drawn from the simulated populations and are examined by a variety of gene-mapping methods.

  19. Pathogenesis of common glomerular diseases – role of the podocyte cytoskeleton

    Directory of Open Access Journals (Sweden)

    Kumagai T

    2012-10-01

    Full Text Available Takanori Kumagai, Flaviana Mouawad, Tomoko TakanoDepartment of Medicine, McGill University Health Centre, Montreal, Quebec, CanadaAbstract: Glomerulus is the filtration unit of the kidney where the first step of urine formation takes place. In the glomerulus, water and small molecules including waste products of the body are filtered into the urine, while large molecules essential for body function such as albumin are retained. When this barrier function of the kidney is impaired, protein leakage into the urine (proteinuria occurs. Proteinuria is not only a hallmark of many glomerular diseases but also a prognostic marker of kidney disease progression. Visceral glomerular epithelial cells (commonly called podocytes are known to have an important role in the maintenance of glomerular barrier function. In the last decade, remarkable progress has been made in podocyte biology, mainly led by the discoveries of important proteins that work together to maintain the intricate morphology and function of podocytes. Most of these so-called podocyte proteins modulate the actin cytoskeleton either directly or indirectly. The aim of the current review is to discuss the pathogenesis of common glomerular diseases with a particular focus on the role of the actin cytoskeleton in podocytes. The diseases covered include minimal change disease, focal segmental glomerulosclerosis (idiopathic and hereditary, membranous nephropathy, hypertensive glomerulosclerosis, and diabetic nephropathy.Keywords: glomerular disease, podocyte, cytoskeleton, proteinuria

  20. Skin and wound issues in patients with Parkinson's disease: an overview of common disorders.

    Science.gov (United States)

    Beitz, Janice M

    2013-06-01

    Parkinson's Disease is a chronic neurodegenerative disorder that is expected to increase in coming decades as the American population continues to age. Although the motor dysfunction (bradykinesia, tremor, rigidity) of Parkinson's Disease is well described in the literature, the nonmotor dysfunction related to autonomic system changes is not as commonly addressed. Ironically, nonmotor changes, such as seborrhea, sialorrhea, hyperhidrosis, and sensory denervation occur earlier in the disease process and exert a profound effect on patients' quality of life. The depletion of dopamine, a critically important neurotransmitter, is the critical pathology of Parkinson's disease. Therapies targeting this abnormality and the effect of insufficient dopamine itself can affect the integumentary system and potentially wound healing. The purpose of this review is to describe changes in the autonomic nervous system due to Parkinson's Disease with a focused overview of common skin and wound care issues that may affect wound care clinician practice. Implications for nurses and other clinicians caring for Parkinson's Disease patients include surveillance for melanoma and other skin cancers, skin protection against excessive moisture or the effects of insufficient moisture, monitoring of wound healing progress, and interventions to prevent or ameliorate complications of immobility.

  1. A HapMap harvest of insights into the genetics of common disease.

    Science.gov (United States)

    Manolio, Teri A; Brooks, Lisa D; Collins, Francis S

    2008-05-01

    The International HapMap Project was designed to create a genome-wide database of patterns of human genetic variation, with the expectation that these patterns would be useful for genetic association studies of common diseases. This expectation has been amply fulfilled with just the initial output of genome-wide association studies, identifying nearly 100 loci for nearly 40 common diseases and traits. These associations provided new insights into pathophysiology, suggesting previously unsuspected etiologic pathways for common diseases that will be of use in identifying new therapeutic targets and developing targeted interventions based on genetically defined risk. In addition, HapMap-based discoveries have shed new light on the impact of evolutionary pressures on the human genome, suggesting multiple loci important for adapting to disease-causing pathogens and new environments. In this review we examine the origin, development, and current status of the HapMap; its prospects for continued evolution; and its current and potential future impact on biomedical science.

  2. Complex regional pain syndrome treated with intravenous immunoglobulin in a patient with common variable immune deficiency.

    Science.gov (United States)

    Tachdjian, Raffi

    2013-12-01

    Common variable immunodeficiency (CVID) represents a large heterogeneous group of antibody-deficiency syndromes associated with a wide range of clinical features and a lack of defined causes in the realm of primary immunodeficiencies. Here, we present a case of CVID in a 62-year-old white male patient with a history of longstanding complex regional pain syndrome (CRPS). His medical history included multiple sinus infections per year and several pneumonias requiring antibiotics. He has had various back surgeries, including a laminectomy at the L4 level 1 year prior to his diagnosis. Thereafter, he underwent four sympathetic nerve blocks with minimal pain relief. Blood chemistries showed a normal white blood cell count with a normal differential, but increased erythrocyte sedimentation rate and C-reactive protein levels. Total Ig (Immunoglobulin)G was 611 mg/dL (normal 700-1,600), IgG1 was 425 mg/dL (341-894), IgG2 was 114 mg/dL (171-632), IgG3 was 14.4 mg/dL (18.4-106), and IgG4 was 7.4 mg/dL (2.4-121). IgA was 47 mg/dL (normal 70-400), IgM was 131 mg/dL (40-230), and IgE was 4.5 kU/L (<4.0). He only had 10 of 23 pneumococcal titers in the protective range post-vaccination. Upon treatment of the CVID with intravenous immunoglobulin, the patient's pain levels were significantly decreased and have been maintained for more than 2 years. Therefore, immunoglobulin therapy appears to have been beneficial in the treatment of the patient's symptoms of CRPS, including pain. Additional studies investigating the mechanism by which immunoglobulin therapy may reduce the inflammation and pain of CRPS are needed.

  3. Common Alzheimer's Disease Research Ontology: National Institute on Aging and Alzheimer's Association collaborative project.

    Science.gov (United States)

    Refolo, Lorenzo M; Snyder, Heather; Liggins, Charlene; Ryan, Laurie; Silverberg, Nina; Petanceska, Suzana; Carrillo, Maria C

    2012-07-01

    Alzheimer's disease is recognized as a public health crisis worldwide. As public and private funding agencies around the world enhance and expand their support of Alzheimer's disease research, there is an urgent need to coordinate funding strategies and leverage resources to maximize the impact on public health and avoid duplication of effort and inefficiency. Such coordination requires a comprehensive assessment of the current landscape of Alzheimer's disease research in the United States and internationally. To this end, the National Institute on Aging at the National Institutes of Health and the Alzheimer's Association developed the Common Alzheimer's Disease Research Ontology (CADRO) as a dynamic portfolio analysis tool that can be used by funding agencies worldwide for strategic planning and coordination.

  4. Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases.

    Science.gov (United States)

    Bucciantini, Monica; Giannoni, Elisa; Chiti, Fabrizio; Baroni, Fabiana; Formigli, Lucia; Zurdo, Jesús; Taddei, Niccolò; Ramponi, Giampietro; Dobson, Christopher M; Stefani, Massimo

    2002-04-04

    A range of human degenerative conditions, including Alzheimer's disease, light-chain amyloidosis and the spongiform encephalopathies, is associated with the deposition in tissue of proteinaceous aggregates known as amyloid fibrils or plaques. It has been shown previously that fibrillar aggregates that are closely similar to those associated with clinical amyloidoses can be formed in vitro from proteins not connected with these diseases, including the SH3 domain from bovine phosphatidyl-inositol-3'-kinase and the amino-terminal domain of the Escherichia coli HypF protein. Here we show that species formed early in the aggregation of these non-disease-associated proteins can be inherently highly cytotoxic. This finding provides added evidence that avoidance of protein aggregation is crucial for the preservation of biological function and suggests common features in the origins of this family of protein deposition diseases.

  5. Modeling the hospital burden of common infectious diseases with application to northeastern Thailand.

    Science.gov (United States)

    Ardkaew, Jurairat; Tongkumchum, Phattrawan

    2011-09-01

    This study aims to identify the incidence patterns of the most common infectious diseases, including acute diarrhea, pyrexia of unknown origin, hemorrhagic conjunctivitis, and pneumonia, in the 7 provinces of northeastern Thailand, based on individual hospital case records of infectious disease routinely reported from 1999 to 2004. Log-linear regression analysis with age-group, season, and district as factors was used, with data from all 4 diseases as outcomes combined into 1 model. confirmed that the highest incidence of each infectious disease occurred in children aged less than 5 years of age, with particularly high rates for diarrhea. In addition, the burden of pyrexia of unknown origin was found to be lower in districts bordering Laos, and the incidence rates were higher from April to June in 1999-2001 and 2004 and from July to September in 2002-2003. Higher incidence rates also occurred in most rural districts of Loei and Udon Thani provinces.

  6. Commonalities and differences between Crohn's disease and ulcerative colitis: the genetic clues to their interpretation.

    Science.gov (United States)

    Actis, Giovanni C; Pellicano, Rinaldo; Tarallo, Sonia; Rosina, Floriano

    2011-12-01

    Traditional knowledge of clinical, laboratorial, and endoscopic orders regarding ulcerative colitis and Crohn's disease has begun to be implemented by the revolutionary data from genetic studies. Ever since many decades ago it has been clear that inflammatory bowel diseases are complex multifactorial disorders wherein gut-confined and/or environmental factors must synergize with genetic components to effect the full-blown disorder. The sequencing of the human genome and the generation of public resources of single nucleotide polymorphisms permitted the conduction of powerful population based genome-wide association studies. The latter have increased the number of the identified susceptibility loci to 99. In this review we touched on two pathways that make true susceptibility genes for inflammatory bowel diseases; gene loci that confer specific risk for ulcerative colitis and Crohn's disease were discussed in detail.

  7. Emerging infectious disease leads to rapid population declines of common British birds.

    Directory of Open Access Journals (Sweden)

    Robert A Robinson

    Full Text Available Emerging infectious diseases are increasingly cited as threats to wildlife, livestock and humans alike. They can threaten geographically isolated or critically endangered wildlife populations; however, relatively few studies have clearly demonstrated the extent to which emerging diseases can impact populations of common wildlife species. Here, we report the impact of an emerging protozoal disease on British populations of greenfinch Carduelis chloris and chaffinch Fringilla coelebs, two of the most common birds in Britain. Morphological and molecular analyses showed this to be due to Trichomonas gallinae. Trichomonosis emerged as a novel fatal disease of finches in Britain in 2005 and rapidly became epidemic within greenfinch, and to a lesser extent chaffinch, populations in 2006. By 2007, breeding populations of greenfinches and chaffinches in the geographic region of highest disease incidence had decreased by 35% and 21% respectively, representing mortality in excess of half a million birds. In contrast, declines were less pronounced or absent in these species in regions where the disease was found in intermediate or low incidence. Also, populations of dunnock Prunella modularis, which similarly feeds in gardens, but in which T. gallinae was rarely recorded, did not decline. This is the first trichomonosis epidemic reported in the scientific literature to negatively impact populations of free-ranging non-columbiform species, and such levels of mortality and decline due to an emerging infectious disease are unprecedented in British wild bird populations. This disease emergence event demonstrates the potential for a protozoan parasite to jump avian host taxonomic groups with dramatic effect over a short time period.

  8. Extreme evolutionary disparities seen in positive selection across seven complex diseases.

    Directory of Open Access Journals (Sweden)

    Erik Corona

    Full Text Available Positive selection is known to occur when the environment that an organism inhabits is suddenly altered, as is the case across recent human history. Genome-wide association studies (GWASs have successfully illuminated disease-associated variation. However, whether human evolution is heading towards or away from disease susceptibility in general remains an open question. The genetic-basis of common complex disease may partially be caused by positive selection events, which simultaneously increased fitness and susceptibility to disease. We analyze seven diseases studied by the Wellcome Trust Case Control Consortium to compare evidence for selection at every locus associated with disease. We take a large set of the most strongly associated SNPs in each GWA study in order to capture more hidden associations at the cost of introducing false positives into our analysis. We then search for signs of positive selection in this inclusive set of SNPs. There are striking differences between the seven studied diseases. We find alleles increasing susceptibility to Type 1 Diabetes (T1D, Rheumatoid Arthritis (RA, and Crohn's Disease (CD underwent recent positive selection. There is more selection in alleles increasing, rather than decreasing, susceptibility to T1D. In the 80 SNPs most associated with T1D (p-value <7.01 x 10(-5 showing strong signs of positive selection, 58 alleles associated with disease susceptibility show signs of positive selection, while only 22 associated with disease protection show signs of positive selection. Alleles increasing susceptibility to RA are under selection as well. In contrast, selection in SNPs associated with CD favors protective alleles. These results inform the current understanding of disease etiology, shed light on potential benefits associated with the genetic-basis of disease, and aid in the efforts to identify causal genetic factors underlying complex disease.

  9. A common BACE1 polymorphism is a risk factor for sporadic Creutzfeldt-Jakob disease.

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    Olga Calero

    Full Text Available The β site APP cleaving enzyme 1 (BACE1 is the rate-limiting β-secretase enzyme in the amyloidogenic processing of APP and Aβ formation, and therefore it has a prominent role in Alzheimer's disease (AD pathology. Recent evidence suggests that the prion protein (PrP interacts directly with BACE1 regulating its β-secretase activity. Moreover, PrP has been proposed as the cellular receptor involved in the impairment of synaptic plasticity and toxicity caused by Aβ oligomers. Provided that common pathophysiologic mechanisms are shared by Alzheimer's and Creutzfeldt-Jakob (CJD diseases, we investigated for the first time to the best of our knowledge a possible association of a common synonymous BACE1 polymorphism (rs638405 with sporadic CJD (sCJD. Our results indicate that BACE1 C-allele is associated with an increased risk for developing sCJD, mainly in PRNP M129M homozygous subjects with early onset. These results extend the very short list of genes (other than PRNP involved in the development of human prion diseases; and support the notion that similar to AD, in sCJD several loci may contribute with modest overall effects to disease risk. These findings underscore the interplay in both pathologies of APP, Aβ oligomers, ApoE, PrP and BACE1, and suggest that aging and perhaps vascular risk factors may modulate disease pathologies in part through these key players.

  10. VERTIGO AS AN ENT DISEASE : GENERAL PHYSICIAN AND THE COMMON MAN’S PERCEPTION

    Directory of Open Access Journals (Sweden)

    Sumit

    2015-08-01

    Full Text Available BACKGROUND : To study consciousness amongst General Physicians and common people, on their perception of Vertigo related to ENT disease. METHODS : Study was conducted in two different places of Eastern India from 2006 to 2015 . The patients with complaints of vertigo attending Otorhinolaryngologists at the first instance or by GP referral were studied . General Physicians also underwent a survey through a questionnaire. RESULTS : From the last 9 years of data , we find a defin ite increment in the number of vertigo patients at our OPD along with an increase in consciousness amongst the general physicians, though majority of doctors still don't think Vertigo to be predominantly an ENT disease

  11. WRIST-ANKLE ACUPUNCTURE FOR ANALGESIA IN TREATING SOME COMMON DISEASES IN ATHLETES

    Institute of Scientific and Technical Information of China (English)

    JIANG Xin

    2006-01-01

    @@ With gradual generalization of acupuncture-moxibustion therapy in developed countries, an increasing attention has been paid to its application in the athletic field. Wrist-ankle acupuncture is a kind of shallow acupuncture, by which 6 points in the wrist and ankle regions are selected and punctured for treating diseases related to individual parts of the body. It is a kind of information therapy concerning biological hologram regularities. The analgesic effects of the therapy in treating some common diseases in 64 athletes are reported as follows.

  12. Takayasu's arteritis following Crohn's disease in a young woman: Any evidence for a common pathogenesis?

    Institute of Scientific and Technical Information of China (English)

    Melissa AL Farrant; Justin C Mason; Newton ACS Wong; Robert J Longman

    2008-01-01

    Takayasu's arteritis and Crohn's disease are chronic inflammatory diseases of uncertain aetiology. They rarely occur together, with only twenty nine cases of co-existent Takayasu's arteritis and Crohn's disease reported in the literature. In 88% of these cases, Takayasu's arteritis was diagnosed simultaneously or following a diagnosis of Crohn's disease. We present a case of a young Caucasian medical student, incidentally found to have bilateral carotid bruits on auscultation by a colleague. Magnetic resonance angiography revealed stenoses of the common carotid arteries with established collaterals, and a diagnosis of Type 1 Takayasu's arteritis was made. An 18F-fluorodeoxyglucose positron emission tomography scan revealed no active disease. Nine months later, she presented with a short history of abdominal pain, vomiting and abdominal distension. Barium follow-through and computer tomography revealed a terminal ileal stricture and proximal small bowel dilation. An extended right hemicoloectomy was performed and histopathology supported a diagnosis of Crohn's disease. This case report is presented with a particular focus on the temporal relationship between these two disease processes and explores whether their concurrence is more than just co-incidence.

  13. Possible Role of Common Spices as a Preventive and Therapeutic Agent for Alzheimer's Disease

    Science.gov (United States)

    Mirmosayyeb, Omid; Tanhaei, Amirpouya; Sohrabi, Hamid R.; Martins, Ralph N.; Tanhaei, Mana; Najafi, Mohammad Amin; Safaei, Ali; Meamar, Rokhsareh

    2017-01-01

    For centuries, spices have been consumed as food additives or medicinal agents. However, there is increasing evidence indicating the plant-based foods in regular diet may lower the risk of neurodegenerative diseases including Alzheimer disease. Spices, as one of the most commonly used plant-based food additives may provide more than just flavors, but as agents that may prevent or even halt neurodegenerative processes associated with aging. In this article, we review the role and application of five commonly used dietary spices including saffron turmeric, pepper family, zingiber, and cinnamon. Besides suppressing inflammatory pathways, these spices may act as antioxidant and inhibit acetyl cholinesterase and amyloid β aggregation. We summarized how spice-derived nutraceuticals mediate such different effects and what their molecular targets might be. Finally, some directions for future research are briefly discussed. PMID:28250905

  14. Possible role of common spices as a preventive and therapeutic agent for Alzheimer′s disease

    Directory of Open Access Journals (Sweden)

    Omid Mirmosayyeb

    2017-01-01

    Full Text Available For centuries, spices have been consumed as food additives or medicinal agents. However, there is increasing evidence indicating the plant-based foods in regular diet may lower the risk of neurodegenerative diseases including Alzheimer disease. Spices, as one of the most commonly used plant-based food additives may provide more than just flavors, but as agents that may prevent or even halt neurodegenerative processes associated with aging. In this article, we review the role and application of five commonly used dietary spices including saffron turmeric, pepper family, zingiber, and cinnamon. Besides suppressing inflammatory pathways, these spices may act as antioxidant and inhibit acetyl cholinesterase and amyloid β aggregation. We summarized how spice-derived nutraceuticals mediate such different effects and what their molecular targets might be. Finally, some directions for future research are briefly discussed.

  15. Possible Role of Common Spices as a Preventive and Therapeutic Agent for Alzheimer's Disease.

    Science.gov (United States)

    Mirmosayyeb, Omid; Tanhaei, Amirpouya; Sohrabi, Hamid R; Martins, Ralph N; Tanhaei, Mana; Najafi, Mohammad Amin; Safaei, Ali; Meamar, Rokhsareh

    2017-01-01

    For centuries, spices have been consumed as food additives or medicinal agents. However, there is increasing evidence indicating the plant-based foods in regular diet may lower the risk of neurodegenerative diseases including Alzheimer disease. Spices, as one of the most commonly used plant-based food additives may provide more than just flavors, but as agents that may prevent or even halt neurodegenerative processes associated with aging. In this article, we review the role and application of five commonly used dietary spices including saffron turmeric, pepper family, zingiber, and cinnamon. Besides suppressing inflammatory pathways, these spices may act as antioxidant and inhibit acetyl cholinesterase and amyloid β aggregation. We summarized how spice-derived nutraceuticals mediate such different effects and what their molecular targets might be. Finally, some directions for future research are briefly discussed.

  16. Molecular insights into amyloid regulation by membrane cholesterol and sphingolipids: common mechanisms in neurodegenerative diseases

    OpenAIRE

    Fantini, Jacques; Yahi, Nouara

    2010-01-01

    Alzheimer, Parkinson and other neurodegenerative diseases involve a series of brain proteins, referred to as ‘amyloidogenic proteins’, with exceptional conformational plasticity and a high propensity for self-aggregation. Although the mechanisms by which amyloidogenic proteins kill neural cells are not fully understood, a common feature is the concentration of unstructured amyloidogenic monomers on bidimensional membrane lattices. Membrane-bound monomers undergo a series of lipid-dependent co...

  17. Cytomegalovirus Colitis with Common Variable Immunodeficiency and Crohn’s Disease

    OpenAIRE

    Betül Ünal; Cumhur İbrahim Başsorgun; Sinem Çil Gönülcü; Aslı Uçar; Fatih Çelik; Gülsüm Özlem Elpek

    2015-01-01

    Here we present an eleven-year-old male patient who had been diagnosed with common variable immunodeficiency (CVID) three years ago due to recurrent sinopulmonary infections. Two years later he had been diagnosed with Crohn’s disease (CD) due to diarrhea episodes which were unresponsive to the treatment. Depending on the active gastrointestinal bleeding and perforation he underwent total colectomy. Despite immunoglobulin and antiviral therapies, general condition of patient deteriorated and h...

  18. Adventitial cystic disease of the common femoral vein presenting as deep vein thrombosis

    Directory of Open Access Journals (Sweden)

    Young-Kyun Kim

    2016-07-01

    Full Text Available Adventitial cystic disease of the common femoral vein is a rare condition. We herein report the case of a 50-year-old woman who presented with painless swelling in her left lower leg that resembled deep vein thrombosis. She underwent femoral exploration and excision of the cystic wall. The presentation, investigation, treatment, and pathology of this condition are discussed with a literature review.

  19. Association of HFE common mutations with Parkinson's disease, Alzheimer's disease and mild cognitive impairment in a Portuguese cohort

    Directory of Open Access Journals (Sweden)

    Morgadinho Ana S

    2006-07-01

    Full Text Available Abstract Background Pathological brain iron deposition has been implicated as a source of neurotoxic reactive oxygen species in Alzheimer (AD and Parkinson diseases (PD. Iron metabolism is associated with the gene hemochromatosis (HFE Human genome nomenclature committee ID:4886, and mutations in HFE are a cause of the iron mismetabolism disease, hemochromatosis. Several reports have tested the association of HFE variants with neurodegenerative diseases, such as AD and PD with conflicting results. Methods Genotypes were analysed for the two most common variants of HFE in a series of 130 AD, 55 Mild Cognitive Impairment (MCI and 132 PD patients. Additionally, a series of 115 healthy age-matched controls was also screened. Results A statistically significant association was found in the PD group when compared to controls, showing that the presence of the C282Y variant allele may confer higher risk for developing the disease. Conclusion Taken together these results suggest that the common variants in HFE may be a risk factor for PD, but not for AD in the Portuguese population.

  20. Systems biology elucidates common pathogenic mechanisms between nonalcoholic and alcoholic-fatty liver disease.

    Directory of Open Access Journals (Sweden)

    Silvia Sookoian

    Full Text Available The abnormal accumulation of fat in the liver is often related either to metabolic risk factors associated with metabolic syndrome in the absence of alcohol consumption (nonalcoholic fatty liver disease, NAFLD or to chronic alcohol consumption (alcoholic fatty liver disease, AFLD. Clinical and histological studies suggest that NAFLD and AFLD share pathogenic mechanisms. Nevertheless, current data are still inconclusive as to whether the underlying biological process and disease pathways of NAFLD and AFLD are alike. Our primary aim was to integrate omics and physiological data to answer the question of whether NAFLD and AFLD share molecular processes that lead to disease development. We also explored the extent to which insulin resistance (IR is a distinctive feature of NAFLD. To answer these questions, we used systems biology approaches, such as gene enrichment analysis, protein-protein interaction networks, and gene prioritization, based on multi-level data extracted by computational data mining. We observed that the leading disease pathways associated with NAFLD did not significantly differ from those of AFLD. However, systems biology revealed the importance of each molecular process behind each of the two diseases, and dissected distinctive molecular NAFLD and AFLD-signatures. Comparative co-analysis of NAFLD and AFLD clarified the participation of NAFLD, but not AFLD, in cardiovascular disease, and showed that insulin signaling is impaired in fatty liver regardless of the noxa, but the putative regulatory mechanisms associated with NAFLD seem to encompass a complex network of genes and proteins, plausible of epigenetic modifications. Gene prioritization showed a cancer-related functional map that suggests that the fatty transformation of the liver tissue is regardless of the cause, an emerging mechanism of ubiquitous oncogenic activation. In conclusion, similar underlying disease mechanisms lead to NAFLD and AFLD, but specific ones depict a

  1. Integrated Genomic and Network-Based Analyses of Complex Diseases and Human Disease Network.

    Science.gov (United States)

    Al-Harazi, Olfat; Al Insaif, Sadiq; Al-Ajlan, Monirah A; Kaya, Namik; Dzimiri, Nduna; Colak, Dilek

    2016-06-20

    A disease phenotype generally reflects various pathobiological processes that interact in a complex network. The highly interconnected nature of the human protein interaction network (interactome) indicates that, at the molecular level, it is difficult to consider diseases as being independent of one another. Recently, genome-wide molecular measurements, data mining and bioinformatics approaches have provided the means to explore human diseases from a molecular basis. The exploration of diseases and a system of disease relationships based on the integration of genome-wide molecular data with the human interactome could offer a powerful perspective for understanding the molecular architecture of diseases. Recently, subnetwork markers have proven to be more robust and reliable than individual biomarker genes selected based on gene expression profiles alone, and achieve higher accuracy in disease classification. We have applied one of these methodologies to idiopathic dilated cardiomyopathy (IDCM) data that we have generated using a microarray and identified significant subnetworks associated with the disease. In this paper, we review the recent endeavours in this direction, and summarize the existing methodologies and computational tools for network-based analysis of complex diseases and molecular relationships among apparently different disorders and human disease network. We also discuss the future research trends and topics of this promising field.

  2. Estimating wildlife disease dynamics in complex systems using an Approximate Bayesian Computation framework.

    Science.gov (United States)

    Kosmala, Margaret; Miller, Philip; Ferreira, Sam; Funston, Paul; Keet, Dewald; Packer, Craig

    2016-01-01

    Emerging infectious diseases of wildlife are of increasing concern to managers and conservation policy makers, but are often difficult to study and predict due to the complexity of host-disease systems and a paucity of empirical data. We demonstrate the use of an Approximate Bayesian Computation statistical framework to reconstruct the disease dynamics of bovine tuberculosis in Kruger National Park's lion population, despite limited empirical data on the disease's effects in lions. The modeling results suggest that, while a large proportion of the lion population will become infected with bovine tuberculosis, lions are a spillover host and long disease latency is common. In the absence of future aggravating factors, bovine tuberculosis is projected to cause a lion population decline of ~3% over the next 50 years, with the population stabilizing at this new equilibrium. The Approximate Bayesian Computation framework is a new tool for wildlife managers. It allows emerging infectious diseases to be modeled in complex systems by incorporating disparate knowledge about host demographics, behavior, and heterogeneous disease transmission, while allowing inference of unknown system parameters.

  3. Common prognostic factors of work disability among employees with a chronic somatic disease: a systematic review of cohort studies

    National Research Council Canada - National Science Library

    Sarah I Detaille; Yvonne F Heerkens; Josephine A Engels; Joost WJ van der Gulden; Frank JH van Dijk

    2009-01-01

    Objective Based on prospective and retrospective disease cohort studies, the aim of this review was to determine common prognostic factors for work disability among employees with rheumatoid arthritis...

  4. Evaluating the contribution of genetics and familial shared environment to common disease using the UK Biobank.

    Science.gov (United States)

    Muñoz, María; Pong-Wong, Ricardo; Canela-Xandri, Oriol; Rawlik, Konrad; Haley, Chris S; Tenesa, Albert

    2016-09-01

    Genome-wide association studies have detected many loci underlying susceptibility to disease, but most of the genetic factors that contribute to disease susceptibility remain unknown. Here we provide evidence that part of the 'missing heritability' can be explained by an overestimation of heritability. We estimated the heritability of 12 complex human diseases using family history of disease in 1,555,906 individuals of white ancestry from the UK Biobank. Estimates using simple family-based statistical models were inflated on average by ∼47% when compared with those from structural equation modeling (SEM), which specifically accounted for shared familial environmental factors. In addition, heritabilities estimated using SNP data explained an average of 44.2% of the simple family-based estimates across diseases and an average of 57.3% of the SEM-estimated heritabilities, accounting for almost all of the SEM heritability for hypertension. Our results show that both genetics and familial environment make substantial contributions to familial clustering of disease.

  5. [Several common biases and control measures during sampling survey of eye diseases in China].

    Science.gov (United States)

    Guan, Huai-jin

    2008-06-01

    Bias is a common artificial error during sampling survey in eye diseases, and is a major impact factor for validity and reliability of the survey. The causes and the control measures of several biases regarding current sampling survey of eye diseases in China were analyzed and discussed, including the sampling bias, non-respondent bias, and diagnostic bias. This review emphasizes that controlling bias is the key to ensure quality of sampling survey. Random sampling, sufficient sample quantity, careful examination and taking history, improving examination rate, accurate diagnosis, strict training and preliminary study, as well as quality control can eliminate or minimize biases and improve the sampling survey quality of eye diseases in China

  6. Growing up in the Ocean: Complex Life Cycles of Common Marine Invertebrates

    Science.gov (United States)

    Bennett, Katie; Hiebert, Laurel

    2010-01-01

    Most people are familiar with the concept that animals come in all shapes and sizes and that the body plan of some animals can completely transform during their lifetime. Well-known examples of such complex life cycles of terrestrial animals include butterflies and frogs. Many people are unaware, however, that complex life cycles are exceedingly…

  7. Knowledge of family physicians on common dermatological diseases and their diagnosis and management trends

    Directory of Open Access Journals (Sweden)

    Kemal Özyurt

    2014-12-01

    Full Text Available Background and Design: In clinical practice, dermatology specialists usually encounter misdiagnosis and inappropriate management approaches of other specialists for several dermatological diseases. This study aims to investigate the knowledge, diagnosis and management trends of family physicians in primary care on common dermatological diseases and their opinions about dermatology education. Materials and Methods: A multicenter study was conducted in six cities in Turkey including a total of 302 family physicians in primary care using an 82-item questionnaire through in-person interview. The questionnaire aimed at identifying demographic characteristics of family physicians, knowledge on common dermatological diseases, and their diagnosis and management trends. Results: Out of 1414 family physicians, 302 (21.53% subjects, who could be contacted and those accepted to respond the questionnaire, were included. 57.6% of participants reported that there was not a microscope, while 94.4% reported that potassium hydroxide solution was not available in their clinics. A higher rate of family physicians mentioned experience difficulties in the management of psoriasis and acne rosacea. The rate of family physicians, who assumed that hepatobiliary disorders and other visceral conditions play a role in the etiopathogenesis of atopic dermatitis, psoriasis and acne vulgaris and those who did not state an opinion about this issue, was high. Incorrect management trends for bacterial skin diseases and nail diseases were observed with higher rates. Conclusion: It is recommended that knowledge should be reinforced through both undergraduate and continuous medical education and, skills of family physicians on the management of dermatological diseases should be improved.

  8. Identification of a common gene expression response in different lung inflammatory diseases in rodents and macaques.

    Directory of Open Access Journals (Sweden)

    Jeroen L A Pennings

    Full Text Available To identify gene expression responses common to multiple pulmonary diseases we collected microarray data for acute lung inflammation models from 12 studies and used these in a meta-analysis. The data used include exposures to air pollutants; bacterial, viral, and parasitic infections; and allergic asthma models. Hierarchical clustering revealed a cluster of 383 up-regulated genes with a common response. This cluster contained five subsets, each characterized by more specific functions such as inflammatory response, interferon-induced genes, immune signaling, or cell proliferation. Of these subsets, the inflammatory response was common to all models, interferon-induced responses were more pronounced in bacterial and viral models, and a cell division response was more prominent in parasitic and allergic models. A common cluster containing 157 moderately down-regulated genes was associated with the effects of tissue damage. Responses to influenza in macaques were weaker than in mice, reflecting differences in the degree of lung inflammation and/or virus replication. The existence of a common cluster shows that in vivo lung inflammation in response to various pathogens or exposures proceeds through shared molecular mechanisms.

  9. DNA repair pathways underlie a common genetic mechanism modulating onset in polyglutamine diseases

    Science.gov (United States)

    Bettencourt, Conceição; Hensman‐Moss, Davina; Flower, Michael; Wiethoff, Sarah; Brice, Alexis; Goizet, Cyril; Stevanin, Giovanni; Koutsis, Georgios; Karadima, Georgia; Panas, Marios; Yescas‐Gómez, Petra; García‐Velázquez, Lizbeth Esmeralda; Alonso‐Vilatela, María Elisa; Lima, Manuela; Raposo, Mafalda; Traynor, Bryan; Sweeney, Mary; Wood, Nicholas; Giunti, Paola; Durr, Alexandra; Holmans, Peter; Houlden, Henry; Tabrizi, Sarah J.

    2016-01-01

    Objective The polyglutamine diseases, including Huntington's disease (HD) and multiple spinocerebellar ataxias (SCAs), are among the commonest hereditary neurodegenerative diseases. They are caused by expanded CAG tracts, encoding glutamine, in different genes. Longer CAG repeat tracts are associated with earlier ages at onset, but this does not account for all of the difference, and the existence of additional genetic modifying factors has been suggested in these diseases. A recent genome‐wide association study (GWAS) in HD found association between age at onset and genetic variants in DNA repair pathways, and we therefore tested whether the modifying effects of variants in DNA repair genes have wider effects in the polyglutamine diseases. Methods We assembled an independent cohort of 1,462 subjects with HD and polyglutamine SCAs, and genotyped single‐nucleotide polymorphisms (SNPs) selected from the most significant hits in the HD study. Results In the analysis of DNA repair genes as a group, we found the most significant association with age at onset when grouping all polyglutamine diseases (HD+SCAs; p = 1.43 × 10–5). In individual SNP analysis, we found significant associations for rs3512 in FAN1 with HD+SCAs (p = 1.52 × 10–5) and all SCAs (p = 2.22 × 10–4) and rs1805323 in PMS2 with HD+SCAs (p = 3.14 × 10–5), all in the same direction as in the HD GWAS. Interpretation We show that DNA repair genes significantly modify age at onset in HD and SCAs, suggesting a common pathogenic mechanism, which could operate through the observed somatic expansion of repeats that can be modulated by genetic manipulation of DNA repair in disease models. This offers novel therapeutic opportunities in multiple diseases. Ann Neurol 2016;79:983–990 PMID:27044000

  10. Disappointing durable remission rates in complex Crohn's disease fistula.

    Science.gov (United States)

    Molendijk, Ilse; Nuij, Veerle J A A; van der Meulen-de Jong, Andrea E; van der Woude, C Janneke

    2014-11-01

    Despite potent drugs and surgical techniques, the treatment of perianal fistulizing Crohn's disease (CD) remains challenging. We assessed treatment strategies for perianal fistulizing CD and their effect on remission, response, and relapse. Patients with perianal fistulizing CD visiting the Erasmus MC between January 1, 1980 and January 1, 2000 were identified. Demographics, fistula characteristics, and received treatments aimed at the outcome of these strategies were noted. In total, 232 patients were identified (98 male; 42.2%). Median follow-up was 10.0 years (range, 0.5-37.5 yr). Complex fistulas were present in 78.0%. Medical treatment (antibiotics, steroids, immunosuppressants, and anti-tumor necrosis factor) commenced in 79.7% of the patients and in 53.2%, surgery (colectomy, fistulectomy, stoma, and rectum amputation) was performed. Simple fistulas healed more often than complex fistulas (88.2% versus 64.6%; P fistula healing rates in simple and complex fistula. Initially, healed fistulas recurred in 26.7% in case of simple fistulas and in 41.9% in case of complex fistulas (P = 0.051). Only 37.0% of the complex fistulas were in remission at the end of follow-up compared with 66.7% of the simple fistulas (P fistulas were in remission after conventional treatment strategies after a median follow-up of 10 years. Simple fistulas were more likely to heal than complex fistulas, and less of these healed fistulas relapsed. However, more than 3 quarters of the patients had complex perianal fistulas.

  11. Mechanism of toxicity of pesticides acting at complex I: relevance to environmental etiologies of Parkinson's disease.

    Science.gov (United States)

    Sherer, Todd B; Richardson, Jason R; Testa, Claudia M; Seo, Byoung Boo; Panov, Alexander V; Yagi, Takao; Matsuno-Yagi, Akemi; Miller, Gary W; Greenamyre, J Timothy

    2007-03-01

    Parkinson's disease (PD) has been linked to mitochondrial dysfunction and pesticide exposure. The pesticide rotenone (ROT) inhibits complex I and reproduces features of PD in animal models, suggesting that environmental agents that inhibit complex I may contribute to PD. We have previously demonstrated that ROT toxicity is dependent upon complex I inhibition and that oxidative stress is the primary mechanism of toxicity. In this study, we examined the in vitro toxicity and mechanism of action of several putative complex I inhibitors that are commonly used as pesticides. The rank order of toxicity of pesticides to neuroblastoma cells was pyridaben > rotenone > fenpyroximate > fenazaquin > tebunfenpyrad. A similar order of potency was observed for reduction of ATP levels and competition for (3)H-dihydrorotenone (DHR) binding to complex I, with the exception of pyridaben (PYR). Neuroblastoma cells stably expressing the ROT-insensitive NADH dehydrogenase of Saccharomyces cerevisiae (NDI1) were resistant to these pesticides, demonstrating the requirement of complex I inhibition for toxicity. We further found that PYR was a more potent inhibitor of mitochondrial respiration and caused more oxidative damage than ROT. The oxidative damage could be attenuated by NDI1 or by the antioxidants alpha-tocopherol and coenzyme Q(10). PYR was also highly toxic to midbrain organotypic slices. These data demonstrate that, in addition to ROT, several commercially used pesticides directly inhibit complex I, cause oxidative damage, and suggest that further study is warranted into environmental agents that inhibit complex I for their potential role in PD.

  12. Fabry disease, a complex pathology not easy to diagnose

    Directory of Open Access Journals (Sweden)

    Paolo Colomba

    2015-12-01

    Full Text Available Fabry disease is a multisystemic lysosomal storage disorder, inherited in an X-linked manner. It is a defect of metabolism of the glycosphingolipids, due to the reduction or absence of the activity of lysosomal enzyme α-galactosidase A. This reduction of activity causes the storage of globotriaosylceramide and derivatives in the lysosomes, triggering a cascade of cellular events, mainly in vascular endothelium. These events are the responsible for the systemic clinical manifestations and the renal, cardiac and cerebrovascular complications, or a combination of them. The symptomatology can lead to the premature death of patient between the fourth or fifth decade of life. The first symptoms can occur at different ages, generally in childhood, with different severity and course. Fabry disease is suspected on the basis of clinical and anamnestic-familial data, and it is confirmed by enzymatic and genetic assays. However, Fabry disease could be a pathology more complex than previously considered, and the diagnostic tests that are currently in use could be not always sufficient to confirm the clinical diagnosis. Probably, other factors could be also involved in the onset of symptomatology. In the last years, the knowledge of the disease is considerably increased but other studies are necessary to make a prompt and reliable diagnosis. An early diagnosis of Fabry disease is essential for the beginning of the enzyme replacement therapy, which can contribute to arrest its progression and improve the quality of life of patients.

  13. Neuroticism and common mental disorders : Meaning and utility of a complex relationship

    NARCIS (Netherlands)

    Ormel, Johan; Jeronimus, Bertus F; Kotov, Roman; Riese, Harriëtte; Bos, Elisabeth H; Hankin, Benjamin; Rosmalen, Judith G M; Oldehinkel, Albertine J

    2013-01-01

    Neuroticism's prospective association with common mental disorders (CMDs) has fueled the assumption that neuroticism is an independent etiologically informative risk factor. This vulnerability model postulates that neuroticism sets in motion processes that lead to CMDs. However, four other models se

  14. Micro RNA, A Review: Pharmacogenomic drug targets for complex diseases

    Directory of Open Access Journals (Sweden)

    Ritesh Bajaj

    2010-01-01

    Full Text Available Micro RNAs (miRNAs are non-coding RNAs that can regulate gene expression to target several mRNAs in a gene regulatory network. MiRNA related Single Nucleotide Polymorphisms (S.N.P.s represent a newly identified type of genetic variability that can be of influence to the risk of certain human diseases and also affect how drugs can be activated and metabolized by patients. This will help in personalized medicines which are used for adminis-trating the correct dosage of drug and drug efficacy. miRNA deregulated expression has been extensively de-scribed in a variety of diseases such as Cancer, Obesity , Diabetes, Schizophrenia and control and self renewal of stem cells. MiRNA can function as oncogenes and/or tumor suppressors. MiRNAs may act as key regulators of processes as diverse as early development, cell proliferation and cell death, apoptosis and fat metabolism and cell differentiation .miRNA expression have shown their role in brain development chronic lymphocytic leukemia, colonic adeno carcinoma, Burkiff′s lymphoma and viral infection. These show their links with viral disease, neu-rodevelopment and cancer. It has been shown that they play a key role in melanoma metastasis. These may be differentially expressed in malignant cells compared to normal cells altering the regulation of expression of many important genes. MiRNA expression has been used for prognosis and early diagnosis of these complex diseases. The present paper focuses on the role of miRNAs in various complex diseases, which will help in improving the drug discovery process and personalized medicines.

  15. Antibiotic resistance as collateral damage: the tragedy of the commons in a two-disease setting.

    Science.gov (United States)

    Gao, Daozhou; Lietman, Thomas M; Porco, Travis C

    2015-05-01

    We propose a simple two-disease epidemic model where one disease exhibits only a drug-sensitive strain, while the other exhibits both drug-sensitive and drug-resistant strains. Treatment for the first disease may select for resistance in the other. We model antibiotic use as a mathematical game through the study of individual incentives and community welfare. The basic reproduction number is derived and the existence and local stability of the model equilibria are analyzed. When the force of infection of each disease is unaffected by the presence of the other, we find that there is a conflict of interest between individual and community, known as a tragedy of the commons, under targeted treatment toward persons infected by the single strain disease, but there is no conflict under mass treatment. However, we numerically show that individual and social incentive to use antibiotics may show disaccord under mass treatment if the restriction on the transmission ability of the dually infected people is removed, or drug resistant infection is worse than drug sensitive infection, or the uninfected state has a comparative disutility over the infected states. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Induction of a systemic lupus erythematosus-like disease in mice by a common human anti-DNA idiotype

    Energy Technology Data Exchange (ETDEWEB)

    Mendlovic, S.; Brocke, S.; Meshorer, A.; Mozes, E. (Weizmann Institute of Science, Rehovot (Israel)); Shoenfeld, Y.; Bakimer, R. (Ben-Gurion Univ., Beer-Sheva (Israel)); Ben-Bassat, M. (Beilinson Medical Center, Petah-Tiqva (Israel))

    1988-04-01

    Systemic lupus erythematosus (SLE) is considered to be the quintessential autoimmune disease. It has not been possible to induce SLE in animal models by DNA immunization or by challenge with anti-DNA antibodies. The authors report a murine model of SLE-like disease induced by immunization of C3H.SW female mice with a common human monoclonal anti-DNA idiotype (16/6 idiotype). Following a booster injection with the 16/6 idiotype, high levels of murine anti-16/6 and anti-anti-16/6 antibodies (associated with anti-DNA activity) were detected in the sera of the immunized mice. Elevated titers of autoantibodies reacting with DNA, poly(I), poly(dT), ribonucleoprotein, autoantigens (Sm, SS-A (Ro), and SS-B (La)), and cardiolipin were noted. The serological findings were associated with increased erythrocyte sedimentation rate, leukopenia, proteinuria, immune complex deposition in the glomerular mesangium, and sclerosis of the glomeruli. The immune complexes in the kidneys were shown to contain the 16/6 idiotype. This experimental SLE-like model may be used to elucidate the mechanisms underlying SLE.

  17. Atherosclerosis and Alzheimer - diseases with a common cause? Inflammation, oxysterols, vasculature

    Science.gov (United States)

    2014-01-01

    Background Aging is accompanied by increasing vulnerability to pathologies such as atherosclerosis (ATH) and Alzheimer disease (AD). Are these different pathologies, or different presentations with a similar underlying pathoetiology? Discussion Both ATH and AD involve inflammation, macrophage infiltration, and occlusion of the vasculature. Allelic variants in common genes including APOE predispose to both diseases. In both there is strong evidence of disease association with viral and bacterial pathogens including herpes simplex and Chlamydophila. Furthermore, ablation of components of the immune system (or of bone marrow-derived macrophages alone) in animal models restricts disease development in both cases, arguing that both are accentuated by inflammatory/immune pathways. We discuss that amyloid β, a distinguishing feature of AD, also plays a key role in ATH. Several drugs, at least in mouse models, are effective in preventing the development of both ATH and AD. Given similar age-dependence, genetic underpinnings, involvement of the vasculature, association with infection, Aβ involvement, the central role of macrophages, and drug overlap, we conclude that the two conditions reflect different manifestations of a common pathoetiology. Mechanism Infection and inflammation selectively induce the expression of cholesterol 25-hydroxylase (CH25H). Acutely, the production of ‘immunosterol’ 25-hydroxycholesterol (25OHC) defends against enveloped viruses. We present evidence that chronic macrophage CH25H upregulation leads to catalyzed esterification of sterols via 25OHC-driven allosteric activation of ACAT (acyl-CoA cholesterol acyltransferase/SOAT), intracellular accumulation of cholesteryl esters and lipid droplets, vascular occlusion, and overt disease. Summary We postulate that AD and ATH are both caused by chronic immunologic challenge that induces CH25H expression and protection against particular infectious agents, but at the expense of longer-term pathology

  18. Atherosclerosis and Alzheimer--diseases with a common cause? Inflammation, oxysterols, vasculature.

    Science.gov (United States)

    Lathe, Richard; Sapronova, Alexandra; Kotelevtsev, Yuri

    2014-03-21

    Aging is accompanied by increasing vulnerability to pathologies such as atherosclerosis (ATH) and Alzheimer disease (AD). Are these different pathologies, or different presentations with a similar underlying pathoetiology? Both ATH and AD involve inflammation, macrophage infiltration, and occlusion of the vasculature. Allelic variants in common genes including APOE predispose to both diseases. In both there is strong evidence of disease association with viral and bacterial pathogens including herpes simplex and Chlamydophila. Furthermore, ablation of components of the immune system (or of bone marrow-derived macrophages alone) in animal models restricts disease development in both cases, arguing that both are accentuated by inflammatory/immune pathways. We discuss that amyloid β, a distinguishing feature of AD, also plays a key role in ATH. Several drugs, at least in mouse models, are effective in preventing the development of both ATH and AD. Given similar age-dependence, genetic underpinnings, involvement of the vasculature, association with infection, Aβ involvement, the central role of macrophages, and drug overlap, we conclude that the two conditions reflect different manifestations of a common pathoetiology. Infection and inflammation selectively induce the expression of cholesterol 25-hydroxylase (CH25H). Acutely, the production of 'immunosterol' 25-hydroxycholesterol (25OHC) defends against enveloped viruses. We present evidence that chronic macrophage CH25H upregulation leads to catalyzed esterification of sterols via 25OHC-driven allosteric activation of ACAT (acyl-CoA cholesterol acyltransferase/SOAT), intracellular accumulation of cholesteryl esters and lipid droplets, vascular occlusion, and overt disease. We postulate that AD and ATH are both caused by chronic immunologic challenge that induces CH25H expression and protection against particular infectious agents, but at the expense of longer-term pathology.

  19. A database of annotated promoters of genes associated with common respiratory and related diseases

    KAUST Repository

    Chowdhary, Rajesh

    2012-07-01

    Many genes have been implicated in the pathogenesis of common respiratory and related diseases (RRDs), yet the underlying mechanisms are largely unknown. Differential gene expression patterns in diseased and healthy individuals suggest that RRDs affect or are affected by modified transcription regulation programs. It is thus crucial to characterize implicated genes in terms of transcriptional regulation. For this purpose, we conducted a promoter analysis of genes associated with 11 common RRDs including allergic rhinitis, asthma, bronchiectasis, bronchiolitis, bronchitis, chronic obstructive pulmonary disease, cystic fibrosis, emphysema, eczema, psoriasis, and urticaria, many of which are thought to be genetically related. The objective of the present study was to obtain deeper insight into the transcriptional regulation of these disease-associated genes by annotating their promoter regions with transcription factors (TFs) and TF binding sites (TFBSs). We discovered many TFs that are significantly enriched in the target disease groups including associations that have been documented in the literature. We also identified a number of putative TFs/TFBSs that appear to be novel. The results of our analysis are provided in an online database that is freely accessible to researchers at http://www.respiratorygenomics.com. Promoter-associated TFBS information and related genomic features, such as histone modification sites, microsatellites, CpG islands, and SNPs, are graphically summarized in the database. Users can compare and contrast underlying mechanisms of specific RRDs relative to candidate genes, TFs, gene ontology terms, micro-RNAs, and biological pathways for the conduct of metaanalyses. This database represents a novel, useful resource for RRD researchers. Copyright © 2012 by the American Thoracic Society.

  20. Minimal Change Disease and IgA Deposition: Separate Entities or Common Pathophysiology?

    Directory of Open Access Journals (Sweden)

    Brandon S. Oberweis

    2013-01-01

    Full Text Available Introduction. Minimal Change Disease (MCD is the most common cause of nephrotic syndrome in children, while IgA nephropathy is the most common cause of glomerulonephritis worldwide. MCD is responsive to glucocorticoids, while the role of steroids in IgA nephropathy remains unclear. We describe a case of two distinct clinical and pathological findings, raising the question of whether MCD and IgA nephropathy are separate entities or if there is a common pathophysiology. Case Report. A 19-year old man with no medical history presented to the Emergency Department with a 20-day history of anasarca and frothy urine, BUN 68 mg/dL, Cr 2.3 mg/dL, urinalysis 3+ RBCs, 3+ protein, and urine protein : creatinine ratio 6.4. Renal biopsy revealed hypertrophic podocytes on light microscopy, podocyte foot process effacement on electron microscopy, and immunofluorescent mesangial staining for IgA. The patient was started on prednisone and exhibited dramatic improvement. Discussion. MCD typically has an overwhelming improvement with glucocorticoids, while the resolution of IgA nephropathy is rare. Our patient presented with MCD with the uncharacteristic finding of hematuria. Given the improvement with glucocorticoids, we raise the question of whether there is a shared pathophysiologic component of these two distinct clinical diseases that represents a clinical variant.

  1. Minimal change disease and IgA deposition: separate entities or common pathophysiology?

    Science.gov (United States)

    Oberweis, Brandon S; Mattoo, Aditya; Wu, Ming; Goldfarb, David S

    2013-01-01

    Introduction. Minimal Change Disease (MCD) is the most common cause of nephrotic syndrome in children, while IgA nephropathy is the most common cause of glomerulonephritis worldwide. MCD is responsive to glucocorticoids, while the role of steroids in IgA nephropathy remains unclear. We describe a case of two distinct clinical and pathological findings, raising the question of whether MCD and IgA nephropathy are separate entities or if there is a common pathophysiology. Case Report. A 19-year old man with no medical history presented to the Emergency Department with a 20-day history of anasarca and frothy urine, BUN 68 mg/dL, Cr 2.3 mg/dL, urinalysis 3+ RBCs, 3+ protein, and urine protein : creatinine ratio 6.4. Renal biopsy revealed hypertrophic podocytes on light microscopy, podocyte foot process effacement on electron microscopy, and immunofluorescent mesangial staining for IgA. The patient was started on prednisone and exhibited dramatic improvement. Discussion. MCD typically has an overwhelming improvement with glucocorticoids, while the resolution of IgA nephropathy is rare. Our patient presented with MCD with the uncharacteristic finding of hematuria. Given the improvement with glucocorticoids, we raise the question of whether there is a shared pathophysiologic component of these two distinct clinical diseases that represents a clinical variant.

  2. [Rendu-Osler-Weber syndrome--a complex systemic disease].

    Science.gov (United States)

    Geisthoff, U W; Koester, M; Fischinger, J; Schneider, G

    2004-09-30

    Hereditary hemorrhagic teleangiectasia (HHT or Rendu-Osler-Weber Syndrome) is an inherited autosomal dominant disorder of the vascular connective tissue. The resulting vascular malformations can occur in virtually any organ. Nosebleeds can massively impact on the quality of life of those afflicted. However, visceral manifestations are likely to be more serious, and may be comparable with a "ticking time bomb". Most commonly affected are the vascular systems of the lungs, liver, brain and gastrointestinal tract. Screening is recommended--at least with regard to the lungs. Difficult constellations of this complex condition may be successfully managed by an interdisciplinary approach.

  3. Common and specific signatures of gene expression and protein-protein interactions in autoimmune diseases.

    Science.gov (United States)

    Tuller, T; Atar, S; Ruppin, E; Gurevich, M; Achiron, A

    2013-03-01

    The aim of this study is to understand intracellular regulatory mechanisms in peripheral blood mononuclear cells (PBMCs), which are either common to many autoimmune diseases or specific to some of them. We incorporated large-scale data such as protein-protein interactions, gene expression and demographical information of hundreds of patients and healthy subjects, related to six autoimmune diseases with available large-scale gene expression measurements: multiple sclerosis (MS), systemic lupus erythematosus (SLE), juvenile rheumatoid arthritis (JRA), Crohn's disease (CD), ulcerative colitis (UC) and type 1 diabetes (T1D). These data were analyzed concurrently by statistical and systems biology approaches tailored for this purpose. We found that chemokines such as CXCL1-3, 5, 6 and the interleukin (IL) IL8 tend to be differentially expressed in PBMCs of patients with the analyzed autoimmune diseases. In addition, the anti-apoptotic gene BCL3, interferon-γ (IFNG), and the vitamin D receptor (VDR) gene physically interact with significantly many genes that tend to be differentially expressed in PBMCs of patients with the analyzed autoimmune diseases. In general, similar cellular processes tend to be differentially expressed in PBMC in the analyzed autoimmune diseases. Specifically, the cellular processes related to cell proliferation (for example, epidermal growth factor, platelet-derived growth factor, nuclear factor-κB, Wnt/β-catenin signaling, stress-activated protein kinase c-Jun NH2-terminal kinase), inflammatory response (for example, interleukins IL2 and IL6, the cytokine granulocyte-macrophage colony-stimulating factor and the B-cell receptor), general signaling cascades (for example, mitogen-activated protein kinase, extracellular signal-regulated kinase, p38 and TRK) and apoptosis are activated in most of the analyzed autoimmune diseases. However, our results suggest that in each of the analyzed diseases, apoptosis and chemotaxis are activated via

  4. Employment characteristics of a complex adult congenital heart disease cohort.

    Science.gov (United States)

    Pickup, L; Gaffey, T; Clift, P; Bowater, S; Thorne, S; Hudsmith, L

    2017-08-01

    Due to advances in surgical techniques and subsequent management, there have been remarkable improvements in the survival of patients with congenital heart disease. In particular, larger numbers of patients with complex disease are now living into adulthood and are entering the workforce. To establish the types of employment complex adult congenital heart disease (ACHD) patients are engaged in, based on the largest cohort of patients with a single-ventricle circulation in the UK. Records of all patients with a univentricular (Fontan) circulation at the Queen Elizabeth Hospital were reviewed. Employment status was categorized according to the Standard Occupational Classification criteria (2010). A total of 210 patient records were reviewed. There was the same proportion of professionals in our cohort compared to the rest of the UK (20% versus 20%). There were greater proportions working in the caring, leisure and other service occupations (15% versus 9%), the elementary occupations (17% versus 11%), sales and customer service occupations (14% versus 8%) and administrative and secretarial occupations (12% versus 11%). The reverse trend was observed for associate professions and technical occupations (7% versus 14%), skilled trades (10% versus 11%), process, plant and machine operatives (3% versus 6%) and managers, directors and senior officials (2% versus 10%). The data show that ACHD patients with a single ventricle are engaged in a diverse range of occupations. It is essential that early education and employment advice are given to this cohort to maximize future employment potential.

  5. Mechanical stress as the common denominator between chronic inflammation, cancer and Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Marcel eLevy Nogueira

    2015-09-01

    Full Text Available The pathogenesis of common diseases such as Alzheimer’s disease (AD and cancer are currently poorly understood. Inflammation is a common risk factor for cancer and AD. Recent data, provided by our group and from others, demonstrate that increased pressure and inflammation are synonymous. There is a continuous increase in pressure from inflammation to fibrosis and then cancer. This in line with the numerous papers reporting high interstitial pressure in cancer. But most authors focus on the role of pressure in the lack of delivery of chemotherapy in the center of the tumor. Pressure may also be a key factor in carcinogenesis. Increased pressure is responsible for oncogene activation and cytokine secretion. Accumulation of mechanical stress plays a key role in the development of diseases of old age such as cardiomyopathy, atherosclerosis and osteoarthritis. Growing evidence suggest also a possible link between mechanical stress in the pathogenesis of AD. The aim of this review is to describe environmental and endogenous mechanical factors possibly playing a pivotal role in the mechanism of chronic inflammation, AD and cancer.

  6. Common mental disorders and psychological distress in systemic lupus erythematosus are not associated with disease activity.

    Science.gov (United States)

    Jarpa, E; Babul, M; Calderón, J; González, M; Martínez, M E; Bravo-Zehnder, M; Henríquez, C; Jacobelli, S; González, A; Massardo, L

    2011-01-01

    Psychiatric diagnosis in patients with systemic lupus erythematosus (SLE) is controversial: variations have been reported in frequency, diagnostic assays, associations with disease activity, autoantibodies, and contributing social factors. Eighty-three consecutive non-selected Chilean patients with SLE were evaluated for: (i) 26 common mental disorders according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), using the Mini-International Neuropsychiatric Interview (MINI-plus); (ii) psychological suffering measured by Hospital Anxiety and Depression Scale (HADS); (iii) ACR 1999 neuropsychiatric (NP)SLE criteria; (iv) SLE disease activity (SLEDAI-2K); (v) cumulative damage (SLICC/ACR); and (vi) anti-ribosomal P antibodies by enzyme-linked immunoassay and immunoblot. Psychiatric diagnoses occurred in 44.6% of patients; the most frequent (21.7%) was major depressive episode (MDE). No association with lupus activity was observed in patients with a DSM-IV diagnosis or MDE or psychological suffering. ACR 1999 NPSLE criteria were present in 42.2% of patients, the majority corresponding to mood (28.9%) or anxiety disorders (15.6%). Suicidal risk was present in 9.6% of patients. Anti-ribosomal P antibodies (13.3%) were not associated with DSM-IV diagnosis. Severe psychiatric disorders in SLE are common and not associated with disease activity.

  7. The Enemy Within: Innate Surveillance-mediated Cell Death, the common mechanism of neurodegenerative disease

    Directory of Open Access Journals (Sweden)

    Robert Ian Richards

    2016-05-01

    Full Text Available Neurodegenerative diseases comprise an array of progressive neurological disorders all characterized by the selective death of neurons in the central nervous system. Although rare (familial and common (sporadic forms can occur for the same disease, it is unclear whether this reflects several distinct pathogenic pathways or the convergence of different causes into a common form of nerve cell death. Remarkably, neurodegenerative diseases are increasingly found to be accompanied by activation of the innate immune surveillance system normally associated with pathogen recognition and response. Innate surveillance is the cell’s quality control system for the purpose of detecting such danger signals and responding in an appropriate manner. Innate surveillance is an ‘intelligent system’, in that the manner of response is relevant to the magnitude and duration of the threat. If possible, the threat is dealt with within the cell in which it is detected, by degrading the danger signal(s and restoring homeostasis. If this is not successful then an inflammatory response is instigated that is aimed at restricting the spread of the threat by elevating degradative pathways, sensitizing neighboring cells, and recruiting specialized cell types to the site. If the danger signal persists, then the ultimate response can include not only the programmed cell death of the original cell, but the contents of this dead cell can also bring about the death of adjacent sensitized cells. These responses are clearly aimed at destroying the ability of the detected pathogen to propagate and spread. Innate surveillance comprises intracellular, extracellular, non-cell autonomous and systemic processes. Recent studies have revealed how multiple steps in these processes involve proteins that, through their mutation, have been linked to many familial forms of neurodegenerative disease. This suggests that individuals harboring these mutations may have an amplified response to

  8. Genetic architecture of quantitative traits and complex diseases.

    Science.gov (United States)

    Fu, Wenqing; O'Connor, Timothy D; Akey, Joshua M

    2013-12-01

    More than 150 years after Mendel discovered the laws of heredity, the genetic architecture of phenotypic variation remains elusive. Here, we discuss recent progress in deciphering how genotypes map onto phenotypes, sources of genetic complexity, and how model organisms are illuminating general principles about the relationship between genetic and phenotypic variation. Moreover, we highlight insights gleaned from large-scale sequencing studies in humans, and how this knowledge informs outstanding questions about the genetic architecture of quantitative traits and complex diseases. Finally, we articulate how the confluence of technologies enabling whole-genome sequencing, comprehensive phenotyping, and high-throughput functional assays of polymorphisms will facilitate a more principled and mechanistic understanding of the genetic architecture of phenotypic variation.

  9. A new conceptual framework for investigating complex genetic disease

    Science.gov (United States)

    Hussain, Shobbir

    2015-01-01

    Some common diseases are known to have an inherited component, however, their population- and familial-incidence patterns do not conform to any known monogenic Mendelian pattern of inheritance and instead they are currently much better explained if an underlying polygenic architecture is posited. Studies that have attempted to identify the causative genetic factors have been designed on this polygenic framework, but so far the yield has been largely unsatisfactory. Based on accumulating recent observations concerning the roles of somatic mosaicism in disease, in this article a second framework which posits a single gene-two hit model which can be modulated by a mutator/anti-mutator genetic background is suggested. I discuss whether such a model can be considered a viable alternative based on current knowledge, its advantages over the current polygenic framework, and describe practical routes via which the new framework can be investigated. PMID:26583033

  10. T-SPOT.TB Test(R) results in adults with Mycobacterium avium complex pulmonary disease.

    Science.gov (United States)

    Adams, Lisa V; Waddell, Richard D; Von Reyn, C Fordham

    2008-01-01

    The tuberculin skin test is limited by its inability to distinguish between infection with Mycobacterium tuberculosis and non-tuberculous mycobacteria (NTM). Newer interferon-gamma release assays using ESAT-6 and CFP-10 antigens should have a higher specificity for tuberculosis but have not been widely tested in adults with pulmonary disease due to NTM. In this study, we tested the T-SPOT.TB Test in patients with pulmonary disease due to Mycobacterium avium complex (MAC), the most common disease-causing NTM. Fourteen patients with prior culture-confirmed pulmonary disease due to MAC, 10 patients with prior culture-confirmed tuberculosis and 4 healthy controls were interviewed and tested with the T-SPOT.TB Test. 13 patients with MAC disease and 4 healthy subjects (negative controls) had non-reactive T-SPOT.TB results and 10 patients with prior tuberculosis (positive controls) had reactive results. One patient with MAC disease had a minimally reactive result on initial testing and a non-reactive result on re-testing. The T-SPOT.TB Test had a specificity of 94% for distinguishing between patients with prior MAC disease and prior tuberculosis disease, and will be useful in low tuberculosis prevalence settings where most mycobacterial infections are due to MAC. Reactions to the T-SPOT.TB Test may persist months to years after treatment of tuberculosis.

  11. An animal model that reflects human disease: the common marmoset (Callithrix jacchus).

    Science.gov (United States)

    Carrion, Ricardo; Patterson, Jean L

    2012-06-01

    The common marmoset is a new world primate belonging to the Callitrichidae family weighing between 350 and 400 g. The marmoset has been shown to be an outstanding model for studying aging, reproduction, neuroscience, toxicology, and infectious disease. With regard to their susceptibility to infectious agents, they are exquisite NHP models for viral, protozoan and bacterial agents, as well as prions. The marmoset provides the advantages of a small animal model in high containment coupled with the immunological repertoire of a nonhuman primate and susceptibility to wild type, non-adapted viruses.

  12. Is there a common basis between hiatal hernia and hemorrhoidal disease?

    Science.gov (United States)

    Sahiner, Zeynep; Uzel, Mehmet; Filik, Levent

    2015-05-01

    In this letter-to-editor, we hypothesize that there is a link between hemorrhoidal disease and hiatal hernia. We underline common risk factors for both and present a cross-sectional patient data. Therefore, we emphasize the necessity of new studies to clarify this coincidence. Clinical benefit of establishment of this link is to delay or prevent development of hiatal hernia as a result of appropriate preventive measures. Accordingly, postoperative period of hiatal hernia operations may also be relieved or recurrence risk may also be decreased with this precautions.

  13. Cytomegalovirus Colitis with Common Variable Immunodeficiency and Crohn’s Disease

    Directory of Open Access Journals (Sweden)

    Betül Ünal

    2015-01-01

    Full Text Available Here we present an eleven-year-old male patient who had been diagnosed with common variable immunodeficiency (CVID three years ago due to recurrent sinopulmonary infections. Two years later he had been diagnosed with Crohn’s disease (CD due to diarrhea episodes which were unresponsive to the treatment. Depending on the active gastrointestinal bleeding and perforation he underwent total colectomy. Despite immunoglobulin and antiviral therapies, general condition of patient deteriorated and he died in the postoperative seventh day. Laboratory analysis was seronegative. CMV inclusion containing cells were detected in postmortem biopsies taken from liver, lungs, and lymph nodes.

  14. Hashimoto′s encephalopathy and motor neuron disease: A common autoimmune pathogenesis?

    Directory of Open Access Journals (Sweden)

    Harzheim Michael

    2006-01-01

    Full Text Available Hashimoto′s encephalopathy is a rare complication of autoimmune thyroiditis not associated with thyroidal function decline. We report a 50-year-old man presenting with lower motor neuron symptoms evolving over 3 years and changes in behavior associated with attentive and cognitive impairment occurring in the last few months. Memory deficits, emotional instability, marked dysarthria, mild symmetric weakness of the lower extremities, and fasciculations were the most striking clinical features. EEG was diffusely slow, cranial MRI revealed multiple subcortical white matter lesions, CSF protein was slightly elevated, electromyographic recordings showed acute and chronic denervation, and extremely high TPO antibody titers were found in the serum. Hashimoto′s encephalopathy and lower motor neuron disease were diagnosed. As repeated high-dose intravenous methylprednisolone administration followed by oral tapering improved both central nervous system and lower motor neuron symptoms, the question was raised whether there was a common autoimmune pathogenesis of both clinically distinct diseases.

  15. Iron Deficiency Is Common During Remission in Children With Inflammatory Bowel Disease.

    Science.gov (United States)

    Wikholm, Emma; Malmborg, Petter; Forssberg, Maria; Hederos, Carl-Axel; Wikström, Sverre

    2016-01-01

    The aim was to study prevalence of iron deficiency in children with inflammatory bowel disease (IBD) during remission. In addition, there was an observational evaluation of hematological response to oral iron. A population-based retrospective study including 90 Swedish children (median 13 years) with IBD was performed. Patient records covered in median 25 months. Iron deficiency was present in 70/77 children (91%) in which iron status could be assessed. In clinical and biochemical remission, iron deficiency was found in 57/67 (85%) of children, and 23 (34%) of them had iron deficiency anemia. Thirty-six iron-deficient children were prescribed oral iron supplementation and 32 (89%) improved hemoglobin levels over 6 months. In conclusion, iron deficiency is common during clinical remission in children with IBD, even in cohorts with low prevalence of anemia. Therefore, regular biochemical screening for iron deficiency is warranted during all stages of disease, irrespective of symptoms and inflammatory blood markers.

  16. Complex Formation of Selected Radionuclides with Ligands Commonly Found in Ground Water: Low Molecular Organic Acids

    DEFF Research Database (Denmark)

    Jensen, Bror Skytte; Jensen, H.

    1985-01-01

    A general approach to the analysis of potentiometric data on complex formation between cations and polybasic amphoteric acids is described. The method is used for the characterisation of complex formation between Cs+, Sr2+, Co2+, La 3+, and Eu3+ with a α-hydroxy acids, tartaric acid and citric ac......, and with the α-amino acids, aspartic acid and L-cysteine. The cations have been chosen as typical components of reactor waste, and the acids because they are often found as products of microbial activity in pits or wherever organic material decays...

  17. Combining information from common type 2 diabetes risk polymorphisms improves disease prediction.

    Directory of Open Access Journals (Sweden)

    Michael N Weedon

    2006-10-01

    Full Text Available A limited number of studies have assessed the risk of common diseases when combining information from several predisposing polymorphisms. In most cases, individual polymorphisms only moderately increase risk (approximately 20%, and they are thought to be unhelpful in assessing individuals' risk clinically. The value of analyzing multiple alleles simultaneously is not well studied. This is often because, for any given disease, very few common risk alleles have been confirmed.Three common variants (Lys23 of KCNJ11, Pro12 of PPARG, and the T allele at rs7903146 of TCF7L2 have been shown to predispose to type 2 diabetes mellitus across many large studies. Risk allele frequencies ranged from 0.30 to 0.88 in controls. To assess the combined effect of multiple susceptibility alleles, we genotyped these variants in a large case-control study (3,668 controls versus 2,409 cases. Individual allele odds ratios (ORs ranged from 1.14 (95% confidence interval [CI], 1.05 to 1.23 to 1.48 (95% CI, 1.36 to 1.60. We found no evidence of gene-gene interaction, and the risks of multiple alleles were consistent with a multiplicative model. Each additional risk allele increased the odds of type 2 diabetes by 1.28 (95% CI, 1.21 to 1.35 times. Participants with all six risk alleles had an OR of 5.71 (95% CI, 1.15 to 28.3 compared to those with no risk alleles. The 8.1% of participants that were double-homozygous for the risk alleles at TCF7L2 and Pro12Ala had an OR of 3.16 (95% CI, 2.22 to 4.50, compared to 4.3% with no TCF7L2 risk alleles and either no or one Glu23Lys or Pro12Ala risk alleles.Combining information from several known common risk polymorphisms allows the identification of population subgroups with markedly differing risks of developing type 2 diabetes compared to those obtained using single polymorphisms. This approach may have a role in future preventative measures for common, polygenic diseases.

  18. What causes myopia? : Complex genetics and epidemiology of a common condition

    NARCIS (Netherlands)

    V.J.M. Verhoeven (Virginie)

    2015-01-01

    markdownabstract__Abstract__ Myopia (nearsightedness) is a highly common eye condition that is predominantly caused by an axial elongation of the eye. Myopia can usually be corrected with negative glasses, contact lenses, and/or laser refractive surgery. Unfortunately, however, high myopia (-6 diop

  19. Current trends in pharmacy benefit designs: a threat to disease management in chronic complex diseases.

    Science.gov (United States)

    Owens, Gary; Emons, Matthew F; Christian-Herman, Jennifer; Lawless, Grant

    2007-04-01

    With a focus on those patients who are candidates for treatment with biologic agents, we review the impact that current pharmacy benefit trends have on patients with chronic complex diseases and how they affect opportunities for disease management in this unique patient population. Dramatic increases in health care costs have led to a variety of strategies to manage cost. Many of these strategies either limit access to care or increase the patient's responsibility for choosing and paying for care, especially for medications. These strategies have a disproportionate impact on patients with chronic complex diseases, particularly those who require the use of biologic medications. A fundamental prerequisite of disease management has been coverage of disease-modifying therapies. If current pharmacy benefit trends continue, unintended consequences will likely occur including lost opportunities for disease management. Current pharmacy benefit trends could adversely impact disease management, particularly for patients requiring the use of biologic agents. Health plans should consider innovative benefit designs that reflect an appropriate level of cost sharing across all key stake-holders, ensuring appropriate access to needed therapies. Additional research is needed to clarify the value of newer approaches to therapies or benefit design changes.

  20. [Sickle cell anemia causes varied symptoms and high morbidity. Serious prognosis in the most common genetic disease in the world].

    Science.gov (United States)

    Kjellander, Christian; Sennström, Maria K B; Stiller, Viveka; Ågren, Anna

    2015-03-03

    Sickle cell anemia is a life-threatening disease, and the most common genetic disease in the world. The prevalence of sickle cell anemia in Sweden is unknown. Sickle cell anemia is an important disease, because of its variable complications, in many medical and surgical specialties. The overview highlights common medical problems encountered in sickle cell anemia presented through a case report of a pregnant woman.

  1. Poverty, disease, and the ecology of complex systems.

    Science.gov (United States)

    Ngonghala, Calistus N; Pluciński, Mateusz M; Murray, Megan B; Farmer, Paul E; Barrett, Christopher B; Keenan, Donald C; Bonds, Matthew H

    2014-04-01

    Understanding why some human populations remain persistently poor remains a significant challenge for both the social and natural sciences. The extremely poor are generally reliant on their immediate natural resource base for subsistence and suffer high rates of mortality due to parasitic and infectious diseases. Economists have developed a range of models to explain persistent poverty, often characterized as poverty traps, but these rarely account for complex biophysical processes. In this Essay, we argue that by coupling insights from ecology and economics, we can begin to model and understand the complex dynamics that underlie the generation and maintenance of poverty traps, which can then be used to inform analyses and possible intervention policies. To illustrate the utility of this approach, we present a simple coupled model of infectious diseases and economic growth, where poverty traps emerge from nonlinear relationships determined by the number of pathogens in the system. These nonlinearities are comparable to those often incorporated into poverty trap models in the economics literature, but, importantly, here the mechanism is anchored in core ecological principles. Coupled models of this sort could be usefully developed in many economically important biophysical systems--such as agriculture, fisheries, nutrition, and land use change--to serve as foundations for deeper explorations of how fundamental ecological processes influence structural poverty and economic development.

  2. Emerging treatments for complex perianal fistula in Crohn's disease

    Institute of Scientific and Technical Information of China (English)

    Carlos Taxonera; David A Schwartz; Damián Garc(i)a-Olmo

    2009-01-01

    Complex perianal fistulas have a negative impact on the quality of life of sufferers and should be treated. Correct diagnosis, characterization and classification of the fistulas are essential to optimize treatment. Nevertheless, in the case of patients whose fistulas are associated with Crohn's disease, complete closure is particularly difficult to achieve. Systemic medical treatments (antibiotics, thiopurines and other immunomodulatory agents, and, more recently, anti-tumor necrosis factor-α agents such as infliximab) have been tried with varying degrees of success. Combined medical (including infliximab) and less aggressive surgical therapy (drainage and seton placement) offer the best outcomes in complex Crohn's fistulas while more aggressive surgical procedures such as fistulotomy or fistulectomy may increase the risk of incontinence. This review will focus on emerging novel treatments for perianal disease in Crohn's patients. These include locally applied infliximab or tacrolimus, fistula plugs, instillation of fibrin glue and the use of adult expanded adipose-derived stem cell injection. More welldesigned controlled studies are required to confirm the effectiveness of these emerging treatments.

  3. Common Ground: An Interactive Visual Exploration and Discovery for Complex Health Data

    Science.gov (United States)

    2014-04-01

    conduct contextual interview at their laboratory. APL has been developing the Essence and Essence II Syndromic surveillance systems and would have been an...disease like the weather.” o “Forecasting is generally not accurate.” Data%trigger%actions%based%on%thresholds% • “ Chicken pox is endemic but 5 or more

  4. Common Warts

    Science.gov (United States)

    Diseases and Conditions Common warts By Mayo Clinic Staff Common warts are small, grainy skin growths that occur most often on your fingers or hands. Rough to the touch, common warts also often feature a pattern of tiny ...

  5. Persistence of the common Hartnup disease D173N allele in populations of European origin.

    Science.gov (United States)

    Azmanov, Dimitar N; Rodgers, Helen; Auray-Blais, Christiane; Giguère, Robert; Bailey, Charles; Bröer, Stefan; Rasko, John E J; Cavanaugh, Juleen A

    2007-11-01

    Hartnup disorder is an aminoaciduria that results from mutations in the recently described gene SLC6A19 on chromosome 5p15.33. The disease is inherited in a simple recessive manner and ten different mutations have been described to date. One mutation, the D173N allele, is present in 42% of Hartnup chromosomes from apparently unrelated families from both Australia and North America. We report an investigation of the origins of the D173N allele using a unique combination of variants including SNPs, microsatellites, and a VNTR across 211 Kb spanning the SLC6A19 locus. All individuals who carry the mutant allele share an identical core haplotype suggesting a single common ancestor, indicating that the elevated frequency of the D173N allele is not a result of recurrent mutation. Analyses of these data indicate that the allele is more than 1000 years old. We compare the reasons for survival of this allele with other major alleles in some other common autosomal recessive diseases occurring in European Caucasians. We postulate that survival of this allele may be a consequence of failure of the allele to completely inactivate the transport of neutral amino acids.

  6. Three classes of inhibitors share a common binding domain in mitochondrial complex I (NADH:ubiquinone oxidoreductase).

    Science.gov (United States)

    Okun, J G; Lümmen, P; Brandt, U

    1999-01-29

    We have developed two independent methods to measure equilibrium binding of inhibitors to membrane-bound and partially purified NADH:ubiquinone oxidoreductase (complex I) to characterize the binding sites for the great variety of hydrophobic compounds acting on this large and complicated enzyme. Taking advantage of a partial quench of fluorescence upon binding of the fenazaquin-type inhibitor 2-decyl-4-quinazolinyl amine to complex I in bovine submitochondrial particles, we determined a Kd of 17 +/- 3 nM and one binding site per complex I. Equilibrium binding studies with [3H]dihydrorotenone and the aminopyrimidine [3H]AE F119209 (4(cis-4-[3H]isopropyl cyclohexylamino)-5-chloro-6-ethyl pyrimidine) using partially purified complex I from Musca domestica exhibited little unspecific binding and allowed reliable determination of dissociation constants. Competition experiments consistently demonstrated that all tested hydrophobic inhibitors of complex I share a common binding domain with partially overlapping sites. Although the rotenone site overlaps with both the piericidin A and the capsaicin site, the latter two sites do not overlap. This is in contrast to the interpretation of enzyme kinetics that have previously been used to define three classes of complex I inhibitors. The existence of only one large inhibitor binding pocket in the hydrophobic part of complex I is discussed in the light of possible mechanisms of proton translocation.

  7. TDP-43/FUS in motor neuron disease: Complexity and challenges.

    Science.gov (United States)

    Guerrero, Erika N; Wang, Haibo; Mitra, Joy; Hegde, Pavana M; Stowell, Sara E; Liachko, Nicole F; Kraemer, Brian C; Garruto, Ralph M; Rao, K S; Hegde, Muralidhar L

    Amyotrophic lateral sclerosis (ALS), a common motor neuron disease affecting two per 100,000 people worldwide, encompasses at least five distinct pathological subtypes, including, ALS-SOD1, ALS-C9orf72, ALS-TDP-43, ALS-FUS and Guam-ALS. The etiology of a major subset of ALS involves toxicity of the TAR DNA-binding protein-43 (TDP-43). A second RNA/DNA binding protein, fused in sarcoma/translocated in liposarcoma (FUS/TLS) has been subsequently associated with about 1% of ALS patients. While mutations in TDP-43 and FUS have been linked to ALS, the key contributing molecular mechanism(s) leading to cell death are still unclear. One unique feature of TDP-43 and FUS pathogenesis in ALS is their nuclear clearance and simultaneous cytoplasmic aggregation in affected motor neurons. Since the discoveries in the last decade implicating TDP-43 and FUS toxicity in ALS, a majority of studies have focused on their cytoplasmic aggregation and disruption of their RNA-binding functions. However, TDP-43 and FUS also bind to DNA, although the significance of their DNA binding in disease-affected neurons has been less investigated. A recent observation of accumulated genomic damage in TDP-43 and FUS-linked ALS and association of FUS with neuronal DNA damage repair pathways indicate a possible role of deregulated DNA binding function of TDP-43 and FUS in ALS. In this review, we discuss the different ALS disease subtypes, crosstalk of etiopathologies in disease progression, available animal models and their limitations, and recent advances in understanding the specific involvement of RNA/DNA binding proteins, TDP-43 and FUS, in motor neuron diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. The model of complexity against common psychological anxiety towards death models

    OpenAIRE

    Álvarez, Leonardo Yovany; Universidad Autónoma de Bucaramanga

    2016-01-01

    Anxiety towards death has been a subject of investigation since different psychological perspectives. It takes part in tanatology courses directed for health careers students and for health professional attending terminal patients. Anxiety towards death is a complex phenomenon which involves the individual coping skills but also the confrontation of the individual´s whole life experience, the integration of it and the expectations and living resolutions, the mourning into a implacable time. T...

  9. Neuroticism and Common Mental Disorders: Meaning and Utility of a Complex Relationship

    Science.gov (United States)

    Ormel, Johan; Riese, Harriëtte; Bos, Elisabeth H.; Hankin, Benjamin; Rosmalen, Judith G. M.; Oldehinkel, Albertine J.

    2015-01-01

    Neuroticism's prospective association with common mental disorders (CMDs) has fueled the assumption that neuroticism is an independent etiologically informative risk factor. This vulnerability model postulates that neuroticism sets in motion processes that lead to CMDs. However, four other models seek to explain the association, including the spectrum model (manifestations of the same process), common cause model (shared determinants), state and scar models (CMD episode adds temporary / permanent neuroticism). To examine their validity we reviewed literature on confounding, operational overlap, stability and change, determinants, and treatment effects. None of the models is able to account for (virtually) all findings. The state and scar model cannot explain the prospective association. The spectrum model has some relevance, especially for internalizing disorders. Common causes are most important but the vulnerability model cannot be excluded although confounding of the prospective association by baseline symptoms and psychiatric history is substantial. In fact, some of the findings, such as interactions with stress and the small decay of neuroticism's effect over time, are consistent with the vulnerability model. We describe research designs that discriminate the remaining models and plea for deconstruction of neuroticism. Neuroticism is etiologically not informative yet but useful as an efficient marker of non-specified general risk. PMID:23702592

  10. Cryptic genetic variation can make "irreducible complexity" a common mode of adaptation in sexual populations.

    Science.gov (United States)

    Trotter, Meredith V; Weissman, Daniel B; Peterson, Grant I; Peck, Kayla M; Masel, Joanna

    2014-12-01

    The existence of complex (multiple-step) genetic adaptations that are "irreducible" (i.e., all partial combinations are less fit than the original genotype) is one of the longest standing problems in evolutionary biology. In standard genetics parlance, these adaptations require the crossing of a wide adaptive valley of deleterious intermediate stages. Here, we demonstrate, using a simple model, that evolution can cross wide valleys to produce "irreducibly complex" adaptations by making use of previously cryptic mutations. When revealed by an evolutionary capacitor, previously cryptic mutants have higher initial frequencies than do new mutations, bringing them closer to a valley-crossing saddle in allele frequency space. Moreover, simple combinatorics implies an enormous number of candidate combinations exist within available cryptic genetic variation. We model the dynamics of crossing of a wide adaptive valley after a capacitance event using both numerical simulations and analytical approximations. Although individual valley crossing events become less likely as valleys widen, by taking the combinatorics of genotype space into account, we see that revealing cryptic variation can cause the frequent evolution of complex adaptations.

  11. Structure of a Blm10 Complex Reveals Common Mechanisms for Proteasome Binding and Gate Opening

    Energy Technology Data Exchange (ETDEWEB)

    Sadre-Bazzaz, K.; Robinson, H.; Whitby, F. G.; Formosa, T.; Hill, C. P.

    2010-03-12

    The proteasome is an abundant protease that is critically important for numerous cellular pathways. Proteasomes are activated in vitro by three known classes of proteins/complexes, including Blm10/PA200. Here, we report a 3.4 {angstrom} resolution crystal structure of a proteasome-Blm10 complex, which reveals that Blm10 surrounds the proteasome entry pore in the 1.2 MDa complex to form a largely closed dome that is expected to restrict access of potential substrates. This architecture and the observation that Blm10 induces a disordered proteasome gate structure challenge the assumption that Blm10 functions as an activator of proteolysis in vivo. The Blm10 C terminus binds in the same manner as seen for 11S activators and inferred for 19S/PAN activators and indicates a unified model for gate opening. We also demonstrate that Blm10 acts to maintain mitochondrial function. Consistent with the structural data, the C-terminal residues of Blm10 are needed for this activity.

  12. Therapeutic treatment of Alzheimer's disease using metal complexing agents.

    Science.gov (United States)

    Price, Katherine A; Crouch, Peter J; White, Anthony R

    2007-11-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by deposition of extracellular amyloid plaques, formation of intracellular neurofibrillary tangles and neuronal dysfunction in the brain. A growing body of evidence indicates a central role for biometals such as copper in many critical aspects of AD. The amyloid beta (Abeta) peptide and its parental molecule, the amyloid precursor protein (APP) both modulate Cu and Zn metabolism in the brain. Therefore, aberrant changes to APP or Abeta metabolism could potentially alter biometal homoestasis in AD, leading to increased free radical production and neuronal oxidative stress. Modulation of metal bioavailability in the brain has been proposed as a potential therapeutic strategy for treatment of AD patients. The lipid permeable metal complexing agent, clioquinol (CQ), has shown promising results in animal models of AD and in small clinical trials involving AD patients. Moreover, a new generation of metal-ligand based therapeutics is currently under development. Patents now cover the generation of novel metal ligand structures designed to modulate metal binding to Abeta and quench metal-mediated free radical generation. However, the mechanism by which CQ and other metal complexing agents slows cognitive decline in AD animal models and patients is unknown. Increasing evidence suggests that ligand-mediated redistribution of metals at a cellular level in the brain may be important. Further research will be necessary to fully understand the complex pathways associated with efficacious metal-based pharmaceuticals for treatment of AD.

  13. Genome-wide interaction-based association analysis identified multiple new susceptibility Loci for common diseases.

    Directory of Open Access Journals (Sweden)

    Yang Liu

    2011-03-01

    Full Text Available Genome-wide interaction-based association (GWIBA analysis has the potential to identify novel susceptibility loci. These interaction effects could be missed with the prevailing approaches in genome-wide association studies (GWAS. However, no convincing loci have been discovered exclusively from GWIBA methods, and the intensive computation involved is a major barrier for application. Here, we developed a fast, multi-thread/parallel program named "pair-wise interaction-based association mapping" (PIAM for exhaustive two-locus searches. With this program, we performed a complete GWIBA analysis on seven diseases with stringent control for false positives, and we validated the results for three of these diseases. We identified one pair-wise interaction between a previously identified locus, C1orf106, and one new locus, TEC, that was specific for Crohn's disease, with a Bonferroni corrected P < 0.05 (P = 0.039. This interaction was replicated with a pair of proxy linked loci (P = 0.013 on an independent dataset. Five other interactions had corrected P < 0.5. We identified the allelic effect of a locus close to SLC7A13 for coronary artery disease. This was replicated with a linked locus on an independent dataset (P = 1.09 × 10⁻⁷. Through a local validation analysis that evaluated association signals, rather than locus-based associations, we found that several other regions showed association/interaction signals with nominal P < 0.05. In conclusion, this study demonstrated that the GWIBA approach was successful for identifying novel loci, and the results provide new insights into the genetic architecture of common diseases. In addition, our PIAM program was capable of handling very large GWAS datasets that are likely to be produced in the future.

  14. A review of Vitamin D effects on common respiratory diseases: Asthma, chronic obstructive pulmonary disease, and tuberculosis.

    Science.gov (United States)

    Hejazi, Mohammad Esmaeil; Modarresi-Ghazani, Faezeh; Entezari-Maleki, Taher

    2016-01-01

    Despite the classic role of Vitamin D in skeletal health, new aspects of Vitamin D have been discovered in tissues and organs other than bones. Epidemiological and observational studies demonstrate a link between Vitamin D deficiency and risk of developing respiratory diseases including asthma, chronic obstructive pulmonary disease (COPD), and tuberculosis (TB). To review the literature, we searched the terms "Vitamin D" (using the set operator) and "asthma," "COPD" and "TB" in electronic databases, including PubMed/MEDLINE, Scopus, and Google Scholar until July 2015. Non-English articles or articles with unavailable full text were excluded. Both in vivo and in vitro studies were included. All the reviewed articles state that Vitamin D deficiency is very common among patients with respiratory diseases. The present data regarding Vitamin D and asthma is still controversial, but data about COPD and TB are more encouraging. The relevant studies have been conducted in different populations therefore it is not particularly possible to compare the data due to genetic variations. In order to point out a role for Vitamin D, large clinical trials with Vitamin D deficient subjects and sufficient Vitamin D supplementation are needed.

  15. Unintended consequences of conservation actions: managing disease in complex ecosystems.

    Directory of Open Access Journals (Sweden)

    Aliénor L M Chauvenet

    Full Text Available Infectious diseases are increasingly recognised to be a major threat to biodiversity. Disease management tools such as control of animal movements and vaccination can be used to mitigate the impact and spread of diseases in targeted species. They can reduce the risk of epidemics and in turn the risks of population decline and extinction. However, all species are embedded in communities and interactions between species can be complex, hence increasing the chance of survival of one species can have repercussions on the whole community structure. In this study, we use an example from the Serengeti ecosystem in Tanzania to explore how a vaccination campaign against Canine Distemper Virus (CDV targeted at conserving the African lion (Panthera leo, could affect the viability of a coexisting threatened species, the cheetah (Acinonyx jubatus. Assuming that CDV plays a role in lion regulation, our results suggest that a vaccination programme, if successful, risks destabilising the simple two-species system considered, as simulations show that vaccination interventions could almost double the probability of extinction of an isolated cheetah population over the next 60 years. This work uses a simple example to illustrate how predictive modelling can be a useful tool in examining the consequence of vaccination interventions on non-target species. It also highlights the importance of carefully considering linkages between human-intervention, species viability and community structure when planning species-based conservation actions.

  16. Polypharmacy and enteral nutrition in patients with complex chronic diseases

    Science.gov (United States)

    Romero Jiménez, Rosa Mª; Ortega Navarro, Cristina; Cuerda Compés, Cristina

    2017-05-08

    Oral medications are often administered through enteral feeding tubes in patients with complex chronic diseases. It is important to consider possible interactions between drugs and enteral nutrition that might lead to unsuccessful treatment or tube occlusion. These patients become subjects for higher risk of problems and errors such as drug incompatibility with enteral nutrition and inappropriate dosage form selection. It is possible to minimize the risk of tube occlusion and incompatibilities problems by recognizing potential medication errors, selecting the most appropriate drug and dosage form and using appropriate administration techniques. In this context, high-alert medications for patients with chronic diseases deserve special attention. Furthermore, risk exposure should be considered among healthcare professionals and patient caregivers handling hazardous drugs. Therefore, main incompatibility problems between drugs and enteral nutrition have been reviewed, including general recommendations for administration of oral medications through enteral feeding tubes and safe handling of hazardous drugs. Specific recommendations for administration of high-alert medications for patients with chronic diseases are also included.

  17. Commonalities in biological pathways, genetics, and cellular mechanism between Alzheimer Disease and other neurodegenerative diseases: An in silico-updated overview.

    Science.gov (United States)

    Ahmad, Khurshid; Baig, Mohammad Hassan; Mushtaq, Gohar; Kamal, Mohammad Amjad; Greig, Nigel H; Choi, Inho

    2017-02-03

    Alzheimer's disease (AD) is the most common and well-studied neurodegenerative disease (ND). Biological pathways, pathophysiology and genetics of AD show commonalities with other NDs viz. Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), Prion Disease and Dentatorubral-pallidoluysian atrophy (DRPLA). Many of the NDs, sharing the common features and molecular mechanisms suggests that pathology may be directly comparable and be implicated in disease prevention and development of highly effective therapies. In this review, a brief description of pathophysiology, clinical symptoms and available treatment of various NDs have been explored with special emphasis on AD. Commonalities in these fatal NDs provide support for therapeutic advancements and enhance the understanding of disease manifestation. The studies concentrating on the commonalities in biological pathways, cellular mechanisms and genetics may provide the scope to researchers to identify few novel common target/s for disease prevention and development of effective common drugs for multi-neurodegenerative diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Learning with distribution of optimized features for recognizing common CT imaging signs of lung diseases

    Science.gov (United States)

    Ma, Ling; Liu, Xiabi; Fei, Baowei

    2017-01-01

    Common CT imaging signs of lung diseases (CISLs) are defined as the imaging signs that frequently appear in lung CT images from patients. CISLs play important roles in the diagnosis of lung diseases. This paper proposes a novel learning method, namely learning with distribution of optimized feature (DOF), to effectively recognize the characteristics of CISLs. We improve the classification performance by learning the optimized features under different distributions. Specifically, we adopt the minimum spanning tree algorithm to capture the relationship between features and discriminant ability of features for selecting the most important features. To overcome the problem of various distributions in one CISL, we propose a hierarchical learning method. First, we use an unsupervised learning method to cluster samples into groups based on their distribution. Second, in each group, we use a supervised learning method to train a model based on their categories of CISLs. Finally, we obtain multiple classification decisions from multiple trained models and use majority voting to achieve the final decision. The proposed approach has been implemented on a set of 511 samples captured from human lung CT images and achieves a classification accuracy of 91.96%. The proposed DOF method is effective and can provide a useful tool for computer-aided diagnosis of lung diseases on CT images.

  19. HUMAN MICROBIOMES AND THEIR ROLES IN DYSBIOSIS, COMMON DISEASES AND NOVEL THERAPEUTIC APPROACHES

    Directory of Open Access Journals (Sweden)

    Jose Ernesto Belizario

    2015-10-01

    Full Text Available The human body is the residence of a large number of commensal (non-pathogenic and pathogenic microbial species that have co-evolved with the human genome, adaptive immune system and diet. With recent advances in DNA-based technologies, we initiated the exploration of bacterial gene functions and their role in human health. The main goal of the human microbiome project is to characterize the abundance, diversity and functionality of the genes present in all microorganisms that permanently live in different sites of the human body. The gut microbiota expresses over 3.3 million bacterial genes, while the human genome expresses only 20 thousand genes. Microbe gene-products exert pivotal functions via the regulation of food digestion and immune system development. Studies are confirming that manipulation of non-pathogenic bacterial strains in the host can stimulate the recovery of the immune response to pathogenic bacteria causing diseases. Different approaches, including the use of nutraceutics (prebiotics and probiotics as well as phages engineered with CRISPR/cas systems and quorum sensing systems have been developed as new therapies for controlling dysbiosis (alterations in microbial community and common diseases (e.g. diabetes and obesity. The designing and production of pharmaceuticals based on our own body’s microbiome is an emerging field and is rapidly growing to be fully explored in the near future. This review provides an outlook on recent findings on the human microbiomes, their impact on health and diseases, and on the development of targeted therapies.

  20. A common brain network links development, aging, and vulnerability to disease.

    Science.gov (United States)

    Douaud, Gwenaëlle; Groves, Adrian R; Tamnes, Christian K; Westlye, Lars Tjelta; Duff, Eugene P; Engvig, Andreas; Walhovd, Kristine B; James, Anthony; Gass, Achim; Monsch, Andreas U; Matthews, Paul M; Fjell, Anders M; Smith, Stephen M; Johansen-Berg, Heidi

    2014-12-09

    Several theories link processes of development and aging in humans. In neuroscience, one model posits for instance that healthy age-related brain degeneration mirrors development, with the areas of the brain thought to develop later also degenerating earlier. However, intrinsic evidence for such a link between healthy aging and development in brain structure remains elusive. Here, we show that a data-driven analysis of brain structural variation across 484 healthy participants (8-85 y) reveals a largely--but not only--transmodal network whose lifespan pattern of age-related change intrinsically supports this model of mirroring development and aging. We further demonstrate that this network of brain regions, which develops relatively late during adolescence and shows accelerated degeneration in old age compared with the rest of the brain, characterizes areas of heightened vulnerability to unhealthy developmental and aging processes, as exemplified by schizophrenia and Alzheimer's disease, respectively. Specifically, this network, while derived solely from healthy subjects, spatially recapitulates the pattern of brain abnormalities observed in both schizophrenia and Alzheimer's disease. This network is further associated in our large-scale healthy population with intellectual ability and episodic memory, whose impairment contributes to key symptoms of schizophrenia and Alzheimer's disease. Taken together, our results suggest that the common spatial pattern of abnormalities observed in these two disorders, which emerge at opposite ends of the life spectrum, might be influenced by the timing of their separate and distinct pathological processes in disrupting healthy cerebral development and aging, respectively.

  1. Common links between metabolic syndrome and inflammatory bowel disease: Current overview and future perspectives.

    Science.gov (United States)

    Michalak, Arkadiusz; Mosińska, Paula; Fichna, Jakub

    2016-08-01

    Metabolic syndrome (MS) features a constellation of central obesity, dyslipidemia, impaired glucose metabolism and often hypertension joined by insulin resistance and chronic inflammation. All these elements greatly raise patient's risk of cardiovascular disease and type 2 diabetes, resulting in an increased mortality. Metabolic syndrome affects approximately 20-25% of the world's adult population and thus it is essential to study its pathophysiology and seek new pharmacological targets. There is a thoroughly studied link between MS and inflammatory diseases of the gastrointestinal (GI) system, i.e. steatohepatitis. However, recent findings also indicate similarities in pathophysiological features between MS and inflammatory bowel disease (IBD), including adipose tissue dysregulation, inadequate immune response, and inflammation. In this review we aim to outline the pathophysiology of MS and emphasize the aspects revealed recently, such as mineralocorticoid activity, involvement of sex hormones and an accompanying increase in prolactin secretion. More importantly, we focus on the common links between MS and IBD. Finally, we describe new strategies and drug targets that may be utilized in MS therapy, namely adiponectin mimetics, GLP-1-based multi agonists, ABCA1 agonists and possible role of miRNA. We also discuss the possible utility of selected agents as adjuvants in IBD therapy.

  2. A Common Framework for the Analysis of Complex Motion? Standstill and Capture Illusions

    Directory of Open Access Journals (Sweden)

    Max Reinhard Dürsteler

    2014-12-01

    Full Text Available A series of illusions was created by presenting stimuli, which consisted of two overlapping surfaces each defined by textures of independent visual features (i.e. modulation of luminance, color, depth, etc.. When presented concurrently with a stationary 2-D luminance texture, observers often fail to perceive the motion of an overlapping stereoscopically defined depth-texture. This illusory motion standstill arises due to a failure to represent two independent surfaces (one for luminance and one for depth textures and motion transparency (the ability to perceive motion of both surfaces simultaneously. Instead the stimulus is represented as a single non-transparent surface taking on the stationary nature of the luminance-defined texture. By contrast, if it is the 2D-luminance defined texture that is in motion, observers often perceive the stationary depth texture as also moving. In this latter case, the failure to represent the motion transparency of the two textures gives rise to illusionary motion capture. Our past work demonstrated that the illusions of motion standstill and motion capture can occur for depth-textures that are rotating, or expanding / contracting, or else spiraling. Here I extend these findings to include stereo-shearing. More importantly, it is the motion (or lack thereof of the luminance texture that determines how the motion of the depth will be perceived. This observation is strongly in favor of a single pathway for complex motion that operates on luminance-defines texture motion signals only. In addition, these complex motion illusions arise with chromatically-defined textures with smooth, transitions between their colors. This suggests that in respect to color motion perception the complex motions’ pathway is only able to accurately process signals from isoluminant colored textures with sharp transitions between colors, and/or moving at high speeds, which is conceivable if it relies on inputs from a hypothetical dual

  3. Analysis of the cartilage proteome from three different mouse models of genetic skeletal diseases reveals common and discrete disease signatures

    Directory of Open Access Journals (Sweden)

    Peter A. Bell

    2013-06-01

    Pseudoachondroplasia and multiple epiphyseal dysplasia are genetic skeletal diseases resulting from mutations in cartilage structural proteins. Electron microscopy and immunohistochemistry previously showed that the appearance of the cartilage extracellular matrix (ECM in targeted mouse models of these diseases is disrupted; however, the precise changes in ECM organization and the pathological consequences remain unknown. Our aim was to determine the effects of matrilin-3 and COMP mutations on the composition and extractability of ECM components to inform how these detrimental changes might influence cartilage organization and degeneration. Cartilage was sequentially extracted using increasing denaturants and the extraction profiles of specific proteins determined using SDS-PAGE/Western blotting. Furthermore, the relative composition of protein pools was determined using mass spectrometry for a non-biased semi-quantitative analysis. Western blotting revealed changes in the extraction of matrilins, COMP and collagen IX in mutant cartilage. Mass spectrometry confirmed quantitative changes in the extraction of structural and non-structural ECM proteins, including proteins with roles in cellular processes such as protein folding and trafficking. In particular, genotype-specific differences in the extraction of collagens XII and XIV and tenascins C and X were identified; interestingly, increased expression of several of these genes has recently been implicated in susceptibility and/or progression of murine osteoarthritis. We demonstrated that mutation of matrilin-3 and COMP caused changes in the extractability of other cartilage proteins and that proteomic analyses of Matn3 V194D, Comp T585M and Comp DelD469 mouse models revealed both common and discrete disease signatures that provide novel insight into skeletal disease mechanisms and cartilage degradation.

  4. Disease and Polygenic Architecture: Avoid Trio Design and Appropriately Account for Unscreened Control Subjects for Common Disease

    Science.gov (United States)

    Peyrot, Wouter J.; Boomsma, Dorret I.; Penninx, Brenda W.J.H.; Wray, Naomi R.

    2016-01-01

    Genome-wide association studies (GWASs) are an optimal design for discovery of disease risk loci for diseases whose underlying genetic architecture includes many common causal loci of small effect (a polygenic architecture). We consider two designs that deserve careful consideration if the true underlying genetic architecture of the trait is polygenic: parent-offspring trios and unscreened control subjects. We assess these designs in terms of quantification of the total contribution of genome-wide genetic markers to disease risk (SNP heritability) and power to detect an associated risk allele. First, we show that trio designs should be avoided when: (1) the disease has a lifetime risk > 1%; (2) trio probands are ascertained from families with more than one affected sibling under which scenario the SNP heritability can drop by more than 50% and power can drop as much as from 0.9 to 0.15 for a sample of 20,000 subjects; or (3) assortative mating occurs (spouse correlation of the underlying liability to the disorder), which decreases the SNP heritability but not the power to detect a single locus in the trio design. Some studies use unscreened rather than screened control subjects because these can be easier to collect; we show that the estimated SNP heritability should then be scaled by dividing by (1 − K × u)2 for disorders with population prevalence K and proportion of unscreened control subjects u. When omitting to scale appropriately, the SNP heritability of, for example, major depressive disorder (K = 0.15) would be underestimated by 28% when none of the control subjects are screened. PMID:26849113

  5. Investigation of non-covalent complexes of glutathione with common amino acids by electrospray ionization mass spectrometry

    Institute of Scientific and Technical Information of China (English)

    Zhao-yun DAI; Yan-qiu CHU; Bo WU; Liang WU; Chuan-fan DING

    2008-01-01

    Aim: To study the non-covalent interaction between glutathione and common amino acids. Methods: A stoichiometry of glutathione and common amino acids were mixed to reach the equilibrium, and then the mixed solution was investigated by electrospray ionization mass spectrometry (ESI-MS). The binding of the com-plexes was further examined by collision-induced dissociation (CID) in a tandem mass spectrometer as well as UV spectroscopy. To avoid distinct ionization effi-ciency discrepancy and signal suppression in the ESI-MS measurements, the interaction between glutathione (GSH) and glutamate (Glu) was quantitatively evaluated. The total concentrations and series of m/z of peak intensities for glu-tathione and amino acids could be achieved, respectively. Due to the existence of some oligomeric species arising from glutathione or amino acids, an improved calculation formula was proposed to calculate the dissociation constants of glu-tathione binding to amino acids. Results: The ESI mass spectra revealed that glutathione could interact easily with Met, Phe, Tyr, Ser, or lie to form non-cova-lent complexes. The binding of the complexes was further confirmed by CID experiments in a tandem mass spectrometer as well as UV spectroscopy. Moreover, an improved calculation formula was successfully applied to determine the disso-ciation constants of glutathione binding to Glu, His, or Gln. Finally, a possible formation mechanism for the complexes of glutathione with amino acids was proposed. Conclusion: The reduced polypeptide y-glutathione can interact with each of 8 common amino acids, including Glu, His, and Gin to form non-covalent complexes with different affinity.

  6. Poverty-related diseases (PRDs): unravelling complexities in disease responses in Cameroon.

    Science.gov (United States)

    Makoge, Valerie; Maat, Harro; Vaandrager, Lenneke; Koelen, Maria

    2017-01-01

    In Cameroon, poverty-related diseases (PRDs) are a major public health concern. Research and policies addressing PRDs are based on a particular understanding of the interaction between poverty and disease, usually an association between poverty indicators and health indicators for a specific country or region. Such indicators are useful but fail to explain the nature of the linkages between poverty and disease or poverty and health. This paper presents results of a study among university students, unravelling how they perceive diseases, the linkages with poverty, their responses to diseases and the motivations behind reported responses. Based on the health belief model, this cross-sectional study was carried out among 272 students at the universities of Buea and Yaoundé in Cameroon. Data were collected using questionnaires containing items matching the research objectives. The questionnaires were self-completed. Malaria was considered as the most common disease perceived and also a major PRD. Contrary to official rankings of HIV/AIDS and TB, cholera and diarrhoea were considered as other major PRDs. Also, typhoid fever was perceived to be more common and a PRD than HIV/AIDS and TB combined. The most prominently attributed cause for disease was (lack of) hygiene. In response, students deployed formal and/or informal healthcare strategies, depending on factors like available money, perceived severity of the disease and disease type. Discrepancies were observed in respondents' response to diseases generally and to malaria in particular. Even though, overall, respondents pre-dominantly reported a formal healthcare response toward diseases in general, for malaria, informal responses dominated. There was an overall strong awareness and (pro)activity among students for dealing with diseases. Although the high use of informal facilities and medication for malaria may well be a reason why eradication is problematic, this seems to be a deliberate strategy linked to an

  7. Tuberous sclerosis complex and polycystic kidney disease contiguous gene syndrome with Moyamoya disease.

    Science.gov (United States)

    Lai, Jonathan; Modi, Lopa; Ramai, Daryl; Tortora, Matthew

    2017-04-01

    Tuberous sclerosis complex (TSC) and autosomal dominant polycystic kidney disease (ADPKD) are two diseases sharing close genetic loci on chromosome 16. Due to contiguous gene syndrome, also known as contiguous gene deletion syndrome, the proximity of TSC2 and PKD1 genes increases the risk of co-deletion resulting in a shared clinical presentation. Furthermore, Moyamoya disease (MMD) is a rare vaso-occlusive disease in the circle of Willis. We present the first case of TSC2/PKD1 contiguous gene syndrome in a patient with MMD along with detailed histopathologic, radiologic, and cytogenetic analyses. We also highlight the clinical presentation and surgical complications in this case. Copyright © 2017 Elsevier GmbH. All rights reserved.

  8. Areca nut chewing and systemic inflammation: evidence of a common pathway for systemic diseases

    Directory of Open Access Journals (Sweden)

    Shafique Kashif

    2012-06-01

    Full Text Available Abstract Background Areca nut, the seed of fruit of an oriental palm, known as Areca catechu, is commonly chewed in many countries. Diabetes, hypertension, cardiovascular diseases, oropharyngeal and oesophageal cancers have been associated with areca nut chewing and the mechanism by which areca nut chewing increases the risk of systemic diseases remains elusive. We hypothesize that systemic inflammation may be elevated among areca nut users, which is linked with many systemic diseases. Therefore, this present study was conducted to examine the systemic inflammation among areca nut chewers and healthy controls. Methods This was an observational cross sectional study carried out on areca nut chewers and healthy individuals in Karachi, Pakistan. Participants were selected from a region of the city by invitation request sent from door to door. Information was collected regarding the socio-demographic profile and the pattern of use, and a blood sample was obtained to measure the level of C-reactive protein (CRP. We carried out multiple logistic regressions to investigate the association between socio-demographic profile, areca nut chewing and CRP levels. Results We carried out final analysis on 1112 individuals of which 556 were areca nut chewers and 556 were the age, gender and area matched controls. Areca nut chewers had a significantly higher proportion of men (15.1%, n = 84 who had an elevated CRP (>10 mg/dl as compared to controls (5.2%, n = 29. Multivariate analyses showed that areca nut chewers had significantly higher odds of an elevated CRP (OR = 3.23, 95% CI 2.08-5.02, p value Conclusions Areca nut chewing has a significant association with systemic inflammation. Further work is required to confirm that systemic inflammation is the main pathway by which areca nut use increases the risk of systemic diseases.

  9. [Disease resistance signal transfer between roots of different tomato plants through common arbuscular mycorrhiza networks].

    Science.gov (United States)

    Xie, Li-Jun; Song, Yuan-Yuan; Zeng, Ren-Sen; Wang, Rui-Long; Wei, Xiao-Chen; Ye, Mao; Hu, Lin; Zhang, Hui

    2012-05-01

    Common mycorrhizal networks (CMNs) are the underground conduits of nutrient exchange between plants. However, whether the CMNs can serve as the underground conduits of chemical communication to transfer the disease resistance signals between plants are unknown. By inoculating arbuscular mycorrhizal fungus (AMF) Glomus mosseae to establish CMNs between 'donor' and 'receiver' tomato plants, and by inoculating Alternaria solani, the causal agent of tomato early blight disease, to the 'donor' plants, this paper studied whether the potential disease resistance signals can be transferred between the 'donor' and 'receiver' plants roots. The real time RT-PCR analysis showed that after inoculation with A. solani, the AMF-inoculated 'donor' plants had strong expression of three test defense-related genes in roots, with the transcript levels of the phenylalanine ammonia-lyase (PAL), lipoxygenase (LOX) and chitinase (PR3) being significantly higher than those in the roots of the 'donor' plants only inoculated with A. solani, not inoculated with both A. solani and AMF, and only inoculated with AMF. More importantly, in the presence of CMNs, the expression levels of the three genes in the roots of the 'receiver' plants were significantly higher than those of the 'receiver' plants without CMNs connection, with the connection blocking, and with the connection but the 'donor' plants not A. solani-inoculated. Compared with the control (without CMNs connection), the transcript level of the PAL, LOX and PR3 in the roots of the 'receiver' plants having CMNs connection with the 'donor' plants was 4.2-, 4.5- and 3.5-fold higher, respectively. In addition, the 'donor' plants activated their defensive responses more quickly than the 'receiver' plants (18 and 65 h vs. 100 and 140 h). These findings suggested that the disease resistance signals produced by the pathogen-induced 'donor' tomato plant roots could be transferred to the 'receiver' plant roots through CMNs.

  10. Systemic disease manifestations associated with epilepsy in tuberous sclerosis complex.

    Science.gov (United States)

    Jeong, Anna; Wong, Michael

    2016-09-01

    Epilepsy is one of the most disabling symptoms of tuberous sclerosis complex (TSC) and is a leading cause of morbidity and mortality in affected individuals. The relationship between systemic disease manifestations and the presence of epilepsy has not been thoroughly investigated. This study utilizes a multicenter TSC Natural History Database including 1,816 individuals to test the hypothesis that systemic disease manifestations of TSC are associated with epilepsy. Univariate analysis was used to identify patient characteristics (e.g., age, gender, race, and TSC mutation status) associated with the presence of epilepsy. Individual logistic regression models were built to examine the association between epilepsy and each candidate systemic or neurologic disease variable, controlling for the patient characteristics found to be significant on univariate analysis. Finally, a multivariable logistic regression model was constructed, using the variables found to be significant on the individual analyses as well as the patient characteristics that were significant on univariate analysis. Nearly 88% of our cohort had a history of epilepsy. After adjusting for age, gender, and TSC mutation status, multiple systemic disease manifestations including cardiac rhabdomyomas (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.3-3.9, p = 0.002), retinal hamartomas (OR 2.1, CI 1.0-4.3, p = 0.04), renal cysts (OR 2.1, CI 1.3-3.4, p = 0.002), renal angiomyolipomas (OR 3.0, CI 1.8-5.1, p < 0.001), shagreen patches (OR 1.7, CI 1.0-2.7, p = 0.04), and facial angiofibromas (OR 1.7, CI 1.1-2.9, p = 0.03) were associated with a higher likelihood of epilepsy. In the multivariable logistic regression model, cardiac rhabdomyomas (OR 1.9, CI 1.0-3.5, p = 0.04) remained significantly associated with the presence of epilepsy. The identification of systemic disease manifestations such as cardiac rhabdomyomas that confer a higher risk of epilepsy development in TSC could contribute to disease

  11. Disruption of a PEX1-PEX6 interaction is the most common cause of the neurologic disorders Zellweger syndrome, neonatal adrenoleukodystrophy, and infantile Refsum disease.

    Science.gov (United States)

    Geisbrecht, B V; Collins, C S; Reuber, B E; Gould, S J

    1998-07-21

    Peroxisomal matrix protein import requires the action of two AAA ATPases, PEX1 and PEX6. Mutations in either the PEX1 or PEX6 gene are the most common cause of the lethal neurologic disorders Zellweger syndrome, neonatal adrenoleukodystrophy, and infantile Refsum disease and account for disease in 80% of all such patients. We report here that overexpression of PEX6 can suppress the phenotypes of certain PEX1-deficient cells, that overexpression of PEX1 can suppress the phenotypes of certain PEX6-deficient cells, and that these instances of suppression are allele-specific and require partial activity of the mutated gene. In addition to genetic evidence for interaction between PEX1 and PEX6, we find that the PEX1 and PEX6 proteins interact in the yeast two-hybrid assay and physically associate with one another in vitro. We previously identified a missense mutation in PEX1, G843D, which attenuates PEX1 function and is the most common cause of these diseases, present in one-third of all such patients. The G843D mutation attenuates the interaction between PEX1 and PEX6 in both the two-hybrid system and in vitro and appears to be suppressed by overexpression of PEX6. We conclude that PEX1 and PEX6 form a complex of central importance to peroxisome biogenesis and that mutations affecting this complex constitute the most common cause of the Zellweger syndrome spectrum of diseases.

  12. Common invasive fungal diseases: an overview of invasive candidiasis, aspergillosis, cryptococcosis, and Pneumocystis pneumonia.

    Science.gov (United States)

    Schmiedel, Yvonne; Zimmerli, Stephan

    2016-01-01

    Every year, Candida, Aspergillus, Cryptococcus and Pneumocystis infect an estimated two million individuals worldwide. Most are immunocompromised or critically ill. Candida is the most common fungal pathogen of the critically ill and of recipients of transplanted abdominal organs. In high-risk haemato-oncological patients, in contrast, the introduction of antifungal prophylaxis with fluconazole and later with mould-active posaconazole has led to a remarkable reduction of invasive candidiasis and is likely to have a similar effect on invasive aspergillosis. Invasive aspergillosis remains the dominant invasive fungal disease (IFD) of haemato-oncological patients and solid-organ transplant recipients and is increasingly found in individuals with exacerbated chronic obstructive pulmonary disease on corticosteroids. In the developed world, owing to antiretroviral therapy Pneumocystis pneumonia and cryptococcosis have become rare in patients with human immunodeficiency virus (HIV) and are mainly found in solid-organ transplant recipients or immunocompromised patients. In the developing world, cryptococcosis remains a common and highly lethal disease of HIV positive individuals. With invasive candidiasis and invasive aspergillosis, timely diagnosis is the principal challenge. The clinical presentation is nonspecific and current diagnostic tests lack sensitivity and specificity. The combination of several tests improves sensitivity, but not specificity. Standardised polymerase chain-reaction-based assays may be promising tools for more rapid and specific diagnosis of candidiasis and invasive aspergillosis. Nevertheless, initiation of treatment is often based solely on clinical suspicion. Empirical therapy, however, may lead to over-treatment of patients without IFD or it may miss its target in the case of resistance. Despite the success of antifungal prophylaxis in reducing the incidence of IFDs in haemato-oncological patients, there are a considerable number of

  13. Systems genetics of complex diseases using RNA-sequencing methods

    DEFF Research Database (Denmark)

    Mazzoni, Gianluca; Kogelman, Lisette; Suravajhala, Prashanth

    2015-01-01

    Next generation sequencing technologies have enabled the generation of huge quantities of biological data, and nowadays extensive datasets at different ‘omics levels have been generated. Systems genetics is a powerful approach that allows to integrate different ‘omics level and understand...... non-coding RNAs (ncRNAs). The integration of transcriptomics data with genomic data in a systems genetics context represents a valuable possibility to go deep into the causal and regulatory mechanisms that generate complex traits and diseases. However RNA-Seq data have to be treated carefully...... principally on merits and demerits of tools for post mapping quality control, normalization, differential expression analysis, gene network analysis, and integration of different omics data in order to generate a comprehensive guideline to systems genetics analysis using RNA-Seq data....

  14. Exploring the potential relevance of human-specific genes to complex disease

    Directory of Open Access Journals (Sweden)

    Cooper David N

    2011-01-01

    Full Text Available Abstract Although human disease genes generally tend to be evolutionarily more ancient than non-disease genes, complex disease genes appear to be represented more frequently than Mendelian disease genes among genes of more recent evolutionary origin. It is therefore proposed that the analysis of human-specific genes might provide new insights into the genetics of complex disease. Cross-comparison with the Human Gene Mutation Database (http://www.hgmd.org revealed a number of examples of disease-causing and disease-associated mutations in putatively human-specific genes. A sizeable proportion of these were missense polymorphisms associated with complex disease. Since both human-specific genes and genes associated with complex disease have often experienced particularly rapid rates of evolutionary change, either due to weaker purifying selection or positive selection, it is proposed that a significant number of human-specific genes may play a role in complex disease.

  15. Toxoplasmosis presented as a submental mass: a common disease, uncommon presentation.

    Science.gov (United States)

    Li, Bo; Zou, Jian; Wang, Wei-Ya; Liu, Shi-Xi

    2015-01-01

    Submental mass secondary to toxoplasmosis is not common in clinical work. A diagnosis of toxoplasmosis is rarely considered by physicians. Here we describe a 50-year-old woman presented with a progressive, painful, submental and left neck swelling for 1 month. After having obtained an insufficient evidence from the fine-needle biopsy, the patient finally received an excisional biopsy which highly indicated the possibility of lymphadenopathy consistent with toxoplasmosis. Diagnosis of toxoplasmosis was finally established by a combination of the pathological criteria, together with the positive serological finding. According to review the clinical presentations, pathological characteristics, diagnostic standard and treatment of this disease, the article aims to remind otolaryngologists who are evaluating a neck mass should be aware of the infectious cause of lymphadenopathy and the possibility of toxoplasmosis.

  16. The binding of MBL to common bacteria in infectious diseases of children

    Institute of Scientific and Technical Information of China (English)

    SHANG Shi-qiang; CHEN Guo-xian; SHEN Jie; YU Xiao-hong; WANG Ke-yi

    2005-01-01

    Objective: To purify Mannan-binding lectin (MBL) from human serum and detect its binding ability to several kinds of bacteria common in infectious diseases of children. Methods: MBL was purified from human serum by affinity chromatography on mannan-Sepharose 4B column. Its binding ability to eight species, 97 strains of bacteria was detected by enzyme-linked lectin assay (ELLA). Results: MBL has different binding ability to bacteria and shows strong binding ability to Klebsiella ornithinolytica and Escherichia coli, but shows relatively lower binding ability to Staphylococcus haemolyticus, Enterobacter cloacae and Staphylococcus epidermidis. To different isolates of Klebsiella pneumoniae, Haemophilus influenzae and Staphylococcus aureus,MBL shows quite different binding ability. Conclusions: MBL has different binding ability to different bacteria, and has relatively stronger binding ability to Gram-negative bacteria. Its binding ability to different isolates of certain kinds of bacteria is quite different.

  17. Serum-sickness-like disease is a common cause of acute arthritis in children.

    Science.gov (United States)

    Kunnamo, I; Kallio, P; Pelkonen, P; Viander, M

    1986-11-01

    Among 283 children in a prospective study of arthritis we found 15 patients with a self-limited serum-sickness-like disease consisting of urticaria or joint erythema and mostly polyarticular arthritis. The mean duration of joint symptoms was 5.9 days. A preceding infection was reported in 12 patients and 12 had received drugs, the therapy starting on average 12.8 days before the onset of joint symptoms. In 9 cases the drug was penicillin. Four patients had recurrent attacks. Circulating immune complexes were detected in the serum of 12 patients, but specific IgE antibodies to penicillin only in 3 patients. The estimated annual incidence of the condition was 4.7/100,000 children under age 16.

  18. EVALUATION OF THICKNESS OF INTIMA-MEDIA COMPLEX OF COMMON CAROTID ARTERIES IN CHILDREN WITH JUVENILE ARTHRITIS AND SYSTEMIC LUPUS ERYTHEMATOSUS

    Directory of Open Access Journals (Sweden)

    A.B. Sugak

    2010-01-01

    Full Text Available Rheumatic diseases in adults are associated with accelerated atherosclerosis, and its early signs can be stated by the thickening of intima-media complex of common carotid arteries (CCA. This symptom is detected during ultrasound examination in 49% of children with systemic lupus erythematosus, in 24% of patients with juvenile rheumatoid arthritis and in 13% of children with juvenile spondylarthritis. Besides, 36% of children with systemic lupus erythematosus and 17% — with systemic type of juvenile rheumatoid arthritis had structure changes of CCA wall. A dependence of these disorders on cholesterol and glucose levels in blood serum, overweight and Cushing syndrome, age, duration and activity of a disease, levels of ESR, C-reactive protein and white blood cells was not showed. Authors detected a correlation between the thickness of intima-media complex of CCA and hemostasis parameters.Key words: children, juvenile arthritis, systemic lupus erythematosus, intima-media complex, ultrasound diagnostics.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2010;9(2:64-69

  19. Understanding Epistatic Interactions between Genes Targeted by Non-coding Regulatory Elements in Complex Diseases

    Directory of Open Access Journals (Sweden)

    Min Kyung Sung

    2014-12-01

    Full Text Available Genome-wide association studies have proven the highly polygenic architecture of complex diseases or traits; therefore, single-locus-based methods are usually unable to detect all involved loci, especially when individual loci exert small effects. Moreover, the majority of associated single-nucleotide polymorphisms resides in non-coding regions, making it difficult to understand their phenotypic contribution. In this work, we studied epistatic interactions associated with three common diseases using Korea Association Resource (KARE data: type 2 diabetes mellitus (DM, hypertension (HT, and coronary artery disease (CAD. We showed that epistatic single-nucleotide polymorphisms (SNPs were enriched in enhancers, as well as in DNase I footprints (the Encyclopedia of DNA Elements [ENCODE] Project Consortium 2012, which suggested that the disruption of the regulatory regions where transcription factors bind may be involved in the disease mechanism. Accordingly, to identify the genes affected by the SNPs, we employed whole-genome multiple-cell-type enhancer data which discovered using DNase I profiles and Cap Analysis Gene Expression (CAGE. Assigned genes were significantly enriched in known disease associated gene sets, which were explored based on the literature, suggesting that this approach is useful for detecting relevant affected genes. In our knowledge-based epistatic network, the three diseases share many associated genes and are also closely related with each other through many epistatic interactions. These findings elucidate the genetic basis of the close relationship between DM, HT, and CAD.

  20. Shared genetic susceptibility to ischemic stroke and coronary artery disease: a genome-wide analysis of common variants.

    Science.gov (United States)

    Dichgans, Martin; Malik, Rainer; König, Inke R; Rosand, Jonathan; Clarke, Robert; Gretarsdottir, Solveig; Thorleifsson, Gudmar; Mitchell, Braxton D; Assimes, Themistocles L; Levi, Christopher; O'Donnell, Christopher J; Fornage, Myriam; Thorsteinsdottir, Unnur; Psaty, Bruce M; Hengstenberg, Christian; Seshadri, Sudha; Erdmann, Jeanette; Bis, Joshua C; Peters, Annette; Boncoraglio, Giorgio B; März, Winfried; Meschia, James F; Kathiresan, Sekar; Ikram, M Arfan; McPherson, Ruth; Stefansson, Kari; Sudlow, Cathie; Reilly, Muredach P; Thompson, John R; Sharma, Pankaj; Hopewell, Jemma C; Chambers, John C; Watkins, Hugh; Rothwell, Peter M; Roberts, Robert; Markus, Hugh S; Samani, Nilesh J; Farrall, Martin; Schunkert, Heribert

    2014-01-01

    Ischemic stroke (IS) and coronary artery disease (CAD) share several risk factors and each has a substantial heritability. We conducted a genome-wide analysis to evaluate the extent of shared genetic determination of the two diseases. Genome-wide association data were obtained from the METASTROKE, Coronary Artery Disease Genome-wide Replication and Meta-analysis (CARDIoGRAM), and Coronary Artery Disease (C4D) Genetics consortia. We first analyzed common variants reaching a nominal threshold of significance (Pstroke (LAS) subtype. Common variants associated with CAD at Pgenetic risk of IS and particularly the LAS subtype with CAD.

  1. Cardiovascular disease and prediabetes as complex illness: People's perspectives.

    Science.gov (United States)

    van Wissen, Kim; Thunders, Michelle; Mcbride-Henry, Karen; Ward, Margaret; Krebs, Jeremy; Page, Rachel

    2017-07-01

    Cardiovascular disease (CVD) and sustained high blood glucose as prediabetes are an established comorbidity. People's experience in reconciling these long-term conditions requires deeper appreciation if nurses are to more effectively support person-centred care for people who have them. Our analysis explores the initial experience of people admitted to hospital with CVD who then find they also have sustained high blood glucose. Our methodology is informed by the philosophy of Gadamer and applies interpretive description to develop an interpretation of participant experiences. The major theme emerging from participant interviews was the 'invisible disequilibrium' characterised by three subthemes: 'losing equilibrium', 'becoming embattled' and 'evolving illness'. This study examines CVD and prediabetes in conjunction with the Gadamerian notion of the 'whole', as being in a social and emotional world in which illness is also a component part. We explore how participants lived within an 'invisible disequilibrium', with prediabetes frequently remaining unnoticed, while CVD was manifest. To identify multiple conditions and support effective intervention to manage them as part of person-centric care, nursing practice should explore the 'whole' of the person's experience, value people's knowledge as potential indicators of complex illness, thereby reducing the risk of accelerating complex illness. © 2017 John Wiley & Sons Ltd.

  2. Genetic mapping of complex discrete human diseases by discriminant analysis

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The objective of the present study is to propose and evaluate a novel multivariate approach for genetic mapping of complex categorical diseases. This approach results from an application of standard stepwise discriminant analysis to detect linkage based on the differential marker identity-by-descent (IBD) distributions among the different groups of sib pairs. Two major advantages of this method are that it allows for simultaneously testing all markers, together with other genetic and environmental factors in a single multivariate setting and it avoids explicitly modeling the complex relationship between the affection status of sib pairs and the underlying genetic determinants. The efficiency and properties of the method are demonstrated via simulations. The proposed multivariate approach has successfully located the true position(s) under various genetic scenarios. The more important finding is that using highly densely spaced markers (1~2 cM) leads to only a marginal loss of statistical efficiency of the proposed methods in terms of gene localization and statistical power. These results have well established its utility and advantages as a fine-mapping tool. A unique property of the proposed method is the ability to map multiple linked trait loci to their precise positions due to its sequential nature, as demonstrated via simulations.

  3. Complex regional pain syndrome: more than a peripheral disease.

    Science.gov (United States)

    Reinersmann, Annika; Maier, Christoph; Schwenkreis, Peter; Lenz, Melanie

    2013-11-01

    SUMMARY At early stages, complex regional pain syndrome (CRPS) is clinically characterized by damage of peripheral tissues and nerves (edema, activation of osteoblasts, hyperalgesia to blunt pressure). These signs are the result of a dysbalance of pro- and anti-inflammatory cytokines, which normalizes approximately 6 months after the beginning of the disease, independent from clinical outcome. At the same time, evolving clinical signs such as allodynia, cold hyperalgesia, reduced tactile acuity or symptoms of disrupted body representation (e.g., neglect-like syndrome, impaired hand laterality recognition or shift of the body midline) suggest a crucial role of the CNS in the pathophysiology of this pain syndrome. Imaging studies have found a severe but reversible reduction of the cortical hand representation (primary and secondary somatosensory cortices and primary motor cortices). Interestingly however, complex multisensory integration in central association areas are unaffected in CRPS, as patients are capable of integrating artificial body parts or recognize 2D forms despite tactile dysfunction. Furthermore, despite its unilateral clinical manifestation, it has been shown that in CRPS but not in other unilateral neuropathic pain syndromes, alterations in cortical excitability occur bilaterally, both in sensory and motor regions. In conclusion, a more widespread and bilateral pattern of CNS reorganization appears to characterize CRPS, which might be related to dysfunctions in the basal ganglia or in thalamo-cortical structures. Consequently, CRPS treatment should involve not only anti-inflammatory measures and pain therapy, but also the integration of neurorehabilitative training programs.

  4. Machado-Joseph disease in Brazil: from the first descriptions to the emergence as the most common spinocerebellar ataxia

    Directory of Open Access Journals (Sweden)

    José Luiz Pedroso

    2012-08-01

    Full Text Available Machado-Joseph disease is an autosomal dominant inherited disorder of Azorean ancestry firstly described in 1972. Since then, several Brazilian researchers have studied clinical and genetic issues related to the disease. Nowadays, Machado-Joseph disease is considered the most common spinocerebellar ataxia worldwide. Machado-Joseph disease still has no specific therapy to arrest progression, but the unclear pathophysiological mechanism, features related to genetic characteristics, phenotype variability, apparently global involvement of the nervous system in the disease and the therapeutic challenges continue to attract investigators in the field of spinocerebellar ataxias. Brazilian researchers have distinguished themselves in the ongoing investigation seeking new knowledge about Machado-Joseph disease.

  5. Fat, epigenome and pancreatic diseases. Interplay and common pathways from a toxic and obesogenic environment.

    Science.gov (United States)

    Di Ciaula, Agostino; Portincasa, Piero

    2014-12-01

    The worldwide obesity epidemic is paralleled by a rise in the incidence of pancreatic disorders ranging from "fatty" pancreas to pancreatitis and cancer. Body fat accumulation and pancreatic dysfunctions have common pathways, mainly acting through insulin resistance and low-grade inflammation, frequently mediated by the epigenome. These mechanisms are affected by lifestyle and by the toxic effects of fat and pollutants. An early origin is common, starting in pediatric age or during the fetal life in response to nutritional factors, endocrine disruptor chemicals (EDCs) or parental exposure to toxics. A "fatty pancreas" is frequent in obese and is able to induce pancreatic damage. The fat is a target of EDCs and of the cytotoxic/mutagenic effects of heavy metals, and is the site of bioaccumulation of lipophilic and persistent pollutants related with insulin resistance and able to promote pancreatic cancer. Increased Body Mass Index (BMI) can act as independent risk factor for a more severe course of acute pancreatitis and obesity is also a well-known risk factor for pancreatic cancer, that is related with BMI, insulin resistance, and duration of exposure to the toxic effects of fat and/or of environmental pollutants. All these mechanisms involve gene-environment interactions through epigenetic factors, and might be manipulated by primary prevention measures. Further studies are needed, pointing to better assess the interplays of modifiable factors on both obesity and pancreatic diseases, and to verify the efficacy of primary prevention strategies involving lifestyle and environmental exposure to toxics.

  6. Common Variation in the LRRK2 Gene is a Risk Factor for Parkinson’s Disease

    Science.gov (United States)

    Mata, Ignacio F.; Checkoway, Harvey; Hutter, Carolyn M.; Samii, Ali; Roberts, John W.; Kim, Hojoong M.; Agarwal, Pinky; Alvarez, Victoria; Ribacoba, Renee; Pastor, Pau; Lorenzo-Betancor, Oswaldo; Infante, Jon; Sierra, María; Gómez-Garre, Pilar; Mir, Pablo; Ritz, Beate; Rhodes, Shannon L; Colcher, Amy; Van Deerlin, Vivianna; Chung, Kathryn A.; Quinn, Joseph F.; Yearout, Dora; Martinez, Erica; Farin, Federico M.; Wan, Jia Y.; Edwards, Karen L.; Zabetian, Cyrus P.

    2012-01-01

    Background Common variants in the LRRK2 gene influence risk of Parkinson’s disease (PD) in Asians, but whether the same is true in European-derived populations is less clear. Methods We genotyped 66 LRRK2 tagging single nucleotide polymorphisms (SNPs) in 575 PD patients and 689 controls from the Northwestern U.S. (Tier 1). PD-associated SNPs (p<0.05) were then genotyped in an independent sample of 3617 cases and 2512 controls from the U.S. and Spain (Tier 2). Logistic regression was used to model additive SNP genotype effects adjusted for age and sex among white individuals. Results Two regions showed independent association with PD in Tier 1, and SNPs in both regions were successfully replicated in Tier 2 (rs10878226, combined odds ratio [OR], 1.20; 95% confidence interval [CI], 1.08-1.33; p=6.3×10−4; rs11176013, OR, 0.89; CI, 0.83-0.95; p=4.6×10−4). Conclusions Our data suggest that common variation within LRRK2 conveys susceptibility for PD in individuals of European ancestry. PMID:23115130

  7. Common variation of the CYP17 gene in Iraqi women with endometriosis disease.

    Science.gov (United States)

    Al-Rubae'i, Salwa H N; Naji, Tamara Sami; Turki, Kisma M

    2017-03-01

    Common variants among genes coding for enzymes in sex steroid biosynthetic pathways may influence the risk of endometriosis in Iraqi women patients in the last years. Cytochrome P450c17a1 (CYP17), a gene that codes for a key enzyme (cytochrome P450c17a1) in a rate-limiting step of estrogen biosynthesis has attracted considerable attention as an important gene for endometriosis. To evaluate the relationship between common genetic variations in CYP17 and endometriosis risk and determine the main effects of those variations on the gene expression. A women-based case control study of Iraqi women aged range (23-46), the associations between selected single-nucleotide polymorphisms (SNPs) in the CYP17 gene and endometriosis diagnosis in fifty women and thirty disease-free controls were evaluated. The study found a significant association (P ≤ 0.01)between endometriosis and selected SNPs of CYP17 gene, with the homozygous genotype conferring decreased risk. A highly significant difference (P ≤ 0.01) in CYP17 gene expression from women with versus without endometriosis and increased by 1.56-fold in women with endometriosis. These findings suggest that variation in or around CYP17 may be associated with endometriosis development in the Iraqi women.

  8. Common variation of the CYP17 gene in Iraqi women with endometriosis disease

    Directory of Open Access Journals (Sweden)

    Salwa H.N. Al-Rubae'i

    2017-03-01

    Full Text Available Common variants among genes coding for enzymes in sex steroid biosynthetic pathways may influence the risk of endometriosis in Iraqi women patients in the last years. Cytochrome P450c17a1 (CYP17, a gene that codes for a key enzyme (cytochrome P450c17a1 in a rate-limiting step of estrogen biosynthesis has attracted considerable attention as an important gene for endometriosis. To evaluate the relationship between common genetic variations in CYP17 and endometriosis risk and determine the main effects of those variations on the gene expression. A women-based case control study of Iraqi women aged range (23–46, the associations between selected single-nucleotide polymorphisms (SNPs in the CYP17 gene and endometriosis diagnosis in fifty women and thirty disease-free controls were evaluated. The study found a significant association (P ≤ 0.01between endometriosis and selected SNPs of CYP17 gene, with the homozygous genotype conferring decreased risk. A highly significant difference (P ≤ 0.01 in CYP17 gene expression from women with versus without endometriosis and increased by 1.56-fold in women with endometriosis. These findings suggest that variation in or around CYP17 may be associated with endometriosis development in the Iraqi women.

  9. Ocular and visual disorders in Parkinson's disease: Common but frequently overlooked.

    Science.gov (United States)

    Ekker, Merel S; Janssen, Sabine; Seppi, Klaus; Poewe, Werner; de Vries, Nienke M; Theelen, Thomas; Nonnekes, Jorik; Bloem, Bastiaan R

    2017-02-21

    Patients with Parkinson's disease (PD) often compensate for their motor deficits by guiding their movements visually. A wide range of ocular and visual disorders threatens the patients' ability to benefit optimally from visual feedback. These disorders are common in patients with PD, yet they have received little attention in both research and clinical practice, leading to unnecessary - but possibly treatable - disability. Based on a literature search covering 50 years, we review the range of ocular and visual disorders in patients with PD, and classify these according to anatomical structures of the visual pathway. We discuss six common disorders in more detail: dry eyes; diplopia; glaucoma and glaucoma-like visual problems; impaired contrast and colour vision; visuospatial and visuoperceptual impairments; and visual hallucinations. In addition, we review the effects of PD-related pharmacological and surgical treatments on visual function, and we offer practical recommendations for clinical management. Greater awareness and early recognition of ocular and visual problems in PD might enable timely instalment of tailored treatments, leading to improved patient safety, greater independence, and better quality of life.

  10. Specific circulating immune complexes in acute chagas' disease

    Directory of Open Access Journals (Sweden)

    Ricardo Corral

    1987-02-01

    Full Text Available The presence of circulating immune complexes formed by IgM and IgG (CIC-IgM and CIC-IgG was investigated, using antigen-specific enzyme-immunoassays (ELISA, in 30 patients with acute Chagas' disease who showed parasitemia and inoculation chagoma. Control population consisted of patients with chronic T. cruzi infection (30, acute toxoplasmosis 10, leishmaniasis (8, rheumatoid arthritis (3 and healthy individuals with negative serology for Chagas* disease (30. Acute chagasic patients were 100% CIC-IgG and 96.66% CIC-IgM positive whereas immunofluorescence tests yielded 90% and 86.66% of positivity for specific IgG and IgM antibodies, respectively. Chronic patients were 68% CIC-IgG and 0% CIC-IgM positive. The 30 negative and the 21 cross-reaction controls proved negative for ELISA (CIC-IgM and CIC-IgG. The high sensitivity of ELISA assays would allow early immunologic diagnosis, as well as prompt treatment, of acute T. cruzi infection, thus eliminating the problem of the false-positive and false-negative results which affects traditional methods for detection of circulating antibodies.

  11. Anterior hypopituitarism is rare and autoimmune disease is common in adults with idiopathic central diabetes insipidus.

    Science.gov (United States)

    Hannon, M J; Orr, C; Moran, C; Behan, L A; Agha, A; Ball, S G; Thompson, C J

    2012-05-01

    Central diabetes insipidus is a rare clinical condition with a heterogenous aetiology. Up to 40% of cases are classified as idiopathic, although many of these are thought to have an autoimmune basis. Published data have suggested that anterior hypopituitarism is common in childhood-onset idiopathic diabetes insipidus. We aimed to assess the incidence of anterior hypopituitarism in a cohort of adult patients with idiopathic diabetes insipidus. We performed a retrospective review of the databases of two pituitary investigation units. This identified 39 patients with idiopathic diabetes insipidus. All had undergone magnetic resonance imaging scanning and dynamic pituitary testing (either insulin tolerance testing or GHRH/arginine and short synacthen testing) to assess anterior pituitary function. One patient had partial growth hormone deficiency; no other anterior pituitary hormonal deficits were found. Thirty-three percent had at least one autoimmune disease in addition to central diabetes insipidus. Our data suggest that anterior hypopituitarism is rare in adult idiopathic diabetes insipidus. Routine screening of these patients for anterior hypopituitarism may not, therefore, be indicated. The significant prevalence of autoimmune disease in this cohort supports the hypothesis that idiopathic diabetes insipidus may have an autoimmune aetiology. © 2012 Blackwell Publishing Ltd.

  12. Anterior Hypopituitarism is Rare and Autoimmune Disease is Common in Adults with Idiopathic Central Diabetes Insipidus.

    LENUS (Irish Health Repository)

    2012-02-01

    Objective: Central diabetes insipidus is a rare clinical condition with a heterogenous aetiology. Up to 40% of cases are classified as idiopathic, though many of these are thought to have an autoimmune basis. Published data has suggested that anterior hypopituitarism is common in childhood onset idiopathic diabetes insipidus. We aimed to assess the incidence of anterior hypopituitarism in a cohort of adult patients with idiopathic diabetes insipidus. Design and Patients: We performed a retrospective review of the databases of two pituitary investigation units. This identified 39 patients with idiopathic diabetes insipidus. All had undergone MRI scanning and dynamic pituitary testing (either insulin tolerance testing or GHRH\\/arginine and short synacthen testing) to assess anterior pituitary function. Results: One patient had partial growth hormone deficiency; no other anterior pituitary hormonal deficits were found. 33% had at least one autoimmune disease in addition to central diabetes insipidus. Conclusions: Our data suggest that anterior hypopituitarism is rare in adult idiopathic diabetes insipidus. Routine screening of these patients for anterior hypopituitarism may not therefore be indicated. The significant prevalence of autoimmune disease in this cohort supports the hypothesis that idiopathic diabetes insipidus may have an autoimmune aetiology.

  13. Can genetic pleiotropy replicate common clinical constellations of cardiovascular disease and risk?

    Directory of Open Access Journals (Sweden)

    Omri Gottesman

    Full Text Available The relationship between obesity, diabetes, hyperlipidemia, hypertension, kidney disease and cardiovascular disease (CVD is established when looked at from a clinical, epidemiological or pathophysiological perspective. Yet, when viewed from a genetic perspective, there is comparatively little data synthesis that these conditions have an underlying relationship. We sought to investigate the overlap of genetic variants independently associated with each of these commonly co-existing conditions from the NHGRI genome-wide association study (GWAS catalog, in an attempt to replicate the established notion of shared pathophysiology and risk. We used pathway-based analyses to detect subsets of pleiotropic genes involved in similar biological processes. We identified 107 eligible GWAS studies related to CVD and its established comorbidities and risk factors and assigned genes that correspond to the associated signals based on their position. We found 44 positional genes shared across at least two CVD-related phenotypes that independently recreated the established relationship between the six phenotypes, but only if studies representing non-European populations were included. Seven genes revealed pleiotropy across three or more phenotypes, mostly related to lipid transport and metabolism. Yet, many genes had no relationship to each other or to genes with established functional connection. Whilst we successfully reproduced established relationships between CVD risk factors using GWAS findings, interpretation of biological pathways involved in the observed pleiotropy was limited. Further studies linking genetic variation to gene expression, as well as describing novel biological pathways will be needed to take full advantage of GWAS results.

  14. Dominant Mutations in the Autoimmune Regulator AIRE Are Associated with Common Organ-Specific Autoimmune Diseases.

    Science.gov (United States)

    Oftedal, Bergithe E; Hellesen, Alexander; Erichsen, Martina M; Bratland, Eirik; Vardi, Ayelet; Perheentupa, Jaakko; Kemp, E Helen; Fiskerstrand, Torunn; Viken, Marte K; Weetman, Anthony P; Fleishman, Sarel J; Banka, Siddharth; Newman, William G; Sewell, W A C; Sozaeva, Leila S; Zayats, Tetyana; Haugarvoll, Kristoffer; Orlova, Elizaveta M; Haavik, Jan; Johansson, Stefan; Knappskog, Per M; Løvås, Kristian; Wolff, Anette S B; Abramson, Jakub; Husebye, Eystein S

    2015-06-16

    The autoimmune regulator (AIRE) gene is crucial for establishing central immunological tolerance and preventing autoimmunity. Mutations in AIRE cause a rare autosomal-recessive disease, autoimmune polyendocrine syndrome type 1 (APS-1), distinguished by multi-organ autoimmunity. We have identified multiple cases and families with mono-allelic mutations in the first plant homeodomain (PHD1) zinc finger of AIRE that followed dominant inheritance, typically characterized by later onset, milder phenotypes, and reduced penetrance compared to classical APS-1. These missense PHD1 mutations suppressed gene expression driven by wild-type AIRE in a dominant-negative manner, unlike CARD or truncated AIRE mutants that lacked such dominant capacity. Exome array analysis revealed that the PHD1 dominant mutants were found with relatively high frequency (>0.0008) in mixed populations. Our results provide insight into the molecular action of AIRE and demonstrate that disease-causing mutations in the AIRE locus are more common than previously appreciated and cause more variable autoimmune phenotypes. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Inflammation, aging, and cancer: tumoricidal versus tumorigenesis of immunity: a common denominator mapping chronic diseases.

    Science.gov (United States)

    Khatami, Mahin

    2009-01-01

    Acute inflammation is a highly regulated defense mechanism of immune system possessing two well-balanced and biologically opposing arms termed apoptosis ('Yin') and wound healing ('Yang') processes. Unresolved or chronic inflammation (oxidative stress) is perhaps the loss of balance between 'Yin' and 'Yang' that would induce co-expression of exaggerated or 'mismatched' apoptotic and wound healing factors in the microenvironment of tissues ('immune meltdown'). Unresolved inflammation could initiate the genesis of many age-associated chronic illnesses such as autoimmune and neurodegenerative diseases or tumors/cancers. In this perspective 'birds' eye' view of major interrelated co-morbidity risk factors that participate in biological shifts of growth-arresting ('tumoricidal') or growth-promoting ('tumorigenic') properties of immune cells and the genesis of chronic inflammatory diseases and cancer will be discussed. Persistent inflammation is perhaps a common denominator in the genesis of nearly all age-associated health problems or cancer. Future challenging opportunities for diagnosis, prevention, and/or therapy of chronic illnesses will require an integrated understanding and identification of developmental phases of inflammation-induced immune dysfunction and age-associated hormonal and physiological readjustments of organ systems. Designing suitable cohort studies to establish the oxido-redox status of adults may prove to be an effective strategy in assessing individual's health toward developing personal medicine for healthy aging.

  16. Occult peripheral artery disease is common and limits the benefit achieved in cardiac rehabilitation.

    Science.gov (United States)

    Tam, Marty C; Longenecker, Chris T; Chow, Chen; Vest, Marianne; Sukeena, Richard; Madan Mohan, Sri K; Carman, Teresa; Parikh, Sahil A; Josephson, Richard A

    2016-04-01

    Cardiac rehabilitation (CR) has proven morbidity and mortality benefits in cardiovascular disease, which directly correlates with exercise performance achieved. Many patients in CR exercise at sub-optimal levels, without obvious limitations. Occult lower-extremity peripheral artery disease (PAD) may be a determinant of diminished exercise capacity and reduced benefit obtained from traditional CR. In this prospective study of 150 consecutive patients enrolled in Phase II CR, we describe the prevalence of PAD, the utility of externally validated screening questionnaires, and the observed impact on CR outcomes. Abnormal ankle-brachial indices (ABI) (1.4) were observed in 19% of those studied. The Edinburgh Claudication Questionnaire was insensitive for detecting PAD by low ABI in this population, and the Walking Impairment Questionnaire and a modified Gardner protocol demonstrated a lack of typical symptoms with low levels of activity. Importantly, at completion of traditional CR, exercise improvement measured in metabolic equivalents (METs) was worse in those with a low ABI compared to those with a normal ABI (+1.39 vs +2.41 METs, p = 0.002). In conclusion, PAD is common in patients in Phase II CR and often clinically occult. Screening based on standard questionnaires appears insensitive in this population, suggesting a need for a broad-based screening strategy with ABI measurements. In this study, undiagnosed PAD significantly attenuated improvements in exercise performance, which potentially has bearings on future clinical events.

  17. Inherited neuronal ion channelopathies: new windows on complex neurological diseases.

    Science.gov (United States)

    Catterall, William A; Dib-Hajj, Sulayman; Meisler, Miriam H; Pietrobon, Daniela

    2008-11-12

    Studies of genetic forms of epilepsy, chronic pain, and migraine caused by mutations in ion channels have given crucial insights into molecular mechanisms, pathogenesis, and therapeutic approaches to complex neurological disorders. Gain-of-function missense mutations in the brain type-I sodium channel Na(V)1.1 are a primary cause of generalized epilepsy with febrile seizures plus. Loss-of-function mutations in Na(V)1.1 channels cause severe myoclonic epilepsy of infancy, an intractable childhood epilepsy. Studies of a mouse model show that this disease is caused by selective loss of sodium current and excitability of GABAergic inhibitory interneurons, which leads to hyperexcitability, epilepsy, and ataxia. Mutations in the peripheral sodium channel Na(V)1.7 cause familial pain syndromes. Gain-of-function mutations cause erythromelalgia and paroxysmal extreme pain disorder as a result of hyperexcitability of sensory neurons, whereas loss-of-function mutations cause congenital indifference to pain because of attenuation of action potential firing. These experiments have defined correlations between genotype and phenotype in chronic pain diseases and focused attention on Na(V)1.7 as a therapeutic target. Familial hemiplegic migraine is caused by mutations in the calcium channel, Ca(V)2.1, which conducts P/Q-type calcium currents that initiate neurotransmitter release. These mutations increase activation at negative membrane potentials and increase evoked neurotransmitter release at cortical glutamatergic synapses. Studies of a mouse genetic model show that these gain-of-function effects lead to cortical spreading depression, aura, and potentially migraine. Overall, these experiments indicate that imbalance in the activity of excitatory and inhibitory neurons is an important underlying cause of these diseases.

  18. Micro RNA, A Review: Pharmacogenomic drug targets for complex diseases

    Directory of Open Access Journals (Sweden)

    Sandhya Bawa

    2010-01-01

    differentially expressed in malignant cells compared to normal cells altering the regulation of expression of many important genes. MiRNA expression has been used for prognosis and early diagnosis of these complex diseases.  The present paper focuses on the role of miRNAs in various complex diseases, which will help in improving the drug discovery process and personalized medicines.

     

  • Trichomoniasis - are we giving the deserved attention to the most common non-viral sexually transmitted disease worldwide?

    Science.gov (United States)

    Menezes, Camila Braz; Frasson, Amanda Piccoli; Tasca, Tiana

    2016-01-01

    Etiology: Trichomonas vaginalis is the etiologic agent of trichomoniasis, the most common non-viral sexually transmitted disease (STD) in the world. Transmission: Trichomoniasis is transmitted by sexual intercourse and transmission via fomites is rare. Epidemiology, incidence and prevalence: The WHO estimates an incidence of 276 million new cases each year and prevalence of 187 million of infected individuals. However, the infection is not notifiable. Pathology/Symptomatology: The T. vaginalis infection results in a variety of clinical manifestations - in most cases the patients are asymptomatic, but some may develop signs typically associated to the disease. Importantly, the main issue concerning trichomoniasis is its relationship with serious health consequences such as cancer, adverse pregnancy outcomes, infertility, and HIV acquisition. Molecular mechanisms of infection: To achieve success in parasitism trichomonads develop a complex process against the host cells that includes dependent- and independent-contact mechanisms. This multifactorial pathogenesis includes molecules such as soluble factors, secreted proteinases, adhesins, lipophosphoglycan that culminate in cytoadherence and cytotoxicity against the host cells. Treatment and curability: The treatment with metronidazole or tinidazole is recommended; however, cure failures remain problematic due to noncompliance, reinfection and/or lack of treatment of sexual partners, inaccurate diagnosis, or drug resistance. Therefore, new therapeutic alternatives are urgently needed. Protection: Strategies for protection including sexual behavior, condom usage, and therapy have not contributed to the decrease on disease prevalence, pointing to the need for innovative approaches. Vaccine development has been hampered by the lack of long-lasting humoral immunity associated to the absence of good animal models.

  • Single-cell whole genome sequencing reveals no evidence for common aneuploidy in normal and Alzheimer's disease neurons

    NARCIS (Netherlands)

    van den Bos, Hilda; Spierings, Diana C J; Taudt, Aaron S; Bakker, Bjorn; Porubský, David; Falconer, Ester; Novoa, Carolina; Halsema, Nancy; Kazemier, Hinke G; Hoekstra-Wakker, Karina; Guryev, Victor; den Dunnen, Wilfred F A; Foijer, Floris; Tatché, Maria Colomé; Boddeke, Hendrikus W G M; Lansdorp, Peter M

    2016-01-01

    Background: Alzheimer's disease (AD) is a neurodegenerative disease of the brain and the most common form of dementia in the elderly. Aneuploidy, a state in which cells have an abnormal number of chromosomes, has been proposed to play a role in neurodegeneration in AD patients. Several studies using

    1. Single-cell whole genome sequencing reveals no evidence for common aneuploidy in normal and Alzheimer's disease neurons

      NARCIS (Netherlands)

      van den Bos, Hilda; Spierings, Diana C J; Taudt, Aaron S; Bakker, Bjorn; Porubský, David; Falconer, Ester; Novoa, Carolina; Halsema, Nancy; Kazemier, Hinke G; Hoekstra-Wakker, Karina; Guryev, Victor; den Dunnen, Wilfred F A; Foijer, Floris; Tatché, Maria Colomé; Boddeke, Hendrikus W G M; Lansdorp, Peter M

      2016-01-01

      BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disease of the brain and the most common form of dementia in the elderly. Aneuploidy, a state in which cells have an abnormal number of chromosomes, has been proposed to play a role in neurodegeneration in AD patients. Several studies using

    2. Polygenic transmission and complex neuro developmental network for attention deficit hyperactivity disorder: genome-wide association study of both common and rare variants.

      Science.gov (United States)

      Yang, Li; Neale, Benjamin M; Liu, Lu; Lee, S Hong; Wray, Naomi R; Ji, Ning; Li, Haimei; Qian, Qiujin; Wang, Dongliang; Li, Jun; Faraone, Stephen V; Wang, Yufeng; Doyle, Alysa E; Reif, Andreas; Rothenberger, Aribert; Franke, Barbara; Sonuga-Barke, Edmund J S; Steinhausen, Hans-Christoph; Buitelaar, Jan K; Kuntsi, Jonna; Biederman, Joseph; Lesch, Klaus-Peter; Kent, Lindsey; Asherson, Philip; Oades, Robert D; Loo, Sandra K; Nelson, Stan F; Faraone, Stephen V; Smalley, Susan L; Banaschewski, Tobias; Arias Vasquez, Alejandro; Todorov, Alexandre; Charach, Alice; Miranda, Ana; Warnke, Andreas; Thapar, Anita; Neale, Benjamin M; Cormand, Bru; Freitag, Christine; Mick, Eric; Mulas, Fernando; Middleton, Frank; HakonarsonHakonarson, Hakon; Palmason, Haukur; Schäfer, Helmut; Roeyers, Herbert; McGough, James J; Romanos, Jasmin; Crosbie, Jennifer; Meyer, Jobst; Ramos-Quiroga, Josep Antoni; Sergeant, Joseph; Elia, Josephine; Langely, Kate; Nisenbaum, Laura; Romanos, Marcel; Daly, Mark J; Ribasés, Marta; Gill, Michael; O'Donovan, Michael; Owen, Michael; Casas, Miguel; Bayés, Mònica; Lambregts-Rommelse, Nanda; Williams, Nigel; Holmans, Peter; Anney, Richard J L; Ebstein, Richard P; Schachar, Russell; Medland, Sarah E; Ripke, Stephan; Walitza, Susanne; Nguyen, Thuy Trang; Renner, Tobias J; Hu, Xiaolan

      2013-07-01

      Attention-deficit hyperactivity disorder (ADHD) is a complex polygenic disorder. This study aimed to discover common and rare DNA variants associated with ADHD in a large homogeneous Han Chinese ADHD case-control sample. The sample comprised 1,040 cases and 963 controls. All cases met DSM-IV ADHD diagnostic criteria. We used the Affymetrix6.0 array to assay both single nucleotide polymorphisms (SNPs) and copy number variants (CNVs). Genome-wide association analyses were performed using PLINK. SNP-heritability and SNP-genetic correlations with ADHD in Caucasians were estimated with genome-wide complex trait analysis (GCTA). Pathway analyses were performed using the Interval enRICHment Test (INRICH), the Disease Association Protein-Protein Link Evaluator (DAPPLE), and the Genomic Regions Enrichment of Annotations Tool (GREAT). We did not find genome-wide significance for single SNPs but did find an increased burden of large, rare CNVs in the ADHD sample (P = 0.038). SNP-heritability was estimated to be 0.42 (standard error, 0.13, P = 0.0017) and the SNP-genetic correlation with European Ancestry ADHD samples was 0.39 (SE 0.15, P = 0.0072). The INRICH, DAPPLE, and GREAT analyses implicated several gene ontology cellular components, including neuron projections and synaptic components, which are consistent with a neurodevelopmental pathophysiology for ADHD. This study suggested the genetic architecture of ADHD comprises both common and rare variants. Some common causal variants are likely to be shared between Han Chinese and Caucasians. Complex neurodevelopmental networks may underlie ADHD's etiology.

    3. The microglial NADPH oxidase complex as a source of oxidative stress in Alzheimer's disease

      Directory of Open Access Journals (Sweden)

      Landreth Gary E

      2006-11-01

      Full Text Available Abstract Alzheimer's disease is the most common cause of dementia in the elderly, and manifests as progressive cognitive decline and profound neuronal loss. The principal neuropathological hallmarks of Alzheimer's disease are the senile plaques and the neurofibrillary tangles. The senile plaques are surrounded by activated microglia, which are largely responsible for the proinflammatory environment within the diseased brain. Microglia are the resident innate immune cells in the brain. In response to contact with fibrillar beta-amyloid, microglia secrete a diverse array of proinflammatory molecules. Evidence suggests that oxidative stress emanating from activated microglia contribute to the neuronal loss characteristic of this disease. The source of fibrillar beta-amyloid induced reactive oxygen species is primarily the microglial nicotinamide adenine dinucleotide phosphate (NADPH oxidase. The NADPH oxidase is a multicomponent enzyme complex that, upon activation, produces the highly reactive free radical superoxide. The cascade of intracellular signaling events leading to NADPH oxidase assembly and the subsequent release of superoxide in fibrillar beta-amyloid stimulated microglia has recently been elucidated. The induction of reactive oxygen species, as well as nitric oxide, from activated microglia can enhance the production of more potent free radicals such as peroxynitrite. The formation of peroxynitrite causes protein oxidation, lipid peroxidation and DNA damage, which ultimately lead to neuronal cell death. The elimination of beta-amyloid-induced oxidative damage through the inhibition of the NADPH oxidase represents an attractive therapeutic target for the treatment of Alzheimer's disease.

    4. Global distribution of consanguinity and their impact on complex diseases: Genetic disorders from an endogamous population

      Directory of Open Access Journals (Sweden)

      Abdulbari Bener

      2017-10-01

      Conclusion: The present study revealed a higher incidence of certain diseases in consanguineous population with a high significant increase in the prevalence of common adult diseases such as diabetes mellitus, cancer, blood disorders, mental disorders, heart diseases, asthma, gastro-intestinal disorders, hypertension, hearing deficit, G6PD and common eye diseases. This confirms the role of genetic factors across the full spectrum of disease and not only for Mendelian disorders.

    5. [Influence of the working conditions on sickness absence due to common diseases].

      Science.gov (United States)

      Vaquero-Álvarez, Manuel; Álvarez-Theurer, Esther; Romero Saldaña, Manuel

      2017-06-13

      To estimate the importance of the working environment in sickness absence, as well as to show possible relationships with clinical-work variables. A descriptive observational study. SITE: Medical Inspection of an Andalusian province. A total of 1016 workers on certified sick leave due to a common illness. A self-report questionnaire was used to collect demographic data, profession, activity, risk assessment, and perceived occupational cause, on patients who voluntarily gave their consent when they were reviewed during 2015. The illness that caused certified sickness absences was verified in the computerised medical records. Using criteria applied by experts, the role of working conditions in each episode of certified sick leave was assessed. Bivariate and multivariate analyses were performed to determine any relationships between the variables. An inadequate work environment was found in 17.1% of the sickness processes. Health and hospitality services activities have a significant association with working conditions as a cause of sick leave (P<.001). With respect to diagnosis, anxiety-depressive disorders (P<.01) and low back pain (P<.05) were associated with working conditions. The factors related to certified sickness absence and work environment were: residence (OR=0.34, 0.21-0.6), normal/higher education (OR=1.7, 1.2-2.4), (OR=2.0 1.3-3.1), large companies (OR=1.97, 1.3-2.9), and job (OR=2.7, 1.6-3, 2). Sickness absence is affected by factors related to the work environment. Specific preventive actions for workers at their workplace could reduce work related diseases classified as a common illness. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

    6. Modeling Parkinson's disease in the common marmoset (Callithrix jacchus): overview of models, methods, and animal care.

      Science.gov (United States)

      Yun, Jun-Won; Ahn, Jae-Bum; Kang, Byeong-Cheol

      2015-12-01

      The common marmoset (Callithrix jacchus) is a small-bodied, popular New World monkey and is used widely in reproductive biology, neuroscience, and drug development, due to its comparative ease of handling, high reproductive efficiency, and its unique behavioral characters. In this review, we discuss the marmoset models in Parkinson's disease (PD), which is a neurological movement disorder primarily resulting from a degeneration of dopaminergic neurons with clinical features of tremor, rigidity, postural instability, and akinesia. The most common PD models involve the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 6-hydroxydopamine to study the pathogenesis and to evaluate novel therapies. Following the systemic or local administration of these neurotoxins, the marmosets with very severe Parkinson's symptoms are recommended to be placed in an intensive care unit with artificial feeding to increase survival rate. All procedures with MPTP should be conducted in a special room with enclosed cages under negative-pressure by trained researchers with personal protection. Behavioral tests are conducted to provide an external measure of the brain pathology. Along with several biomarkers, including α-synuclein and DJ-1, non-invasive neuroimaging techniques such as positron emission tomography and magnetic resonance imaging are used to evaluate the functional changes associated with PD. With the recent growing interest in potential and novel therapies such as stem cell and gene therapy for PD in Korea, the marmoset can be considered as a suitable non-human primate model in PD research to bridge the gap between rodent studies and clinical applications.

    7. Cerebral ABC transporter-common mechanisms may modulate neurodegenerative diseases and depression in elderly subjects.

      Science.gov (United States)

      Pahnke, Jens; Fröhlich, Christina; Paarmann, Kristin; Krohn, Markus; Bogdanovic, Nenad; Årsland, Dag; Winblad, Bengt

      2014-11-01

      In elderly subjects, depression and dementia often coincide but the actual reason is currently unknown. Does a causal link exist or is it just a reactive effect of the knowledge to suffer from dementia? The ABC transporter superfamily may represent a causal link between these mental disorders. Since the transporters ABCB1 and ABCC1 have been discovered as major β-amyloid-exporting molecules at the blood-brain barrier and ABCC1 was found to be directly activated by St. John's wort (SJW), depression and dementia certainly share an important pathophysiologic link. It was recognized that herbal anti-depressant formulations made from SJW are at least as effective for the treatment of unipolar depression in old age as classical pharmacotherapy, while having fewer side effects (Cochrane reports, 2008). SJW is known to activate various metabolizing and transport systems in the body, with cytochrome P450 enzymes and ABC transporters being most important. Does the treatment of depression in elderly subjects using pharmacological compounds or phytomedical extracts target a mechanism that also accounts for peptide storage in Alzheimer's disease and perhaps other proteopathies of the brain? In this review we summarize recent data that point to a common mechanism and present the first promising causal treatment results of demented elderly subjects with distinct SJW extracts. Insufficient trans-barrier clearance may indeed present a common problem in all the proteopathies of the brain where toxic peptides are deposited in a location-specific manner. Thus, activation of efflux molecules holds promise for future treatment of this large group of devastating disorders.

    8. Serum albumin and body weight as biomarkers for the antemortem identification of bone and gastrointestinal disease in the common marmoset.

      Science.gov (United States)

      Baxter, Victoria K; Shaw, Gillian C; Sotuyo, Nathaniel P; Carlson, Cathy S; Olson, Erik J; Zink, M Christine; Mankowski, Joseph L; Adams, Robert J; Hutchinson, Eric K; Metcalf Pate, Kelly A

      2013-01-01

      The increasing use of the common marmoset (Callithrix jacchus) in research makes it important to diagnose spontaneous disease that may confound experimental studies. Bone disease and gastrointestinal disease are two major causes of morbidity and mortality in captive marmosets, but currently no effective antemortem tests are available to identify affected animals prior to the terminal stage of disease. In this study we propose that bone disease and gastrointestinal disease are associated disease entities in marmosets and aim to establish the efficacy of several economical antemortem tests in identifying and predicting disease. Tissues from marmosets were examined to define affected animals and unaffected controls. Complete blood count, serum chemistry values, body weight, quantitative radiographs, and tissue-specific biochemical markers were evaluated as candidate biomarkers for disease. Bone and gastrointestinal disease were associated, with marmosets being over seven times more likely to have either concurrent bone and gastrointestinal disease or neither disease as opposed to lesions in only one organ system. When used in tandem, serum albumin disease. Progressive body weight loss of 0.05% of peak body weight per day predicted which marmosets would develop disease prior to the terminal stage. Bone tissue-specific tests, such as quantitative analysis of radiographs and serum parathyroid hormone levels, were effective for distinguishing between marmosets with bone disease and those without. These results provide an avenue for making informed decisions regarding the removal of affected marmosets from studies in a timely manner, preserving the integrity of research results.

    9. Prevalence of Common Skin Diseases and Their Associated Factors among Military Personnel in Korea: A Cross-sectional Study

      OpenAIRE

      Bae, Jung Min; Ha, Beomman; Lee, Hongsun; Park, Chang Keun; Kim, Hyun Joon; Park, Young Min

      2012-01-01

      This study was conducted to clarify the prevalence of common skin diseases and their associated factors among military personnel in Korea. Four dermatologists visited adjacent military units and examined soldiers. A structured questionnaire that included questions about known skin diseases, demographic information, and questions for the Perceived Stress Index was completed for each participant. The soldiers that had been diagnosed with a skin disease answered one additional questionnaire (Ski...

    10. Shared genetic susceptibility to ischemic stroke and coronary artery disease – a genome-wide analysis of common variants

      Science.gov (United States)

      Dichgans, Martin; Malik, Rainer; König, Inke R.; Rosand, Jonathan; Clarke, Robert; Gretarsdottir, Solveig; Thorleifsson, Gudmar; Mitchell, Braxton D.; Assimes, Themistocles L.; Levi, Christopher; O′Donnell, Christopher J.; Fornage, Myriam; Thorsteinsdottir, Unnur; Psaty, Bruce M.; Hengstenberg, Christian; Seshadri, Sudha; Erdmann, Jeanette; Bis, Joshua C.; Peters, Annette; Boncoraglio, Giorgio B.; März, Winfried; Meschia, James F.; Kathiresan, Sekar; Ikram, M. Arfan; McPherson, Ruth; Stefansson, Kari; Sudlow, Cathie; Reilly, Muredach P.; Thompson, John R.; Sharma, Pankaj; Hopewell, Jemma C.; Chambers, John C.; Watkins, Hugh; Rothwell, Peter M.; Roberts, Robert; Markus, Hugh S.; Samani, Nilesh J.; Farrall, Martin; Schunkert, Heribert

      2014-01-01

      Summary Background and Purpose Ischemic stroke (IS) and coronary artery disease (CAD) share several risk factors and each have a substantial heritability. We conducted a genome-wide analysis to evaluate the extent of shared genetic determination of the two diseases. Methods Genome-wide association data were obtained from the METASTROKE, CARDIoGRAM, and C4D consortia. We first analyzed common variants reaching a nominal threshold of significance (pstroke (LAS) subtype. Results Common variants associated with CAD at pgenetic risk of ischemic stroke and particularly the large artery stroke subtype with coronary artery disease. PMID:24262325

    11. Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease

      Science.gov (United States)

      Beilina, Alexandria; Rudenko, Iakov N.; Kaganovich, Alice; Civiero, Laura; Chau, Hien; Kalia, Suneil K.; Kalia, Lorraine V.; Lobbestael, Evy; Chia, Ruth; Ndukwe, Kelechi; Ding, Jinhui; Nalls, Mike A.; Olszewski, Maciej; Hauser, David N.; Kumaran, Ravindran; Lozano, Andres M.; Baekelandt, Veerle; Greene, Lois E.; Taymans, Jean-Marc; Greggio, Elisa; Cookson, Mark R.; Nalls, Mike A.; Plagnol, Vincent; Martinez, Maria; Hernandez, Dena G; Sharma, Manu; Sheerin, Una-Marie; Saad, Mohamad; Simón-Sánchez, Javier; Schulte, Claudia; Lesage, Suzanne; Sveinbjörnsdóttir, Sigurlaug; Arepalli, Sampath; Barker, Roger; Ben-Shlomo, Yoav; Berendse, Henk W; Berg, Daniela; Bhatia, Kailash; de Bie, Rob M A; Biffi, Alessandro; Bloem, Bas; Bochdanovits, Zoltan; Bonin, Michael; Bras, Jose M; Brockmann, Kathrin; Brooks, Janet; Burn, David J; Charlesworth, Gavin; Chen, Honglei; Chong, Sean; Clarke, Carl E; Cookson, Mark R; Cooper, J Mark; Corvol, Jean Christophe; Counsell, Carl; Damier, Philippe; Dartigues, Jean-François; Deloukas, Panos; Deuschl, Günther; Dexter, David T; van Dijk, Karin D; Dillman, Allissa; Durif, Frank; Dürr, Alexandra; Edkins, Sarah; Evans, Jonathan R; Foltynie, Thomas; Gao, Jianjun; Gardner, Michelle; Gibbs, J Raphael; Goate, Alison; Gray, Emma; Guerreiro, Rita; Gústafsson, Ómar; Harris, Clare; van Hilten, Jacobus J; Hofman, Albert; Hollenbeck, Albert; Holton, Janice; Hu, Michele; Huang, Xuemei; Huber, Heiko; Hudson, Gavin; Hunt, Sarah E; Huttenlocher, Johanna; Illig, Thomas; München, Helmholtz Zentrum; Jónsson, Pálmi V; Lambert, Jean-Charles; Langford, Cordelia; Lees, Andrew; Lichtner, Peter; München, Helmholtz Zentrum; Limousin, Patricia; Lopez, Grisel; Lorenz, Delia; McNeill, Alisdair; Moorby, Catriona; Moore, Matthew; Morris, Huw R; Morrison, Karen E; Mudanohwo, Ese; O’Sullivan, Sean S; Pearson, Justin; Perlmutter, Joel S; Pétursson, Hjörvar; Pollak, Pierre; Post, Bart; Potter, Simon; Ravina, Bernard; Revesz, Tamas; Riess, Olaf; Rivadeneira, Fernando; Rizzu, Patrizia; Ryten, Mina; Sawcer, Stephen; Schapira, Anthony; Scheffer, Hans; Shaw, Karen; Shoulson, Ira; Sidransky, Ellen; Smith, Colin; Spencer, Chris C A; Stefánsson, Hreinn; Steinberg, Stacy; Stockton, Joanna D; Strange, Amy; Talbot, Kevin; Tanner, Carlie M; Tashakkori-Ghanbaria, Avazeh; Tison, François; Trabzuni, Daniah; Traynor, Bryan J; Uitterlinden, André G; Velseboer, Daan; Vidailhet, Marie; Walker, Robert; van de Warrenburg, Bart; Wickremaratchi, Mirdhu; Williams, Nigel; Williams-Gray, Caroline H; Winder-Rhodes, Sophie; Stefánsson, Kári; Hardy, John; Heutink, Peter; Brice, Alexis; Gasser, Thomas; Singleton, Andrew B; Wood, Nicholas W; Chinnery, Patrick F; Arepalli, Sampath; Cookson, Mark R; Dillman, Allissa; Ferrucci, Luigi; Gibbs, J Raphael; Hernandez, Dena G; Johnson, Robert; Longo, Dan L; Majounie, Elisa; Nalls, Michael A; O’Brien, Richard; Singleton, Andrew B; Traynor, Bryan J; Troncoso, Juan; van der Brug, Marcel; Zielke, H Ronald; Zonderman, Alan B

      2014-01-01

      Mutations in leucine-rich repeat kinase 2 (LRRK2) cause inherited Parkinson disease (PD), and common variants around LRRK2 are a risk factor for sporadic PD. Using protein–protein interaction arrays, we identified BCL2-associated athanogene 5, Rab7L1 (RAB7, member RAS oncogene family-like 1), and Cyclin-G–associated kinase as binding partners of LRRK2. The latter two genes are candidate genes for risk for sporadic PD identified by genome-wide association studies. These proteins form a complex that promotes clearance of Golgi-derived vesicles through the autophagy–lysosome system both in vitro and in vivo. We propose that three different genes for PD have a common biological function. More generally, data integration from multiple unbiased screens can provide insight into human disease mechanisms. PMID:24510904

    12. Evidence for significant overlap between common risk variants for Crohn's disease and ankylosing spondylitis.

      Directory of Open Access Journals (Sweden)

      Debby Laukens

      Full Text Available BACKGROUND: A multicenter genome-wide association scan for Crohn's Disease (CD has recently reported 40 CD susceptibility loci, including 29 novel ones (19 significant and 10 putative. To gain insight into the genetic overlap between CD and ankylosing spondylitis (AS, these markers were tested for association in AS patients. PRINCIPAL FINDINGS: Two previously established associations, namely with the MHC and IL23R loci, were confirmed. In addition, rs2872507, which maps to a locus associated with asthma and influences the expression of the ORMDL3 gene in lymphoblastoid cells, showed a significant association with AS (p = 0.03. In gut biopsies of AS and CD patients, ORMDL3 expression was not significantly different from controls and no correlation was found with the rs2872507 genotype (Spearman's rho: -0.067. The distribution of p-values for the remaining 36 SNPs was significantly skewed towards low p-values unless the top 5 ranked SNPs (ORMDL3, NKX2-3, PTPN2, ICOSLG and MST1 were excluded from the analysis. CONCLUSIONS: Association analysis using risk variants for CD led to the identification of a new risk variant associated with AS (ORMDL3, underscoring a role for ER stress in AS. In addition, two known and five potentially relevant associations were detected, contributing to common susceptibility of CD and AS.

    13. Common variants associated with plasma triglycerides and risk for coronary artery disease

      Science.gov (United States)

      Do, Ron; Willer, Cristen J.; Schmidt, Ellen M.; Sengupta, Sebanti; Gao, Chi; Peloso, Gina M.; Gustafsson, Stefan; Kanoni, Stavroula; Ganna, Andrea; Chen, Jin; Buchkovich, Martin L.; Mora, Samia; Beckmann, Jacques S.; Bragg-Gresham, Jennifer L.; Chang, Hsing-Yi; Demirkan, Ayşe; Den Hertog, Heleen M.; Donnelly, Louise A.; Ehret, Georg B.; Esko, Tõnu; Feitosa, Mary F.; Ferreira, Teresa; Fischer, Krista; Fontanillas, Pierre; Fraser, Ross M.; Freitag, Daniel F.; Gurdasani, Deepti; Heikkilä, Kauko; Hyppönen, Elina; Isaacs, Aaron; Jackson, Anne U.; Johansson, Åsa; Johnson, Toby; Kaakinen, Marika; Kettunen, Johannes; Kleber, Marcus E.; Li, Xiaohui; Luan, Jian'an; Lyytikäinen, Leo-Pekka; Magnusson, Patrik K.E.; Mangino, Massimo; Mihailov, Evelin; Montasser, May E.; Müller-Nurasyid, Martina; Nolte, Ilja M.; O'Connell, Jeffrey R.; Palmer, Cameron D.; Perola, Markus; Petersen, Ann-Kristin; Sanna, Serena; Saxena, Richa; Service, Susan K.; Shah, Sonia; Shungin, Dmitry; Sidore, Carlo; Song, Ci; Strawbridge, Rona J.; Surakka, Ida; Tanaka, Toshiko; Teslovich, Tanya M.; Thorleifsson, Gudmar; Van den Herik, Evita G.; Voight, Benjamin F.; Volcik, Kelly A.; Waite, Lindsay L.; Wong, Andrew; Wu, Ying; Zhang, Weihua; Absher, Devin; Asiki, Gershim; Barroso, Inês; Been, Latonya F.; Bolton, Jennifer L.; Bonnycastle, Lori L; Brambilla, Paolo; Burnett, Mary S.; Cesana, Giancarlo; Dimitriou, Maria; Doney, Alex S.F.; Döring, Angela; Elliott, Paul; Epstein, Stephen E.; Eyjolfsson, Gudmundur Ingi; Gigante, Bruna; Goodarzi, Mark O.; Grallert, Harald; Gravito, Martha L.; Groves, Christopher J.; Hallmans, Göran; Hartikainen, Anna-Liisa; Hayward, Caroline; Hernandez, Dena; Hicks, Andrew A.; Holm, Hilma; Hung, Yi-Jen; Illig, Thomas; Jones, Michelle R.; Kaleebu, Pontiano; Kastelein, John J.P.; Khaw, Kay-Tee; Kim, Eric; Klopp, Norman; Komulainen, Pirjo; Kumari, Meena; Langenberg, Claudia; Lehtimäki, Terho; Lin, Shih-Yi; Lindström, Jaana; Loos, Ruth J.F.; Mach, François; McArdle, Wendy L; Meisinger, Christa; Mitchell, Braxton D.; Müller, Gabrielle; Nagaraja, Ramaiah; Narisu, Narisu; Nieminen, Tuomo V.M.; Nsubuga, Rebecca N.; Olafsson, Isleifur; Ong, Ken K.; Palotie, Aarno; Papamarkou, Theodore; Pomilla, Cristina; Pouta, Anneli; Rader, Daniel J.; Reilly, Muredach P.; Ridker, Paul M.; Rivadeneira, Fernando; Rudan, Igor; Ruokonen, Aimo; Samani, Nilesh; Scharnagl, Hubert; Seeley, Janet; Silander, Kaisa; Stančáková, Alena; Stirrups, Kathleen; Swift, Amy J.; Tiret, Laurence; Uitterlinden, Andre G.; van Pelt, L. Joost; Vedantam, Sailaja; Wainwright, Nicholas; Wijmenga, Cisca; Wild, Sarah H.; Willemsen, Gonneke; Wilsgaard, Tom; Wilson, James F.; Young, Elizabeth H.; Zhao, Jing Hua; Adair, Linda S.; Arveiler, Dominique; Assimes, Themistocles L.; Bandinelli, Stefania; Bennett, Franklyn; Bochud, Murielle; Boehm, Bernhard O.; Boomsma, Dorret I.; Borecki, Ingrid B.; Bornstein, Stefan R.; Bovet, Pascal; Burnier, Michel; Campbell, Harry; Chakravarti, Aravinda; Chambers, John C.; Chen, Yii-Der Ida; Collins, Francis S.; Cooper, Richard S.; Danesh, John; Dedoussis, George; de Faire, Ulf; Feranil, Alan B.; Ferrières, Jean; Ferrucci, Luigi; Freimer, Nelson B.; Gieger, Christian; Groop, Leif C.; Gudnason, Vilmundur; Gyllensten, Ulf; Hamsten, Anders; Harris, Tamara B.; Hingorani, Aroon; Hirschhorn, Joel N.; Hofman, Albert; Hovingh, G. Kees; Hsiung, Chao Agnes; Humphries, Steve E.; Hunt, Steven C.; Hveem, Kristian; Iribarren, Carlos; Järvelin, Marjo-Riitta; Jula, Antti; Kähönen, Mika; Kaprio, Jaakko; Kesäniemi, Antero; Kivimaki, Mika; Kooner, Jaspal S.; Koudstaal, Peter J.; Krauss, Ronald M.; Kuh, Diana; Kuusisto, Johanna; Kyvik, Kirsten O.; Laakso, Markku; Lakka, Timo A.; Lind, Lars; Lindgren, Cecilia M.; Martin, Nicholas G.; März, Winfried; McCarthy, Mark I.; McKenzie, Colin A.; Meneton, Pierre; Metspalu, Andres; Moilanen, Leena; Morris, Andrew D.; Munroe, Patricia B.; Njølstad, Inger; Pedersen, Nancy L.; Power, Chris; Pramstaller, Peter P.; Price, Jackie F.; Psaty, Bruce M.; Quertermous, Thomas; Rauramaa, Rainer; Saleheen, Danish; Salomaa, Veikko; Sanghera, Dharambir K.; Saramies, Jouko; Schwarz, Peter E.H.; Sheu, Wayne H-H; Shuldiner, Alan R.; Siegbahn, Agneta; Spector, Tim D.; Stefansson, Kari; Strachan, David P.; Tayo, Bamidele O.; Tremoli, Elena; Tuomilehto, Jaakko; Uusitupa, Matti; van Duijn, Cornelia M.; Vollenweider, Peter; Wallentin, Lars; Wareham, Nicholas J.; Whitfield, John B.; Wolffenbuttel, Bruce H.R.; Altshuler, David; Ordovas, Jose M.; Boerwinkle, Eric; Palmer, Colin N.A.; Thorsteinsdottir, Unnur; Chasman, Daniel I.; Rotter, Jerome I.; Franks, Paul W.; Ripatti, Samuli; Cupples, L. Adrienne; Sandhu, Manjinder S.; Rich, Stephen S.; Boehnke, Michael; Deloukas, Panos; Mohlke, Karen L.; Ingelsson, Erik; Abecasis, Goncalo R.; Daly, Mark J.; Neale, Benjamin M.; Kathiresan, Sekar

      2013-01-01

      Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiologic studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P<5×10−8 for each) to examine the role of triglycerides on risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglycerides, and show that the direction and magnitude of both are factors in determining CAD risk. Second, we consider loci with only a strong magnitude of association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol, a polymorphism's strength of effect on triglycerides is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD. PMID:24097064

    14. Genotype Characterization of Commonly Used Newcastle Disease Virus Vaccine Strains of India

      Science.gov (United States)

      Gaikwad, Satish; Kataria, Jag Mohan; Vakharia, Vikram N.

      2014-01-01

      Newcastle disease is an avian pathogen causing severe economic losses to the Indian poultry industry due to recurring outbreaks in vaccinated and unvaccinated flocks. India being an endemic country, advocates vaccination against the virus using lentogenic and mesogenic strains. Two virus strains which are commonly used for vaccination are strain F (a lentogenic virus) and strain R2B (a mesogenic virus). Strain F is given to 0–7 days old chicks and R2B is given to older birds which are around 6–8 weeks old. To understand the genetic makeup of these two strains, a complete genome study and phylogenetic analysis of the F, HN genes of these vaccine strains were carried out. Both the viral strains had a genome length of 15,186 nucleotides and consisted of six genes with conserved complimentary 3' leader and 5' trailer regions. The fusion protein cleavage site of strain F is GGRQGRL and strain R2B is RRQKRF. Although both the viral strains had different virulence attributes, the length of the HN protein was similar with 577 amino acids. Phylogenetic analysis of F, HN and complete genome sequences grouped these two strains in genotype II category which are considered as early genotypes and corroborated with their years of isolation. PMID:24897503

    15. Diabetes and cancer: two diseases with obesity as a common risk factor

      Science.gov (United States)

      Garg, S K; Maurer, H; Reed, K; Selagamsetty, R

      2014-01-01

      There is a growing body of evidence to support a connection between diabetes (predominantly type 2), obesity and cancer. Multiple meta-analyses of epidemiological data show that people with diabetes are at increased risk of developing many different types of cancers, along with an increased risk of cancer mortality. Several pathophysiological mechanisms for this relationship have been postulated, including insulin resistance and hyperinsulinaemia, enhanced inflammatory processes, dysregulation of sex hormone production and hyperglycaemia. In addition to these potential mechanisms, a number of common risk factors, including obesity, may be behind the association between diabetes and cancer. Indeed, obesity is associated with an increased risk of cancer and diabetes. Abdominal adiposity has been shown to play a role in creating a systemic pro-inflammatory environment, which could result in the development of both diabetes and cancer. Here, we examine the relationship between diabetes, obesity and cancer, and investigate the potential underlying causes of increased cancer risk in individuals with diabetes. Current treatment recommendations for reducing the overall disease burden are also explored and possible areas for future research are considered. PMID:23668396

    16. Glucocerebrosidase mutations are not a common risk factor for Parkinson disease in North Africa.

      Science.gov (United States)

      Nishioka, Kenya; Vilariño-Güell, Carles; Cobb, Stephanie A; Kachergus, Jennifer M; Ross, Owen A; Wider, Christian; Gibson, Rachel A; Hentati, Faycal; Farrer, Matthew J

      2010-06-21

      Mutations in the glucocerebrosidase gene (GBA) have recently been associated with an increased risk of Parkinson disease (PD). GBA mutations have been observed to be particularly prevalent in the Ashkenazi Jewish population. Interestingly, this population also has a high incidence of the Lrrk2 p.G2019S mutation which is similar in North African Arab-Berber populations. Herein, our sequencing of the GBA gene, in 33 North African Arab-Berber familial parkinsonism probands, identified two novel mutations in three individuals (p.K-26R and p.K186R). Segregation analysis of these two variants did not support a pathogenic role. Genotyping of p.K-26R, p.K186R and the common p.N370S in an ethnically matched series consisting of 395 patients with PD and 372 control subjects did not show a statistically significant association (P>0.05). The p.N370S mutation was only identified in 1 sporadic patient with PD and 3 control subjects indicating that the frequency of this mutation in the North African Arab-Berber population is much lower than that observed in Ashkenazi Jews, and therefore arose in the latter after expansion of the Lrrk2 p.G2019S variant in North Africa.

    17. Esterase’s properties in commonly used Indian spices for Alzheimer’s disease model

      Directory of Open Access Journals (Sweden)

      Prabha M

      2015-04-01

      Full Text Available Esterase family of Hydrolases such as Acetylcholinesterase (AchE,Butyrylcholinesterase (BchE and Carboxyl esterase (CE havebeen estimated in Alzheimer’s disease (AD model, normal brain ofstriatum, frontal cortex, hippocampus and in liver. In AD a loss ofacetylcholine activity directly correlates with memory dysfunctiondue to the activation of acetylcholinesterase andbutyrylcholinesterase enzymes. Therefore the effective treatmentmethods include restoration of cholinergic function and elevation ofACh level through inhibiting AChE and BChE. Hence to inhibitthese enzymes four commonly used Indian kitchen spices viz.,Cuminum cyminum, Elettaria cardamomum, Cinnamomum verum,Syzygium aromaticum were selected because the extracts of thesespices contain cholinesterase inhibitory activity in vitro. Thesespices were extracted with cold and hot aqueous solution and theanti- cholinesterase potential was measured in vitro. Elettariacardamomum cold extract showed significant inhibition for AchE inall regions of brain for control and AD. Whereas Cinnamomumverum hot extract showed elevated activity for carboxyl esterasewhich is a neuroprotective factor. These findings suggest thatdietary supplementation of cardamom and cinnamon in moderateamounts may aid in prevention delay in onset of AD.

    18. Common variants associated with plasma triglycerides and risk for coronary artery disease.

      Science.gov (United States)

      Do, Ron; Willer, Cristen J; Schmidt, Ellen M; Sengupta, Sebanti; Gao, Chi; Peloso, Gina M; Gustafsson, Stefan; Kanoni, Stavroula; Ganna, Andrea; Chen, Jin; Buchkovich, Martin L; Mora, Samia; Beckmann, Jacques S; Bragg-Gresham, Jennifer L; Chang, Hsing-Yi; Demirkan, Ayşe; Den Hertog, Heleen M; Donnelly, Louise A; Ehret, Georg B; Esko, Tõnu; Feitosa, Mary F; Ferreira, Teresa; Fischer, Krista; Fontanillas, Pierre; Fraser, Ross M; Freitag, Daniel F; Gurdasani, Deepti; Heikkilä, Kauko; Hyppönen, Elina; Isaacs, Aaron; Jackson, Anne U; Johansson, Asa; Johnson, Toby; Kaakinen, Marika; Kettunen, Johannes; Kleber, Marcus E; Li, Xiaohui; Luan, Jian'an; Lyytikäinen, Leo-Pekka; Magnusson, Patrik K E; Mangino, Massimo; Mihailov, Evelin; Montasser, May E; Müller-Nurasyid, Martina; Nolte, Ilja M; O'Connell, Jeffrey R; Palmer, Cameron D; Perola, Markus; Petersen, Ann-Kristin; Sanna, Serena; Saxena, Richa; Service, Susan K; Shah, Sonia; Shungin, Dmitry; Sidore, Carlo; Song, Ci; Strawbridge, Rona J; Surakka, Ida; Tanaka, Toshiko; Teslovich, Tanya M; Thorleifsson, Gudmar; Van den Herik, Evita G; Voight, Benjamin F; Volcik, Kelly A; Waite, Lindsay L; Wong, Andrew; Wu, Ying; Zhang, Weihua; Absher, Devin; Asiki, Gershim; Barroso, Inês; Been, Latonya F; Bolton, Jennifer L; Bonnycastle, Lori L; Brambilla, Paolo; Burnett, Mary S; Cesana, Giancarlo; Dimitriou, Maria; Doney, Alex S F; Döring, Angela; Elliott, Paul; Epstein, Stephen E; Eyjolfsson, Gudmundur Ingi; Gigante, Bruna; Goodarzi, Mark O; Grallert, Harald; Gravito, Martha L; Groves, Christopher J; Hallmans, Göran; Hartikainen, Anna-Liisa; Hayward, Caroline; Hernandez, Dena; Hicks, Andrew A; Holm, Hilma; Hung, Yi-Jen; Illig, Thomas; Jones, Michelle R; Kaleebu, Pontiano; Kastelein, John J P; Khaw, Kay-Tee; Kim, Eric; Klopp, Norman; Komulainen, Pirjo; Kumari, Meena; Langenberg, Claudia; Lehtimäki, Terho; Lin, Shih-Yi; Lindström, Jaana; Loos, Ruth J F; Mach, François; McArdle, Wendy L; Meisinger, Christa; Mitchell, Braxton D; Müller, Gabrielle; Nagaraja, Ramaiah; Narisu, Narisu; Nieminen, Tuomo V M; Nsubuga, Rebecca N; Olafsson, Isleifur; Ong, Ken K; Palotie, Aarno; Papamarkou, Theodore; Pomilla, Cristina; Pouta, Anneli; Rader, Daniel J; Reilly, Muredach P; Ridker, Paul M; Rivadeneira, Fernando; Rudan, Igor; Ruokonen, Aimo; Samani, Nilesh; Scharnagl, Hubert; Seeley, Janet; Silander, Kaisa; Stančáková, Alena; Stirrups, Kathleen; Swift, Amy J; Tiret, Laurence; Uitterlinden, Andre G; van Pelt, L Joost; Vedantam, Sailaja; Wainwright, Nicholas; Wijmenga, Cisca; Wild, Sarah H; Willemsen, Gonneke; Wilsgaard, Tom; Wilson, James F; Young, Elizabeth H; Zhao, Jing Hua; Adair, Linda S; Arveiler, Dominique; Assimes, Themistocles L; Bandinelli, Stefania; Bennett, Franklyn; Bochud, Murielle; Boehm, Bernhard O; Boomsma, Dorret I; Borecki, Ingrid B; Bornstein, Stefan R; Bovet, Pascal; Burnier, Michel; Campbell, Harry; Chakravarti, Aravinda; Chambers, John C; Chen, Yii-Der Ida; Collins, Francis S; Cooper, Richard S; Danesh, John; Dedoussis, George; de Faire, Ulf; Feranil, Alan B; Ferrières, Jean; Ferrucci, Luigi; Freimer, Nelson B; Gieger, Christian; Groop, Leif C; Gudnason, Vilmundur; Gyllensten, Ulf; Hamsten, Anders; Harris, Tamara B; Hingorani, Aroon; Hirschhorn, Joel N; Hofman, Albert; Hovingh, G Kees; Hsiung, Chao Agnes; Humphries, Steve E; Hunt, Steven C; Hveem, Kristian; Iribarren, Carlos; Järvelin, Marjo-Riitta; Jula, Antti; Kähönen, Mika; Kaprio, Jaakko; Kesäniemi, Antero; Kivimaki, Mika; Kooner, Jaspal S; Koudstaal, Peter J; Krauss, Ronald M; Kuh, Diana; Kuusisto, Johanna; Kyvik, Kirsten O; Laakso, Markku; Lakka, Timo A; Lind, Lars; Lindgren, Cecilia M; Martin, Nicholas G; März, Winfried; McCarthy, Mark I; McKenzie, Colin A; Meneton, Pierre; Metspalu, Andres; Moilanen, Leena; Morris, Andrew D; Munroe, Patricia B; Njølstad, Inger; Pedersen, Nancy L; Power, Chris; Pramstaller, Peter P; Price, Jackie F; Psaty, Bruce M; Quertermous, Thomas; Rauramaa, Rainer; Saleheen, Danish; Salomaa, Veikko; Sanghera, Dharambir K; Saramies, Jouko; Schwarz, Peter E H; Sheu, Wayne H-H; Shuldiner, Alan R; Siegbahn, Agneta; Spector, Tim D; Stefansson, Kari; Strachan, David P; Tayo, Bamidele O; Tremoli, Elena; Tuomilehto, Jaakko; Uusitupa, Matti; van Duijn, Cornelia M; Vollenweider, Peter; Wallentin, Lars; Wareham, Nicholas J; Whitfield, John B; Wolffenbuttel, Bruce H R; Altshuler, David; Ordovas, Jose M; Boerwinkle, Eric; Palmer, Colin N A; Thorsteinsdottir, Unnur; Chasman, Daniel I; Rotter, Jerome I; Franks, Paul W; Ripatti, Samuli; Cupples, L Adrienne; Sandhu, Manjinder S; Rich, Stephen S; Boehnke, Michael; Deloukas, Panos; Mohlke, Karen L; Ingelsson, Erik; Abecasis, Goncalo R; Daly, Mark J; Neale, Benjamin M; Kathiresan, Sekar

      2013-11-01

      Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.

    19. Diabetes mellitus and periodontitis: a tale of two common interrelated diseases.

      Science.gov (United States)

      Lalla, Evanthia; Papapanou, Panos N

      2011-06-28

      Diabetes mellitus (a group of metabolic disorders characterized by hyperglycemia) and periodontitis (a microbially induced inflammatory disorder that affects the supporting structures of teeth) are both common, chronic conditions. Multiple studies have demonstrated that diabetes mellitus (type 1 and type 2) is an established risk factor for periodontitis. Findings from mechanistic studies indicate that diabetes mellitus leads to a hyperinflammatory response to the periodontal microbiota and also impairs resolution of inflammation and repair, which leads to accelerated periodontal destruction. The cell surface receptor for advanced glycation end products and its ligands are expressed in the periodontium of individuals with diabetes mellitus and seem to mediate these processes. The association between the two diseases is bidirectional, as periodontitis has been reported to adversely affect glycemic control in patients with diabetes mellitus and to contribute to the development of diabetic complications. In addition, meta-analyses conclude that periodontal therapy in individuals with diabetes mellitus can result in a modest improvement of glycemic control. The effect of periodontal infections on diabetes mellitus is potentially explained by the resulting increase in levels of systemic proinflammatory mediators, which exacerbates insulin resistance. As our understanding of the relationship between diabetes mellitus and periodontitis deepens, increased patient awareness of the link between diabetes mellitus and oral health and collaboration among medical and dental professionals for the management of affected individuals become increasingly important.

    20. Neuroinflammation as a Common Mechanism Associated with the Modifiable Risk Factors for Alzheimer's and Parkinson`s Diseases.

      Science.gov (United States)

      McKenzie, Jordan Alexander; Spielman, Lindsay J; Pointer, Caitlin B; Lowry, Jessica R; Bajwa, Ekta; Lee, Carolyn W; Klegeris, Andis

      2017-03-15

      Alzheimer's disease (AD) and Parkinson's disease (PD) are among the most common causes of dementia, which increasingly contribute to morbidity and mortality worldwide. A common hallmark in the pathogenesis of these two diseases is neuroinflammation, which is initially triggered by the presence of pathological structures associated with these disorders. Chronic neuroinflammation is sustained by persistent and aberrant microglial activation in the brain, which results in damage and death of neighboring cells, including neurons and glial cells. Two types of risk factors contribute to the development of AD and PD: non-modifiable risk factors and modifiable risk factors. Non-modifiable risk factors include genetic susceptibility that increases an individual's risk of developing the disease, whereas modifiable risk factors include a wide variety of health- and lifestyle-related factors that may be altered by changing individual behaviors. Exposure to environmental toxins could be viewed as a partially modifiable risk factor. This review focuses on four modifiable risk factors including physical inactivity, vascular disease-related conditions, obesity and type two diabetes mellitus, all of which have been identified as risk factors for the development of AD and PD. We highlight that control of the modifiable risk factors is a valid approach for managing the increased incidence of AD and PD. We describe neuroinflammatory mechanisms, which are common to AD and PD, that may link both these neurodegenerative diseases with the four common modifiable risk factors. Understanding these mechanisms could help identify novel therapeutic targets for combating these neurodegenerative diseases.

    1. Copy number variants and common disorders: filling the gaps and exploring complexity in genome-wide association studies.

      Directory of Open Access Journals (Sweden)

      Xavier Estivill

      2007-10-01

      Full Text Available Genome-wide association scans (GWASs using single nucleotide polymorphisms (SNPs have been completed successfully for several common disorders and have detected over 30 new associations. Considering the large sample sizes and genome-wide SNP coverage of the scans, one might have expected many of the common variants underpinning the genetic component of various disorders to have been identified by now. However, these studies have not evaluated the contribution of other forms of genetic variation, such as structural variation, mainly in the form of copy number variants (CNVs. Known CNVs account for over 15% of the assembled human genome sequence. Since CNVs are not easily tagged by SNPs, might have a wide range of copy number variability, and often fall in genomic regions not well covered by whole-genome arrays or not genotyped by the HapMap project, current GWASs have largely missed the contribution of CNVs to complex disorders. In fact, some CNVs have already been reported to show association with several complex disorders using candidate gene/region approaches, underpinning the importance of regions not investigated in current GWASs. This reveals the need for new generation arrays (some already in the market and the use of tailored approaches to explore the full dimension of genome variability beyond the single nucleotide scale.

    2. Awareness and knowledge of common eye diseases among the academic staff (non-medical faculties) of University of Malaya.

      Science.gov (United States)

      Chew, Y K; Reddy, S C; Karina, R

      2004-08-01

      A cross sectional study was conducted to assess the level of awareness and knowledge of common eye diseases (cataract, glaucoma, diabetic retinopathy and refractive errors) among 473 academic staff (non-medical faculties) of University Malaya. The awareness of cataract was in 88.2%, diabetic retinopathy in 83.5%, refractive errors in 75.3% and glaucoma in 71.5% of the study population. The knowledge about all the above common eye diseases was moderate, except presbyopia which was poor. Multivariate analysis revealed that females, older people, and those having family history of eye diseases were significantly more aware and more knowledgeable about the eye diseases. Health education about eye diseases would be beneficial to seek early treatment and prevent visual impairment in the society.

    3. Summary of contributions to GAW Group 15: family-based samples are useful in identifying common polymorphisms associated with complex traits.

      Science.gov (United States)

      Knight, Stacey; Uh, Hae-Won; Martinez, Maria

      2009-01-01

      Traditionally, family-based samples have been used for genetic analyses of single-gene traits caused by rare but highly penetrant risk variants. The utility of family-based genetic data for analyzing common complex traits is unclear and contains numerous challenges. To assess the utility as well as to address these challenges, members of Genetic Analysis Workshop 16 Group 15 analyzed Framingham Heart Study data using family-based designs ranging from parent--offspring trios to large pedigrees. We investigated different methods including traditional linkage tests, family-based association tests, and population-based tests that correct for relatedness between subjects, and tests to detect parent-of-origin effects. The analyses presented an assortment of positive findings. One contribution found increased power to detect epistatic effects through linkage using ascertainment of sibships based on extreme quantitative values or presence of disease associated with the quantitative value. Another contribution found four single-nucleotide polymorphisms (SNPs) showing a maternal effect, two SNPs with an imprinting effect, and one SNP having both effects on a binary high blood pressure trait. Finally, three contributions illustrated the advantage of using population-based methods to detect association to complex binary or quantitative traits. Our findings highlight the contribution of family-based samples to the genetic dissection of complex traits. (c) 2009 Wiley-Liss, Inc.

    4. Spectrum analysis of common inherited metabolic diseases in Chinese patients screened and diagnosed by tandem mass spectrometry.

      Science.gov (United States)

      Han, Lianshu; Han, Feng; Ye, Jun; Qiu, Wenjuan; Zhang, Huiwen; Gao, Xiaolan; Wang, Yu; Ji, Wenjun; Gu, Xuefan

      2015-03-01

      Information concerning inherited metabolic diseases in China is scarce. We investigated the prevalence and age distributions of amino acid, organic acid, and fatty acid oxidation disorders in Chinese patients. Blood levels of amino acids and acylcarnitines (tandem mass spectrometry) were measured in 18,303 patients with suspected inherited metabolic diseases. Diagnosis was based on clinical features, blood levels of amino acids or acylcarnitines, urinary organic acid levels (gas chromatography-mass spectrometry), and (in some) gene mutation tests. Inherited metabolic diseases were confirmed in 1,135 patients (739 males, 396 females). Median age was 12 months (1 day to 59 years). There were 28 diseases: 12 amino acid disorders (580 patients, 51.1%), with hyperphenylalaninemia (HPA) being the most common; nine organic acidemias (408 patients, 35.9%), with methylmalonic acidemia (MMA) as the most common; and seven fatty acid oxidation defects (147 patients, 13.0%), with multiple acyl-coenzyme A dehydrogenase deficiency (MADD) being the most common. Onset was mainly at 1-6 months for citrin deficiency, 0-6 months for MMA, and in newborns for ornithine transcarbamylase deficiency (OTCD). HPA was common in patients aged 1-3 years, and MADD was common in patients >18 years. In China, HPA, citrin deficiency, MMA, and MADD are the most common inherited disorders, particularly in newborns/infants. © 2014 Wiley Periodicals, Inc.

    5. Evaluation of Presumably Disease Causing SCN1A Variants in a Cohort of Common Epilepsy Syndromes.

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      Dennis Lal

      Full Text Available The SCN1A gene, coding for the voltage-gated Na+ channel alpha subunit NaV1.1, is the clinically most relevant epilepsy gene. With the advent of high-throughput next-generation sequencing, clinical laboratories are generating an ever-increasing catalogue of SCN1A variants. Variants are more likely to be classified as pathogenic if they have already been identified previously in a patient with epilepsy. Here, we critically re-evaluate the pathogenicity of this class of variants in a cohort of patients with common epilepsy syndromes and subsequently ask whether a significant fraction of benign variants have been misclassified as pathogenic.We screened a discovery cohort of 448 patients with a broad range of common genetic epilepsies and 734 controls for previously reported SCN1A mutations that were assumed to be disease causing. We re-evaluated the evidence for pathogenicity of the identified variants using in silico predictions, segregation, original reports, available functional data and assessment of allele frequencies in healthy individuals as well as in a follow up cohort of 777 patients.We identified 8 known missense mutations, previously reported as pathogenic, in a total of 17 unrelated epilepsy patients (17/448; 3.80%. Our re-evaluation indicates that 7 out of these 8 variants (p.R27T; p.R28C; p.R542Q; p.R604H; p.T1250M; p.E1308D; p.R1928G; NP_001159435.1 are not pathogenic. Only the p.T1174S mutation may be considered as a genetic risk factor for epilepsy of small effect size based on the enrichment in patients (P = 6.60 x 10-4; OR = 0.32, fishers exact test, previous functional studies but incomplete penetrance. Thus, incorporation of previous studies in genetic counseling of SCN1A sequencing results is challenging and may produce incorrect conclusions.

    6. Mycobacterium avium Complex Infection in a Patient with Sickle Cell Disease and Severe Iron Overload

      Directory of Open Access Journals (Sweden)

      Kamal Shemisa

      2014-01-01

      Full Text Available A 34-year-old female with sickle cell anemia (hemoglobin SS disease and severe iron overload presented to our institution with the subacute presentation of recurrent pain crisis, fever of unknown origin, pancytopenia, and weight loss. A CT scan demonstrated both lung and liver nodules concerning for granulomatous disease. Subsequent biopsies of the liver and bone marrow confirmed the presence of noncaseating granulomas and blood cultures isolated Mycobacterium avium complex MAC. Disseminated MAC is considered an opportunistic infection typically diagnosed in the immunocompromised and rarely in immunocompetent patients. An appreciable number of mycobacterial infection cases have been reported in sickle cell disease patients without immune dysfunction. It has been reported that iron overload is known to increase the risk for mycobacterial infection in vitro and in vivo studies. While iron overload is primarily known to cause end organ dysfunction, the clinical relationship with sickle cell disease and disseminated MAC infection has not been reported. Clinical iron overload is a common condition diagnosed in the sub-Saharan African population. High dietary iron, genetic defects in iron trafficking, as well as hemoglobinopathy are believed to be the etiologies for iron overload in this region. Patients with iron overload in this region were 17-fold more likely to die from Mycobacterium tuberculosis. Both experimental and clinical evidence suggest a possible link to iron overload and mycobacterial infections; however larger observational studies are necessary to determine true causality.

    7. Molecular Diagnostics in the Mycosphaerella Leaf Spot Disease Complex of Banana and for Radopholus similis

      NARCIS (Netherlands)

      Arzanlou, M.; Kema, G.H.J.; Waalwijk, C.; Carlier, I.; Vries, de P.M.; Guzmán, M.; Araya Vargas, M.; Helder, J.; Crous, P.W.

      2009-01-01

      Mycosphaerella leaf spots and nematodes threaten banana cultivation worldwide. The Mycosphaerella disease complex involves three related ascomycetous fungi: Mycosphaerella fijiensis, M. musicola and M. eumusae. The exact distribution of these three species and their disease epidemiology remain

    8. Molecular Diagnostics in the Mycosphaerella Leaf Spot Disease Complex of Banana and for Radopholus similis

      NARCIS (Netherlands)

      Arzanlou, M.; Kema, G.H.J.; Waalwijk, C.; Carlier, I.; Vries, de P.M.; Guzmán, M.; Araya Vargas, M.; Helder, J.; Crous, P.W.

      2009-01-01

      Mycosphaerella leaf spots and nematodes threaten banana cultivation worldwide. The Mycosphaerella disease complex involves three related ascomycetous fungi: Mycosphaerella fijiensis, M. musicola and M. eumusae. The exact distribution of these three species and their disease epidemiology remain uncle

    9. Asthma: a simple concept but in reality a complex disease.

      Science.gov (United States)

      Holgate, Stephen T

      2011-12-01

      Asthma is a disorder of the conducting airways that contract too easily and too much to cause variable airflow obstruction with symptoms of wheeze, cough, chest tightness and shortness of breath. Based on this knowledge, initial treatments were directed to dilating the contracted airways with anticholinergic and adrenergic drugs. The recognition that allergic-type inflammation underlay the hyperresponsive airways in asthma led to the introduction of anti-inflammatory drugs such as sodium cromoglicate and corticosteroids. Over the 2 decades that followed, these drugs have been progressively improved by increasing their therapeutic index and duration of action. A review of the recent literature indicates that since the 1980s, the explosive increase in knowledge of the cell and mediator mechanisms of asthma has only led to modest improvements in therapy including the introduction of leukotriene modifiers and a blocking monoclonal antibody against IgE. Indeed, biologics targeting allergic cytokines and effector cells have on the whole proven disappointing despite initial promise being shown in animal models. Part of the difficulty lies in the oversimplified concept that asthma is only driven by allergic processes when in reality there are many environmental causes and triggers and the view that it is a homogeneous disorder only varying in severity. The more recent views that asthma is a complex disorder made up of different subtypes with differing causes, treatment responses and natural histories creates a new opportunity for stratified medicine in which therapies acting upstream selectively target specific disease subtypes identified by specific diagnostic biomarkers. © 2011 The Author. European Journal of Clinical Investigation © 2011 Stichting European Society for Clinical Investigation Journal Foundation.

    10. Deciphering the four-letter code : The genetic basis of complex traits and common disease

      NARCIS (Netherlands)

      Pulit, S.L.

      2016-01-01

      Deoxyribonucleic acid (DNA) is made up of four bases: adenine (A), cytosine (C), guanine (G), and thymine (T). Assembled in a strategic fashion, these bases code for the unique genomes of all walks of life, from viruses, to rodents, to primates. The human genome, mapped completely for the first time

    11. Deciphering the four-letter code : The genetic basis of complex traits and common disease

      NARCIS (Netherlands)

      Pulit, S.L.

      2016-01-01

      Deoxyribonucleic acid (DNA) is made up of four bases: adenine (A), cytosine (C), guanine (G), and thymine (T). Assembled in a strategic fashion, these bases code for the unique genomes of all walks of life, from viruses, to rodents, to primates. The human genome, mapped completely for the first time

    12. Identification of Early-Stage Alzheimer's Disease Using Sulcal Morphology and Other Common Neuroimaging Indices

      Science.gov (United States)

      Cai, Kunpeng; Xu, Hong; Guan, Hao; Zhu, Wanlin; Jiang, Jiyang; Cui, Yue; Zhang, Jicong; Liu, Tao; Wen, Wei

      2017-01-01

      Identifying Alzheimer’s disease (AD) at its early stage is of major interest in AD research. Previous studies have suggested that abnormalities in regional sulcal width and global sulcal index (g-SI) are characteristics of patients with early-stage AD. In this study, we investigated sulcal width and three other common neuroimaging morphological measures (cortical thickness, cortical volume, and subcortical volume) to identify early-stage AD. These measures were evaluated in 150 participants, including 75 normal controls (NC) and 75 patients with early-stage AD. The global sulcal index (g-SI) and the width of five individual sulci (the superior frontal, intra-parietal, superior temporal, central, and Sylvian fissure) were extracted from 3D T1-weighted images. The discriminative performances of the other three traditional neuroimaging morphological measures were also examined. Information Gain (IG) was used to select a subset of features to provide significant information for separating NC and early-stage AD subjects. Based on the four modalities of the individual measures, i.e., sulcal measures, cortical thickness, cortical volume, subcortical volume, and combinations of these individual measures, three types of classifiers (Naïve Bayes, Logistic Regression and Support Vector Machine) were applied to compare the classification performances. We observed that sulcal measures were either superior than or equal to the other measures used for classification. Specifically, the g-SI and the width of the Sylvian fissure were two of the most sensitive sulcal measures and could be useful neuroanatomical markers for detecting early-stage AD. There were no significant differences between the three classifiers that we tested when using the same neuroanatomical features. PMID:28129351

    13. GLOSSI: a method to assess the association of genetic loci-sets with complex diseases

      Directory of Open Access Journals (Sweden)

      Asmann Yan W

      2009-04-01

      Full Text Available Abstract Background The developments of high-throughput genotyping technologies, which enable the simultaneous genotyping of hundreds of thousands of single nucleotide polymorphisms (SNP have the potential to increase the benefits of genetic epidemiology studies. Although the enhanced resolution of these platforms increases the chance of interrogating functional SNPs that are themselves causative or in linkage disequilibrium with causal SNPs, commonly used single SNP-association approaches suffer from serious multiple hypothesis testing problems and provide limited insights into combinations of loci that may contribute to complex diseases. Drawing inspiration from Gene Set Enrichment Analysis developed for gene expression data, we have developed a method, named GLOSSI (Gene-loci Set Analysis, that integrates prior biological knowledge into the statistical analysis of genotyping data to test the association of a group of SNPs (loci-set with complex disease phenotypes. The most significant loci-sets can be used to formulate hypotheses from a functional viewpoint that can be validated experimentally. Results In a simulation study, GLOSSI showed sufficient power to detect loci-sets with less than 10% of SNPs having moderate-to-large effect sizes and intermediate minor allele frequency values. When applied to a biological dataset where no single SNP-association was found in a previous study, GLOSSI was able to identify several loci-sets that are significantly related to blood pressure response to an antihypertensive drug. Conclusion GLOSSI is valuable for association of SNPs at multiple genetic loci with complex disease phenotypes. In contrast to methods based on the Kolmogorov-Smirnov statistic, the approach is parametric and only utilizes information from within the interrogated loci-set. It properly accounts for dependency among SNPs and allows the testing of loci-sets of any size.

    14. Prevalence of common skin diseases and their associated factors among military personnel in Korea: a cross-sectional study.

      Science.gov (United States)

      Bae, Jung Min; Ha, Beomman; Lee, Hongsun; Park, Chang Keun; Kim, Hyun Joon; Park, Young Min

      2012-10-01

      This study was conducted to clarify the prevalence of common skin diseases and their associated factors among military personnel in Korea. Four dermatologists visited adjacent military units and examined soldiers. A structured questionnaire that included questions about known skin diseases, demographic information, and questions for the Perceived Stress Index was completed for each participant. The soldiers that had been diagnosed with a skin disease answered one additional questionnaire (Skindex-29) which assess the influence of an individual's skin disease on daily life. Of 1,321 soldiers examined, 798 (60.4%) had one or more skin diseases. The three most common skin problems were acne (35.6%), tinea pedis (15.2%) and atopic dermatitis (5.1%). The diseases closely related to the period of military service were acne, tinea pedis, viral warts and corns. The diseases related to the amount of stress were atopic dermatitis, seborrheic dermatitis, and acne. The most troublesome skin diseases were atopic dermatitis, tinea cruris, and seborrheic dermatitis. These results demonstrated that the prevalence of skin disease among military personnel in Korea is very high, and that some of the skin disorders may have a significant influence on their daily lives.

    15. Identification of the second common Jewish Gaucher disease mutation makes possible population-based screening for the heterozygous state

      Energy Technology Data Exchange (ETDEWEB)

      Beutler, E.; Gelbart, T.; Kuhl, W.; Sorge, J.; West, C. (Scripps Research Inst., La Jolla, CA (United States))

      1991-12-01

      Gaucher disease is an autosomal recessive glycolipid storage disease characterized by a deficiency of glucocerebrosidase. The disease is most common in persons of Ashkenazi Jewish ancestry and the most common mutation, accounting for about 75% of the mutant alleles in this population, is known to be an A {yields} G substitution at cDNA nucleotide (nt) 1,226. Screening for this disease has not been possible because nearly 25% of the mutant alleles had not been identified, but linkage analysis led to the suggestion that most of these could be accounted for by a single mutation. The authors now report the discovery of this mutation. The insertion of a single nucleotide, a second guanine at cDNA nt 84 (the 84GG mutation), has been detected in the 5{prime} coding region of the glucocerebrosidase gene. The amount mRNA produced is shown to be normal but since the frameshift produces early termination, no translation product is seen. This finding is consistent with the virtual absence of antigen found in patients carrying this mutation. The 84GG mutation accounts for most of the previously unidentified Gaucher disease mutations in Jewish patients. The common Jewish mutation at nt 1,448 accounted for 95% of all of the Gaucher disease-producing alleles in 71 Jewish patients. This now makes it possible to screen for heterozygotes on a DNA level with a relatively low risk of missing couples at risk for producing infants with Gaucher disease.

    16. Overlap, common features, and essential differences in pediatric granulomatous inflammatory bowel disease.

      NARCIS (Netherlands)

      Damen, G.M.; Krieken, J.H.J.M. van; Hoppenreijs, E.P.A.H.; Os, E. van; Tolboom, J.J.M.; Warris, A.; Yntema, J.L.; Nieuwenhuis, E.E.; Escher, J.C.

      2010-01-01

      Overlap in the clinical presentation of pediatric granulomatous inflammatory bowel disease may be substantial, depending on the mode of presentation. Chronic granulomatous disease (CGD) may present with granulomatous colitis, perianal abscesses, hepatic abscesses or granulomas, failure to thrive,

    17. Overlap, common features, and essential differences in pediatric granulomatous inflammatory bowel disease.

      NARCIS (Netherlands)

      Damen, G.M.; Krieken, J.H.J.M. van; Hoppenreijs, E.P.A.H.; Os, E. van; Tolboom, J.J.M.; Warris, A.; Yntema, J.L.; Nieuwenhuis, E.E.; Escher, J.C.

      2010-01-01

      Overlap in the clinical presentation of pediatric granulomatous inflammatory bowel disease may be substantial, depending on the mode of presentation. Chronic granulomatous disease (CGD) may present with granulomatous colitis, perianal abscesses, hepatic abscesses or granulomas, failure to thrive, an

    18. Sonographic findings of common musculoskeletal disease in patients with diabetes mellitis

      Energy Technology Data Exchange (ETDEWEB)

      Park, Min Ho; Park, Ji Seon [Dept. of Medicine, Graduate School, Kyung Hee University, Seoul (Korea, Republic of); Ahn, Sung Eun; Ryu, Kyung Nam [Dept. of Radiology, Kyung Hee University Hospital, Seoul (Korea, Republic of); Park, So Young; Jin, Wook [Dept. of Radiology, Kyung Hee University Hospital at Gangdong, Seoul (Korea, Republic of)

      2016-04-15

      Diabetes mellitus (DM) can accompany many musculoskeletal (MSK) diseases. It is difficult to distinguish the DM-related MSK diseases based on clinical symptoms alone. Sonography is frequently used as a first imaging study for these MSK symptoms and is helpful to differentiate the various DM-related MSK diseases. This pictorial essay focuses on sonographic findings of various MSK diseases that can occur in diabetic patients.

    19. [The application of genetic risk score in genetic studies of complex human diseases].

      Science.gov (United States)

      Dayan, Niu; Weili, Yan

      2015-12-01

      Complex diseases such as cardiovascular disease, type 2 diabetes, essential hypertension, asthma, obesity and cancer have spread across the globe and become the predominant cause of death. There are growing concerns over the role of genetic susceptibility in pathogenesis of complex diseases. However, the related susceptibility genes and sequence variations are still unknown. To elucidate the genetic basis of complex diseases, researchers have identified a large number of genetic variants associated with complex diseases through genome-wide association studies (GWAS) and candidate gene studies recently. The identification of these causal and/or associated variants promotes the development of approaches for complex diseases prediction and prevention. Genetic risk score (GRS), an emerging method for exploring correlation between single nucleotide polymorphisms (SNPs) and clinical phenotypes of complex diseases, integrates weak effects of multiple SNPs and dramatically enhances predictability of complex diseases by gene polymorphisms. This method has been applied successfully in genetic studies of many complex diseases. Here we focus on the introduction of the computational methods and evaluation criteria of GRS, enumerate a series of achievements through GRS application, discuss some limitations during application, and finally prospect the future of GRS.

    20. Hyperactivation of HUSH complex function by Charcot-Marie-Tooth disease mutation in MORC2.

      Science.gov (United States)

      Tchasovnikarova, Iva A; Timms, Richard T; Douse, Christopher H; Roberts, Rhys C; Dougan, Gordon; Kingston, Robert E; Modis, Yorgo; Lehner, Paul J

      2017-07-01

      Dominant mutations in the MORC2 gene have recently been shown to cause axonal Charcot-Marie-Tooth (CMT) disease, but the cellular function of MORC2 is poorly understood. Here, through a genome-wide CRISPR-Cas9-mediated forward genetic screen, we identified MORC2 as an essential gene required for epigenetic silencing by the HUSH complex. HUSH recruits MORC2 to target sites in heterochromatin. We exploited a new method, differential viral accessibility (DIVA), to show that loss of MORC2 results in chromatin decompaction at these target loci, which is concomitant with a loss of H3K9me3 deposition and transcriptional derepression. The ATPase activity of MORC2 is critical for HUSH-mediated silencing, and the most common alteration affecting the ATPase domain in CMT patients (p.Arg252Trp) hyperactivates HUSH-mediated repression in neuronal cells. These data define a critical role for MORC2 in epigenetic silencing by the HUSH complex and provide a mechanistic basis underpinning the role of MORC2 mutations in CMT disease.

    1. Bilateral painful parotid lumps and a lump in the groin: An uncommon presentation of common Kikuchi's disease

      Science.gov (United States)

      Mirgh, Sumeet Prakash; Satiya, Jinendra; Sorabjee, Jehangir Soli

      2016-01-01

      Kikuchi-Fujimoto disease (KFD) is an under-recognized disease most commonly presenting with cervical lymphadenopathy, fever, and cytopenias in young females. Bilateral parotid enlargement is usually caused by infections (e.g., mumps) and autoimmune conditions (e.g., Sjogren syndrome). Parotid enlargement, inguinal lymphadenopathy, and pyrexia of unknown origin are uncommon presenting features of KFD and should be suspected in the appropriate setting. PMID:27843864

    2. Bilateral painful parotid lumps and a lump in the groin: An uncommon presentation of common Kikuchi's disease

      Directory of Open Access Journals (Sweden)

      Sumeet Prakash Mirgh

      2016-01-01

      Full Text Available Kikuchi-Fujimoto disease (KFD is an under-recognized disease most commonly presenting with cervical lymphadenopathy, fever, and cytopenias in young females. Bilateral parotid enlargement is usually caused by infections (e.g., mumps and autoimmune conditions (e.g., Sjogren syndrome. Parotid enlargement, inguinal lymphadenopathy, and pyrexia of unknown origin are uncommon presenting features of KFD and should be suspected in the appropriate setting.

    3. Type 2 diabetes: genetic data sharing to advance complex disease research.

      Science.gov (United States)

      Flannick, Jason; Florez, Jose C

      2016-09-01

      As with other complex diseases, unbiased association studies followed by physiological and experimental characterization have for years formed a paradigm for identifying genes or processes of relevance to type 2 diabetes mellitus (T2D). Recent large-scale common and rare variant genome-wide association studies (GWAS) suggest that substantially larger association studies are needed to identify most T2D loci in the population. To hasten clinical translation of genetic discoveries, new paradigms are also required to aid specialized investigation of nascent hypotheses. We argue for an integrated T2D knowledgebase, designed for a worldwide community to access aggregated large-scale genetic data sets, as one paradigm to catalyse convergence of these efforts.

    4. Protein misfolding in the late-onset neurodegenerative diseases: common themes and the unique case of amyotrophic lateral sclerosis.

      Science.gov (United States)

      Mulligan, Vikram Khipple; Chakrabartty, Avijit

      2013-08-01

      Enormous strides have been made in the last 100 years to extend human life expectancy and to combat the major infectious diseases. Today, the major challenges for medical science are age-related diseases, including cancer, heart disease, lung disease, renal disease, and late-onset neurodegenerative disease. Of these, only the neurodegenerative diseases represent a class of disease so poorly understood that no general strategies for prevention or treatment exist. These diseases, which include Alzheimer's disease, Parkinson's disease, Huntington's disease, the transmissible spongiform encephalopathies, and amyotrophic lateral sclerosis (ALS), are generally fatal and incurable. The first section of this review summarizes the diversity and common features of the late-onset neurodegenerative diseases, with a particular focus on protein misfolding and aggregation-a recurring theme in the molecular pathology. The second section focuses on the particular case of ALS, a late-onset neurodegenerative disease characterized by the death of central nervous system motor neurons, leading to paralysis and patient death. Of the 10% of ALS cases that show familial inheritance (familial ALS), the largest subset is caused by mutations in the SOD1 gene, encoding the Cu, Zn superoxide dismutase (SOD1). The unusual kinetic stability of SOD1 has provided a unique opportunity for detailed structural characterization of conformational states potentially involved in SOD1-associated ALS. This review discusses past studies exploring the stability, folding, and misfolding behavior of SOD1, as well as the therapeutic possibilities of using detailed knowledge of misfolding pathways to target the molecular mechanisms underlying ALS and other neurodegenerative diseases.

    5. Properties of human disease genes and the role of genes linked to Mendelian disorders in complex disease aetiology

      Science.gov (United States)

      Spataro, Nino; Rodríguez, Juan Antonio; Navarro, Arcadi

      2017-01-01

      Abstract Do genes presenting variation that has been linked to human disease have different biological properties than genes that have never been related to disease? What is the relationship between disease and fitness? Are the evolutionary pressures that affect genes linked to Mendelian diseases the same to those acting on genes whose variation contributes to complex disorders? The answers to these questions could shed light on the architecture of human genetic disorders and may have relevant implications when designing mapping strategies in future genetic studies. Here we show that, relative to non-disease genes, human disease (HD) genes have specific evolutionary profiles and protein network properties. Additionally, our results indicate that the mutation-selection balance renders an insufficient account of the evolutionary history of some HD genes and that adaptive selection could also contribute to shape their genetic architecture. Notably, several biological features of HD genes depend on the type of pathology (complex or Mendelian) with which they are related. For example, genes harbouring both causal variants for Mendelian disorders and risk factors for complex disease traits (Complex-Mendelian genes), tend to present higher functional relevance in the protein network and higher expression levels than genes associated only with complex disorders. Moreover, risk variants in Complex-Mendelian genes tend to present higher odds ratios than those on genes associated with the same complex disorders but with no link to Mendelian diseases. Taken together, our results suggest that genetic variation at genes linked to Mendelian disorders plays an important role in driving susceptibility to complex disease. PMID:28053046

    6. Beclin 1 complex in autophagy and Alzheimer disease.

      Science.gov (United States)

      Jaeger, Philipp A; Wyss-Coray, Tony

      2010-10-01

      Beclin 1 is a protein involved in the regulation of autophagy and has been shown to be reduced in patients with Alzheimer disease. This review summarizes the current research data that link disturbances in autophagy, a cellular degradation and maintenance pathway, to the development of Alzheimer disease and related neurodegenerative diseases. It also provides a brief overview of the existing pharmacological interventions available to modulate autophagy activity in mammalian cells.

    7. Drug susceptibility testing and pharmacokinetics question current treatment regimens in Mycobacterium simiae complex disease.

      NARCIS (Netherlands)

      Ingen, J. van; Totten, S.E.; Heifets, L.B.; Boeree, M.J.; Daley, C.L.

      2012-01-01

      The Mycobacterium simiae complex bacteria can cause opportunistic infections in humans. In the case of definite disease, there are no evidence-based treatment regimens and outcomes are very disappointing. To increase the evidence base underpinning treatment regimens for M. simiae complex disease, dr

    8. Medical diseases and depression in older adults: common features and etiological relation

      OpenAIRE

      Bastidas-Bilbao, Hamer

      2014-01-01

      A systematic review was conducted of 51 English-language papers published since 2000 in the following databases: PsycNet, Ebsco, and Science Direct. Findings reveal a high comorbidity of depression in older adults. Moreover, they also exhibit stroke, diabetes, Alzheimer’s disease and Parkinsonism, with patterns of symptoms similar to those seen in depression resulting from disease impairment. Analysis shows that these diseases can also precede depression, even without an anatomical-functional...

    9. Common dermatologic diseases among students at a tertiary care center in Lebanon.

      Science.gov (United States)

      Khattar, Joe A; Hamadeh, Ghassan N; Rahi, Amal C; Musharrafieh, Umayya M

      2010-01-01

      There are few publications on prevalence of skin diseases in Lebanon. To find the prevalence of dermatologic diseases among students seen at the university health services of the American University of Beirut. Medical charts were retrospectively reviewed. Chi-square tests were used to assess any significant difference between male and female prevalence amongst all types of skin diseases met; p-value image in society.

    10. Complex Type 2 Reactions in Three Patients with Hansen's Disease from a Southern United States Clinic.

      Science.gov (United States)

      Leon, Kristoffer E; Salinas, Jorge L; McDonald, Robert W; Sheth, Anandi N; Fairley, Jessica K

      2015-11-01

      In non-endemic countries, leprosy, or Hansen's disease (HD), remains rare and is often underrecognized. Consequently, the literature is currently lacking in clinical descriptions of leprosy complications in the United States. Immune-mediated inflammatory states known as reactions are common complications of HD. Type 1 reactions are typical of borderline cases and occur in 30% of patients and present as swelling and inflammation of existing skin lesions, neuritis, and nerve dysfunction. Type 2 reactions are systemic events that occur at the lepromatous end of the disease spectrum, and typical symptoms include fever, arthralgias, neuritis, and classic painful erythematous skin nodules known as erythema nodosum leprosum. We report three patients with lepromatous leprosy seen at a U.S. HD clinic with complicated type 2 reactions. The differences in presentations and clinical courses highlight the complexity of the disease and the need for increased awareness of unique manifestations of lepromatous leprosy in non-endemic areas. © The American Society of Tropical Medicine and Hygiene.

    11. GWAS signals across the HLA regions: revealing a clue for common etiology underlying infectious tumors and other immunity diseases

      Institute of Scientific and Technical Information of China (English)

      Yin Yao Shugart; Ying Wang; Wei-Hua Jia; Yi-Xin Zeng

      2011-01-01

      Increasing evidence suggests that multiple genes in the human leukocyte antigen (HLA) regions play an important role in development of cancers and immunity disorders. However, the biological mechanisms of the HLA associations are not well understood. We recently conducted a survey of all genome-wide association studies (GWAS) with significant findings in the HLA regions and concluded that diseases such as cancer and immune disorders are more likely to be associated with genetic variants located in the HLA regions than other diseases. This finding is suggestive for testing a hypothesis of a common etiology of infectious tumors and other immunity diseases.

    12. The Impact of Evolutionary Driving Forces on Human Complex Diseases: A Population Genetics Approach

      Directory of Open Access Journals (Sweden)

      Amr T. M. Saeb

      2016-01-01

      Full Text Available Investigating the molecular evolution of human genome has paved the way to understand genetic adaptation of humans to the environmental changes and corresponding complex diseases. In this review, we discussed the historical origin of genetic diversity among human populations, the evolutionary driving forces that can affect genetic diversity among populations, and the effects of human movement into new environments and gene flow on population genetic diversity. Furthermore, we presented the role of natural selection on genetic diversity and complex diseases. Then we reviewed the disadvantageous consequences of historical selection events in modern time and their relation to the development of complex diseases. In addition, we discussed the effect of consanguinity on the incidence of complex diseases in human populations. Finally, we presented the latest information about the role of ancient genes acquired from interbreeding with ancient hominids in the development of complex diseases.

    13. Relationship between common lipoprotein lipase gene sequence variants, hyperinsulinemia, and risk of ischemic heart disease: A population-based study

      DEFF Research Database (Denmark)

      Jeppesen, Jørgen; Hansen, Tine Willum; Torp-Pedersen, Christian;

      2010-01-01

      Hyperinsulinemia and lipoprotein lipase (LPL) are important determinants of fasting and postprandial plasma triglyceride levels. High insulin and high triglyceride levels are associated with an increased risk of ischemic heart disease (IHD). This study aimed to find out whether common LPL gene...

    14. Two Common Second Causes of Dizziness in Patients With Ménièreʼs Disease

      NARCIS (Netherlands)

      van Esch, Babette F.; van Benthem, Peter Paul G; van der Zaag-Loonen, Hester J.; Bruintjes, Tjasse D.

      2016-01-01

      OBJECTIVE:: There are no epidemiological studies quantifying the prevalence of second causes of dizziness in Ménièreʼs disease (MD). Therefore, we aimed to quantify which dizziness-inducing causes are prevalent alongside MD. Moreover, we analyzed which second cause of dizziness was more common in a

    15. Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease

      NARCIS (Netherlands)

      Trynka, Gosia; Hunt, Karen A.; Bockett, Nicholas A.; Romanos, Jihane; Mistry, Vanisha; Szperl, Agata; Bakker, Sjoerd F.; Bardella, Maria Teresa; Bhaw-Rosun, Leena; Castillejo, Gemma; de la Concha, Emilio G.; de Almeida, Rodrigo Coutinho; Dias, Kerith-Rae M.; van Diemen, Cleo C.; Dubois, Patrick C. A.; Duerr, Richard H.; Edkins, Sarah; Franke, Lude; Fransen, Karin; Gutierrez, Javier; Heap, Graham A. R.; Hrdlickova, Barbara; Hunt, Sarah; Plaza Izurieta, Leticia; Izzo, Valentina; Joosten, Leo A. B.; Langford, Cordelia; Mazzilli, Maria Cristina; Mein, Charles A.; Midah, Vandana; Mitrovic, Mitja; Mora, Barbara; Morelli, Marinita; Nutland, Sarah; Nunez, Concepcion; Onengut-Gumuscu, Suna; Pearce, Kerra; Platteel, Mathieu; Polanco, Isabel; Potter, Simon; Ribes-Koninckx, Carmen; Ricano-Ponce, Isis; Rich, Stephen S.; Rybak, Anna; Luis Santiago, Jose; Senapati, Sabyasachi; Sood, Ajit; Szajewska, Hania; Troncone, Riccardo; Varade, Jezabel; Wallace, Chris; Wolters, Victorien M.; Zhernakova, Alexandra; Thelma, B. K.; Cukrowska, Bozena; Urcelay, Elena; Ramon Bilbao, Jose; Mearin, M. Luisa; Barisani, Donatella; Barrett, Jeffrey C.; Plagnol, Vincent; Deloukas, Panos; Wijmenga, Cisca; van Heel, David A.

      2011-01-01

      Using variants from the 1000 Genomes Project pilot European CEU dataset and data from additional resequencing studies, we densely genotyped 183 non-HLA risk loci previously associated with immune-mediated diseases in 12,041 individuals with celiac disease (cases) and 12,228 controls. We identified 1

    16. Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease

      NARCIS (Netherlands)

      Trynka, G.; Hunt, K.A.; Bockett, N.A.; Romanos, J.; Mistry, V.; Szperl, A.; Bakker, S.F.; Bardella, M.T.; Bhaw-Rosun, L.; Castillejo, G.; Concha, E. de la; Almeida, R.C. de; Dias, K.R.; Diemen, C.C. van; Dubois, P.C.; Duerr, R.H.; Edkins, S.; Franke, L.; Fransen, K.; Gutierrez, J.; Heap, G.A.; Hrdlickova, B.; Hunt, S.; Izurieta, L.P.; Izzo, V.; Joosten, L.A.B.; Langford, C.; Mazzilli, M.C.; Mein, C.A.; Midah, V.; Mitrovic, M.; Mora, B.; Morelli, M.; Nutland, S.; Nunez, C.; Onengut-Gumuscu, S.; Pearce, K.; Platteel, M.; Polanco, I.; Potter, S.; Ribes-Koninckx, C.; Ricano-Ponce, I.; Rich, S.S.; Rybak, A.; Santiago, J.L.; Senapati, S.; Sood, A.; Szajewska, H.; Troncone, R.; Varade, J.; Wallace, C.; Wolters, V.M.; Zhernakova, A.; Thelma, B.K.; Cukrowska, B.; Urcelay, E.; Bilbao, J.R.; Mearin, M.L.; Barisani, D.; Barrett, J.C.; Plagnol, V.; Deloukas, P.; Wijmenga, C.; Heel, D.A. van

      2011-01-01

      Using variants from the 1000 Genomes Project pilot European CEU dataset and data from additional resequencing studies, we densely genotyped 183 non-HLA risk loci previously associated with immune-mediated diseases in 12,041 individuals with celiac disease (cases) and 12,228 controls. We identified 1

    17. Common and different genetic background for rheumatoid arthritis and coeliac disease

      NARCIS (Netherlands)

      Coenen, Marieke J H; Trynka, Gosia; Heskamp, Sandra; Franke, Barbara; van Diemen, Cleo C; Smolonska, Joanna; van Leeuwen, Maria; Brouwer, Elisabeth; Boezen, Hendrika; Postma, Dirkje S; Platteel, Mathieu; Zanen, Pieter; Lammers, Jan-Willem W J; Groen, Hendricus; Mali, Willem P T M; Mulder, Chris J; Tack, Greetje J; Verbeek, Wieke H M; Wolters, Victorien M; Houwen, Roderick H J; Mearin, M Luisa; van Heel, David A; Radstake, Timothy R D J; van Riel, Piet L C M; Wijmenga, Cisca; Barrera, Pilar; Zhernakova, Alexandra

      2009-01-01

      Recent genome-wide association studies (GWAS) have revealed genetic risk factors in autoimmune and inflammatory disorders. Several of the associated genes and underlying pathways are shared by various autoimmune diseases. Rheumatoid arthritis (RA) and coeliac disease (CD) are two autoimmune

    18. Current Guidelines, Common Clinical Pitfalls, and Future Directions for Laboratory Diagnosis of Lyme Disease, United States

      Science.gov (United States)

      Moore, Andrew; Nelson, Christina; Molins, Claudia; Mead, Paul

      2016-01-01

      In the United States, Lyme disease is caused by Borrelia burgdorferi and transmitted to humans by blacklegged ticks. Patients with an erythema migrans lesion and epidemiologic risk can receive a diagnosis without laboratory testing. For all other patients, laboratory testing is necessary to confirm the diagnosis, but proper interpretation depends on symptoms and timing of illness. The recommended laboratory test in the United States is 2-tiered serologic analysis consisting of an enzyme-linked immunoassay or immunofluorescence assay, followed by reflexive immunoblotting. Sensitivity of 2-tiered testing is low (30%–40%) during early infection while the antibody response is developing (window period). For disseminated Lyme disease, sensitivity is 70%–100%. Specificity is high (>95%) during all stages of disease. Use of other diagnostic tests for Lyme disease is limited. We review the rationale behind current US testing guidelines, appropriate use and interpretation of tests, and recent developments in Lyme disease diagnostics. PMID:27314832

    19. Easing Arthritis: Research offers new hope for people with common joint disease.

      Science.gov (United States)

      ... Navigation Bar Home Current Issue Past Issues Easing Arthritis: Research offers new hope for people with common ... likely help with that. Need more information on Arthritis? From MedlinePlus.gov : For a slideshow with sound ...

    20. Transhepatic perforation of the gallbladder: rare complication of a common disease

      Directory of Open Access Journals (Sweden)

      Shrestha KR

      2010-05-01

      Full Text Available Acute cholecystitis leading to gallbladder perforation is relatively common. However, transhepatic perforation of the gallbladder leading to biliary peritonitis is very rare. We present a rare case of biliary peritonitis caused by transhepatic perforation of the gallbladder.

    1. Nephrolithiasis as a common urinary system manifestation of inflammatory bowel diseases; a clinical review and meta-analysis.

      Science.gov (United States)

      Ganji-Arjenaki, Mahboube; Nasri, Hamid; Rafieian-Kopaei, Mahmoud

      2017-07-01

      The extra-intestinal manifestations of inflammatory bowel disease (IBD) are common and involve other organs or systems for example; urinary system. For this review, we used a variety of sources by searching through Web of Science, PubMed, EMBASE, Scopus and directory of open access journals (DOAJ). Urinary complications may occur in up to 22% of patients and nephrolithiasis or renal/kidney stones have been suggested to be a common manifestation of disease in forms of uric acid, calcium phosphate or calcium oxalate. We performed a meta-analysis on five clinical trials and reported that correlation between IBD and formation of stone in renal system is positive and significant (Fix-effect model; CI: 95%, P <0.001, and randomeffect model; CI: 95%, P = 0.03). Based on the reports of the clinical trials, calcium oxalate is more prevalent in Crohn's disease (CD) than in ulcerative colitis (UC).

    2. Primary care nursing activities with patients affected by physical chronic disease and common mental disorders: a qualitative descriptive study.

      Science.gov (United States)

      Girard, Ariane; Hudon, Catherine; Poitras, Marie-Eve; Roberge, Pasquale; Chouinard, Maud-Christine

      2017-05-01

      To describe nursing activities in primary care with patients affected by physical chronic disease and common mental disorders. Patients in primary care who are affected by physical chronic disease and common mental disorders such as anxiety and depression require care and follow-up based on their physical and mental health condition. Primary care nurses are increasingly expected to contribute to the care and follow-up of this growing clientele. However, little is known about the actual activities carried out by primary care nurses in providing this service in the Province of Quebec (Canada). A qualitative descriptive study was conducted. Data were obtained through semistructured individual interviews with 13 nurses practising among patients with physical chronic disease in seven Family Medicine Groups in Quebec (Canada). Participants described five activity domains: assessment of physical and mental health condition, care planning, interprofessional collaboration, therapeutic relationship and health promotion. The full potential of primary care nurses is not always exploited, and some activities could be improved. Evidence for including nurses in collaborative care for patients affected by physical chronic disease and common mental disorders has been shown but is not fully implemented in Family Medicine Groups. Future research should emphasise collaboration among mental health professionals, primary care nurses and family physicians in the care of patients with physical chronic disease and common mental disorders. Primary care nurses would benefit from gaining more knowledge about common mental disorders and from identifying the resources they need to contribute to managing them in an interdisciplinary team. © 2016 John Wiley & Sons Ltd.

    3. Possible protective action of neurotrophic factors and natural compounds against common neurodegenerative diseases

      Institute of Scientific and Technical Information of China (English)

      Tadahiro Numakawa

      2014-01-01

      It has been suggested that altered levels/function of brain-derived neurotrophic factor (BDNF) play a role in the pathophysiology of neurodegenerative diseases including Alzheimer’s disease. BDNF positively contributes to neural survival and synapse maintenance via stimulating its high afifnity receptor TrkB, making upregulation of BDNF and/or activation of BDNF-related intracellular signaling an attractive approach to treating neurodegenerative diseases. In this short review, I brielfy introduce small natural compounds such as lfavonoids that successfully increase activation of the BDNF system and discuss their beneifcial effects against neurodegeneration.

    4. Prediction of a common structural scaffold for proteasome lid, COP9-signalosome and eIF3 complexes

      Directory of Open Access Journals (Sweden)

      Hofmann Kay

      2005-03-01

      Full Text Available Abstract Background The 'lid' subcomplex of the 26S proteasome and the COP9 signalosome (CSN complex share a common architecture consisting of six subunits harbouring a so-called PCI domain (proteasome, CSN, eIF3 at their C-terminus, plus two subunits containing MPN domains (Mpr1/Pad1 N-terminal. The translation initiation complex eIF3 also contains PCI- and MPN-domain proteins, but seems to deviate from the 6+2 stoichiometry. Initially, the PCI domain was defined as the region of detectable sequence similarity between the components mentioned above. Results During an exhaustive bioinformatical analysis of proteasome components, we detected multiple instances of tetratrico-peptide repeats (TPR in the N-terminal region of most PCI proteins, suggesting that their homology is not restricted to the PCI domain. We also detected a previously unrecognized PCI domain in the eIF3 component eIF3k, a protein whose 3D-structure has been determined recently. By using profile-guided alignment techniques, we show that the structural elements found in eIF3k are most likely conserved in all PCI proteins, resulting in a structural model for the canonical PCI domain. Conclusion Our model predicts that the homology domain PCI is not a true domain in the structural sense but rather consists of two subdomains: a C-terminal 'winged helix' domain with a key role in PCI:PCI interaction, preceded by a helical repeat region. The TPR-like repeats detected in the N-terminal region of PCI proteins most likely form an uninterrupted extension of the repeats found within the PCI domain boundaries. This model allows an interpretation of several puzzling experimental results.

    5. Using Genome-Wide Pathway Analysis to Unravel the Etiology of Complex Diseases

      NARCIS (Netherlands)

      Elbers, Clara C.; van Eijk, Kristel R.; Franke, Lude; Mulder, Flip; van der Schouw, Yvonne T.; Wijmenga, Cisca; Onland-Moret, N. Charlotte

      2009-01-01

      Several genome-wide association studies (GWAS) have been published on various complex diseases. Although, new loci are found to be associated with these diseases, still only very little of the genetic risk for these diseases can be explained. As GWAS are still underpowered to find small main effects

    6. Study designs for identification of rare disease variants in complex diseases: the utility of family-based designs.

      Science.gov (United States)

      Ionita-Laza, Iuliana; Ottman, Ruth

      2011-11-01

      The recent progress in sequencing technologies makes possible large-scale medical sequencing efforts to assess the importance of rare variants in complex diseases. The results of such efforts depend heavily on the use of efficient study designs and analytical methods. We introduce here a unified framework for association testing of rare variants in family-based designs or designs based on unselected affected individuals. This framework allows us to quantify the enrichment in rare disease variants in families containing multiple affected individuals and to investigate the optimal design of studies aiming to identify rare disease variants in complex traits. We show that for many complex diseases with small values for the overall sibling recurrence risk ratio, such as Alzheimer's disease and most cancers, sequencing affected individuals with a positive family history of the disease can be extremely advantageous for identifying rare disease variants. In contrast, for complex diseases with large values of the sibling recurrence risk ratio, sequencing unselected affected individuals may be preferable.

    7. Evidence for a Simplicity Principle: Teaching Common Complex Grapheme-to-Phonemes Improves Reading and Motivation in At-Risk Readers

      Science.gov (United States)

      Chen, Victoria; Savage, Robert S.

      2014-01-01

      This study examines the effects of teaching common complex grapheme-to-phoneme correspondences (GPCs) on reading and reading motivation for at-risk readers using a randomised control trial design with taught intervention and control conditions. One reading programme taught children complex GPCs ordered by their frequency of occurrence in…

    8. Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease

      NARCIS (Netherlands)

      Meurs, van J.B.J.; Pare, G.; Schwartz, S.M.; Hazra, A.; Tanaka, T.; Vermeulen, S.H.; Cotlarciuc, I.; Yuan, X.; Malarstig, A.; Bandinelli, S.; Bis, J.C.; Morn, H.; Brown, M.J.; Chen, C.; Chen, Y.D.; Clarke, R.J.; Dehghan, A.; Erdmann, J.; Ferrucci, L.; Hamsten, A.; Hofman, A.; Hunten, D.J.; Goel, A.; Johnson, A.D.; Kathiresan, S.; Kampman, E.; Kiel, D.P.; Kiemeney, L.A.; Chambers, J.C.; Kraft, P.; Lindemans, J.; McKnight, B.; Nelson, C.P.; O'Donnell, C.J.; Psaty, B.M.; Ridken, P.M.; Rivadeneira, F.; Rose, L.M.; Seedoif, U.; Siscovick, D.S.; Schunkert, H.; Selhub, J.; Ueland, P.M.; Vollenweiden, P.; Waeben, G.; Waterworth, D.M.; Watkins, H.; Witteman, J.C.M.; Heijen, den M.; Jacques, P.; Uitterlinden, A.G.; Koonet, J.S.; Rader, D.J.; Reilly, M.P.; Moose, V.; Chasman, D.I.; Samani, N.J.; Ahmadi, K.R.

      2013-01-01

      Background: The strong observational association between total homocysteine (tHcy) concentrations and risk of coronary artery disease (CAD) and the null associations in the homocysteinelowering trials have prompted the need to identify genetic variants associated with homocysteine concentrations and

    9. A common genetic background could explain early-onset Crohn's disease.

      Science.gov (United States)

      Bianco, Anna Monica; Zanin, Valentina; Girardelli, Martina; Magnolato, Andrea; Martelossi, Stefano; Martellossi, Stefano; Tommasini, Alberto; Marcuzzi, Annalisa; Crovella, Sergio

      2012-04-01

      Crohn's disease (CD) is a multifactorial disease, in which environmental, microbial and genetic factors play important roles. CD is characterized by a chronic granulomatous inflammation by necrotic scarring with aspects of full-thickness wall. In spite of affecting mainly young adults, sometimes, CD can be present in the first year of life (early onset Crohn disease, EOCD) showing an unpredictable course and being often more severe than at older ages. In this paper we propose the hypothesis that EOCD patients should be analyzed using a Mendelian approach with family studies aimed to identify new loci directly involved in the early onset Crohn's disease. So we will leave the classic association study approach used until now for the identification of genes responsible for susceptibility to CD and propose linkage family analysis as alternative and powerful tool for the identification of new genetic variants associated with familiar cases of EOCD.

    10. Review article: moving towards common therapeutic goals in Crohn's disease and rheumatoid arthritis.

      Science.gov (United States)

      Allen, P B; Olivera, P; Emery, P; Moulin, D; Jouzeau, J-Y; Netter, P; Danese, S; Feagan, B; Sandborn, W J; Peyrin-Biroulet, L

      2017-04-01

      Crohn's disease (CD) and rheumatoid arthritis are chronic, progressive and disabling conditions that frequently lead to structural tissue damage. Based on strategies originally developed for rheumatoid arthritis, the treatment goal for CD has recently moved from exclusively controlling symptoms to both clinical remission and complete mucosal healing (deep remission), with the final aim of preventing bowel damage and disability. To review the similarities and differences in treatment goals between CD and rheumatoid arthritis. This review examined manuscripts from 1982 to 2016 that discussed and/or proposed therapeutic goals with their supportive evidence in CD and rheumatoid arthritis. Proposed therapeutic strategies to improve outcomes in both rheumatoid arthritis and CD include: (i) evaluation of musculoskeletal or organ damage and disability, (ii) tight control, (iii) treat-to-target, (iv) early intervention and (v) disease modification. In contrast to rheumatoid arthritis, there is a paucity of disease-modification trials in CD. Novel therapeutic strategies in CD based on tight control of objective signs of inflammation are expected to change disease course and patients' lives by halting progression or, ideally, preventing the occurrence of bowel damage. Most of these strategies require validation in prospective studies, whereas several disease-modification trials have addressed these issues in rheumatoid arthritis over the last decade. The recent approval of new drugs in CD such as vedolizumab and ustekinumab should facilitate initiation of disease-modification trials in CD in the near future. © 2017 John Wiley & Sons Ltd.

    11. Psychosis in an adolescent girl: a common manifestation in Niemann-Pick Type C disease

      Science.gov (United States)

      2014-01-01

      Niemann-Pick disease type C (NP-C) is a rare autosomal-recessively inherited lysosomal storage disorder. It is caused by mutations in the NPC1 (95%) or NPC2 gene. It is a progressive and highly heterogeneous disease, characterized by the presentation of visceral, neurological, and psychiatric symptoms. Apart from the patients that die early from organic failure, most of the patients with juvenile and adolescent/adult onset of the disease, develop neurological and psychiatric symptoms. In some cases psychiatric signs, mostly psychosis, can be the first sign of the disease. A delay in diagnosis is often seen. By describing the case of a 16-year old girl, we would like to highlight current opinion about NP-C disease and resume recent findings on the clinical presentation, diagnosis and treatment. We focus on the psychiatric signs, and most important the specific combinations that are typical for the disease. There is no curative treatment for NP-C. Miglustat is used to modify neurological signs in NP-C. PMID:25071864

    12. Identification of all pachytene bivalents in the common shrew using DAPI-staining of synaptonemal complex spreads.

      Science.gov (United States)

      Belonogova, N M; Karamysheva, T V; Biltueva, L S; Perepelov, E A; Minina, J M; Polyakov, A V; Zhdanova, N S; Rubtsov, N B; Searle, J B; Borodin, P M

      2006-01-01

      A major problem in studies of synaptonemal complexes (SC) is the difficulty in distinguishing individual chromosomes. This problem can be solved combining SC immunostaining with FISH of chromosome-specific sequences. However, this procedure is expensive, time-consuming and applicable only to a very limited number of species. In this paper we show how a combination of SC immunostaining and DAPI staining can allow identification of all chromosome arms in surface-spreads of the SC of the common shrew (Sorex araneus L.). Enhancement of brightness and contrast of the images with photo editing software allowed us to reveal clear DAPI-positive and negative bands with relative sizes and positions similar to DAPI landmarks on mitotic metaphase chromosomes. Using FISH with DNA probes prepared from chromosome arms m and n we demonstrated correct recognition of the chromosomes mp and hn on the basis of their DAPI pattern. We show that the approach we describe here may be applied to other species and can provide an important tool for identification of individual bivalents in pachytene surface-spreads.

    13. Are there genetic paths common to obesity, cardiovascular disease outcomes, and cardiovascular risk factors?

      Science.gov (United States)

      Rankinen, Tuomo; Sarzynski, Mark A; Ghosh, Sujoy; Bouchard, Claude

      2015-02-27

      Clustering of obesity, coronary artery disease, and cardiovascular disease risk factors is observed in epidemiological studies and clinical settings. Twin and family studies have provided some supporting evidence for the clustering hypothesis. Loci nearest a lead single nucleotide polymorphism (SNP) showing genome-wide significant associations with coronary artery disease, body mass index, C-reactive protein, blood pressure, lipids, and type 2 diabetes mellitus were selected for pathway and network analyses. Eighty-seven autosomal regions (181 SNPs), mapping to 56 genes, were found to be pleiotropic. Most pleiotropic regions contained genes associated with coronary artery disease and plasma lipids, whereas some exhibited coaggregation between obesity and cardiovascular disease risk factors. We observed enrichment for liver X receptor (LXR)/retinoid X receptor (RXR) and farnesoid X receptor/RXR nuclear receptor signaling among pleiotropic genes and for signatures of coronary artery disease and hepatic steatosis. In the search for functionally interacting networks, we found that 43 pleiotropic genes were interacting in a network with an additional 24 linker genes. ENCODE (Encyclopedia of DNA Elements) data were queried for distribution of pleiotropic SNPs among regulatory elements and coding sequence variations. Of the 181 SNPs, 136 were annotated to ≥ 1 regulatory feature. An enrichment analysis found over-representation of enhancers and DNAse hypersensitive regions when compared against all SNPs of the 1000 Genomes pilot project. In summary, there are genomic regions exerting pleiotropic effects on cardiovascular disease risk factors, although only a few included obesity. Further studies are needed to resolve the clustering in terms of DNA variants, genes, pathways, and actionable targets.

    14. Beyond membrane channelopathies: alternative mechanisms underlying complex human disease

      Institute of Scientific and Technical Information of China (English)

      Konstantinos Dean BOUDOULAS; Peter J MOHLER

      2011-01-01

      Over the past fifteen years, our understanding of the molecular mechanisms underlying human disease has flourished in large part due to the discovery of gene mutations linked with membrane ion channels and transporters. In fact, ion channel defects ("channelopathies" - the focus of this review series) have been associated with a spectrum of serious human disease phenotypes including cystic fibrosis, cardiac arrhythmia, diabetes, skeletal muscle defects, and neurological disorders. However, we now know that human disease, particularly excitable cell disease, may be caused by defects in non-ion channel polypeptides including in cellular components residing well beneath the plasma membrane. For example, over the past few years, a new class of potentially fatal cardiac arrhythmias has been linked with cytoplasmic proteins that include sub-membrane adapters such as ankyrin-B (ANK2),ankyrin-G (ANK3), and alpha-1 syntrophin, membrane coat proteins including caveolin-3 (CAV3), signaling platforms including yotiao (AKAPg), and cardiac enzymes (GPD1L). The focus of this review is to detail the exciting role of lamins, yet another class of gene products that have provided elegant new insight into human disease.

    15. HDL and atherosclerotic cardiovascular disease: genetic insights into complex biology.

      Science.gov (United States)

      Rosenson, Robert S; Brewer, H Bryan; Barter, Philip J; Björkegren, Johan L M; Chapman, M John; Gaudet, Daniel; Kim, Daniel Seung; Niesor, Eric; Rye, Kerry-Anne; Sacks, Frank M; Tardif, Jean-Claude; Hegele, Robert A

      2017-08-10

      Plasma levels of HDL cholesterol (HDL-C) predict the risk of cardiovascular disease at the epidemiological level, but a direct causal role for HDL in cardiovascular disease remains controversial. Studies in animal models and humans with rare monogenic disorders link only particular HDL-associated mechanisms with causality, including those mechanisms related to particle functionality rather than cholesterol content. Mendelian randomization studies indicate that most genetic variants that affect a range of pathways that increase plasma HDL-C levels are not usually associated with reduced risk of cardiovascular disease, with some exceptions, such as cholesteryl ester transfer protein variants. Furthermore, only a fraction of HDL-C variation has been explained by known loci from genome-wide association studies (GWAS), suggesting the existence of additional pathways and targets. Systems genetics can enhance our understanding of the spectrum of HDL pathways, particularly those pathways that involve new and non-obvious GWAS loci. Bioinformatic approaches can also define new molecular interactions inferred from both large-scale genotypic data and RNA sequencing data to reveal biologically meaningful gene modules and networks governing HDL metabolism with direct relevance to disease end points. Targeting these newly recognized causal networks might inform the development of novel therapeutic strategies to reduce the risk of cardiovascular disease.

    16. GmPGIP3 enhanced resistance to both take-all and common root rot diseases in transgenic wheat.

      Science.gov (United States)

      Wang, Aiyun; Wei, Xuening; Rong, Wei; Dang, Liang; Du, Li-Pu; Qi, Lin; Xu, Hui-Jun; Shao, Yanjun; Zhang, Zengyan

      2015-05-01

      Take-all (caused by the fungal pathogen Gaeumannomyces graminis var. tritici, Ggt) and common root rot (caused by Bipolaris sorokiniana) are devastating root diseases of wheat (Triticum aestivum L.). Development of resistant wheat cultivars has been a challenge since no resistant wheat accession is available. GmPGIP3, one member of polygalacturonase-inhibiting protein (PGIP) family in soybean (Glycine max), exhibited inhibition activity against fungal endopolygalacturonases (PGs) in vitro. In this study, the GmPGIP3 transgenic wheat plants were generated and used to assess the effectiveness of GmPGIP3 in protecting wheat from the infection of Ggt and B. sorokiniana. Four independent transgenic lines were identified by genomic PCR, Southern blot, and reverse transcription PCR (RT-PCR). The introduced GmPGIP3 was integrated into the genomes of these transgenic lines and could be expressed. The expressing GmPGIP3 protein in these transgenic wheat lines could inhibit the PGs produced by Ggt and B. sorokiniana. The disease response assessments postinoculation showed that the GmPGIP3-expressing transgenic wheat lines displayed significantly enhanced resistance to both take-all and common root rot diseases caused by the infection of Ggt and B. sorokiniana. These data suggested that GmPGIP3 is an attractive gene resource in improving resistance to both take-all and common root rot diseases in wheat.

    17. Thickening of the cauda equina roots: a common finding in Krabbe disease

      Energy Technology Data Exchange (ETDEWEB)

      Hwang, Misun; Rodriguez, David [Department of Radiology of University of Pittsburgh Medical Center, Pittsburgh, PA (United States); Zuccoli, Giulio; Panigrahy, Ashok [Section of Neuroradiology, Children' s Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, PA (United States); Poe, Michele D.; Escolar, Maria L. [Department of Pediatrics at Children' s Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, PA (United States)

      2016-10-15

      Evaluation of Krabbe disease burden and eligibility for hematopoietic stem cell transplantation are often based on neuroimaging findings using the modified Loes scoring system, which encompasses central but not peripheral nervous system changes. We show that quantitative evaluation of thickened cauda equina nerve roots may improve the evaluation of Krabbe disease and therapeutic guidance. Lumbar spine MRI scans of patients obtained between March 2013 and September 2013 were retrospectively evaluated and compared to those of controls. Quantitative evaluation of cauda equina roots was performed on the axial plane obtained approximately 5 mm below the conus medullaris. The largest nerves in the right and left anterior quadrants of the spinal canal were acquired. Fifteen symptomatic patients with Krabbe disease (5-44 months old) and eleven age-matched controls were evaluated. The average areas (mm{sup 2}) of anterior right and left nerves were 1.40 and 1.23, respectively, for patients and 0.61 and 0.60 for controls (differences: 0.79 and 0.63; p < 0.001). Cauda equina nerve root thickening is associated with Krabbe disease in both treated and untreated patients. Adding lumbar spine MRI to the current neurodiagnostic protocols, which fails to account for peripheral nerve abnormalities, will likely facilitate the diagnosis of Krabbe disease. (orig.)

    18. The Development of a General Auxiliary Diagnosis System for Common Disease of Animal

      Science.gov (United States)

      Xiao, Jianhua; Wang, Hongbin; Zhang, Ru; Luan, Peixian; Li, Lin; Xu, Danning

      In order to development one expert system for animal disease in china, and this expert system can help veterinary surgeon diagnose all kinds of disease of animal. The design of an intelligent medical system for diagnosis of animal diseases is presented in this paper. The system comprises three major parts: a disease case management system (DCMS), a Knowledge management system (KMS) and an Expert System (ES). The DCMS is used to manipulate patient data include all kinds of data about the animal and the symptom, diagnosis result etc. The KMS is used to acquire knowledge from disease cases and manipulate knowledge by human. The ES is used to perform diagnosis. The program is designed in N-layers system; they are data layer, security layer, business layer, appearance layer, and user interface. When diagnosis, user can select some symptoms in system group by system. One conclusion with three possibilities (final diagnosis result, suspect diagnosis result, and no diagnosis result) is output. By diagnosis some times, one most possible result can be get. By application, this system can increased the accurate of diagnosis to some extent, but the statistics result was not compute now.

    19. Perinatal inflammation: a common factor in the early origins of cardiovascular disease?

      Science.gov (United States)

      Nguyen, Maria U; Wallace, Megan J; Pepe, Salvatore; Menheniott, Trevelyan R; Moss, Timothy J; Burgner, David

      2015-10-01

      Cardiovascular disease continues to be the leading cause of global morbidity and mortality. Traditional risk factors account for only part of the attributable risk. The origins of atherosclerosis are in early life, a potential albeit largely unrecognized window of opportunity for early detection and treatment of subclinical cardiovascular disease. There are robust epidemiological data indicating that poor intrauterine growth and/or prematurity, and perinatal factors such as maternal hypercholesterolaemia, smoking, diabetes and obesity, are associated with adverse cardiovascular intermediate phenotypes in childhood and adulthood. Many of these early-life risk factors result in a heightened inflammatory state. Inflammation is a central mechanism in the development of atherosclerosis and cardiovascular disease, but few studies have investigated the role of overt perinatal infection and inflammation (chorioamnionitis) as a potential contributor to cardiovascular risk. Limited evidence from human and experimental models suggests an association between chorioamnionitis and cardiac and vascular dysfunction. Early life inflammatory events may be an important mechanism in the early development of cardiovascular risk and may provide insights into the associations between perinatal factors and adult cardiovascular disease. This review aims to summarise current data on the early life origins of atherosclerosis and cardiovascular disease, with particular focus on perinatal inflammation.

    20. Cataracts and Other Common Eye Diseases | NIH MedlinePlus the Magazine

      Science.gov (United States)

      ... had cataract surgery. Common symptoms are: Blurry vision Colors that seem faded Glare Not being able to see well at night Double vision Frequent prescription changes in your eyewear At first new glasses, brighter lighting, anti-glare sunglasses, or magnifying lenses ...

    1. Common and Uncommon Conditions of Breast Disease in Children and Adolescents: A Pictorial Review

      Energy Technology Data Exchange (ETDEWEB)

      Cho, Hyoun; Kim, Kyu Soon; Kim, Da Mi [Dept. of f Radiology, Eulji University Hospital, Daejeon (Korea, Republic of); Kim, You Me [Dept. of Radiology, Dankook University Hospital, Cheonan (Korea, Republic of); Kim, Hak Hee [Dept. of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

      2013-02-15

      The purpose of this study is to review various breast diseases in children and adolescents and to illustrate the sonographic findings. We reviewed the cases at our institution in order to identify breast disease in children and adolescent patients who underwent sonography and mammography. Breast disease in children and adolescents included developmental disturbance, infection, benign tumors and inherent defects. In contrast to adults, the radiologic findings of malignant breast conditions in pediatric populations have rarely been reported; however, we show ductal carcinoma in situ with juvenile fibroadenoma and rhabdomyosarcoma. During childhood and adolescence, the recognition and correct identification of physiologic breast development and specific lesions in breast entities on radiologic findings is most helpful in identifying and characterizing abnormalities and in guiding further investigation.

    2. A case of Behcet's disease with aneurysms of common carotid arteries and abdominal aorta

      Energy Technology Data Exchange (ETDEWEB)

      Choo, Yeon Myung; Chang, Kee Hyun; Choi, Sung Jae [Seoul National University College of Medicine, Seoul (Korea, Republic of)

      1984-06-15

      One case of Behcet's disease with multiple aneurysms in both common carotid arteries and abdominal aorta is presented with brief review of the literatures. A 26-year-old woman had slowly enlarging pulsatile masses in both sides of neck and recurrent ulcerations in oral cavity and genitalia. One day prior to admission, aphasia, right facial nerve palsy and right hemiplegia suddenly developed. Brain CT showed acute infarction in left basal ganglia. Both Carotid Angiography and abdominal Aortography demonstrated multiple aneurysms in both common carotid arteries and abdominal aorta with organizing thrombi and thromboembolism of internal carotid artery.

    3. Deciphering deterioration mechanisms of complex diseases based on the construction of dynamic networks and systems analysis

      Science.gov (United States)

      Li, Yuanyuan; Jin, Suoqin; Lei, Lei; Pan, Zishu; Zou, Xiufen

      2015-03-01

      The early diagnosis and investigation of the pathogenic mechanisms of complex diseases are the most challenging problems in the fields of biology and medicine. Network-based systems biology is an important technique for the study of complex diseases. The present study constructed dynamic protein-protein interaction (PPI) networks to identify dynamical network biomarkers (DNBs) and analyze the underlying mechanisms of complex diseases from a systems level. We developed a model-based framework for the construction of a series of time-sequenced networks by integrating high-throughput gene expression data into PPI data. By combining the dynamic networks and molecular modules, we identified significant DNBs for four complex diseases, including influenza caused by either H3N2 or H1N1, acute lung injury and type 2 diabetes mellitus, which can serve as warning signals for disease deterioration. Function and pathway analyses revealed that the identified DNBs were significantly enriched during key events in early disease development. Correlation and information flow analyses revealed that DNBs effectively discriminated between different disease processes and that dysfunctional regulation and disproportional information flow may contribute to the increased disease severity. This study provides a general paradigm for revealing the deterioration mechanisms of complex diseases and offers new insights into their early diagnoses.

    4. Ultrasound findings of the physiological changes and most common breast diseases during pregnancy and lactation

      Directory of Open Access Journals (Sweden)

      Antônio Arildo Reginaldo de Holanda

      Full Text Available Abstract Because of the physiological changes that occur during pregnancy and lactation, diagnostic ultrasound of the breast during these periods is a challenge for physicians. Therefore, a comprehensive understanding of imaging, anatomy, and physiology of the breast is important to effectively diagnosing diseases that can arise in women who are pregnancy or lactating. The aim of this article was to review the physiological changes that occur in the breasts during pregnancy and lactation, as well as to describe the main features of the breast diseases that occur most frequently during these periods.

    5. Ultrasound findings of the physiological changes and most common breast diseases during pregnancy and lactation*

      Science.gov (United States)

      de Holanda, Antônio Arildo Reginaldo; Gonçalves, Ana Katherine da Silveira; de Medeiros, Robinson Dias; de Oliveira, António Manuel Gouveia; Maranhão, Técia Maria de Oliveira

      2016-01-01

      Because of the physiological changes that occur during pregnancy and lactation, diagnostic ultrasound of the breast during these periods is a challenge for physicians. Therefore, a comprehensive understanding of imaging, anatomy, and physiology of the breast is important to effectively diagnosing diseases that can arise in women who are pregnancy or lactating. The aim of this article was to review the physiological changes that occur in the breasts during pregnancy and lactation, as well as to describe the main features of the breast diseases that occur most frequently during these periods. PMID:28057965

    6. Deep vein thrombosis with tuberculosis: a rate presentation of common disease

      Directory of Open Access Journals (Sweden)

      Prasad Muley

      2014-01-01

      Full Text Available Tuberculosis remains an infectious disease with high prevalence worldwide. An association between tuberculosis-induced inflammation and hypercoagulable state has been described in the literature. Deep vein thrombosis is a rare complication of the disease, and very few cases are reported worldwide. Furthermore, such manifestation is very rare in the paediatric age group. The paediatrician’s awareness of this phenomenon is important for early diagnosis and prompt treatment. Here, we report two cases of severe pulmonary tuberculosis associated with deep vein thrombosis in the pediatric age group.

    7. An integer programming framework for inferring disease complexes from network data

      Science.gov (United States)

      Mazza, Arnon; Klockmeier, Konrad; Wanker, Erich; Sharan, Roded

      2016-01-01

      Motivation: Unraveling the molecular mechanisms that underlie disease calls for methods that go beyond the identification of single causal genes to inferring larger protein assemblies that take part in the disease process. Results: Here, we develop an exact, integer-programming-based method for associating protein complexes with disease. Our approach scores proteins based on their proximity in a protein–protein interaction network to a prior set that is known to be relevant for the studied disease. These scores are combined with interaction information to infer densely interacting protein complexes that are potentially disease-associated. We show that our method outperforms previous ones and leads to predictions that are well supported by current experimental data and literature knowledge. Availability and Implementation: The datasets we used, the executables and the results are available at www.cs.tau.ac.il/roded/disease_complexes.zip Contact: roded@post.tau.ac.il PMID:27307626

    8. Magnetic resonance enterography in Crohn’s disease: How we do it and common imaging findings

      Science.gov (United States)

      Mantarro, Annalisa; Scalise, Paola; Guidi, Elisa; Neri, Emanuele

      2017-01-01

      Crohn’s disease (CD) is a chronic inflammatory disease of the gastrointestinal tract, with unpredictable clinical course by phases of relapses alternating with other of quiescence. The etiology is multifactorial and is still not completely known; globally the westernization of lifestyle is causing an increasing incidence of CD, with peak age of 20-30 years. The diagnostic workup begins with the evaluation of the clinical history, physical examination and laboratory tests. However, the clinical assessment is subjected interobserver variability and, occasionally, the symptoms of acute and chronic inflammation may be indistinguishable. In this regards, the role of magnetic resonance (MR) enterography is crucial to determine the extension, the disease activity and the presence of any complications without ionizing radiations, making this method very suitable for young population affected by CD. The purpose of this review article is to illustrate the MR enterography technique and the most relevant imaging findings of CD, allowing the detection of small bowel involvement and the assessment of disease activity. PMID:28298964

    9. Defective folding and rapid degradation of mutant proteins is a common disease mechanism in genetic disorders

      DEFF Research Database (Denmark)

      Gregersen, N; Bross, P; Jørgensen, M M

      2000-01-01

      of such 'conformational disease' are illustrated by reference to cystic fibrosis, phenylketonuria and short-chain acyl-CoA dehydrogenase deficiency. Other cellular components such as chaperones and proteases, as well as environmental factors, may combine to modulate the phenotype of such disorders and this may open up...

    10. Gene expression profiling in necrotizing enterocolitis reveals pathways common to those reported in Crohn's disease

      NARCIS (Netherlands)

      É. Tremblay (Éric); M.-P. Thibault (Marie-Pier); E. Ferretti (Emanuela); C. Babakissa (Corentin); V. Bertelle (Valérie); M. Bettolli (Marcos); K.M. Burghardt (Karolina Maria); J.-F. Colombani (Jean-François); D. Grynspan (David); E. Levy (Emile); P. Lu (Peng); S. Mayer (Sandeep); D. Ménard (Daniel); O. Mouterde (Olivier); I.B. Renes (Ingrid); E.G. Seidman (Ernest G.); J.-F. Beaulieu (Jean-François)

      2016-01-01

      textabstractBackground: Necrotizing enterocolitis (NEC) is the most frequent life-threatening gastrointestinal disease experienced by premature infants in neonatal intensive care units. The challenge for neonatologists is to detect early clinical manifestations of NEC. One strategy would be to ident

    11. Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease

      NARCIS (Netherlands)

      J.B.J. van Meurs (Joyce); G. Paré (Guillaume); S.M. Schwartz (Stephen); A. Hazra (Aditi); T. Tanaka; S.H.H.M. Vermeulen (Sita); I. Cotlarciuc (Ioana); X. Yuan (Xin); A. Mälarstig (Anders); S. Bandinelli (Stefania); J.C. Bis (Joshua); H.J. Blom (Henk); M.J. Brown (Morris); C. Chen (Christopher); R. Clarke (Robert); A. Dehghan (Abbas); J. Erdmann (Jeanette); L. Ferrucci; A. Hamsten (Anders); A. Hofman (Albert); D. Hunter (David); A. Goel (Anuj); A.D. Johnson (Andrew); S. Kathiresan (Sekar); E. Kampman (Ellen); D.P. Kiel (Douglas); L.A.L.M. Kiemeney (Bart); J.C. Chambers (John); P. Kraft (Peter); J. Lindemans (Jan); B. McKnight (Barbara); C.P. Nelson (Christopher P.); C.J. O'Donnell (Christopher); B.M. Psaty (Bruce); P.M. Ridker (Paul); F. Rivadeneira Ramirez (Fernando); L.M. Rose (Lynda); U. Seedorf (Udo); D.S. Siscovick (David); H. Schunkert (Heribert); J. Selhub (Jacob); P.M. Ueland (Per); P. Vollenweider (Peter); G. Waeber (Gérard); D. Waterworth (Dawn); H. Watkins (Hugh); J.C.M. Witteman (Jacqueline); M. den Heijer (Martin); P.F. Jacques (Paul); A.G. Uitterlinden (André); J.S. Kooner (Jaspal); D.J. Rader (Daniel); M.P. Reilly (Muredach); V. Mooser (Vincent); D.I. Chasman (Daniel); N.J. Samani (Nilesh); K.R. Ahmadi (Kourosh)

      2013-01-01

      textabstractBackground: The strong observational association between total homocysteine (tHcy) concentrations and risk of coronary artery disease (CAD) and the null associations in the homocysteinelowering trials have prompted the need to identify genetic variants associated with homocysteine concen

    12. Differential Contributions of Rare and Common, Coding and Noncoding Ret Mutations to Multifactorial Hirschsprung Disease Liability

      NARCIS (Netherlands)

      Emison, Eileen Sproat; Garcia-Barcelo, Merce; Grice, Elizabeth A.; Lantieri, Francesca; Amiel, Jeanne; Burzynski, Grzegorz; Fernandez, Raquel M.; Hao, Li; Kashuk, Carl; West, Kristen; Miao, Xiaoping; Tam, Paul K. H.; Griseri, Paola; Ceccherini, Isabella; Pelet, Anna; Jannot, Anne-Sophie; de Pontual, Loic; Henrion-Caude, Alexandra; Lyonnet, Stanislas; Verheij, Joke B. G. M.; Hofstra, Robert M. W.; Antinolo, Guillermo; Borrego, Salud; McCallion, Andrew S.; Chakravarti, Aravinda

      2010-01-01

      The major gene for Hirschsprung disease (HSCR) encodes the receptor tyrosine kinase RET. In a study of 690 European- and 192 Chinese-descent probands and their parents or controls, we demonstrate the ubiquity of a >4-fold susceptibility from a C -> T allele (rs2435357: p = 3.9 x 10(-43) in European

    13. Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease

      Science.gov (United States)

      The strong observational association between total homocysteine (tHcy) concentrations and risk of coronary artery disease (CAD) and the null associations in the homocysteine-lowering trials have prompted the need to identify genetic variants associated with homocysteine concentrations and risk of CA...

    14. Mallory bodies in alcoholic and non-alcoholic liver disease contain a common antigenic determinant.

      Science.gov (United States)

      Fleming, K A; Morton, J A; Barbatis, C; Burns, J; Canning, S; McGee, J O

      1981-05-01

      An immunohistochemical technique is described for the detection of Mallory bodies (MBs) in paraffin sections of liver tissue. This is based on proteolytic digestion of sections before exposure to an antiserum which recognises a unique antigenic determinant in MBs. With the use of this procedure it has been shown in alcoholic liver disease, primary biliary cirrhosis. Indian childhood cirrhosis, Wilson's disease, diabetes mellitus, and hepatocellular cancer that the MBs found in these disorders contain this unique antigenic determinant. It is postulated, therefore, that the mechanism of formation of MBs is similar in liver diseases of diverse aetiology. In addition, it has been demonstrated that the immunohistochemical procedure is more sensitive than routine staining; MBs were detected in five out of 12 fatty livers by immunohistochemical and only in one by H and E staining. As MBs in fatty livers were not associated with polymorph filtration or fibrogenesis it is argued that MB formation is not an absolute prerequisite for the progression of acute to chronic liver disease.

    15. Depression and Alzheimer's disease: is stress the initiating factor in a common neuropathological cascade?

      DEFF Research Database (Denmark)

      Aznar, Susana; Knudsen, Gitte M

      2011-01-01

      The existence of a high co-morbidity between Alzheimer's disease (AD) and depression has been known for a long time. More interesting though are recent studies indicating that depression and number of depressive episodes earlier in life is associated with increased risk of AD development. This su...

    16. Common immunogenetic profile in children with multiple autoimmune diseases: the signature of HLA-DQ pleiotropic genes.

      Science.gov (United States)

      Larizza, Daniela; Calcaterra, Valeria; Klersy, Catherine; Badulli, Carla; Caramagna, Claudia; Ricci, Antonio; Brambilla, Paola; Salvaneschi, Laura; Martinetti, Miryam

      2012-09-01

      Type 1 diabetes mellitus (T1DM), celiac disease (CD) and autoimmune thyroid disease (ATD) are autoimmune conditions relatively common in paediatric age and frequently occur in association in the same subject. This event is not by chance and requires an explanation. Here, we studied the distribution of HLA-DQ αβ heterodimers in 334 Italian children with T1DM, ATD and CD alone or in association and in 224 Italian healthy controls. In particular, 164 patients had T1DM (133 alone, 20+ATD, 7+CD and 4+CD+ATD), 118 had ATD (110 alone, 8+CD) and 52 had CD (40 alone, 11+ATD and 1+T1DM). 51 patients suffered from multiple autoimmune diseases. The risk for multiple autoimmune diseases was significantly associated with the increased number of HLA-DQ markers of susceptibility for both T1DM (p = 0.003) and CD (p = 0.006). The presence of one or more diabetogenic DQ molecules significantly increased the probability of developing not only T1DM (p autoimmune diseases although with a different risk according to the number and type of susceptible HLA-DQ heterodimers as reported in the algorithm proposed here. It is likely that combinations of DQA1 and DQB1 alleles are the real culprits of the progression towards multiple autoimmune diseases and HLA-DQ genomic typing will improve the capability to predict associated autoimmune diseases in infancy.

    17. Variable agreement among experts regarding Mycobacterium avium complex lung disease.

      Science.gov (United States)

      Marras, Theodore K; Prevots, D Rebecca; Jamieson, Frances B; Winthrop, Kevin L

      2015-02-01

      Data regarding many clinical aspects of pulmonary Mycobacterium avium complex (pMAC) are lacking. Guidelines rely substantially upon expert opinion, integrated through face-to-face meetings, variably weighting individual opinions. We surveyed North American non-tuberculous mycobacteria experts regarding clinical aspects of pMAC using Delphi methods. Nineteen of 26 invited experts (73%) responded, with extensive variability. Convergence could not be reached for most questions. Respondents described extensive uncertainty around specific issues. Findings underscore urgent need for more research.

    18. Systems medicine: helping us understand the complexity of disease

      OpenAIRE

      Vandamme, D.; Fitzmaurice, W.; Kholodenko, B.; Kolch, W.

      2013-01-01

      Advances in genomics and other -omic fields in the last decade have resulted in unprecedented volumes of complex data now being available. These data can enable physicians to provide their patients with care that is more personalized, predictive, preventive and participatory. The expertise required to manage and understand this data is to be found in fields outside of medical science, thus multidisciplinary collaboration coupled to a systems approach is key to unlocking its potential, with co...

    19. Lung-dominant connective tissue disease among patients with interstitial lung disease: prevalence, functional stability, and common extrathoracic features

      Directory of Open Access Journals (Sweden)

      Daniel Antunes Silva Pereira

      2015-04-01

      Full Text Available OBJECTIVE: To describe the characteristics of a cohort of patients with lung-dominant connective tissue disease (LD-CTD. METHODS: This was a retrospective study of patients with interstitial lung disease (ILD, positive antinuclear antibody (ANA results (≥ 1/320, with or without specific autoantibodies, and at least one clinical feature suggestive of connective tissue disease (CTD. RESULTS: Of the 1,998 patients screened, 52 initially met the criteria for a diagnosis of LD-CTD: 37% were male; the mean age at diagnosis was 56 years; and the median follow-up period was 48 months. During follow-up, 8 patients met the criteria for a definitive diagnosis of a CTD. The remaining 44 patients comprised the LD-CTD group, in which the most prevalent extrathoracic features were arthralgia, gastroesophageal reflux disease, and Raynaud's phenomenon. The most prevalent autoantibodies in this group were ANA (89% and anti-SSA (anti-Ro, 27%. The mean baseline and final FVC was 69.5% and 74.0% of the predicted values, respectively (p > 0.05. Nonspecific interstitial pneumonia and usual interstitial pneumonia patterns were found in 45% and 9% of HRCT scans, respectively; 36% of the scans were unclassifiable. A similar prevalence was noted in histological samples. Diffuse esophageal dilatation was identified in 52% of HRCT scans. Nailfold capillaroscopy was performed in 22 patients; 17 showed a scleroderma pattern. CONCLUSIONS: In our LD-CTD group, there was predominance of females and the patients showed mild spirometric abnormalities at diagnosis, with differing underlying ILD patterns that were mostly unclassifiable on HRCT and by histology. We found functional stability on follow-up. Esophageal dilatation on HRCT and scleroderma pattern on nailfold capillaroscopy were frequent findings and might come to serve as diagnostic criteria.

    20. Toxoplasmosis presented as a submental mass: a common disease, uncommon presentation

      OpenAIRE

      2015-01-01

      Submental mass secondary to toxoplasmosis is not common in clinical work. A diagnosis of toxoplasmosis is rarely considered by physicians. Here we describe a 50-year-old woman presented with a progressive, painful, submental and left neck swelling for 1 month. After having obtained an insufficient evidence from the fine-needle biopsy, the patient finally received an excisional biopsy which highly indicated the possibility of lymphadenopathy consistent with toxoplasmosis. Diagnosis of toxoplas...

    1. Rare presentation of a common disease: Idiopathic hypoparathyroidism presenting with extrapyramidal symptoms and status epilepticus

      Directory of Open Access Journals (Sweden)

      Kaushik Ghosh

      2012-01-01

      Full Text Available We report of an 18-year-old male who presented with an epileptiform disorder, features of hypocalcemia, and an extrapyramidal symptom in the form of choreoathetosis. On evaluation he had idiopathic hypoparathyroidism with extensive calcifications in the extrapyramidal system of the brain; basal ganglion, as well as in the cerebral cortex and cerebellum, which is a rare entity. We report the rare presentation of a common disorder, which requires to be considered in evaluating hypoparathyroidism.

    2. The molecular basis of HEXA mRNA deficiency caused by the most common Tay-Sachs disease mutation.

      OpenAIRE

      Boles, D. J.; Proia, R L

      1995-01-01

      Tay-Sachs disease (TSD) is a catastrophic neurodegenerative disorder caused by mutations in the HEXA gene. The most common TSD allele worldwide contains a 4-bp insertion in exon 11 that produces a downstream premature termination codon. Despite normal transcription of this allele, HEXA mRNA is severely reduced, indicating that the HEXA transcript must be unstable. Minigenes of HEXA were constructed and expressed in mouse L cells, to investigate the relationship between the 4-bp insertion and ...

    3. Gut microbiota, immunity and disease: a complex relationship

      Directory of Open Access Journals (Sweden)

      Michele M Kosiewicz

      2011-09-01

      Full Text Available Our immune system has evolved to recognize and eradicate pathogenic microbes. However, we have a symbiotic relationship with multiple species of bacteria that occupy the gut and comprise the natural commensal flora or microbiota. The microbiota is critically important for the breakdown of nutrients, and also assists in preventing colonization by potentially pathogenic bacteria. In addition, the gut commensal bacteria appears to be critical for the development of an optimally functioning immune system. Various studies have shown that individual species of the microbiota can induce very different types of immune cells (e.g., Th17 cells, Foxp3+ regulatory T cells and responses, suggesting that the composition of the microbiota can have an important influence on the immune response. Although the microbiota resides in the gut, it appears to have a significant impact on the systemic immune response. Indeed, specific gut commensal bacteria have been shown to affect disease development in organs other than the gut, and depending on the species, have been found to have a wide range of effects on diseases from induction and exacerbation to inhibition and protection. In this review, we will focus on the role that the gut microbiota plays in the development and progression of inflammatory/autoimmune disease, and we will also touch upon its role in allergy and cancer.

    4. Asymptomatic sleep abnormalities are a common early feature in patients with Huntington's disease.

      Science.gov (United States)

      Goodman, Anna O G; Rogers, Lorraine; Pilsworth, Samantha; McAllister, Catherine J; Shneerson, John M; Morton, A Jennifer; Barker, Roger A

      2011-04-01

      Huntington's disease (HD) is a fatal neurodegenerative disease characterized by motor, cognitive, and psychiatric disturbance. In this article, we used polysomnography, actigraphy and a variety of validated questionnaires to ascertain the extent to which sleep changes are identifiable and measurable in mild stage HD, and importantly, to see whether patients are negatively impacted by the changes in their sleep. We found significant differences in sleep architecture and sleep efficiency in patients compared with controls using polysomnography. However, patient scores on the Functional Outcomes of Sleep Questionnaire, Medical Outcomes of Sleep Scale, and Epworth Sleepiness Scale were not significantly different to controls. These results suggest that although marked changes in sleep architecture are present in early HD and can be detected using polysomnography, patients do not necessarily recognize or report these abnormalities.

    5. The influence of common free radicals and antioxidants on development of Alzheimer's Disease.

      Science.gov (United States)

      Wojtunik-Kulesza, Karolina A; Oniszczuk, Anna; Oniszczuk, Tomasz; Waksmundzka-Hajnos, Monika

      2016-03-01

      Alzheimer's Disease (AD) is one of the most important neurodegenerative disorders in the 21st century for the continually aging population. Despite an increasing number of patients, there are only few drugs to treat the disease. Numerous studies have shown several causes of the disorder, one of the most important being oxidative stress. Oxidative stress is connected with a disturbance between the levels of free radicals and antioxidants in organisms. Solutions to this problem are antioxidants, which counteract the negative impact of the reactive molecules. Unfortunately, the currently available drugs against AD do not exhibit activity toward these structures. Due to the fact that natural substances are extremely significant in new drug development, numerous studies are focused on substances which exhibit a few activities including antioxidants and other anti-AD behaviors. This review article presents the most important studies connected with the influence of free radicals on development of AD and antioxidants as potential drugs toward AD.

    6. Arenavirus Coinfections Are Common in Snakes with Boid Inclusion Body Disease

      Science.gov (United States)

      Salmenperä, P.; Sironen, T.; Hetzel, U.; Korzyukov, Y.; Kipar, A.; Vapalahti, O.

      2015-01-01

      Recently, novel arenaviruses were found in snakes with boid inclusion body disease (BIBD); these form the new genus Reptarenavirus within the family Arenaviridae. We used next-generation sequencing and de novo sequence assembly to investigate reptarenavirus isolates from our previous study. Four of the six isolates and all of the samples from snakes with BIBD contained at least two reptarenavirus species. The viruses sequenced comprise four novel reptarenavirus species and a representative of a new arenavirus genus. PMID:26041290

    7. Impact of oxygen deficiency on the disease status of common dab Limanda limanda

      DEFF Research Database (Denmark)

      Mellergaard, Stig; Nielsen, Else

      1995-01-01

      in September, while not for epidermal papilloma (p correlated (p correlation was observed between stock density (expressed as catch per unit effort) and the diseases in question. It is probably the stress...... did not change significantly during the investigation period. The prevalence of lymphocystis and epidermal papilloma was negatively correlated with the minimum oxygen levels measured in August and September the previous year; this negative correlation was significant (p

    8. Iron Deficiency Is Common During Remission in Children With Inflammatory Bowel Disease

      OpenAIRE

      Emma Wikholm MD; Petter Malmborg MD, PhD; Maria Forssberg MD; Carl-Axel Hederos MD, PhD; Sverre Wikström MD, PhD

      2016-01-01

      The aim was to study prevalence of iron deficiency in children with inflammatory bowel disease (IBD) during remission. In addition, there was an observational evaluation of hematological response to oral iron. A population-based retrospective study including 90 Swedish children (median 13 years) with IBD was performed. Patient records covered in median 25 months. Iron deficiency was present in 70/77 children (91%) in which iron status could be assessed. In clinical and biochemical remission, ...

    9. Dentistry and Ayurveda - IV: Classification and management of common oral diseases

      Directory of Open Access Journals (Sweden)

      Amruthesh Sunita

      2008-01-01

      Full Text Available This article, the fourth in the series titled ′Dentistry and Ayurveda,′ describes in brief the panchakarma therapy, which is a distinctive feature of the Ayurvedic method of detoxifying the body. The various therapies and medicines used in Ayurveda have been elaborated. Further, an attempt has been made to correlate dental diseases in Ayurveda with the modern-day classification, clinical features, and management.

    10. Common genetic variations in CLOCK transcription factor are associated with nonalcoholic fatty liver disease

      Institute of Scientific and Technical Information of China (English)

      Silvia Sookoian; Gustavo Casta(n)o; Carolina Gemma; Tomas Fernández Gianotti; Carlos Jose Pirola

      2007-01-01

      AIM: To investigate the role of gene variants and derived haplotypes of the CLOCK transcription factor in nonalcoholic fatty liver disease (NAFLD) and their relation with the disease severity.METHODS: A total of 136 patients with NAFLD and 64 healthy individuals were studied. Liver biopsy was performed in 91 patients. Six tag SNPs showing a minor allele frequency > 10% (rs1554483 C/G; rs11932595A/G; rs4580704 C/G; rs6843722 A/C; rs6850524 C/G and rs4864548 A/G) encompassing 117 kb of chromosome 4and representing 115 polymorphic sites (r2>0.8) were genotyped.RESULTS: rs11932595 and rs6843722 showed significant associations with NAFLD (empiric P = 0.0449and 0.023, respectively). A significant association was also observed between clinical or histologic spectrum of NAFLD and rs1554483 (empiric P = 0.0399), rs6843722(empiric P = 0.0229) and rs6850524 (empiric P =0.00899) and between fibrosis score and rs1554483(empiric P = 0.02697), rs6843722 (empiric P = 0.01898)and rs4864548 (empiric P = 0.02697). Test of haplotypic association showed that CLOCK gene variant haplotypes frequencies in NAFLD individuals significantly differed from those in controls (empiric P = 0.0097).CONCLUSION: Our study suggests a potential role of the CLOCK polymorphisms and their haplotypes in susceptibility to NAFLD and disease severity.

    11. Disassembled DJ-1 high molecular weight complex in cortex mitochondria from Parkinson's disease patients

      Directory of Open Access Journals (Sweden)

      Adler Charles

      2009-07-01

      Full Text Available Abstract Correction to Nural H, He P, Beach T, Sue L, Xia W, Shen Y. Disassembled DJ-1 high molecular weight complex in cortex mitochondria from Parkinson's disease patients Molecular Neurodegeneration 2009, 4:23.

    12. Towards a Unified Theory of Health-Disease: I. Health as a complex model-object

      Directory of Open Access Journals (Sweden)

      Naomar Almeida-Filho

      2013-06-01

      Full Text Available Theory building is one of the most crucial challenges faced by basic, clinical and population research, which form the scientific foundations of health practices in contemporary societies. The objective of the study is to propose a Unified Theory of Health-Disease as a conceptual tool for modeling health-disease-care in the light of complexity approaches. With this aim, the epistemological basis of theoretical work in the health field and concepts related to complexity theory as concerned to health problems are discussed. Secondly, the concepts of model-object, multi-planes of occurrence, modes of health and disease-illness-sickness complex are introduced and integrated into a unified theoretical framework. Finally, in the light of recent epistemological developments, the concept of Health-Disease-Care Integrals is updated as a complex reference object fit for modeling health-related processes and phenomena.

    13. Towards a unified theory of health-disease: I. Health as a complex model-object.

      Science.gov (United States)

      Almeida-Filho, Naomar

      2013-06-01

      Theory building is one of the most crucial challenges faced by basic, clinical and population research, which form the scientific foundations of health practices in contemporary societies. The objective of the study is to propose a Unified Theory of Health-Disease as a conceptual tool for modeling health-disease-care in the light of complexity approaches. With this aim, the epistemological basis of theoretical work in the health field and concepts related to complexity theory as concerned to health problems are discussed. Secondly, the concepts of model-object, multi-planes of occurrence, modes of health and disease-illness-sickness complex are introduced and integrated into a unified theoretical framework. Finally, in the light of recent epistemological developments, the concept of Health-Disease-Care Integrals is updated as a complex reference object fit for modeling health-related processes and phenomena.

    14. Association between chronic kidney dysfunction and the complexity of coronary artery disease in elderly patients

      Institute of Scientific and Technical Information of China (English)

      颜利求

      2013-01-01

      Objective To investigate the association between chronic kidney dysfunction and the complexity of coronary artery disease in elderly patients.Methods A prospective study was conducted on 1380 consecutive patients

    15. Network approaches to systems biology analysis of complex disease: integrative methods for multi-omics data.

      Science.gov (United States)

      Yan, Jingwen; Risacher, Shannon L; Shen, Li; Saykin, Andrew J

      2017-06-30

      In the past decade, significant progress has been made in complex disease research across multiple omics layers from genome, transcriptome and proteome to metabolome. There is an increasing awareness of the importance of biological interconnections, and much success has been achieved using systems biology approaches. However, because of the typical focus on one single omics layer at a time, existing systems biology findings explain only a modest portion of complex disease. Recent advances in multi-omics data collection and sharing present us new opportunities for studying complex diseases in a more comprehensive fashion, and yet simultaneously create new challenges considering the unprecedented data dimensionality and diversity. Here, our goal is to review extant and emerging network approaches that can be applied across multiple biological layers to facilitate a more comprehensive and integrative multilayered omics analysis of complex diseases. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

    16. A Mobile Care Coordination System for the Management of Complex Chronic Disease.

      Science.gov (United States)

      Haynes, Sarah; Kim, Katherine K

      2016-01-01

      There is global concern about healthcare cost, quality, and access as the prevalence of complex and chronic diseases, such as heart disease, continues to grow. Care for patients with complex chronic disease involves diverse practitioners and multiple transitions between medical centers, physician practices, clinics, community resources, and patient homes. There are few systems that provide the flexibility to manage these varied and complex interactions. Participatory and user-centered design methodology was applied to the first stage of building a mobile platform for care coordination for complex, chronic heart disease. Key informant interviews with patients, caregivers, clinicians, and care coordinators were conducted. Thematic analysis led to identification of priority user functions including shared care plan, medication management, symptom management, nutrition, physical activity, appointments, personal monitoring devices, and integration of data and workflow. Meaningful stakeholder engagement contributes to a person-centered system that enhances health and efficiency.

    17. An inventory of plants commonly used in the treatment of some disease conditions in Ogbomoso, South West, Nigeria.

      Science.gov (United States)

      Olorunnisola, O S; Adetutu, A; Afolayan, A J

      2015-02-23

      This study was designed to take an inventory of medicinal plants, recipes and methods commonly used traditionally to treat some cardiovascular and inflammatory diseases in five local government areas in Ogbomoso, Oyo State, Nigeria. First-hand field survey through semi-structured questionnaire was employed in the 5 months study. A total of 101 plant species (medicinal plants (80.90%), spices (17.5%) and vegetables (1.53%)) belonging to 51 different families were mentioned for the treatment of various types of cardiovascular and inflammatory diseases. The survey revealed that 51.5% of the plants mentioned are used for the management of inflammatory diseases, 34.7% for the treatment of cardiovascular diseases and 11.9% of the plants are used for the treatment of both diseases. Euphorbiaceae (7.9%) are the most frequently used families of plants for the treatment of the various types of diseases mentioned, followed by Caesalpiaceae, (4.9%), Apocynoceae (4.9%) and Poaceae (4.9%). Fifty-nine recipes are usually prepared for the treatment of the six types of inflammatory diseases while twenty-three recipes are reportedly used for the treatment of the four types of cardiovascular diseases mentioned in this study. The recipes covered in the survey were mostly prepared from leaves (37.6%) and roots (23.8%) decoction or infusions. Medications are mostly administered orally with few numbers of the recipes showing side effect. The study has documented indigenous plants in Ogbomoso as a potential source for the development of new drugs for the treatment of cardiovascular and inflammatory diseases. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

    18. Analysis of the Retromer complex-WASH complex interaction illuminates new avenues to explore in Parkinson disease.

      Science.gov (United States)

      Seaman, Matthew Nj; Freeman, Caroline L

      2014-01-01

      The retromer complex mediates endosomal protein sorting by concentrating membrane proteins (cargo) into nascent tubules formed through the action of sorting nexin (SNX) proteins. The WASH complex is recruited to endosomes by binding to the VPS35 subunit of retromer and facilitates cargo protein sorting by promoting formation of endosomally-localized F-actin. The VPS35 protein is mutated in Parkinson disease (PD) and a recent report has revealed that the PD-causing mutation impairs the association of retromer with the WASH complex leading to perturbed endosomal protein sorting. Another important player in endosomal protein sorting is the DNAJC13/RME-8 protein, which associates with SNX1 and has also recently been linked to PD. An additional recent report has now shown that RME-8 also interacts with the WASH complex thus establishing retromer and WASH complex-mediated endosomal protein sorting as a key pathway linked to the pathology of PD and providing new avenues to explore in the search for insights into the disease mechanism.

    19. Analysis of altered complexity of gait dynamics with aging and Parkinson’s disease using ternary Lempel–Ziv complexity

      Directory of Open Access Journals (Sweden)

      Chandrakar Kamath

      2016-12-01

      Full Text Available Fluctuations in stride interval series show complex dynamical behavior in healthy young adults. Hypothesizing that these stride interval complexity changes would be altered by changes in neurological function associated with aging and certain disease states, we aimed to develop a tool to facilitate clinical judgments to assess the complex dynamical behavior in the stride series in discerning young, elderly, and Parkinson’s disease (PD classes. This novel approach, which employs a new variant of coarse-graining in conjunction with Lempel–Ziv complexity measure, yields useful, reliable, and predictive results. We also show the presence of nonlinear deterministic structures in the stride time series and appropriateness of the application of our nonlinear approach through surrogate data analysis. The findings show that the fluctuations are more complex/random in elderly and PD classes than those in young class. These findings may add to the growing body of literature supporting the clinical utility of this new approach to stride time series.

    20. Pityriasis Alba--Common Disease, Enigmatic Entity: Up-to-Date Review of the Literature.

      Science.gov (United States)

      Miazek, Nina; Michalek, Irmina; Pawlowska-Kisiel, Malgorzata; Olszewska, Malgorzata; Rudnicka, Lidia

      2015-01-01

      Pityriasis alba (PA) is a skin disorder that affects children and adolescents. Although it is common worldwide, its incidence is markedly higher in darker skin phototypes. Its characteristic features include an extended, multistage course and spontaneous remissions and recurrences. Preceded by erythematous changes, patches of hypopigmented skin of up to a few centimeters in diameter appear on the upper body. Pruritus may accompany it. Even though its etiology is unknown, possible reported triggering factors include sunlight, beauty treatments, and microorganisms, among others. Calcineurin inhibitors play the most crucial role in PA pharmacotherapy. PA often coexists with atopic dermatitis and is considered one of its milder forms.

    1. Depression and Alzheimer's disease: is stress the initiating factor in a common neuropathological cascade?

      DEFF Research Database (Denmark)

      Aznar, Susana; Knudsen, Gitte M

      2011-01-01

      . This suggests the existence of common neuropathological mechanisms behind depression and AD. Here we propose that the brain changes associated with depressive episodes that compromise the brain's ability to cope with stress may constitute risk factors for development of AD. Furthermore, in individuals...... with a genetic linkage to depression, there may be an increased vulnerability towards the initiation of a detrimental neurodegenerative cascade. The following review will deal with the various observations reported within the different neurobiological systems known to be involved and affected in depression, like...

    2. Clinical correlates of common corneal neovascular diseases:a literature review

      Directory of Open Access Journals (Sweden)

      Nizar Saleh Abdelfattah

      2015-02-01

      Full Text Available A large subset of corneal pathologies involves the formation of new blood and lymph vessels (neovascularization, leading to compromised visual acuity. This article aims to review the clinical causes and presentations of corneal neovascularization (CNV by examining the mechanisms behind common CNV-related corneal pathologies, with a particular focus on herpes simplex stromal keratitis, contact lenses-induced keratitis and CNV secondary to keratoplasty. Moreover, we reviewed CNV in the context of different types of corneal transplantation and keratoprosthesis, and summarized the most relevant treatments available so far.

    3. Detection of Secondary Causes and Coexisting Diseases in Hypertensive Patients: OSA and PA Are the Common Causes Associated with Hypertension

      Directory of Open Access Journals (Sweden)

      Lei Wang

      2017-01-01

      Full Text Available Background. Since the control rate of blood pressure is lower in mainland China, the aim of this study is to investigate the proportion of secondary causes and coexisting diseases of hypertension in hypertensive patients. Methods. Data on consecutive patients with hypertension who visited the Hypertension Center. Diseases were detected using an established strict screening protocol. Results. Detection rate of secondary causes and coexisting diseases of hypertension was 39.5% among 3003 hypertensive patients. Obstructive sleep apnea (OSA was the most common, accounting for 24.7% of patients, followed by primary aldosteronism (PA (5.8% and PA + OSA (4.9%. Endocrine hypertension accounted for 12.1% of patients, including 10.7% of patients with PA, 1.1% with hypothyroidism, 0.1% with pheochromocytoma, 0.1% with Cushing’s syndrome, and 0.1% with hyperthyroidism, respectively. Those who smoke, those who are obese, and those who have diabetes accounted for 31.3%, 27.5%, and 16.6% of total patients, respectively. There were overlapping conditions in secondary causes and coexisting diseases of hypertension. OSA was the most common in each age- and BMI-stratified group. Conclusion. Findings from the current study suggest an increasing frequency of secondary forms of hypertension, highlighting the burden of OSA and PA in hypertensive patients.

    4. A Common Variant of IL-6R is Associated with Elevated IL-6 Pathway Activity in Alzheimer's Disease Brains.

      Science.gov (United States)

      Haddick, Patrick C G; Larson, Jessica L; Rathore, Nisha; Bhangale, Tushar R; Phung, Qui T; Srinivasan, Karpagam; Hansen, David V; Lill, Jennie R; Pericak-Vance, Margaret A; Haines, Jonathan; Farrer, Lindsay A; Kauwe, John S; Schellenberg, Gerard D; Cruchaga, Carlos; Goate, Alison M; Behrens, Timothy W; Watts, Ryan J; Graham, Robert R; Kaminker, Joshua S; van der Brug, Marcel

      2017-01-01

      The common p.D358A variant (rs2228145) in IL-6R is associated with risk for multiple diseases and with increased levels of soluble IL-6R in the periphery and central nervous system (CNS). Here, we show that the p.D358A allele leads to increased proteolysis of membrane bound IL-6R and demonstrate that IL-6R peptides with A358 are more susceptible to cleavage by ADAM10 and ADAM17. IL-6 responsive genes were identified in primary astrocytes and microglia and an IL-6 gene signature was increased in the CNS of late onset Alzheimer's disease subjects in an IL6R allele dependent manner. We conducted a screen to identify variants associated with the age of onset of Alzheimer's disease in APOE ɛ4 carriers. Across five datasets, p.D358A had a meta P = 3 ×10-4 and an odds ratio = 1.3, 95% confidence interval 1.12 -1.48. Our study suggests that a common coding region variant of the IL-6 receptor results in neuroinflammatory changes that may influence the age of onset of Alzheimer's disease in APOE ɛ4 carriers.

    5. Parkinson’s disease and mitochondrial complex I: a perspective on the Ndi1 therapy

      OpenAIRE

      Marella, Mathieu; Seo, Byoung Boo; Yagi, Takao; Matsuno-Yagi, Akemi

      2009-01-01

      Mitochondrial impairment has been collecting more and more attention as a contributing factor to the etiology of Parkinson’s disease. Above all, the NADH-quinone oxidoreductase, complex I, of the respiratory chain seems to be most culpable. Complex I dysfunction is translated to an increased production of reactive oxygen species and a decreased energy supply. In the brain, the dopaminergic neurons are one of the most susceptible cells. Their death is directly linked to the disease apparition....

    6. Effects of Chronic Obstructive Pulmonary Disease and Obstructive Sleep Apnea on Cognitive Functions: Evidence for a Common Nature

      Directory of Open Access Journals (Sweden)

      Georgia Andreou

      2014-01-01

      Full Text Available Patients with chronic obstructive pulmonary disease (COPD and obstructive sleep apnea syndrome (OSAS show similar neurocognitive impairments. Effects are more apparent in severe cases, whereas in moderate and mild cases the effects are equivocal. The exact mechanism that causes cognitive dysfunctions in both diseases is still unknown and only suggestions have been made for each disease separately. The primary objective of this review is to present COPD and OSAS impact on cognitive functions. Secondly, it aims to examine the potential mechanisms by which COPD and OSAS can be linked and provide evidence for a common nature that affects cognitive functions in both diseases. Patients with COPD and OSAS compared to normal distribution show significant deficits in the cognitive abilities of attention, psychomotor speed, memory and learning, visuospatial and constructional abilities, executive skills, and language. The severity of these deficits in OSAS seems to correlate with the physiological events such as sleep defragmentation, apnea/hypopnea index, and hypoxemia, whereas cognitive impairments in COPD are associated with hypoventilation, hypoxemia, and hypercapnia. These factors as well as vascocerebral diseases and changes in systemic hemodynamic seem to act in an intermingling and synergistic way on the cause of cognitive dysfunctions in both diseases. However, low blood oxygen pressure seems to be the dominant factor that contributes to the presence of cognitive deficits in both COPD and OSAS.

    7. Systems Pharmacology Dissecting Holistic Medicine for Treatment of Complex Diseases: An Example Using Cardiocerebrovascular Diseases Treated by TCM

      Science.gov (United States)

      Wang, Yonghua; Zheng, Chunli; Huang, Chao; Li, Yan; Chen, Xuetong; Wu, Ziyin; Wang, Zhenzhong; Xiao, Wei; Zhang, Boli

      2015-01-01

      Holistic medicine is an interdisciplinary field of study that integrates all types of biological information (protein, small molecules, tissues, organs, external environmental signals, etc.) to lead to predictive and actionable models for health care and disease treatment. Despite the global and integrative character of this discipline, a comprehensive picture of holistic medicine for the treatment of complex diseases is still lacking. In this study, we develop a novel systems pharmacology approach to dissect holistic medicine in treating cardiocerebrovascular diseases (CCDs) by TCM (traditional Chinese medicine). Firstly, by applying the TCM active ingredients screened out by a systems-ADME process, we explored and experimentalized the signed drug-target interactions for revealing the pharmacological actions of drugs at a molecule level. Then, at a/an tissue/organ level, the drug therapeutic mechanisms were further investigated by a target-organ location method. Finally, a translational integrating pathway approach was applied to extract the diseases-therapeutic modules for understanding the complex disease and its therapy at systems level. For the first time, the feature of the drug-target-pathway-organ-cooperations for treatment of multiple organ diseases in holistic medicine was revealed, facilitating the development of novel treatment paradigm for complex diseases in the future. PMID:26101539

    8. Systems Pharmacology Dissecting Holistic Medicine for Treatment of Complex Diseases: An Example Using Cardiocerebrovascular Diseases Treated by TCM

      Directory of Open Access Journals (Sweden)

      Yonghua Wang

      2015-01-01

      Full Text Available Holistic medicine is an interdisciplinary field of study that integrates all types of biological information (protein, small molecules, tissues, organs, external environmental signals, etc. to lead to predictive and actionable models for health care and disease treatment. Despite the global and integrative character of this discipline, a comprehensive picture of holistic medicine for the treatment of complex diseases is still lacking. In this study, we develop a novel systems pharmacology approach to dissect holistic medicine in treating cardiocerebrovascular diseases (CCDs by TCM (traditional Chinese medicine. Firstly, by applying the TCM active ingredients screened out by a systems-ADME process, we explored and experimentalized the signed drug-target interactions for revealing the pharmacological actions of drugs at a molecule level. Then, at a/an tissue/organ level, the drug therapeutic mechanisms were further investigated by a target-organ location method. Finally, a translational integrating pathway approach was applied to extract the diseases-therapeutic modules for understanding the complex disease and its therapy at systems level. For the first time, the feature of the drug-target-pathway-organ-cooperations for treatment of multiple organ diseases in holistic medicine was revealed, facilitating the development of novel treatment paradigm for complex diseases in the future.

    9. Gait dynamics in Parkinson's disease: Common and distinct behavior among stride length, gait variability, and fractal-like scaling

      Science.gov (United States)

      Hausdorff, Jeffrey M.

      2009-06-01

      Parkinson's disease (PD) is a common, debilitating neurodegenerative disease. Gait disturbances are a frequent cause of disability and impairment for patients with PD. This article provides a brief introduction to PD and describes the gait changes typically seen in patients with this disease. A major focus of this report is an update on the study of the fractal properties of gait in PD, the relationship between this feature of gait and stride length and gait variability, and the effects of different experimental conditions on these three gait properties. Implications of these findings are also briefly described. This update highlights the idea that while stride length, gait variability, and fractal scaling of gait are all impaired in PD, distinct mechanisms likely contribute to and are responsible for the regulation of these disparate gait properties.

    10. S100A4: a common mediator of epithelial-mesenchymal transition, fibrosis and regeneration in diseases?

      DEFF Research Database (Denmark)

      Schneider, Mikael; Hansen, Jakob L; Sheikh, Søren P

      2008-01-01

      Multiple reports have focused on S100A4's role in cancer progression, specifically its ability to enhance metastasis. However, recent studies have linked S100A4 to several diseases besides cancer, including kidney fibrosis, cirrhosis, pulmonary disease, cardiac hypertrophy and fibrosis, arthritis...... and neuronal injuries. Common to all these diseases is the involvement of fibrotic and inflammatory processes, i.e. processes greatly dependent on tissue remodelling, cell motility and epithelial-mesenchymal transition. Therefore, the basic biological mechanisms behind S100A4's effects are emerging. S100A4...... belongs to the S100 family of proteins that contain two Ca(2+)-binding sites including a canonical EF-hand motif. S100A4 is involved in the regulation of a wide range of biological effects including cell motility, survival, differentiation and contractility. S100A4 has both intracellular and extracellular...

    11. S100A4: a common mediator of epithelial-mesenchymal transition, fibrosis and regeneration in diseases?

      DEFF Research Database (Denmark)

      Schneider, M.; Sheikh, S.P.; Hansen, Jakob Lerche

      2008-01-01

      Multiple reports have focused on S100A4's role in cancer progression, specifically its ability to enhance metastasis. However, recent studies have linked S100A4 to several diseases besides cancer, including kidney fibrosis, cirrhosis, pulmonary disease, cardiac hypertrophy and fibrosis, arthritis...... and neuronal injuries. Common to all these diseases is the involvement of fibrotic and inflammatory processes, i.e. processes greatly dependent on tissue remodelling, cell motility and epithelial-mesenchymal transition. Therefore, the basic biological mechanisms behind S100A4's effects are emerging. S100A4...... belongs to the S100 family of proteins that contain two Ca2+-binding sites including a canonical EF-hand motif. S100A4 is involved in the regulation of a wide range of biological effects including cell motility, survival, differentiation and contractility. S100A4 has both intracellular and extracellular...

    12. Deconstruction of Vulnerability to Complex Diseases: Enhanced Effect Sizes and Power of Intermediate Phenotypes

      Directory of Open Access Journals (Sweden)

      David Goldman

      2007-01-01

      Full Text Available The deconstruction of vulnerability to complex disease with the help of intermediate phenotypes, including the heritable and disease-associated endophenotypes, is a legacy of Henri Begleiter. Systematic searches for genes influencing complex disorders, including bipolar disorder, have recently been completed using whole genome association (WGA, identifying a series of validated loci. Using this information, it is possible to compare effect sizes of disease loci discovered in very large samples to the effect sizes of replicated functional loci determining intermediate phenotypes that are of essential interest in psychiatric disorders. It is shown that the genes influencing intermediate phenotypes tend to have a larger effect size. Furthermore, the WGA results reveal that the number of loci of large effect size for complex diseases is limited, and yet multiple functional loci have already been identified for intermediate phenotypes relevant to psychiatric diseases, and without the benefit of WGA.

    13. Identification of a Common Epitope between Enterovirus 71 and Human MED25 Proteins Which May Explain Virus-Associated Neurological Disease

      Directory of Open Access Journals (Sweden)

      Peihu Fan

      2015-03-01

      Full Text Available Enterovirus 71 (EV71 is a major causative pathogen of hand, foot and mouth disease with especially severe neurologic complications, which mainly account for fatalities from this disease. To date, the pathogenesis of EV71 in the central neurons system has remained unclear. Cytokine-mediated immunopathogenesis and nervous tissue damage by virus proliferation are two widely speculated causes of the neurological disease. To further study the pathogenesis, we identified a common epitope (co-epitope between EV71 VP1 and human mediator complex subunit 25 (MED25 highly expressed in brain stem. A monoclonal antibody (2H2 against the co-epitope was prepared, and its interaction with MED25 was examined by ELISA, immunofluorescence assay and Western blot in vitro and by live small animal imaging in vivo. Additionally, 2H2 could bind to both VP1 and MED25 with the affinity constant (Kd of 10−7 M as determined by the ForteBio Octet System. Intravenously injected 2H2 was distributed in brain stem of mice after seven days of EV71 infection. Interestingly, 2H2-like antibodies were detected in the serum of EV71-infected patients. These findings suggest that EV71 infection induces the production of antibodies that can bind to autoantigens expressed in nervous tissue and maybe further trigger autoimmune reactions resulting in neurological disease.

    14. 'Hair-on-end' skull changes resembling thalassemia caused by marrow expansion in uncorrected complex cyanotic heart disease

      Energy Technology Data Exchange (ETDEWEB)

      Walor, David M.; Berdon, Walter E. [Columbia University Medical Center, Department of Radiology Children' s Hospital of New York, New York, NY (United States); Westra, Sjirk J. [Massachusetts General Hospital, Department of Radiology, Boston, MA (United States)

      2005-07-01

      ''Hair-on-end'' skull changes resembling thalassemia were rarely described in the 1950s and 1960s in children with cyanotic congenital heart diseases; these changes were described almost entirely in patients with tetralogy of Fallot or D-transposition of the great arteries. As these lesions have become correctable, the osseous changes, never common, seem now only to exist in a small number of patients with uncorrectable complex cyanotic congenital heart disease who survive in a chronic hypoxic state. We present two cases: a case of marked marrow expansion in the skull of a 5-year-old boy with uncorrectable cyanotic heart disease studied by CT, and a second case of an 8-year-old with tetralogy of Fallot and pulmonary atresia studied by plain skull radiographs. The true incidence of these findings is unknown. (orig.)

    15. Dissection of a Complex Disease Susceptibility Region Using a Bayesian Stochastic Search Approach to Fine Mapping.

      Directory of Open Access Journals (Sweden)

      Chris Wallace

      2015-06-01

      Full Text Available Identification of candidate causal variants in regions associated with risk of common diseases is complicated by linkage disequilibrium (LD and multiple association signals. Nonetheless, accurate maps of these variants are needed, both to fully exploit detailed cell specific chromatin annotation data to highlight disease causal mechanisms and cells, and for design of the functional studies that will ultimately be required to confirm causal mechanisms. We adapted a Bayesian evolutionary stochastic search algorithm to the fine mapping problem, and demonstrated its improved performance over conventional stepwise and regularised regression through simulation studies. We then applied it to fine map the established multiple sclerosis (MS and type 1 diabetes (T1D associations in the IL-2RA (CD25 gene region. For T1D, both stepwise and stochastic search approaches identified four T1D association signals, with the major effect tagged by the single nucleotide polymorphism, rs12722496. In contrast, for MS, the stochastic search found two distinct competing models: a single candidate causal variant, tagged by rs2104286 and reported previously using stepwise analysis; and a more complex model with two association signals, one of which was tagged by the major T1D associated rs12722496 and the other by rs56382813. There is low to moderate LD between rs2104286 and both rs12722496 and rs56382813 (r2 ≃ 0:3 and our two SNP model could not be recovered through a forward stepwise search after conditioning on rs2104286. Both signals in the two variant model for MS affect CD25 expression on distinct subpopulations of CD4+ T cells, which are key cells in the autoimmune process. The results support a shared causal variant for T1D and MS. Our study illustrates the benefit of using a purposely designed model search strategy for fine mapping and the advantage of combining disease and protein expression data.

    16. An investigation to identify potential risk factors associated with common chronic diseases among the older population in India

      Directory of Open Access Journals (Sweden)

      Enemona Emmanuel Adaji

      2017-01-01

      Full Text Available Background: In India, chronic diseases are the leading cause of death and their prevalence has constantly increased over the last decade. Objective: This study aimed to identify risk factors associated with common chronic diseases among people aged 50 years and over in India. Materials and Methods: Data from Wave 1 of the 2007/2008 Indian Study on Global Ageing and Adult Health (SAGE was used to investigate the association between lifestyle choices and chronic diseases using logistic regression. Result: The fully adjusted model showed that significant independent risk factors for angina included area of residence, being diagnosed with diabetes, chronic lung disease (CLD [highest odds ratio (OR 4.77, 95% confidence interval (CI: 2.95-7.70] and arthritis. For arthritis, risk factors included having underlying diabetes, CLD diagnosis, or angina (highest OR 2.32, 95% CI: 1.63-3.31. Risk factors associated with CLD included arthritis, angina (highest OR 4.76, 95% CI: 2.94-7.72, alcohol use, and tobacco use. Risk factors associated with diabetes included level of education, area of residence, socioeconomic status, angina (highest OR 3.59, 95% CI: 2.44-5.29, CLD, arthritis, stroke, and vegetable consumption. Finally, risk factors associated with stroke included diabetes and angina (highest OR 3.34, 95% CI: 1.72-6.50. The presence of any other comorbidity was significantly associated with all five chronic diseases studied. Conclusion: The results show that within the older population, the contribution of lifestyle risk factors to the common chronic diseases investigated in this study was limited. Our findings showed that the major health issue within the study population was multimorbidity.

    17. An Ocular Protein Triad Can Classify Four Complex Retinal Diseases

      Science.gov (United States)

      Kuiper, J. J. W.; Beretta, L.; Nierkens, S.; van Leeuwen, R.; ten Dam-van Loon, N. H.; Ossewaarde-van Norel, J.; Bartels, M. C.; de Groot-Mijnes, J. D. F.; Schellekens, P.; de Boer, J. H.; Radstake, T. R. D. J.

      2017-01-01

      Retinal diseases generally are vision-threatening conditions that warrant appropriate clinical decision-making which currently solely dependents upon extensive clinical screening by specialized ophthalmologists. In the era where molecular assessment has improved dramatically, we aimed at the identification of biomarkers in 175 ocular fluids to classify four archetypical ocular conditions affecting the ret