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Sample records for human diseases results

  1. Simian virus 40 infection in humans and association with human diseases: results and hypotheses

    International Nuclear Information System (INIS)

    Barbanti-Brodano, Giuseppe; Sabbioni, Silvia; Martini, Fernanda; Negrini, Massimo; Corallini, Alfredo; Tognon, Mauro

    2004-01-01

    Simian virus 40 (SV40) is a monkey virus that was introduced in the human population by contaminated poliovaccines, produced in SV40-infected monkey cells, between 1955 and 1963. Epidemiological evidence now suggests that SV40 may be contagiously transmitted in humans by horizontal infection, independent of the earlier administration of SV40-contaminated poliovaccines. This evidence includes detection of SV40 DNA sequences in human tissues and of SV40 antibodies in human sera, as well as rescue of infectious SV40 from a human tumor. Detection of SV40 DNA sequences in blood and sperm and of SV40 virions in sewage points to the hematic, sexual, and orofecal routes as means of virus transmission in humans. The site of latent infection in humans is not known, but the presence of SV40 in urine suggests the kidney as a possible site of latency, as it occurs in the natural monkey host. SV40 in humans is associated with inflammatory kidney diseases and with specific tumor types: mesothelioma, lymphoma, brain, and bone. These human tumors correspond to the neoplasms that are induced by SV40 experimental inoculation in rodents and by generation of transgenic mice with the SV40 early region gene directed by its own early promoter-enhancer. The mechanisms of SV40 tumorigenesis in humans are related to the properties of the two viral oncoproteins, the large T antigen (Tag) and the small t antigen (tag). Tag acts mainly by blocking the functions of p53 and RB tumor suppressor proteins, as well as by inducing chromosomal aberrations in the host cell. These chromosome alterations may hit genes important in oncogenesis and generate genetic instability in tumor cells. The clastogenic activity of Tag, which fixes the chromosome damage in the infected cells, may explain the low viral load in SV40-positive human tumors and the observation that Tag is expressed only in a fraction of tumor cells. 'Hit and run' seems the most plausible mechanism to support this situation. The small tag

  2. Human Environmental Disease Network

    DEFF Research Database (Denmark)

    Taboureau, Olivier; Audouze, Karine

    2017-01-01

    During the past decades, many epidemiological, toxicological and biological studies have been performed to assess the role of environmental chemicals as potential toxicants for diverse human disorders. However, the relationships between diseases based on chemical exposure have been rarely studied...... by computational biology. We developed a human environmental disease network (EDN) to explore and suggest novel disease-disease and chemical-disease relationships. The presented scored EDN model is built upon the integration on systems biology and chemical toxicology using chemical contaminants information...... and their disease relationships from the reported TDDB database. The resulting human EDN takes into consideration the level of evidence of the toxicant-disease relationships allowing including some degrees of significance in the disease-disease associations. Such network can be used to identify uncharacterized...

  3. A review of the disease and the results of a serosurvey of humans ...

    African Journals Online (AJOL)

    Sera from 494 humans, 180 cattle, 180 goats and 27 dogs, collected from different regions of Zimbabwe, were examined by indirect fluorescence for antibodies reactive with phase 11 Coxiella burnetii antigen. Overall, 37% of hwnans were reactive at a titre of 1140 or greater, and there was no evidence of age- or ...

  4. Influenza as a human disease

    Indian Academy of Sciences (India)

    First page Back Continue Last page Graphics. Influenza as a human disease. Commonly perceived as a mild disease, affects every one, sometimes a couple of times in a year. Globally, seasonal influenza epidemics result in about three to five million yearly cases of severe illness and about 250,000 to 500,000 yearly ...

  5. Epidemiological characteristics of human brucellosis in Hamadan Province during 2009-2015: results from the National Notifiable Diseases Surveillance System.

    Science.gov (United States)

    Nematollahi, Shahrzad; Ayubi, Erfan; Karami, Manoochehr; Khazaei, Salman; Shojaeian, Masoud; Zamani, Reza; Mansori, Kamyar; Gholamaliee, Behzad

    2017-08-01

    Human brucellosis and recurrent brucellosis is an ever-increasing public health concern, especially in endemic areas like Iran. Nevertheless, little is known regarding the epidemiology and determinants of recurrent brucellosis. Therefore, the objective of this study was to investigate epidemiological patterns and potential determinants of recurrent brucellosis in Hamadan Province during the years 2009-2015. Data on reported cases of new and recurrent brucellosis from 2009 to 2015 were obtained from the provincial Notifiable Diseases Surveillance System at Hamadan University of Medical Sciences. Incidence rates per 100000 were estimated at the county level. Binary logistic regression was used to estimate the effects of background characteristics and recurrent brucellosis. The power of discrimination of the model for recurrent brucellosis was assessed using the area under the curve (AUC). Among 7318 brucellosis cases, the total frequency (%) of recurrent cases was 472 (6.45%). The rate of recurrent brucellosis was higher in females, people aged 50 years and over, people with a history of consuming unpasteurized dairy products with no history of contact with animals, and in the winter season. Multivariable logistic regression analysis showed that female sex (adjusted odds ratio (AOR) 1.36, 95% confidence interval (CI) 1.13-1.65), age ≥55 years (AOR 4.15, 95% CI 2.32-7.42), consumption of unpasteurized dairy products (AOR 1.16, 95% CI 0.96-1.40), and winter season (AOR 1.32, 95% CI 1.03-1.71) are potential risk factors for recurrent brucellosis. The final model that involved all the determinants showed moderate discrimination (AUC 0.61). Female sex, older age, and winter months were found to be significant determinants of recurrent human brucellosis. Enhanced surveillance systems with an emphasis on these population characteristics will allow effective preventive and protective measures to be implemented and might alleviate the recurrence of brucellosis in the

  6. Parkinson's disease-related LRRK2 G2019S mutation results from independent mutational events in humans.

    Science.gov (United States)

    Lesage, Suzanne; Patin, Etienne; Condroyer, Christel; Leutenegger, Anne-Louise; Lohmann, Ebba; Giladi, Nir; Bar-Shira, Anat; Belarbi, Soraya; Hecham, Nassima; Pollak, Pierre; Ouvrard-Hernandez, Anne-Marie; Bardien, Soraya; Carr, Jonathan; Benhassine, Traki; Tomiyama, Hiroyuki; Pirkevi, Caroline; Hamadouche, Tarik; Cazeneuve, Cécile; Basak, A Nazli; Hattori, Nobutaka; Dürr, Alexandra; Tazir, Meriem; Orr-Urtreger, Avi; Quintana-Murci, Lluis; Brice, Alexis

    2010-05-15

    Mutations in the leucine-rich-repeat kinase 2 (LRRK2) gene have been identified in families with autosomal dominant Parkinson's disease (PD) and in sporadic cases; the G2019S mutation is the single most frequent. Intriguingly, the frequency of this mutation in PD patients varies greatly among ethnic groups and geographic origins: it is present at <0.1% in East Asia, approximately 2% in European-descent patients and can reach frequencies of up to 15-40% in PD Ashkenazi Jews and North African Arabs. To ascertain the evolutionary dynamics of the G2019S mutation in different populations, we genotyped 74 markers spanning a 16 Mb genomic region around G2019S, in 191 individuals carrying the mutation from 126 families of different origins. Sixty-seven families were of North-African Arab origin, 18 were of North/Western European descent, 37 were of Jewish origin, mostly from Eastern Europe, one was from Japan, one from Turkey and two were of mixed origins. We found the G2019S mutation on three different haplotypes. Network analyses of the three carrier haplotypes showed that G2019S arose independently at least twice in humans. In addition, the population distribution of the intra-allelic diversity of the most widespread carrier haplotype, together with estimations of the age of G2019S determined by two different methods, suggests that one of the founding G2019S mutational events occurred in the Near East at least 4000 years ago.

  7. Humanized mouse models: Application to human diseases.

    Science.gov (United States)

    Ito, Ryoji; Takahashi, Takeshi; Ito, Mamoru

    2018-05-01

    Humanized mice are superior to rodents for preclinical evaluation of the efficacy and safety of drug candidates using human cells or tissues. During the past decade, humanized mouse technology has been greatly advanced by the establishment of novel platforms of genetically modified immunodeficient mice. Several human diseases can be recapitulated using humanized mice due to the improved engraftment and differentiation capacity of human cells or tissues. In this review, we discuss current advanced humanized mouse models that recapitulate human diseases including cancer, allergy, and graft-versus-host disease. © 2017 Wiley Periodicals, Inc.

  8. Linking Microbiota to Human Diseases

    DEFF Research Database (Denmark)

    Wu, Hao; Tremaroli, Valentina; Bäckhed, F

    2015-01-01

    The human gut microbiota encompasses a densely populated ecosystem that provides essential functions for host development, immune maturation, and metabolism. Alterations to the gut microbiota have been observed in numerous diseases, including human metabolic diseases such as obesity, type 2...

  9. in Human Liver Diseases

    Directory of Open Access Journals (Sweden)

    Minoru Fujimoto

    2010-01-01

    Full Text Available Toll-like receptor (TLR signaling pathways are strictly coordinated by several mechanisms to regulate adequate innate immune responses. Recent lines of evidence indicate that the suppressor of cytokine signaling (SOCS family proteins, originally identified as negative-feedback regulators in cytokine signaling, are involved in the regulation of TLR-mediated immune responses. SOCS1, a member of SOCS family, is strongly induced upon TLR stimulation. Cells lacking SOCS1 are hyperresponsive to TLR stimulation. Thus, SOCS1 is an important regulator for both cytokine and TLR-induced responses. As an immune organ, the liver contains various types of immune cells such as T cells, NK cells, NKT cells, and Kupffer cells and is continuously challenged with gut-derived bacterial and dietary antigens. SOCS1 may be implicated in pathophysiology of the liver. The studies using SOCS1-deficient mice revealed that endogenous SOCS1 is critical for the prevention of liver diseases such as hepatitis, cirrhosis, and cancers. Recent studies on humans suggest that SOCS1 is involved in the development of various liver disorders in humans. Thus, SOCS1 and other SOCS proteins are potential targets for the therapy of human liver diseases.

  10. Feasibility study of novel endoscopic Cerenkov luminescence imaging system in detecting and quantifying gastrointestinal disease: first human results

    International Nuclear Information System (INIS)

    Hu, Hao; Li, Shujun; Yao, Liping; Liang, Jie; Nie, Yongzhan; Wu, Kaichun; Cao, Xin; Lin, Yenan; Liu, Muhan; Liang, Jimin; Chen, Xueli; Kang, Fei; Wang, Jing; Wang, Min

    2015-01-01

    Cerenkov luminescence imaging (CLI) provides potential to use clinical radiotracers for optical imaging. The goal of this study was to present a newly developed endoscopic CLI (ECLI) system and illustrate its feasibility and potential in distinguishing and quantifying cancerous lesions of the GI tract. The ECLI system was established by integrating an electron-multiplying charge-coupled device camera with a flexible fibre endoscope. Phantom experiments and animal studies were conducted to test and illustrate the system in detecting and quantifying the presence of radionuclide in vitro and in vivo. A pilot clinical study was performed to evaluate our system in clinical settings. Phantom and mice experiments demonstrated its ability to acquire both the luminescent and photographic images with high accuracy. Linear quantitative relationships were also obtained when comparing the ECLI radiance with the radiotracer activity (r 2 = 0.9779) and traditional CLI values (r 2 = 0.9025). Imaging of patients revealed the potential of ECLI in the identification and quantification of cancerous tissue from normal, which showed good consistence with the clinical PET examination. The new ECLI system shows good consistence with the clinical PET examination and has great potential for clinical translation and in aiding detection of the GI tract disease. (orig.)

  11. Feasibility study of novel endoscopic Cerenkov luminescence imaging system in detecting and quantifying gastrointestinal disease: first human results

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Hao; Li, Shujun; Yao, Liping; Liang, Jie; Nie, Yongzhan; Wu, Kaichun [Fourth Military Medical University, State Key Laboratory of Cancer Biology, Department of Digestive Diseases, Xijing Hospital, Xi' an (China); Cao, Xin; Lin, Yenan; Liu, Muhan; Liang, Jimin; Chen, Xueli [Xidian University, School of Life Science and Technology, Xi' an (China); Kang, Fei; Wang, Jing [Fourth Military Medical University, Department of Nuclear Medicine, Xijing Hospital, Xi' an (China); Wang, Min [Xi' an Children' s Hospital, Department of Gastroenterology, Xi' an (China)

    2015-06-01

    Cerenkov luminescence imaging (CLI) provides potential to use clinical radiotracers for optical imaging. The goal of this study was to present a newly developed endoscopic CLI (ECLI) system and illustrate its feasibility and potential in distinguishing and quantifying cancerous lesions of the GI tract. The ECLI system was established by integrating an electron-multiplying charge-coupled device camera with a flexible fibre endoscope. Phantom experiments and animal studies were conducted to test and illustrate the system in detecting and quantifying the presence of radionuclide in vitro and in vivo. A pilot clinical study was performed to evaluate our system in clinical settings. Phantom and mice experiments demonstrated its ability to acquire both the luminescent and photographic images with high accuracy. Linear quantitative relationships were also obtained when comparing the ECLI radiance with the radiotracer activity (r{sup 2} = 0.9779) and traditional CLI values (r{sup 2} = 0.9025). Imaging of patients revealed the potential of ECLI in the identification and quantification of cancerous tissue from normal, which showed good consistence with the clinical PET examination. The new ECLI system shows good consistence with the clinical PET examination and has great potential for clinical translation and in aiding detection of the GI tract disease. (orig.)

  12. Proteins aggregation and human diseases

    Science.gov (United States)

    Hu, Chin-Kun

    2015-04-01

    Many human diseases and the death of most supercentenarians are related to protein aggregation. Neurodegenerative diseases include Alzheimer's disease (AD), Huntington's disease (HD), Parkinson's disease (PD), frontotemporallobar degeneration, etc. Such diseases are due to progressive loss of structure or function of neurons caused by protein aggregation. For example, AD is considered to be related to aggregation of Aβ40 (peptide with 40 amino acids) and Aβ42 (peptide with 42 amino acids) and HD is considered to be related to aggregation of polyQ (polyglutamine) peptides. In this paper, we briefly review our recent discovery of key factors for protein aggregation. We used a lattice model to study the aggregation rates of proteins and found that the probability for a protein sequence to appear in the conformation of the aggregated state can be used to determine the temperature at which proteins can aggregate most quickly. We used molecular dynamics and simple models of polymer chains to study relaxation and aggregation of proteins under various conditions and found that when the bending-angle dependent and torsion-angle dependent interactions are zero or very small, then protein chains tend to aggregate at lower temperatures. All atom models were used to identify a key peptide chain for the aggregation of insulin chains and to find that two polyQ chains prefer anti-parallel conformation. It is pointed out that in many cases, protein aggregation does not result from protein mis-folding. A potential drug from Chinese medicine was found for Alzheimer's disease.

  13. Transfer RNA and human disease

    Directory of Open Access Journals (Sweden)

    Jamie A Abbott

    2014-06-01

    Full Text Available Pathological mutations in tRNA genes and tRNA processing enzymes are numerous and result in very complicated clinical phenotypes. Mitochondrial tRNA (mt-tRNA genes are hotspots for pathological mutations and over 200 mt-tRNA mutations have been linked to various disease states. Often these mutations prevent tRNA aminoacylation. Disrupting this primary function affects protein synthesis and the expression, folding, and function of oxidative phosphorylation enzymes. Mitochondrial tRNA mutations manifest in a wide panoply of diseases related to cellular energetics, including COX deficiency (cytochrome C oxidase, mitochondrial myopathy, MERRF (Myoclonic Epilepsy with Ragged Red Fibers, and MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes. Diseases caused by mt-tRNA mutations can also affect very specific tissue types, as in the case of neurosensory non-syndromic hearing loss and pigmentary retinopathy, diabetes mellitus, and hypertrophic cardiomyopathy. Importantly, mitochondrial heteroplasmy plays a role in disease severity and age of onset as well. Not surprisingly, mutations in enzymes that modify cytoplasmic and mitochondrial tRNAs are also linked to a diverse range of clinical phenotypes. In addition to compromised aminoacylation of the tRNAs, mutated modifying enzymes can also impact tRNA expression and abundance, tRNA modifications, tRNA folding, and even tRNA maturation (e.g., splicing. Some of these pathological mutations in tRNAs and processing enzymes are likely to affect non-canonical tRNA functions, and contribute to the diseases without significantly impacting on translation. This chapter will review recent literature on the relation of mitochondrial and cytoplasmic tRNA, and enzymes that process tRNAs, to human disease. We explore the mechanisms involved in the clinical presentation of these various diseases with an emphasis on neurological disease.

  14. Transfer RNA and human disease.

    Science.gov (United States)

    Abbott, Jamie A; Francklyn, Christopher S; Robey-Bond, Susan M

    2014-01-01

    Pathological mutations in tRNA genes and tRNA processing enzymes are numerous and result in very complicated clinical phenotypes. Mitochondrial tRNA (mt-tRNA) genes are "hotspots" for pathological mutations and over 200 mt-tRNA mutations have been linked to various disease states. Often these mutations prevent tRNA aminoacylation. Disrupting this primary function affects protein synthesis and the expression, folding, and function of oxidative phosphorylation enzymes. Mitochondrial tRNA mutations manifest in a wide panoply of diseases related to cellular energetics, including COX deficiency (cytochrome C oxidase), mitochondrial myopathy, MERRF (Myoclonic Epilepsy with Ragged Red Fibers), and MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes). Diseases caused by mt-tRNA mutations can also affect very specific tissue types, as in the case of neurosensory non-syndromic hearing loss and pigmentary retinopathy, diabetes mellitus, and hypertrophic cardiomyopathy. Importantly, mitochondrial heteroplasmy plays a role in disease severity and age of onset as well. Not surprisingly, mutations in enzymes that modify cytoplasmic and mitochondrial tRNAs are also linked to a diverse range of clinical phenotypes. In addition to compromised aminoacylation of the tRNAs, mutated modifying enzymes can also impact tRNA expression and abundance, tRNA modifications, tRNA folding, and even tRNA maturation (e.g., splicing). Some of these pathological mutations in tRNAs and processing enzymes are likely to affect non-canonical tRNA functions, and contribute to the diseases without significantly impacting on translation. This chapter will review recent literature on the relation of mitochondrial and cytoplasmic tRNA, and enzymes that process tRNAs, to human disease. We explore the mechanisms involved in the clinical presentation of these various diseases with an emphasis on neurological disease.

  15. Proteins aggregation and human diseases

    International Nuclear Information System (INIS)

    Hu, Chin-Kun

    2015-01-01

    Many human diseases and the death of most supercentenarians are related to protein aggregation. Neurodegenerative diseases include Alzheimer's disease (AD), Huntington's disease (HD), Parkinson's disease (PD), frontotemporallobar degeneration, etc. Such diseases are due to progressive loss of structure or function of neurons caused by protein aggregation. For example, AD is considered to be related to aggregation of Aβ40 (peptide with 40 amino acids) and Aβ42 (peptide with 42 amino acids) and HD is considered to be related to aggregation of polyQ (polyglutamine) peptides. In this paper, we briefly review our recent discovery of key factors for protein aggregation. We used a lattice model to study the aggregation rates of proteins and found that the probability for a protein sequence to appear in the conformation of the aggregated state can be used to determine the temperature at which proteins can aggregate most quickly. We used molecular dynamics and simple models of polymer chains to study relaxation and aggregation of proteins under various conditions and found that when the bending-angle dependent and torsion-angle dependent interactions are zero or very small, then protein chains tend to aggregate at lower temperatures. All atom models were used to identify a key peptide chain for the aggregation of insulin chains and to find that two polyQ chains prefer anti-parallel conformation. It is pointed out that in many cases, protein aggregation does not result from protein mis-folding. A potential drug from Chinese medicine was found for Alzheimer's disease. (paper)

  16. Human communicable diseases

    International Nuclear Information System (INIS)

    2003-01-01

    The rising incidence of malaria and tuberculosis in sub-Saharan Africa is causing great hardship, not only to the individuals affected but also to the economies of the countries where they are rife. Both diseases are becoming more resistant to the drugs that are currently available for treatment and drug resistant strains are posing a global threat. The International Atomic Energy Agency (IAEA) is responding by sponsoring a programme to build technical competency in molecular and radioisotope-based techniques. (IAEA)

  17. Viral diseases and human evolution

    Directory of Open Access Journals (Sweden)

    Leal Élcio de Souza

    2000-01-01

    Full Text Available The interaction of man with viral agents was possibly a key factor shaping human evolution, culture and civilization from its outset. Evidence of the effect of disease, since the early stages of human speciation, through pre-historical times to the present suggest that the types of viruses associated with man changed in time. As human populations progressed technologically, they grew in numbers and density. As a consequence different viruses found suitable conditions to thrive and establish long-lasting associations with man. Although not all viral agents cause disease and some may in fact be considered beneficial, the present situation of overpopulation, poverty and ecological inbalance may have devastating effets on human progress. Recently emerged diseases causing massive pandemics (eg., HIV-1 and HCV, dengue, etc. are becoming formidable challenges, which may have a direct impact on the fate of our species.

  18. Annotating the human genome with Disease Ontology

    Science.gov (United States)

    Osborne, John D; Flatow, Jared; Holko, Michelle; Lin, Simon M; Kibbe, Warren A; Zhu, Lihua (Julie); Danila, Maria I; Feng, Gang; Chisholm, Rex L

    2009-01-01

    Background The human genome has been extensively annotated with Gene Ontology for biological functions, but minimally computationally annotated for diseases. Results We used the Unified Medical Language System (UMLS) MetaMap Transfer tool (MMTx) to discover gene-disease relationships from the GeneRIF database. We utilized a comprehensive subset of UMLS, which is disease-focused and structured as a directed acyclic graph (the Disease Ontology), to filter and interpret results from MMTx. The results were validated against the Homayouni gene collection using recall and precision measurements. We compared our results with the widely used Online Mendelian Inheritance in Man (OMIM) annotations. Conclusion The validation data set suggests a 91% recall rate and 97% precision rate of disease annotation using GeneRIF, in contrast with a 22% recall and 98% precision using OMIM. Our thesaurus-based approach allows for comparisons to be made between disease containing databases and allows for increased accuracy in disease identification through synonym matching. The much higher recall rate of our approach demonstrates that annotating human genome with Disease Ontology and GeneRIF for diseases dramatically increases the coverage of the disease annotation of human genome. PMID:19594883

  19. Cohesin and Human Disease

    Science.gov (United States)

    Liu, Jinglan; Krantz, Ian D.

    2016-01-01

    Cornelia de Lange syndrome (CdLS) is a dominant multisystem disorder caused by a disruption of cohesin function. The cohesin ring complex is composed of four protein subunits and more than 25 additional proteins involved in its regulation. The discovery that this complex also has a fundamental role in long-range regulation of transcription in Drosophila has shed light on the mechanism likely responsible for its role in development. In addition to the three cohesin proteins involved in CdLS, a second multisystem, recessively inherited, developmental disorder, Roberts-SC phocomelia, is caused by mutations in another regulator of the cohesin complex, ESCO2. Here we review the phenotypes of these disorders, collectively termed cohesinopathies, as well as the mechanism by which cohesin disruption likely causes these diseases. PMID:18767966

  20. Loss of spastin function results in disease-specific axonal defects in human pluripotent stem cell-based models of hereditary spastic paraplegia

    Science.gov (United States)

    Denton, Kyle R.; Lei, Ling; Grenier, Jeremy; Rodionov, Vladimir; Blackstone, Craig; Li, Xue-Jun

    2013-01-01

    Human neuronal models of hereditary spastic paraplegias (HSP) that recapitulate disease-specific axonal pathology hold the key to understanding why certain axons degenerate in patients and to developing therapies. SPG4, the most common form of HSP, is caused by autosomal dominant mutations in the SPAST gene, which encodes the microtubule-severing ATPase spastin. Here, we have generated a human neuronal model of SPG4 by establishing induced pluripotent stem cells (iPSCs) from an SPG4 patient and differentiating these cells into telencephalic glutamatergic neurons. The SPG4 neurons displayed a significant increase in axonal swellings, which stained strongly for mitochondria and tau, indicating the accumulation of axonal transport cargoes. In addition, mitochondrial transport was decreased in SPG4 neurons, revealing that these patient iPSC-derived neurons recapitulate disease-specific axonal phenotypes. Interestingly, spastin protein levels were significantly decreased in SPG4 neurons, supporting a haploinsufficiency mechanism. Furthermore, cortical neurons derived from spastin-knockdown human embryonic stem cells (hESCs) exhibited similar axonal swellings, confirming that the axonal defects can be caused by loss of spastin function. These spastin-knockdown hESCs serve as an additional model for studying HSP. Finally, levels of stabilized acetylated-tubulin were significantly increased in SPG4 neurons. Vinblastine, a microtubule-destabilizing drug, rescued this axonal swelling phenotype in neurons derived from both SPG4 iPSCs and spastin-knockdown hESCs. Thus, this study demonstrates the successful establishment of human pluripotent stem cell-based neuronal models of SPG4, which will be valuable for dissecting the pathogenic cellular mechanisms and screening compounds to rescue the axonal degeneration in HSP. PMID:24123785

  1. Tight junctions and human diseases.

    Science.gov (United States)

    Sawada, Norimasa; Murata, Masaki; Kikuchi, Keisuke; Osanai, Makoto; Tobioka, Hirotoshi; Kojima, Takashi; Chiba, Hideki

    2003-09-01

    Tight junctions are intercellular junctions adjacent to the apical end of the lateral membrane surface. They have two functions, the barrier (or gate) function and the fence function. The barrier function of tight junctions regulates the passage of ions, water, and various macromolecules, even of cancer cells, through paracellular spaces. The barrier function is thus relevant to edema, jaundice, diarrhea, and blood-borne metastasis. On the other hand, the fence function maintains cell polarity. In other words, tight junctions work as a fence to prevent intermixing of molecules in the apical membrane with those in the lateral membrane. This function is deeply involved in cancer cell biology, in terms of loss of cell polarity. Of the proteins comprising tight junctions, integral membrane proteins occludin, claudins, and JAMs have been recently discovered. Of these molecules, claudins are exclusively responsible for the formation of tight-junction strands and are connected with the actin cytoskeleton mediated by ZO-1. Thus, both functions of tight junctions are dependent on the integrity of the actin cytoskeleton as well as ATP. Mutations in the claudin14 and the claudin16 genes result in hereditary deafness and hereditary hypomagnesemia, respectively. Some pathogenic bacteria and viruses target and affect the tight-junction function, leading to diseases. In this review, the relationship between tight junctions and human diseases is summarized.

  2. Molecular Pathology of Human Prion Diseases

    Directory of Open Access Journals (Sweden)

    2009-03-01

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

  3. [Adolescents' knowledge and behavior on sexuality, infectious transmitted diseases, and human papillomavirus vaccination: results of a survey in a French high school].

    Science.gov (United States)

    Grondin, C; Duron, S; Robin, F; Verret, C; Imbert, P

    2013-08-01

    Teenager sexuality is a public health issue. In teenagers attending a high school, we assessed their knowledge and behavior on sexuality, infectious transmitted diseases, human papilloma virus (HPV) vaccination, and cervical cancer. Then in girls, we estimated the anti-HPV vaccination coverage and focused on factors associated with poor knowledge of these topics. This was a knowledge, attitudes, and practices cross-sectional study conducted at the beginning of the 2010-2011 school year in the Saint-Cyr military high school, using an anonymous self-administered questionnaire. Among 669 adolescents (M/F sex-ratio, 2.3; mean age, 17 years [IC 95%, 15-20]), 40% had already had sex and 92% had used contraception. Boys and girls had a poor level of knowledge on infectious transmitted diseases. Regarding knowledge on HPV and cervical cancer, a better level was significantly associated with female gender (P=10(-4)). In multivariate analysis, male gender, age under 18 years, lack of dialogue with parents on these subjects, low socioeconomic status of parents, and absence of health education were significantly associated with poor knowledge on these topics. These data should help healthcare providers better target access and content of sexual health education training. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  4. Humanized Mouse Model of Ebola Virus Disease Mimics the Immune Responses in Human Disease.

    Science.gov (United States)

    Bird, Brian H; Spengler, Jessica R; Chakrabarti, Ayan K; Khristova, Marina L; Sealy, Tara K; Coleman-McCray, JoAnn D; Martin, Brock E; Dodd, Kimberly A; Goldsmith, Cynthia S; Sanders, Jeanine; Zaki, Sherif R; Nichol, Stuart T; Spiropoulou, Christina F

    2016-03-01

    Animal models recapitulating human Ebola virus disease (EVD) are critical for insights into virus pathogenesis. Ebola virus (EBOV) isolates derived directly from human specimens do not, without adaptation, cause disease in immunocompetent adult rodents. Here, we describe EVD in mice engrafted with human immune cells (hu-BLT). hu-BLT mice developed EVD following wild-type EBOV infection. Infection with high-dose EBOV resulted in rapid, lethal EVD with high viral loads, alterations in key human antiviral immune cytokines and chemokines, and severe histopathologic findings similar to those shown in the limited human postmortem data available. A dose- and donor-dependent clinical course was observed in hu-BLT mice infected with lower doses of either Mayinga (1976) or Makona (2014) isolates derived from human EBOV cases. Engraftment of the human cellular immune system appeared to be essential for the observed virulence, as nonengrafted mice did not support productive EBOV replication or develop lethal disease. hu-BLT mice offer a unique model for investigating the human immune response in EVD and an alternative animal model for EVD pathogenesis studies and therapeutic screening. Published by Oxford University Press for the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  5. Genomic uracil and human disease

    DEFF Research Database (Denmark)

    Hagen, Lars; Pena Diaz, Javier; Kavli, Bodil

    2006-01-01

    Uracil is present in small amounts in DNA due to spontaneous deamination of cytosine and incorporation of dUMP during replication. While deamination generates mutagenic U:G mismatches, incorporated dUMP results in U:A pairs that are not directly mutagenic, but may be cytotoxic. In most cells, mut...... retroviral infections. Ung(-/-) mice have a similar phenotype and develop B-cell lymphomas late in life. However, there is no evidence indicating that UNG deficiency causes lymphomas in humans....

  6. Mitochondrial Fusion Proteins and Human Diseases

    Directory of Open Access Journals (Sweden)

    Michela Ranieri

    2013-01-01

    Full Text Available Mitochondria are highly dynamic, complex organelles that continuously alter their shape, ranging between two opposite processes, fission and fusion, in response to several stimuli and the metabolic demands of the cell. Alterations in mitochondrial dynamics due to mutations in proteins involved in the fusion-fission machinery represent an important pathogenic mechanism of human diseases. The most relevant proteins involved in the mitochondrial fusion process are three GTPase dynamin-like proteins: mitofusin 1 (MFN1 and 2 (MFN2, located in the outer mitochondrial membrane, and optic atrophy protein 1 (OPA1, in the inner membrane. An expanding number of degenerative disorders are associated with mutations in the genes encoding MFN2 and OPA1, including Charcot-Marie-Tooth disease type 2A and autosomal dominant optic atrophy. While these disorders can still be considered rare, defective mitochondrial dynamics seem to play a significant role in the molecular and cellular pathogenesis of more common neurodegenerative diseases, for example, Alzheimer’s and Parkinson’s diseases. This review provides an overview of the basic molecular mechanisms involved in mitochondrial fusion and focuses on the alteration in mitochondrial DNA amount resulting from impairment of mitochondrial dynamics. We also review the literature describing the main disorders associated with the disruption of mitochondrial fusion.

  7. Animal models for human genetic diseases

    African Journals Online (AJOL)

    Sharif Sons

    The study of human genetic diseases can be greatly aided by animal models because of their similarity .... and gene targeting in embryonic stem cells) has been a powerful tool in .... endonucleases that are designed to make a doublestrand.

  8. Roentgenosemiotics and diagnosis of human diseases

    International Nuclear Information System (INIS)

    Mikhajlov, A.N.

    1989-01-01

    Modern concepts concerning roentgenologic semiotics, diagnosis of almost all the human diseases as well as the features of roentgenologic examintion of organs and systems are described. Roentgenologic symptoms and syndroms are systematized and standardized by anatomy branches. 48 refs

  9. Protein Misfolding and Human Disease

    DEFF Research Database (Denmark)

    Gregersen, Niels; Bross, Peter Gerd; Vang, Søren

    2006-01-01

    phenylketonuria, Parkinson's disease, α-1-antitrypsin deficiency, familial neurohypophyseal diabetes insipidus, and short-chain acyl-CoA dehydrogenase deficiency. Despite the differences, an emerging paradigm suggests that the cellular effects of protein misfolding provide a common framework that may contribute...

  10. Physiochemical basis of human degenerative disease.

    Science.gov (United States)

    Zeliger, Harold I; Lipinski, Boguslaw

    2015-03-01

    The onset of human degenerative diseases in humans, including type 2 diabetes, cardiovascular disease, neurological disorders, neurodevelopmental disease and neurodegenerative disease has been shown to be related to exposures to persistent organic pollutants, including polychlorinated biphenyls, chlorinated pesticides, polybrominated diphenyl ethers and others, as well as to polynuclear aromatic hydrocarbons, phthalates, bisphenol-A and other aromatic lipophilic species. The onset of these diseases has also been related to exposures to transition metal ions. A physiochemical mechanism for the onset of degenerative environmental disease dependent upon exposure to a combination of lipophilic aromatic hydrocarbons and transition metal ions is proposed here. The findings reported here also, for the first time, explain why aromatic hydrocarbons exhibit greater toxicity than aliphatic hydrocarbons of equal carbon numbers.

  11. Physiochemical basis of human degenerative disease

    Directory of Open Access Journals (Sweden)

    Zeliger Harold I.

    2015-03-01

    Full Text Available The onset of human degenerative diseases in humans, including type 2 diabetes, cardiovascular disease, neurological disorders, neurodevelopmental disease and neurodegenerative disease has been shown to be related to exposures to persistent organic pollutants, including polychlorinated biphenyls, chlorinated pesticides, polybrominated diphenyl ethers and others, as well as to polynuclear aromatic hydrocarbons, phthalates, bisphenol-A and other aromatic lipophilic species. The onset of these diseases has also been related to exposures to transition metal ions. A physiochemical mechanism for the onset of degenerative environmental disease dependent upon exposure to a combination of lipophilic aromatic hydrocarbons and transition metal ions is proposed here. The findings reported here also, for the first time, explain why aromatic hydrocarbons exhibit greater toxicity than aliphatic hydrocarbons of equal carbon numbers.

  12. Human diseases associated with defective DNA repair

    International Nuclear Information System (INIS)

    Friedberg, E.C.; Ehmann, U.K.; Williams, J.I.

    1979-01-01

    The observations on xeroderma pigmentosum (XP) cells in culture were the first indications of defective DNA repair in association with human disease. Since then, a wealth of information on DNA repair in XP, and to a lesser extent in other diseases, has accumulated in the literature. Rather than clarifying the understanding of DNA repair mechanisms in normal cells and of defective DNA repair in human disease, the literature suggests an extraordinary complexity of both of the phenomena. In this review a number of discrete human diseases are considered separately. An attempt was made to systematically describe the pertinent clinical features and cellular and biochemical defects in these diseases, with an emphasis on defects in DNA metabolism, particularly DNA repair. Wherever possible observations have been correlated and unifying hypotheses presented concerning the nature of the basic defect(s) in these diseases. Discussions of the following diseases are presented: XP, ataxia telangiectasia; Fanconi's anemia; Hutchinson-Gilford progeria syndrome; Bloom's syndrome, Cockayne's syndrome; Down's syndrome; retinoblastoma; chronic lymphocytic leukemia; and other miscellaneous human diseases with possble DNA repair defects

  13. Global biogeography of human infectious diseases.

    Science.gov (United States)

    Murray, Kris A; Preston, Nicholas; Allen, Toph; Zambrana-Torrelio, Carlos; Hosseini, Parviez R; Daszak, Peter

    2015-10-13

    The distributions of most infectious agents causing disease in humans are poorly resolved or unknown. However, poorly known and unknown agents contribute to the global burden of disease and will underlie many future disease risks. Existing patterns of infectious disease co-occurrence could thus play a critical role in resolving or anticipating current and future disease threats. We analyzed the global occurrence patterns of 187 human infectious diseases across 225 countries and seven epidemiological classes (human-specific, zoonotic, vector-borne, non-vector-borne, bacterial, viral, and parasitic) to show that human infectious diseases exhibit distinct spatial grouping patterns at a global scale. We demonstrate, using outbreaks of Ebola virus as a test case, that this spatial structuring provides an untapped source of prior information that could be used to tighten the focus of a range of health-related research and management activities at early stages or in data-poor settings, including disease surveillance, outbreak responses, or optimizing pathogen discovery. In examining the correlates of these spatial patterns, among a range of geographic, epidemiological, environmental, and social factors, mammalian biodiversity was the strongest predictor of infectious disease co-occurrence overall and for six of the seven disease classes examined, giving rise to a striking congruence between global pathogeographic and "Wallacean" zoogeographic patterns. This clear biogeographic signal suggests that infectious disease assemblages remain fundamentally constrained in their distributions by ecological barriers to dispersal or establishment, despite the homogenizing forces of globalization. Pathogeography thus provides an overarching context in which other factors promoting infectious disease emergence and spread are set.

  14. Parkinson's disease as a result of aging

    OpenAIRE

    Rodriguez, Manuel; Rodriguez-Sabate, Clara; Morales, Ingrid; Sanchez, Alberto; Sabate, Magdalena

    2015-01-01

    It is generally considered that Parkinson's disease is induced by specific agents that degenerate a clearly defined population of dopaminergic neurons. Data commented in this review suggest that this assumption is not as clear as is often thought and that aging may be critical for Parkinson's disease. Neurons degenerating in Parkinson's disease also degenerate in normal aging, and the different agents involved in the etiology of this illness are also involved in aging. Senescence is a wider p...

  15. Melatonin and human mitochondrial diseases

    Directory of Open Access Journals (Sweden)

    Reza Sharafati-Chaleshtori

    2017-01-01

    Full Text Available Mitochondrial dysfunction is one of the main causative factors in a wide variety of complications such as neurodegenerative disorders, ischemia/reperfusion, aging process, and septic shock. Decrease in respiratory complex activity, increase in free radical production, increase in mitochondrial synthase activity, increase in nitric oxide production, and impair in electron transport system and/or mitochondrial permeability are considered as the main factors responsible for mitochondrial dysfunction. Melatonin, the pineal gland hormone, is selectively taken up by mitochondria and acts as a powerful antioxidant, regulating the mitochondrial bioenergetic function. Melatonin increases the permeability of membranes and is the stimulator of antioxidant enzymes including superoxide dismutase, glutathione peroxidase, glutathione reductase, and catalase. It also acts as an inhibitor of lipoxygenase. Melatonin can cause resistance to oxidation damage by fixing the microsomal membranes. Melatonin has been shown to retard aging and inhibit neurodegenerative disorders, ischemia/reperfusion, septic shock, diabetes, cancer, and other complications related to oxidative stress. The purpose of the current study, other than introducing melatonin, was to present the recent findings on clinical effects in diseases related to mitochondrial dysfunction including diabetes, cancer, gastrointestinal diseases, and diseases related to brain function.

  16. Plebotomine Vectors of Human Disease.

    Science.gov (United States)

    1984-12-30

    incriminated as vectors of Leishmania mexicana among rodents and/or humans from Mexico to the Amazon Basin. Specimens referable to L. olmeca olmeca...in the format similar to that given for the species group baityi included in this report. Additional phlebotomines from Tanzania, Brazil, Peru and...species group baityi included in this report. Additional phlebotomines from Tanzania, Brazil, Peru and Venezuela were slide-mounted and added to the

  17. Glutathione dysregulation and the etiology and progression of human diseases.

    NARCIS (Netherlands)

    Ballatori, N.; Krance, S.M.; Notenboom, S.; Shi, S.; Tieu, K.; Hammond, C.L.

    2009-01-01

    Glutathione (GSH) plays an important role in a multitude of cellular processes, including cell differentiation, proliferation, and apoptosis, and as a result, disturbances in GSH homeostasis are implicated in the etiology and/or progression of a number of human diseases, including cancer, diseases

  18. [Diseases transmitted through water for human consumption].

    Science.gov (United States)

    Franco, E; Dentamaro, M

    2003-01-01

    The water for human consumption maintains a biological risk and can transmit diseases. The classical waterborne and the presently frequent diseases caused by protozoi Giardia and Cryptosporidium are considered and Arcobacter butzleri, a new waterborne pathogen, is described. Many measures have been adopted by institutions to ensure the quality of the drinking water. Managers and public health operators is working in order to verify the efficiency of more suitable indicators for its monitoring.

  19. Modeling human disease using organotypic cultures

    DEFF Research Database (Denmark)

    Schweiger, Pawel J; Jensen, Kim B

    2016-01-01

    animal models and in vitro cell culture systems. However, it has been exceedingly difficult to model disease at the tissue level. Since recently, the gap between cell line studies and in vivo modeling has been narrowing thanks to progress in biomaterials and stem cell research. Development of reliable 3D...... culture systems has enabled a rapid expansion of sophisticated in vitro models. Here we focus on some of the latest advances and future perspectives in 3D organoids for human disease modeling....

  20. Mouse Chromosome Engineering for Modeling Human Disease

    OpenAIRE

    van der Weyden, Louise; Bradley, Allan

    2006-01-01

    Chromosomal rearrangements occur frequently in humans and can be disease-associated or phenotypically neutral. Recent technological advances have led to the discovery of copy-number changes previously undetected by cytogenetic techniques. To understand the genetic consequences of such genomic changes, these mutations need to be modeled in experimentally tractable systems. The mouse is an excellent organism for this analysis because of its biological and genetic similarity to humans, and the e...

  1. Immunotherapy of Human Papilloma Virus Induced Disease

    Science.gov (United States)

    van der Burg, Sjoerd H

    2012-01-01

    Immunotherapy is the generic name for treatment modalities aiming to reinforce the immune system against diseases in which the immune system plays a role. The design of an optimal immunotherapeutic treatment against chronic viruses and associated diseases requires a detailed understanding of the interactions between the target virus and its host, in order to define the specific strategies that may have the best chance to deliver success at each stage of disease. Recently, a first series of successes was reported for the immunotherapy of Human Papilloma Virus (HPV)-induced premalignant diseases but there is definitely room for improvement. Here I discuss a number of topics that in my opinion require more study as the answers to these questions allows us to better understand the underlying mechanisms of disease and as such to tailor treatment. PMID:23341861

  2. Reduced penetrance in human inherited disease

    African Journals Online (AJOL)

    Rabah M. Shawky

    2014-01-31

    Jan 31, 2014 ... tant role in cellular senescence, tumorigenesis and in several diseases including type ... between epigenetic DNA modifications and human life span has also been shown .... penetrance mutation that is age dependent especially when compared with the ..... on healthy aging and longevity. Immunity Aging ...

  3. Primatology. Human diseases threaten great apes.

    Science.gov (United States)

    Ferber, D

    2000-08-25

    Researchers are uncovering disturbing evidence that scientists and tourists are infecting wild primates with human pathogens. In response, ape specialists, including the American Society of Primatologists, are now calling for stricter health standards for researchers and tourists. They are also urging researchers to learn how to diagnose disease in their study animals.

  4. Emerging arboviral human diseases in Southern Europe.

    Science.gov (United States)

    Papa, Anna

    2017-08-01

    Southern Europe is characterized by unique landscape and climate which attract tourists, but also arthropod vectors, some of them carrying pathogens. Among several arboviral diseases that emerged in the region during the last decade, West Nile fever accounted for high number of human cases and fatalities, while Crimean-Congo hemorrhagic fever expanded its geographic distribution, and is considered as a real threat for Europe. Viruses evolve rapidly and acquire mutations making themselves stronger and naive populations more vulnerable. In an effort to tackle efficiently the emerging arboviral diseases, preparedness and strategic surveillance are needed for the early detection of the pathogen and containment and mitigation of probable outbreaks. In this review, the main human arboviral diseases that emerged in Southern Europe are described. © 2017 Wiley Periodicals, Inc.

  5. DEGAS: de novo discovery of dysregulated pathways in human diseases.

    Directory of Open Access Journals (Sweden)

    Igor Ulitsky

    Full Text Available BACKGROUND: Molecular studies of the human disease transcriptome typically involve a search for genes whose expression is significantly dysregulated in sick individuals compared to healthy controls. Recent studies have found that only a small number of the genes in human disease-related pathways show consistent dysregulation in sick individuals. However, those studies found that some pathway genes are affected in most sick individuals, but genes can differ among individuals. While a pathway is usually defined as a set of genes known to share a specific function, pathway boundaries are frequently difficult to assign, and methods that rely on such definition cannot discover novel pathways. Protein interaction networks can potentially be used to overcome these problems. METHODOLOGY/PRINCIPAL FINDINGS: We present DEGAS (DysrEgulated Gene set Analysis via Subnetworks, a method for identifying connected gene subnetworks significantly enriched for genes that are dysregulated in specimens of a disease. We applied DEGAS to seven human diseases and obtained statistically significant results that appear to home in on compact pathways enriched with hallmarks of the diseases. In Parkinson's disease, we provide novel evidence for involvement of mRNA splicing, cell proliferation, and the 14-3-3 complex in the disease progression. DEGAS is available as part of the MATISSE software package (http://acgt.cs.tau.ac.il/matisse. CONCLUSIONS/SIGNIFICANCE: The subnetworks identified by DEGAS can provide a signature of the disease potentially useful for diagnosis, pinpoint possible pathways affected by the disease, and suggest targets for drug intervention.

  6. Resolution of Disease Phenotypes Resulting from Multilocus Genomic Variation.

    Science.gov (United States)

    Posey, Jennifer E; Harel, Tamar; Liu, Pengfei; Rosenfeld, Jill A; James, Regis A; Coban Akdemir, Zeynep H; Walkiewicz, Magdalena; Bi, Weimin; Xiao, Rui; Ding, Yan; Xia, Fan; Beaudet, Arthur L; Muzny, Donna M; Gibbs, Richard A; Boerwinkle, Eric; Eng, Christine M; Sutton, V Reid; Shaw, Chad A; Plon, Sharon E; Yang, Yaping; Lupski, James R

    2017-01-05

    Whole-exome sequencing can provide insight into the relationship between observed clinical phenotypes and underlying genotypes. We conducted a retrospective analysis of data from a series of 7374 consecutive unrelated patients who had been referred to a clinical diagnostic laboratory for whole-exome sequencing; our goal was to determine the frequency and clinical characteristics of patients for whom more than one molecular diagnosis was reported. The phenotypic similarity between molecularly diagnosed pairs of diseases was calculated with the use of terms from the Human Phenotype Ontology. A molecular diagnosis was rendered for 2076 of 7374 patients (28.2%); among these patients, 101 (4.9%) had diagnoses that involved two or more disease loci. We also analyzed parental samples, when available, and found that de novo variants accounted for 67.8% (61 of 90) of pathogenic variants in autosomal dominant disease genes and 51.7% (15 of 29) of pathogenic variants in X-linked disease genes; both variants were de novo in 44.7% (17 of 38) of patients with two monoallelic variants. Causal copy-number variants were found in 12 patients (11.9%) with multiple diagnoses. Phenotypic similarity scores were significantly lower among patients in whom the phenotype resulted from two distinct mendelian disorders that affected different organ systems (50 patients) than among patients with disorders that had overlapping phenotypic features (30 patients) (median score, 0.21 vs. 0.36; P=1.77×10 -7 ). In our study, we found multiple molecular diagnoses in 4.9% of cases in which whole-exome sequencing was informative. Our results show that structured clinical ontologies can be used to determine the degree of overlap between two mendelian diseases in the same patient; the diseases can be distinct or overlapping. Distinct disease phenotypes affect different organ systems, whereas overlapping disease phenotypes are more likely to be caused by two genes encoding proteins that interact within

  7. Human endogenous retroviruses in neurologic disease.

    Science.gov (United States)

    Christensen, Tove

    2016-01-01

    Endogenous retroviruses are pathogenic - in other species than the human. Disease associations for Human Endogenous RetroViruses (HERVs) are emerging, but so far an unequivocal pathogenetic cause-effect relationship has not been established. A role for HERVs has been proposed in neurological and neuropsychiatric diseases as diverse as multiple sclerosis (MS) and schizophrenia (SCZ). Particularly for MS, many aspects of the activation and involvement of specific HERV families (HERV-H/F and HERV-W/MSRV) have been reported, both for cells in the circulation and in the central nervous system. Notably envelope genes and their gene products (Envs) appear strongly associated with the disease. For SCZ, for ALS, and for HIV-associated dementia (HAD), indications are accumulating for involvement of the HERV-K family, and also HERV-H/F and/or HERV-W. Activation is reasonably a prerequisite for causality as most HERV sequences remain quiescent in non-pathological conditions, so the importance of regulatory pathways and epigenetics involved in regulating HERV activation, derepression, and also involvement of retroviral restriction factors, is emerging. HERV-directed antiretrovirals have potential as novel therapeutic paradigms in neurologic disease, particularly in MS. The possible protective or ameliorative effects of antiretroviral therapy in MS are substantiated by reports that treatment of HIV infection may be associated with a significantly decreased risk of MS. Further studies of HERVs, their role in neurologic diseases, and their potential as therapeutic targets are essential. © 2016 APMIS. Published by John Wiley & Sons Ltd.

  8. Circular stapled anopexy for haemorrhoidal disease: results.

    Science.gov (United States)

    Lehur, P A; Gravié, J F; Meurette, G

    2001-11-01

    Stapled anopexy is a new approach for haemorrhoids requiring surgical treatment. This study reviews the available information concerning the present results of this procedure. Medline and hand search of the literature was conducted to identify available information on the procedure, with a special interest for the on-going or published randomized clinical trials. The advantages of the stapled approach of haemorrhoids were analyzed in the different areas of concern, including postoperative pain reduction, length of hospital stay and sick-leave, postoperative wound care and type and rate of complications. Continence status, symptom cure and patient satisfaction following stapled anopexy are also reported. Stapled anopexy is probably less painful than conventional haemorrhoidectomy. Other advantages in the short term result from this new approach. Long term efficacy of the procedure is still unknown.

  9. Wildlife disease prevalence in human-modified landscapes.

    Science.gov (United States)

    Brearley, Grant; Rhodes, Jonathan; Bradley, Adrian; Baxter, Greg; Seabrook, Leonie; Lunney, Daniel; Liu, Yan; McAlpine, Clive

    2013-05-01

    Human-induced landscape change associated with habitat loss and fragmentation places wildlife populations at risk. One issue in these landscapes is a change in the prevalence of disease which may result in increased mortality and reduced fecundity. Our understanding of the influence of habitat loss and fragmentation on the prevalence of wildlife diseases is still in its infancy. What is evident is that changes in disease prevalence as a result of human-induced landscape modification are highly variable. The importance of infectious diseases for the conservation of wildlife will increase as the amount and quality of suitable habitat decreases due to human land-use pressures. We review the experimental and observational literature of the influence of human-induced landscape change on wildlife disease prevalence, and discuss disease transmission types and host responses as mechanisms that are likely to determine the extent of change in disease prevalence. It is likely that transmission dynamics will be the key process in determining a pathogen's impact on a host population, while the host response may ultimately determine the extent of disease prevalence. Finally, we conceptualize mechanisms and identify future research directions to increase our understanding of the relationship between human-modified landscapes and wildlife disease prevalence. This review highlights that there are rarely consistent relationships between wildlife diseases and human-modified landscapes. In addition, variation is evident between transmission types and landscape types, with the greatest positive influence on disease prevalence being in urban landscapes and directly transmitted disease systems. While we have a limited understanding of the potential influence of habitat loss and fragmentation on wildlife disease, there are a number of important areas to address in future research, particularly to account for the variability in increased and decreased disease prevalence. Previous studies

  10. Molecular biology of human muscle disease

    Energy Technology Data Exchange (ETDEWEB)

    Dunne, P.W.; Epstein, H.F. (Baylor Coll. of Medicine, Houston, TX (United States))

    1991-01-01

    The molecular revolution that is transforming the entire biomedical field has had far-reaching impact in its application to inherited human muscle disease. The gene for Duchenne muscular dystrophy was one of the first cloned without knowledge of the defective protein product. This success was based upon the availability of key chromosomal aberrations that provided molecular landmarks for the disease locus. Subsequent discoveries regarding the mode of expression for this gene, the structure and localization of its protein product dystrophin, and molecular diagnosis of affected and carrier individuals constitute a paradigm for investigation of human genetics. Finding the gene for myotonic muscular dystrophy is requiring the brute force approach of cloning several million bases of DNA, identifying expressed sequences, and characterizing candidate genes. The gene that causes hypertrophic cardiomyopathy has been found serendipitously to be one of the genetic markers on chromosome 14, the {beta} myosin heavy chain.

  11. The nuclear envelopathies and human diseases

    Directory of Open Access Journals (Sweden)

    Jeang Kuan-Teh

    2009-10-01

    Full Text Available Abstract The nuclear envelope (NE consists of two membrane layers that segregate the nuclear from the cytoplasmic contents. Recent progress in our understanding of nuclear-lamina associated diseases has revealed intriguing connections between the envelope components and nuclear processes. Here, we review the functions of the nuclear envelope in chromosome organization, gene expression, DNA repair and cell cycle progression, and correlate deficiencies in envelope function with human pathologies.

  12. Results of complex treatment of Hodgkin's disease

    International Nuclear Information System (INIS)

    Kolygin, B.A.; Lebedev, S.V.; Borodina, A.F.; Kochurova, N.V.; Malinin, A.P.; Safonova, S.A.; Punanov, Yu.A.

    2000-01-01

    The evaluation of remote results of the complex treatment (polychemotherapy plus radiotherapy) for identification of the forecasting factor which may be applied, by stratification into the risk groups, is carried out. The group of 334 children up to 15 years with lymphogranulomatosis, subjected to not less than 2 cycles of inductive polychemotherapy and consolidating radiotherapy, is analyzed. The irradiation was conducted at the radiotherapeutic devices ROCUS LUE-25 and LUEV-15 M1. The complete remission after the treatment program was fixed by 95.1% of the patients the partial remission-by 6.3%; no effect was noted by 0.6% of the patients. Actuarial 10-year survival constituted 85.9%, the frequency of nonrelapsing flow - 74.3% [ru

  13. The role of chemerin in human disease

    Directory of Open Access Journals (Sweden)

    Magdalena Stojek

    2017-02-01

    Full Text Available Adipose tissue is not merely a storage depot of triacylglycerols but also a major endocrine organ. Its cells, including adipocytes, synthesize and secrete a range of biologically active molecules termed adipokines. Adipokines that display the properties of cytokines are often called adipocytokines. In recent years there has been increasing interest in a new adipokine called chemerin. Chemerin is a protein synthesized mostly by the adipose tissue and the liver as inactive pre-pro-chemerin. After the intracellular hydrolytic cutting off of the 20-amino-acid N-terminal polypeptide, it is secreted into the bloodstream as inactive pro-chemerin. Biologically active chemerin is then derived from pro-chemerin after cleavage of the C-terminal fragment by serum proteases involved in inflammation, coagulation and fibrinolysis. Proteolytic cleavage leads to formation of several chemerin-derived peptides, both biologically active (often with opposing functions and inactive.Within the last decade, there has been a growing number of publications regarding the role of chemerin in human disease. It seems to be implicated in the inflammatory response, metabolic syndrome, cardiovascular disease and alimentary tract disorders. The article presents the most recent information on the role of chemerin in human disease, and specifically alimentary tract disorders. The available evidence suggests that chemerin is an important link between adipose tissue mass, metabolic processes, the immune system and inflammation, and therefore plays a major role in human pathophysiology.

  14. Human Reliability Data Bank: evaluation results

    International Nuclear Information System (INIS)

    Comer, M.K.; Donovan, M.D.; Gaddy, C.D.

    1985-01-01

    The US Nuclear Regulatory Commission (NRC), Sandia National Laboratories (SNL), and General Physics Corporation are conducting a research program to determine the practicality, acceptability, and usefulness of a Human Reliability Data Bank for nuclear power industry probabilistic risk assessment (PRA). As part of this program, a survey was conducted of existing human reliability data banks from other industries, and a detailed concept of a Data Bank for the nuclear industry was developed. Subsequently, a detailed specification for implementing the Data Bank was developed. An evaluation of this specification was conducted and is described in this report. The evaluation tested data treatment, storage, and retrieval using the Data Bank structure, as modified from NUREG/CR-2744, and detailed procedures for data processing and retrieval, developed prior to this evaluation and documented in the test specification. The evaluation consisted of an Operability Demonstration and Evaluation of the data processing procedures, a Data Retrieval Demonstration and Evaluation, a Retrospective Analysis that included a survey of organizations currently operating data banks for the nuclear power industry, and an Internal Analysis of the current Data Bank System

  15. Insect Peptides - Perspectives in Human Diseases Treatment.

    Science.gov (United States)

    Chowanski, Szymon; Adamski, Zbigniew; Lubawy, Jan; Marciniak, Pawel; Pacholska-Bogalska, Joanna; Slocinska, Malgorzata; Spochacz, Marta; Szymczak, Monika; Urbanski, Arkadiusz; Walkowiak-Nowicka, Karolina; Rosinski, Grzegorz

    2017-01-01

    Insects are the largest and the most widely distributed group of animals in the world. Their diversity is a source of incredible variety of different mechanisms of life processes regulation. There are many agents that regulate immunology, reproduction, growth and development or metabolism. Hence, it seems that insects may be a source of numerous substances useful in human diseases treatment. Especially important in the regulation of insect physiology are peptides, like neuropeptides, peptide hormones or antimicrobial peptides. There are two main aspects where they can be helpful, 1) Peptides isolated from insects may become potential drugs in therapy of different diseases, 2) A lot of insect peptide hormones show structural or functional homology to mammalian peptide hormones and the comparative studies may give a new look on human disorders. In our review we focused on three group of insect derived peptides: 1) immune-active peptides, 2) peptide hormones and 3) peptides present in venoms. In our review we try to show the considerable potential of insect peptides in searching for new solutions for mammalian diseases treatment. We summarise the knowledge about properties of insect peptides against different virulent agents, anti-inflammatory or anti-nociceptive properties as well as compare insect and mammalian/vertebrate peptide endocrine system to indicate usefulness of knowledge about insect peptide hormones in drug design. The field of possible using of insect delivered peptide to therapy of various human diseases is still not sufficiently explored. Undoubtedly, more attention should be paid to insects due to searching new drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Human Genome Sequencing in Health and Disease

    Science.gov (United States)

    Gonzaga-Jauregui, Claudia; Lupski, James R.; Gibbs, Richard A.

    2013-01-01

    Following the “finished,” euchromatic, haploid human reference genome sequence, the rapid development of novel, faster, and cheaper sequencing technologies is making possible the era of personalized human genomics. Personal diploid human genome sequences have been generated, and each has contributed to our better understanding of variation in the human genome. We have consequently begun to appreciate the vastness of individual genetic variation from single nucleotide to structural variants. Translation of genome-scale variation into medically useful information is, however, in its infancy. This review summarizes the initial steps undertaken in clinical implementation of personal genome information, and describes the application of whole-genome and exome sequencing to identify the cause of genetic diseases and to suggest adjuvant therapies. Better analysis tools and a deeper understanding of the biology of our genome are necessary in order to decipher, interpret, and optimize clinical utility of what the variation in the human genome can teach us. Personal genome sequencing may eventually become an instrument of common medical practice, providing information that assists in the formulation of a differential diagnosis. We outline herein some of the remaining challenges. PMID:22248320

  17. Remote results of pathogenetic therapy of cystic breast disease

    Directory of Open Access Journals (Sweden)

    G. Kh. Khanafiev

    2014-01-01

    Full Text Available With 2000 year of pathogenetic treatment of fibrocystic breast disease preventing cystadenocarcinoma has led to positive results. In 2000–2001 years the percentage devoted to oncological indications for surgical treatment of patients with fibrocystic disease of the breast, was less than 3 % of the total number of operated on for various diseases of the breast.

  18. Finding aroma clues in the human breath to diagnose diseases

    Science.gov (United States)

    A. Dan Wilson

    2016-01-01

    History of human odor analysis in disease diagnosis The use of the sense of smell as an indicator of human disease probably originated with Hippocrates (circa 400 BC). Early medical practitioners recognized that the presence of human diseases changed the odors released from the body and breath. Physicians once relied heavily on their sense of smell to provide useful...

  19. Human prion diseases in the United States.

    Directory of Open Access Journals (Sweden)

    Robert C Holman

    Full Text Available BACKGROUND: Prion diseases are a family of rare, progressive, neurodegenerative disorders that affect humans and animals. The most common form of human prion disease, Creutzfeldt-Jakob disease (CJD, occurs worldwide. Variant CJD (vCJD, a recently emerged human prion disease, is a zoonotic foodborne disorder that occurs almost exclusively in countries with outbreaks of bovine spongiform encephalopathy. This study describes the occurrence and epidemiology of CJD and vCJD in the United States. METHODOLOGY/PRINCIPAL FINDINGS: Analysis of CJD and vCJD deaths using death certificates of US residents for 1979-2006, and those identified through other surveillance mechanisms during 1996-2008. Since CJD is invariably fatal and illness duration is usually less than one year, the CJD incidence is estimated as the death rate. During 1979 through 2006, an estimated 6,917 deaths with CJD as a cause of death were reported in the United States, an annual average of approximately 247 deaths (range 172-304 deaths. The average annual age-adjusted incidence for CJD was 0.97 per 1,000,000 persons. Most (61.8% of the CJD deaths occurred among persons >or=65 years of age for an average annual incidence of 4.8 per 1,000,000 persons in this population. Most deaths were among whites (94.6%; the age-adjusted incidence for whites was 2.7 times higher than that for blacks (1.04 and 0.40, respectively. Three patients who died since 2004 were reported with vCJD; epidemiologic evidence indicated that their infection was acquired outside of the United States. CONCLUSION/SIGNIFICANCE: Surveillance continues to show an annual CJD incidence rate of about 1 case per 1,000,000 persons and marked differences in CJD rates by age and race in the United States. Ongoing surveillance remains important for monitoring the stability of the CJD incidence rates, and detecting occurrences of vCJD and possibly other novel prion diseases in the United States.

  20. Human prion diseases: surgical lessons learned from iatrogenic prion transmission.

    Science.gov (United States)

    Bonda, David J; Manjila, Sunil; Mehndiratta, Prachi; Khan, Fahd; Miller, Benjamin R; Onwuzulike, Kaine; Puoti, Gianfranco; Cohen, Mark L; Schonberger, Lawrence B; Cali, Ignazio

    2016-07-01

    The human prion diseases, or transmissible spongiform encephalopathies, have captivated our imaginations since their discovery in the Fore linguistic group in Papua New Guinea in the 1950s. The mysterious and poorly understood "infectious protein" has become somewhat of a household name in many regions across the globe. From bovine spongiform encephalopathy (BSE), commonly identified as mad cow disease, to endocannibalism, media outlets have capitalized on these devastatingly fatal neurological conditions. Interestingly, since their discovery, there have been more than 492 incidents of iatrogenic transmission of prion diseases, largely resulting from prion-contaminated growth hormone and dura mater grafts. Although fewer than 9 cases of probable iatrogenic neurosurgical cases of Creutzfeldt-Jakob disease (CJD) have been reported worldwide, the likelihood of some missed cases and the potential for prion transmission by neurosurgery create considerable concern. Laboratory studies indicate that standard decontamination and sterilization procedures may be insufficient to completely remove infectivity from prion-contaminated instruments. In this unfortunate event, the instruments may transmit the prion disease to others. Much caution therefore should be taken in the absence of strong evidence against the presence of a prion disease in a neurosurgical patient. While the Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) have devised risk assessment and decontamination protocols for the prevention of iatrogenic transmission of the prion diseases, incidents of possible exposure to prions have unfortunately occurred in the United States. In this article, the authors outline the historical discoveries that led from kuru to the identification and isolation of the pathological prion proteins in addition to providing a brief description of human prion diseases and iatrogenic forms of CJD, a brief history of prion disease nosocomial transmission

  1. Glycogen Storage Disease Type Ia in Canines: A Model for Human Metabolic and Genetic Liver Disease

    OpenAIRE

    Specht, Andrew; Fiske, Laurie; Erger, Kirsten; Cossette, Travis; Verstegen, John; Campbell-Thompson, Martha; Struck, Maggie B.; Lee, Young Mok; Chou, Janice Y.; Byrne, Barry J.; Correia, Catherine E.; Mah, Cathryn S.; Weinstein, David A.; Conlon, Thomas J.

    2011-01-01

    A canine model of Glycogen storage disease type Ia (GSDIa) is described. Affected dogs are homozygous for a previously described M121I mutation resulting in a deficiency of glucose-6-phosphatase-α. Metabolic, clinicopathologic, pathologic, and clinical manifestations of GSDIa observed in this model are described and compared to those observed in humans. The canine model shows more complete recapitulation of the clinical manifestations seen in humans including “lactic acidosis”, larger size,...

  2. Leveraging human-centered design in chronic disease prevention.

    Science.gov (United States)

    Matheson, Gordon O; Pacione, Chris; Shultz, Rebecca K; Klügl, Martin

    2015-04-01

    Bridging the knowing-doing gap in the prevention of chronic disease requires deep appreciation and understanding of the complexities inherent in behavioral change. Strategies that have relied exclusively on the implementation of evidence-based data have not yielded the desired progress. The tools of human-centered design, used in conjunction with evidence-based data, hold much promise in providing an optimal approach for advancing disease prevention efforts. Directing the focus toward wide-scale education and application of human-centered design techniques among healthcare professionals will rapidly multiply their effective ability to bring the kind of substantial results in disease prevention that have eluded the healthcare industry for decades. This, in turn, would increase the likelihood of prevention by design. Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  3. Human endogenous retroviruses and chosen disease parameters in morphea

    Science.gov (United States)

    Dańczak-Pazdrowska, Aleksandra; Szramka-Pawlak, Beata; Żaba, Ryszard; Osmola-Mańkowska, Agnieszka; Silny, Wojciech

    2017-01-01

    Introduction Morphea (localized scleroderma) is a relatively rare disease characterized by excessive skin fibrosis. Human endogenous retroviruses (HERV) are largely distributed within the human genome with hundreds of thousands of elements. The HERV have been widely studied in autoimmune disorders, yet hardly ever assessed in diseases with a good prognosis such as morphea. Aim In this study we focus on the possible relations between the expression of chosen HERV and factors influencing the pathomechanism of the disease, such as age, sex, titres of anti-nuclear antibodies, as well as duration, activity, and severity of the disease (LoSSI index). Material and methods Real-time polymerase chain reaction (PCR) targeting six HERV sequences of interest were performed on samples derived from peripheral blood mononuclear cells (PBMC) and skin biopsies. Results In PBMC we found a statistically significant negative correlation between HERV-W env expression and LoSSI index (p = 0.01). Additionally, HERV-W env was downregulated in patients with the active form of morphea. In all other cases we found no correlation whatsoever nor statistically significant differences below the p = 0.05 threshold. Conclusions Morphea seems to be an autoimmune disease where the impact of HERV is not so apparent. It seems that probing many patients for the expression of just a few sequences is not as effective as previously expected. For initial studies of HERV in other diseases we recommend high throughput techniques such as HERV-dedicated DNA microarrays or massive parallel sequencing. PMID:28261031

  4. Human endogenous retroviruses and chosen disease parameters in morphea

    Directory of Open Access Journals (Sweden)

    Michał J. Kowalczyk

    2017-02-01

    Full Text Available Introduction: Morphea (localized scleroderma is a relatively rare disease characterized by excessive skin fibrosis. Human endogenous retroviruses (HERV are largely distributed within the human genome with hundreds of thousands of elements. The HERV have been widely studied in autoimmune disorders, yet hardly ever assessed in diseases with a good prognosis such as morphea. Aim: In this study we focus on the possible relations between the expression of chosen HERV and factors influencing the pathomechanism of the disease, such as age, sex, titres of anti-nuclear antibodies, as well as duration, activity, and severity of the disease (LoSSI index. Material and methods: Real-time polymerase chain reaction (PCR targeting six HERV sequences of interest were performed on samples derived from peripheral blood mononuclear cells (PBMC and skin biopsies. Results: In PBMC we found a statistically significant negative correlation between HERV-W env expression and LoSSI index (p = 0.01. Additionally, HERV-W env was downregulated in patients with the active form of morphea. In all other cases we found no correlation whatsoever nor statistically significant differences below the p = 0.05 threshold. Conclusions : Morphea seems to be an autoimmune disease where the impact of HERV is not so apparent. It seems that probing many patients for the expression of just a few sequences is not as effective as previously expected. For initial studies of HERV in other diseases we recommend high throughput techniques such as HERV-dedicated DNA microarrays or massive parallel sequencing.

  5. A framework for annotating human genome in disease context.

    Science.gov (United States)

    Xu, Wei; Wang, Huisong; Cheng, Wenqing; Fu, Dong; Xia, Tian; Kibbe, Warren A; Lin, Simon M

    2012-01-01

    Identification of gene-disease association is crucial to understanding disease mechanism. A rapid increase in biomedical literatures, led by advances of genome-scale technologies, poses challenge for manually-curated-based annotation databases to characterize gene-disease associations effectively and timely. We propose an automatic method-The Disease Ontology Annotation Framework (DOAF) to provide a comprehensive annotation of the human genome using the computable Disease Ontology (DO), the NCBO Annotator service and NCBI Gene Reference Into Function (GeneRIF). DOAF can keep the resulting knowledgebase current by periodically executing automatic pipeline to re-annotate the human genome using the latest DO and GeneRIF releases at any frequency such as daily or monthly. Further, DOAF provides a computable and programmable environment which enables large-scale and integrative analysis by working with external analytic software or online service platforms. A user-friendly web interface (doa.nubic.northwestern.edu) is implemented to allow users to efficiently query, download, and view disease annotations and the underlying evidences.

  6. Role of Carbamylated Biomolecules in Human Diseases.

    Science.gov (United States)

    Badar, Asim; Arif, Zarina; Alam, Khursheed

    2018-04-01

    Carbamylation (or carbamoylation) is a non-enzymatic modification of biomolecules mediated by cyanate, a dissociation product of urea. Proteins are more sensitive to carbamylation. Two major sites of carbamylation reaction are: N α -amino moiety of a protein N-terminus and the N ɛ -amino moiety of proteins' lysine residues. In kidney diseases, urea accumulates and the burden of carbamylation increases. This may lead to alteration in the structure and function of many important proteins relevant in maintenance of homeostasis. Carbamylated proteins namely, carbamylated-haemoglobin and carbamylated-low density lipoprotein (LDL) have been implicated in hypoxia and atherosclerosis, respectively. Furthermore, carbamylation of insulin, oxytocin, and erythropoietin have caused changes in the action of these hormones vis-à-vis the metabolic pathways they control. In this short review, authors have compiled the data on role of carbamylated proteins, enzymes, hormones, LDL, and so on, in human diseases. © 2018 IUBMB Life, 70(4):267-275, 2018. © 2018 International Union of Biochemistry and Molecular Biology.

  7. Disease-specific induced pluripotent stem cells: a platform for human disease modeling and drug discovery.

    Science.gov (United States)

    Jang, Jiho; Yoo, Jeong-Eun; Lee, Jeong-Ah; Lee, Dongjin R; Kim, Ji Young; Huh, Yong Jun; Kim, Dae-Sung; Park, Chul-Yong; Hwang, Dong-Youn; Kim, Han-Soo; Kang, Hoon-Chul; Kim, Dong-Wook

    2012-03-31

    The generation of disease-specific induced pluripotent stem cell (iPSC) lines from patients with incurable diseases is a promising approach for studying disease mechanisms and drug screening. Such innovation enables to obtain autologous cell sources in regenerative medicine. Herein, we report the generation and characterization of iPSCs from fibroblasts of patients with sporadic or familial diseases, including Parkinson's disease (PD), Alzheimer's disease (AD), juvenile-onset, type I diabetes mellitus (JDM), and Duchenne type muscular dystrophy (DMD), as well as from normal human fibroblasts (WT). As an example to modeling disease using disease-specific iPSCs, we also discuss the previously established childhood cerebral adrenoleukodystrophy (CCALD)- and adrenomyeloneuropathy (AMN)-iPSCs by our group. Through DNA fingerprinting analysis, the origins of generated disease-specific iPSC lines were identified. Each iPSC line exhibited an intense alkaline phosphatase activity, expression of pluripotent markers, and the potential to differentiate into all three embryonic germ layers: the ectoderm, endoderm, and mesoderm. Expression of endogenous pluripotent markers and downregulation of retrovirus-delivered transgenes [OCT4 (POU5F1), SOX2, KLF4, and c-MYC] were observed in the generated iPSCs. Collectively, our results demonstrated that disease-specific iPSC lines characteristically resembled hESC lines. Furthermore, we were able to differentiate PD-iPSCs, one of the disease-specific-iPSC lines we generated, into dopaminergic (DA) neurons, the cell type mostly affected by PD. These PD-specific DA neurons along with other examples of cell models derived from disease-specific iPSCs would provide a powerful platform for examining the pathophysiology of relevant diseases at the cellular and molecular levels and for developing new drugs and therapeutic regimens.

  8. Analogs of human genetic skin disease in domesticated animals

    Directory of Open Access Journals (Sweden)

    Justin Finch, MD

    2017-09-01

    The genetic skin diseases we will review are pigmentary mosaicism, piebaldism, albinism, Griscelli syndrome, ectodermal dysplasias, Waardenburg syndrome, and mucinosis in both humans and domesticated animals.

  9. A Novel Human Body Area Network for Brain Diseases Analysis.

    Science.gov (United States)

    Lin, Kai; Xu, Tianlang

    2016-10-01

    Development of wireless sensor and mobile communication technology provide an unprecedented opportunity for realizing smart and interactive healthcare systems. Designing such systems aims to remotely monitor the health and diagnose the diseases for users. In this paper, we design a novel human body area network for brain diseases analysis, which is named BABDA. Considering the brain is one of the most complex organs in the human body, the BABDA system provides four function modules to ensure the high quality of the analysis result, which includes initial data collection, data correction, data transmission and comprehensive data analysis. The performance evaluation conducted in a realistic environment with several criteria shows the availability and practicability of the BABDA system.

  10. Human Parasitic Diseases in Bulgaria in Between 2013-2014

    Science.gov (United States)

    Rainova, Iskra; Harizanov, Rumen; Kaftandjiev, Iskren; Tsvetkova, Nina; Mikov, Ognyan; Kaneva, Eleonora

    2018-01-01

    Background: In Bulgaria, more than 20 autochthonous human parasitic infections have been described and some of them are widespread. Over 50 imported protozoan and helminthic infections represent diagnostic and therapeutic challenges and pose epidemiological risks due to the possibility of local transmission. Aims: To establish the distribution of autochthonous and imported parasitic diseases among the population of the country over a 2-year period (2013-2014) and to evaluate their significance in the public health system. Study Design: Cross sectional study. Methods: We used the annual reports by regional health inspectorates and data from the National Reference Laboratory at the National Centre of Infectious and Parasitic Diseases on all individuals infected with parasitic diseases in the country. Prevalence was calculated for parasitic diseases with few or absent clinical manifestations (oligosymptomatic or asymptomatic infections). Incidence per 100.000 was calculated for diseases with an overt clinical picture or those that required hospitalisation and specialised medical interventions (e.g. surgery). Results: During the research period, parasitological studies were conducted on 1441.244 persons, and parasitic infections were diagnosed in 22.039 individuals. Distribution of various parasitic pathogens among the population displayed statistically significant differences in prevalence for some intestinal parasites (enterobiasis 0.81%, giardiasis 0.34% and blastocystosis 0.22%). For certain zoonotic diseases such as cystic echinococcosis (average incidence of 3.99 per 100.000) and trichinellosis (average incidence of 0.8 per 100.000), the incidence exceeds several times the annual incidence recorded in the European Union. Conclusion: Parasitic diseases still pose a substantial problem with social and medical impacts on the residents of our country. Improved efficiency regarding autochthonous and imported parasitic diseases is essential in providing the public

  11. DNA repair processes and their impairment in some human diseases

    International Nuclear Information System (INIS)

    Cleaver, J.E.

    1977-01-01

    Some human diseases show enhanced sensitivity to the action of environmental mutagens, and among these several are known which are defective in the repair of damaged DNA. Xeroderma pigmentosum (XP) is mainly defective in excision repair of a large variety of damaged DNA bases caused by ultraviolet light and chemical mutagens. XP involves at least 6 distinct groups, some of which may lack cofactors required for excising damage from chromatin. As a result of these defects the sensitivity of XP cells to many mutagens is increased 5- to 10-fold. Ataxia telangiectasia and Fanconi's anemia may similarly involve defects in repair of certain DNA base damage or cross-links, respectively. But most of these and other mutagen-sensitive diseases only show increases of about 2-fold in sensitivity to mutagens, and the biochemical defects in the diseases may be more complex and less directly involved in DNA repair than in XP. (Auth.)

  12. HUMAN PAPILLOMA VIRUS. PREVENTION OF HPV-ASSOCIATED DISEASES

    Directory of Open Access Journals (Sweden)

    F. C. Shakhtakhtinskaya

    2015-01-01

    Full Text Available High prevalence of sexually transmitted diseases among the population attracts attention of specialists in all countries due to frequent development of complications resulting in reproductive dysfunction. The article presents one of the urgent issues of modern medicine — papillomavirus infection, which is the most common sexually transmitted disease. 70–80% of the sexually active persons contract human papilloma virus at one point. HPV induces a broad range of oncological reproductive diseases, including cervical, vulvar, vaginal and anal cancer and anogenital condylomae, which are observed both in men and women. The only reliable method of preventing papillomavirus infection is vaccination. The authors present new data on the use of the quadrivalent vaccine, including a new immunization pattern for 9–14-years-old girls.

  13. Human genome-microbiome interaction: metagenomics frontiers for the aetiopathology of autoimmune diseases.

    Science.gov (United States)

    Gundogdu, Aycan; Nalbantoglu, Ufuk

    2017-04-01

    A short while ago, the human genome and microbiome were analysed simultaneously for the first time as a multi-omic approach. The analyses of heterogeneous population cohorts showed that microbiome components were associated with human genome variations. In-depth analysis of these results reveals that the majority of those relationships are between immune pathways and autoimmune disease-associated microbiome components. Thus, it can be hypothesized that autoimmunity may be associated with homeostatic disequilibrium of the human-microbiome interactome. Further analysis of human genome-human microbiome relationships in disease contexts with tailored systems biology approaches may yield insights into disease pathogenesis and prognosis.

  14. Human genome-microbiome interaction: metagenomics frontiers for the aetiopathology of autoimmune diseases

    Science.gov (United States)

    Nalbantoglu, Ufuk

    2017-01-01

    A short while ago, the human genome and microbiome were analysed simultaneously for the first time as a multi-omic approach. The analyses of heterogeneous population cohorts showed that microbiome components were associated with human genome variations. In-depth analysis of these results reveals that the majority of those relationships are between immune pathways and autoimmune disease-associated microbiome components. Thus, it can be hypothesized that autoimmunity may be associated with homeostatic disequilibrium of the human-microbiome interactome. Further analysis of human genome–human microbiome relationships in disease contexts with tailored systems biology approaches may yield insights into disease pathogenesis and prognosis. PMID:28785422

  15. Indeterminate human immunodeficiency virus western blot results in Iranian patients with discordant screening assay results

    International Nuclear Information System (INIS)

    Ravanshad, M.; Sabahi, F.; Mahboudi, F.; Sabahi, F.

    2006-01-01

    The Western blot (WB) assay is the most widely accepted confirmatory assay for the detection and confirmation of antibodies to human immunodeficiency virus type 1 (HIV-1) and 2 (HIV-2). However, indeterminate WB reactivity to HIV-1 and HIV-2 proteins may occur in individuals who do not appear to be infected with HIV. In this study, we describe the results of indeterminate WB reactivity in Iranian patients with discordant screening assays. The samples were obtained from Iranian Blood Transfusion Center, Tehran, Iran and evaluated in the Biotechnology Process Development Center, Pasteur Institute of Iran, Tehran, Iran between 2003 and 2004. A total of 4707 were tested for the presence of HIV-1 antibodies. Six hundred and four (12.8%) patients tested for HIV were positive for HIV-1 antibody. Nine (1.49%) have discordant results among screening assays and indeterminate WB results as interpreted by Centers for Disease Control and Prevention (CDC) criteria. Most (66.7%) of these indeterminate WB results were due to p24 reactivity. However, 2(22.2%) display reactivity to both gp41 and gp120 proteins [Positive by World Health Organization (WHO) criteria]. Of 9 WB assays initially indeterminate by the CDC criteria and with follow-up samples 8(88.8%) became negative when retested subsequently while one (11.1%) remained indeterminate for more than a year and were thus considered negative. In addition all the indeterminate samples were negative when assessed by polymerase chain reaction assay. In general, there were was an 88.8% concordance between the CDC and WHO criteria for an indeterminate WB result. The CDC II criteria for an indeterminate WB result. The CDC II criteria best met the specified objectives for diagnosis in our setting. (author)

  16. Immunomodulatory activity of interleukin-27 in human chronic periapical diseases.

    Science.gov (United States)

    Li, Juan; Wang, Rong; Huang, Shi-Guang

    2017-01-01

    This study aims to observe expression of IL-27 on different cells in periapical tissues of different types of human chronic periapical diseases. Periapical tissue specimens of 60 donors, including healthy control (n=20), periapical granuloma group (n=20) and radicular cysts group (n=20), were fixed in 10% buffered formalin, stained with hematoxylin and eosin for histopathology. Then specimens were stained with double- immuno-fluorescence assay for identification of IL-27-tryptase (mast cells, MCs), IL-27-CD14 (mononuclear phagocyte cells, MPs) and IL-27-CD31 (endothelial cells, ECs) double-positive cells in periapical tissues. The results indicated that compared with healthy control, the densities (cells/mm 2 ) of IL-27-tryptase, IL-27-CD14 and IL-27-CD31 double-positive cells were significantly increased in human chronic periapical diseases (periapical granuloma group and radicular cysts group) ( P cysts group was significantly higher than those in periapical granuloma group ( P periapical granuloma group had no significant difference with those in radicular cysts group ( P =0.170 and 0.138, respectively). IL-27-CD14 double positive cells density achieved to peak among three cell groups in radicular cysts groups. In conclusion, IL-27 expressed in MCs, MPs and ECs of human chronic periapical diseases with different degrees. IL-27-tryptase double-positive cells may participate in pathogenic mechanism of chronic periapical diseases, especially for formation of fibrous in periapical cysts. IL-27-CD14 and IL-27-CD31 double-positive cells may participate in immunologic response to resist periapical infection, and they may play an dual role in pathogenesis and localization of periapical diseases.

  17. Global Considerations in Human Immunodeficiency Virus-Associated Respiratory Disease.

    Science.gov (United States)

    Rylance, Jamie; Meghji, Jamilah; Miller, Robert F; Ferrand, Rashida A

    2016-04-01

    Respiratory tract infection, particularly tuberculosis, is a major cause of mortality among human immunodeficiency virus (HIV)-infected individuals. Antiretroviral therapy (ART) has resulted in a dramatic increase in survival, although coverage of HIV treatment remains low in many parts of the world. There is a concurrent growing burden of chronic noninfectious respiratory disease as a result of increased survival. Many risk factors associated with the development of respiratory disease, such as cigarette smoking and intravenous drug use, are overrepresented among people living with HIV. In addition, there is emerging evidence that HIV infection may directly cause or accelerate the course of chronic lung disease. This review summarizes the clinical spectrum and epidemiology of respiratory tract infections and noninfectious pulmonary pathologies, and factors that explain the global variation in HIV-associated respiratory disease. The potential for enhancing diagnoses of noninfective chronic conditions through the use of clinical algorithms is discussed. We also consider issues in assessment and management of HIV-related respiratory disease in view of the increasing global scale up of ART. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  18. Human Environmental Disease Network: A computational model to assess toxicology of contaminants.

    Science.gov (United States)

    Taboureau, Olivier; Audouze, Karine

    2017-01-01

    During the past decades, many epidemiological, toxicological and biological studies have been performed to assess the role of environmental chemicals as potential toxicants associated with diverse human disorders. However, the relationships between diseases based on chemical exposure rarely have been studied by computational biology. We developed a human environmental disease network (EDN) to explore and suggest novel disease-disease and chemical-disease relationships. The presented scored EDN model is built upon the integration of systems biology and chemical toxicology using information on chemical contaminants and their disease relationships reported in the TDDB database. The resulting human EDN takes into consideration the level of evidence of the toxicant-disease relationships, allowing inclusion of some degrees of significance in the disease-disease associations. Such a network can be used to identify uncharacterized connections between diseases. Examples are discussed for type 2 diabetes (T2D). Additionally, this computational model allows confirmation of already known links between chemicals and diseases (e.g., between bisphenol A and behavioral disorders) and also reveals unexpected associations between chemicals and diseases (e.g., between chlordane and olfactory alteration), thus predicting which chemicals may be risk factors to human health. The proposed human EDN model allows exploration of common biological mechanisms of diseases associated with chemical exposure, helping us to gain insight into disease etiology and comorbidity. This computational approach is an alternative to animal testing supporting the 3R concept.

  19. Is periodontal disease a reason or result for premature birth?

    Directory of Open Access Journals (Sweden)

    Turgut Demir

    2012-01-01

    Full Text Available Introduction: It is a known fact that there is a connection between periodontal disease and certain systemic conditions. Even though there are some contradictory results in the conducted studies, periodontal disease has been accepted as a risk factor affecting the negative terminations of pregnancy in recent years (premature birth [PB], low birth weight. This consideration is associated with a positive correlation between two conditions in some studies. The Hypothesis: Although there is such a relationship between periodontal disease and PB, the linking mechanism has not been explained as presence of the relation cannot reveal the cause-effect relationship. It should be discussed whether or not this positive connection is caused by the fact that periodontal disease is an independent risk factor for PB, or the change (hormonal, inflammatory in the systemic condition in PB cases causes a risk for periodontal disease. Evaluation of the Hypothesis: The fact that in PB cases the changes in steroid hormone levels might increase the incidence and severity of periodontal disease as in pregnancy, or there could be a common risk factor that may cause both cases, has not been revealed yet and should be taken into consideration.

  20. Ofatumumab, a human anti-CD20 monoclonal antibody, for treatment of rheumatoid arthritis with an inadequate response to one or more disease-modifying antirheumatic drugs: results of a randomized, double-blind, placebo-controlled, phase I/II study

    DEFF Research Database (Denmark)

    Østergaard, Mikkel; Baslund, Bo; Rigby, William

    2010-01-01

    To investigate the safety and efficacy of ofatumumab, a novel human anti-CD20 monoclonal antibody (mAb), in patients with active rheumatoid arthritis (RA) whose disease did not respond to > or = 1 disease-modifying antirheumatic drug....

  1. Entomologic index for human risk of Lyme disease.

    Science.gov (United States)

    Mather, T N; Nicholson, M C; Donnelly, E F; Matyas, B T

    1996-12-01

    An entomologic index based on density estimates of Lyme disease spirochete-infected nymphal deer ticks (lxodes scapularis) was developed to assess human risk of Lyme disease. The authors used a standardized protocol to determine tick density and infection in numerous forested sites in six Rhode Island towns. An entomologic risk index calculated for each town was compared with the number of human Lyme disease cases reported to the Rhode Island State Health Department for the same year. A strong positive relation between entomologic risk index and the Lyme disease case rate for each town suggested that the entomologic index was predictive of Lyme disease risk.

  2. Long-term results of peripheral arterial disease rehabilitation

    NARCIS (Netherlands)

    Menard, J.R.; Smith, H.E.; Riebe, D.; Braun, C.M.; Blissmer, B.; Patterson, R.B.

    2004-01-01

    Purpose Although the Peripheral Arterial Disease Rehabilitation Program (PADRx) improves walking ability and quality of life over brief periods of follow-up, the long-term durability of results has not been established. This study examined functional status, walking ability, and quality of life in

  3. Cole Disease Results from Mutations in ENPP1.

    Science.gov (United States)

    Eytan, Ori; Morice-Picard, Fanny; Sarig, Ofer; Ezzedine, Khaled; Isakov, Ofer; Li, Qiaoli; Ishida-Yamamoto, Akemi; Shomron, Noam; Goldsmith, Tomer; Fuchs-Telem, Dana; Adir, Noam; Uitto, Jouni; Orlow, Seth J; Taieb, Alain; Sprecher, Eli

    2013-10-03

    The coexistence of abnormal keratinization and aberrant pigmentation in a number of cornification disorders has long suggested a mechanistic link between these two processes. Here, we deciphered the genetic basis of Cole disease, a rare autosomal-dominant genodermatosis featuring punctate keratoderma, patchy hypopigmentation, and uncommonly, cutaneous calcifications. Using a combination of exome and direct sequencing, we showed complete cosegregation of the disease phenotype with three heterozygous ENPP1 mutations in three unrelated families. All mutations were found to affect cysteine residues in the somatomedin-B-like 2 (SMB2) domain in the encoded protein, which has been implicated in insulin signaling. ENPP1 encodes ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), which is responsible for the generation of inorganic pyrophosphate, a natural inhibitor of mineralization. Previously, biallelic mutations in ENPP1 were shown to underlie a number of recessive conditions characterized by ectopic calcification, thus providing evidence of profound phenotypic heterogeneity in ENPP1-associated genetic diseases. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  4. Nutrition, epigenetic mechanisms, and human disease

    National Research Council Canada - National Science Library

    Maulik, Nilanjana; Maulik, Gautam

    2011-01-01

    .... The text discusses the basics of nutrigenomics and epigenetic regulation, types of nutrition influencing genetic imprinting, and the role of nutrition in modulating an individual's predisposition to disease...

  5. Glycogen storage disease type Ia in canines: a model for human metabolic and genetic liver disease.

    Science.gov (United States)

    Specht, Andrew; Fiske, Laurie; Erger, Kirsten; Cossette, Travis; Verstegen, John; Campbell-Thompson, Martha; Struck, Maggie B; Lee, Young Mok; Chou, Janice Y; Byrne, Barry J; Correia, Catherine E; Mah, Cathryn S; Weinstein, David A; Conlon, Thomas J

    2011-01-01

    A canine model of Glycogen storage disease type Ia (GSDIa) is described. Affected dogs are homozygous for a previously described M121I mutation resulting in a deficiency of glucose-6-phosphatase-α. Metabolic, clinicopathologic, pathologic, and clinical manifestations of GSDIa observed in this model are described and compared to those observed in humans. The canine model shows more complete recapitulation of the clinical manifestations seen in humans including "lactic acidosis", larger size, and longer lifespan compared to other animal models. Use of this model in preclinical trials of gene therapy is described and briefly compared to the murine model. Although the canine model offers a number of advantages for evaluating potential therapies for GSDIa, there are also some significant challenges involved in its use. Despite these challenges, the canine model of GSDIa should continue to provide valuable information about the potential for generating curative therapies for GSDIa as well as other genetic hepatic diseases.

  6. Glycogen Storage Disease Type Ia in Canines: A Model for Human Metabolic and Genetic Liver Disease

    Directory of Open Access Journals (Sweden)

    Andrew Specht

    2011-01-01

    Full Text Available A canine model of Glycogen storage disease type Ia (GSDIa is described. Affected dogs are homozygous for a previously described M121I mutation resulting in a deficiency of glucose-6-phosphatase-α. Metabolic, clinicopathologic, pathologic, and clinical manifestations of GSDIa observed in this model are described and compared to those observed in humans. The canine model shows more complete recapitulation of the clinical manifestations seen in humans including “lactic acidosis”, larger size, and longer lifespan compared to other animal models. Use of this model in preclinical trials of gene therapy is described and briefly compared to the murine model. Although the canine model offers a number of advantages for evaluating potential therapies for GSDIa, there are also some significant challenges involved in its use. Despite these challenges, the canine model of GSDIa should continue to provide valuable information about the potential for generating curative therapies for GSDIa as well as other genetic hepatic diseases.

  7. Optimisation of Surgical Results in de-Quervain’s Disease

    Directory of Open Access Journals (Sweden)

    B Jagannath Kamath

    2014-11-01

    Full Text Available Background: De Quervain’s disease poses more problems with respect to management than the diagnosis. Surgery is resorted to when the conservative methods fail. There are known complications of the surgical intervention. Surgeon contemplating the surgery should be aware of these and make every attempt to optimize the results and avoid the above mentioned complication. Methods: Sixty symptomatic wrists in 57 individuals suffering from de Quervain’s disease who needed surgery were studied preoperatively with ultrasound. Number of tendons and the sub septae identified in the ultrasound examination preoperatively were confirmed on the table during the surgery. The release was brought about under local anesthesia, with magnification taking care to avoid injury to the cephalic vein and superficial branch of radial nerve, not to violate the anterior margin of the sheath, thus preventing complications. A negative post release finkelstein test was ensured before the wound closure. Results: All 60 patients who underwent release for de Quervain’s disease were symptom free, satisfied and fully functional. Conclusions: De-Quervain's disease not relieved by conservative methods needs surgical release under local anesthesia with a transverse incision with Preoperative ultrasound examination for the number of tendons and subseptae. Avoiding the violation of the volar aspect of the sheath, loupe magnification, tourniquet and post release Finkelstein’s test before wound closure, will ensure optimal results.

  8. Multinational corporations and infectious disease: Embracing human rights management techniques.

    Science.gov (United States)

    Salcito, Kendyl; Singer, Burton H; Weiss, Mitchell G; Winkler, Mirko S; Krieger, Gary R; Wielga, Mark; Utzinger, Jürg

    2014-01-01

    Global health institutions have called for governments, international organisations and health practitioners to employ a human rights-based approach to infectious diseases. The motivation for a human rights approach is clear: poverty and inequality create conditions for infectious diseases to thrive, and the diseases, in turn, interact with social-ecological systems to promulgate poverty, inequity and indignity. Governments and intergovernmental organisations should be concerned with the control and elimination of these diseases, as widespread infections delay economic growth and contribute to higher healthcare costs and slower processes for realising universal human rights. These social determinants and economic outcomes associated with infectious diseases should interest multinational companies, partly because they have bearing on corporate productivity and, increasingly, because new global norms impose on companies a responsibility to respect human rights, including the right to health. We reviewed historical and recent developments at the interface of infectious diseases, human rights and multinational corporations. Our investigation was supplemented with field-level insights at corporate capital projects that were developed in areas of high endemicity of infectious diseases, which embraced rights-based disease control strategies. Experience and literature provide a longstanding business case and an emerging social responsibility case for corporations to apply a human rights approach to health programmes at global operations. Indeed, in an increasingly globalised and interconnected world, multinational corporations have an interest, and an important role to play, in advancing rights-based control strategies for infectious diseases. There are new opportunities for governments and international health agencies to enlist corporate business actors in disease control and elimination strategies. Guidance offered by the United Nations in 2011 that is widely embraced

  9. Human action perspectives based on individual plant examination results

    International Nuclear Information System (INIS)

    Forester, J.; Thompson, C.; Drouin, M.; Lois, E.

    1996-01-01

    This paper provides perspectives on human actions gained from reviewing 76 individual plant examination (IPE) submittals. Human actions found to be important in boiling water reactors (BWRs) and in pressurized water reactors (PWRs) are presented and the events most frequently found important are discussed. Since there are numerous factors that can influence the quantification of human error probabilities (HEPs) and introduce significant variability in the resulting HEPs (which in turn can influence which events are found to be important), the variability in HEPs for similar events across IPEs is examined to assess the extent to which variability in results is due to real versus artifactual differences. Finally, similarities and differences in human action observations across BWRs and PWRs are examined

  10. The genus Malassezia and human disease

    Directory of Open Access Journals (Sweden)

    Inamadar A

    2003-07-01

    Full Text Available Sabouraud's Pityrosporum is now recognized as Malassezia. With taxonomic revision of the genus, newer species have been included. The role of this member of the normal human skin flora in different cutaneous and systemic disorders is becoming clearer. The immunological responses it induces in the human body are conflicting and their relevance to clinical features is yet to be explored.

  11. Using Human Induced Pluripotent Stem Cells to Model Skeletal Diseases.

    Science.gov (United States)

    Barruet, Emilie; Hsiao, Edward C

    2016-01-01

    Musculoskeletal disorders affecting the bones and joints are major health problems among children and adults. Major challenges such as the genetic origins or poor diagnostics of severe skeletal disease hinder our understanding of human skeletal diseases. The recent advent of human induced pluripotent stem cells (human iPS cells) provides an unparalleled opportunity to create human-specific models of human skeletal diseases. iPS cells have the ability to self-renew, allowing us to obtain large amounts of starting material, and have the potential to differentiate into any cell types in the body. In addition, they can carry one or more mutations responsible for the disease of interest or be genetically corrected to create isogenic controls. Our work has focused on modeling rare musculoskeletal disorders including fibrodysplasia ossificans progressive (FOP), a congenital disease of increased heterotopic ossification. In this review, we will discuss our experiences and protocols differentiating human iPS cells toward the osteogenic lineage and their application to model skeletal diseases. A number of critical challenges and exciting new approaches are also discussed, which will allow the skeletal biology field to harness the potential of human iPS cells as a critical model system for understanding diseases of abnormal skeletal formation and bone regeneration.

  12. Modeling human gastrointestinal inflammatory diseases using microphysiological culture systems.

    Science.gov (United States)

    Hartman, Kira G; Bortner, James D; Falk, Gary W; Ginsberg, Gregory G; Jhala, Nirag; Yu, Jian; Martín, Martín G; Rustgi, Anil K; Lynch, John P

    2014-09-01

    Gastrointestinal illnesses are a significant health burden for the US population, with 40 million office visits each year for gastrointestinal complaints and nearly 250,000 deaths. Acute and chronic inflammations are a common element of many gastrointestinal diseases. Inflammatory processes may be initiated by a chemical injury (acid reflux in the esophagus), an infectious agent (Helicobacter pylori infection in the stomach), autoimmune processes (graft versus host disease after bone marrow transplantation), or idiopathic (as in the case of inflammatory bowel diseases). Inflammation in these settings can contribute to acute complaints (pain, bleeding, obstruction, and diarrhea) as well as chronic sequelae including strictures and cancer. Research into the pathophysiology of these conditions has been limited by the availability of primary human tissues or appropriate animal models that attempt to physiologically model the human disease. With the many recent advances in tissue engineering and primary human cell culture systems, it is conceivable that these approaches can be adapted to develop novel human ex vivo systems that incorporate many human cell types to recapitulate in vivo growth and differentiation in inflammatory microphysiological environments. Such an advance in technology would improve our understanding of human disease progression and enhance our ability to test for disease prevention strategies and novel therapeutics. We will review current models for the inflammatory and immunological aspects of Barrett's esophagus, acute graft versus host disease, and inflammatory bowel disease and explore recent advances in culture methodologies that make these novel microphysiological research systems possible. © 2014 by the Society for Experimental Biology and Medicine.

  13. Chronic Inflammatory Periodontal Disease in Patients with Human Immunodeficiency Virus.

    OpenAIRE

    Vania López Rodríguez; Emilio Carpio Muñoz; Vicente Fardales Macías; Iralys Benítez Guzmán

    2009-01-01

    Background: The Chronic Inflammatory Periodontal Disease is related with multiple risk factors. Those patients with human immunodeficiency virus have higher risk of presenting this disease and it is usually more serious in these cases. Objective: To describe the prevalence of Chronic Inflammatory Periodontal Disease in patients with HIV. Methods: Descriptive, observational, cross-sectional study including patients with HIV in Sancti Spiritus province. The occurrence of the disease was determi...

  14. Extracellular RNAs: development as biomarkers of human disease

    Directory of Open Access Journals (Sweden)

    Joseph F. Quinn

    2015-08-01

    Full Text Available Ten ongoing studies designed to test the possibility that extracellular RNAs may serve as biomarkers in human disease are described. These studies, funded by the NIH Common Fund Extracellular RNA Communication Program, examine diverse extracellular body fluids, including plasma, serum, urine and cerebrospinal fluid. The disorders studied include hepatic and gastric cancer, cardiovascular disease, chronic kidney disease, neurodegenerative disease, brain tumours, intracranial haemorrhage, multiple sclerosis and placental disorders. Progress to date and the plans for future studies are outlined.

  15. Disease emergence and resurgence—the wildlife-human connection

    Science.gov (United States)

    Friend, Milton; Hurley, James W.; Nol, Pauline; Wesenberg, Katherine

    2006-01-01

    In 2000, the Global Outbreak Alert and Response Network (GOARN) was organized as a global disease watchdog group to coordinate disease outbreak information and health crisis response. The World Health Organization (WHO) is the headquarters for this network. Understandably, the primary focus for WHO is human health. However, diseases such as the H5N1 avian influenza epizootic in Asian bird populations demonstrate the need for integrating knowledge about disease emergence in animals and in humans.Aside from human disease concerns, H5N1 avian influenza has major economic consequences for the poultry industry worldwide. Many other emerging diseases, such as severe acute respiratory syndrome (SARS), monkeypox, Ebola fever, and West Nile fever, also have an important wildlife component. Despite these wildlife associations, the true integration of the wildlife component in approaches towards disease emergence remains elusive. This separation between wildlife and other species’ interests is counterproductive because the emergence of zoonotic viruses and other pathogens maintained by wildlife reservoir hosts is poorly understood.This book is about the wildlife component of emerging diseases. It is intended to enhance the reader’s awareness of the role of wildlife in disease emergence. By doing so, perhaps a more holistic approach to disease prevention and control will emerge for the benefit of human, domestic animal, and free-ranging wildlife populations alike. The perspectives offered are influenced by more than four decades of my experiences as a wildlife disease practitioner. Although wildlife are victims to many of the same disease agents affecting humans and domestic animals, many aspects of disease in free-ranging wildlife require different approaches than those commonly applied to address disease in humans or domestic animals. Nevertheless, the broader community of disease investigators and health care professionals has largely pursued a separatist approach for

  16. Disease Human - MDC_CardiovascularMortality2006

    Data.gov (United States)

    NSGIC Local Govt | GIS Inventory — Polygon feature class based on Zip Code boundaries showing the rate of deaths due to major cardiovascular diseases per 1000 residents of Miami-Dade County in 2006.

  17. Disease Human - MDC_CLRDMortality2006

    Data.gov (United States)

    NSGIC Local Govt | GIS Inventory — Polygon feature class based on Zip Code boundaries showing the rate of deaths per 100,000 residents due to Chronic Lower Respiratory Disease (CLRD) in Miami-Dade...

  18. Obstetric and gynecological diseases and complications resulting from vaginal dysbacteriosis.

    Science.gov (United States)

    Kovachev, Stefan Miladinov

    2014-08-01

    Accurate knowledge of the composition and ecology of vaginal microbial environment of a healthy woman is necessary for the understanding of normal flora and how to reduce the risk for diseases. Vagina and its microflora form a balanced ecosystem in which dominated bacteria are vaginal lactobacilli. There are dynamic changes in this ecosystem having structure and composition depending on many factors. The term dysbacteriosis defines any movement outside the normal range for the given biotope of obligate and/or facultative microflora. Such a change in the quantity and quality of the respective microbial balance is fraught with danger and requires correction and recovery. The purpose of this overview is to examine obstetric and gynecological diseases that can cause vaginal impaired microbial balance. Vaginal dysbacteriosis is a cause, predecessor, and often also consequence of vaginal infections. In essence, any vaginal infection can be seen as dysbacteriosis, developed to the most severe extent. Here, there is a dominant microorganism other than lactic acid bacteria in the vagina (clinically manifested or not, respectively), depletion of defense mechanisms of the vagina associated with the shift of lactobacilli from their dominant role in the vaginal balance, decrease in their number and species diversity, and a resulting change in the healthy status of the vagina. Vaginal dysbacteriosis can be found in pathogenetic mechanism, whereby many obstetric and gynecological diseases develop. Most of these diseases lead directly to increased maternal and infant morbidity and mortality, so it is important to understand the reasons for them and the arrangements for their prevention.

  19. RNA FISH for detecting expanded repeats in human diseases.

    Science.gov (United States)

    Urbanek, Martyna O; Krzyzosiak, Wlodzimierz J

    2016-04-01

    RNA fluorescence in situ hybridization (FISH) is a widely used technique for detecting transcripts in fixed cells and tissues. Many variants of RNA FISH have been proposed to increase signal strength, resolution and target specificity. The current variants of this technique facilitate the detection of the subcellular localization of transcripts at a single molecule level. Among the applications of RNA FISH are studies on nuclear RNA foci in diseases resulting from the expansion of tri-, tetra-, penta- and hexanucleotide repeats present in different single genes. The partial or complete retention of mutant transcripts forming RNA aggregates within the nucleoplasm has been shown in multiple cellular disease models and in the tissues of patients affected with these atypical mutations. Relevant diseases include, among others, myotonic dystrophy type 1 (DM1) with CUG repeats, Huntington's disease (HD) and spinocerebellar ataxia type 3 (SCA3) with CAG repeats, fragile X-associated tremor/ataxia syndrome (FXTAS) with CGG repeats, myotonic dystrophy type 2 (DM2) with CCUG repeats, amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) with GGGGCC repeats and spinocerebellar ataxia type 32 (SCA32) with GGCCUG. In this article, we summarize the results obtained with FISH to examine RNA nuclear inclusions. We provide a detailed protocol for detecting RNAs containing expanded CAG and CUG repeats in different cellular models, including fibroblasts, lymphoblasts, induced pluripotent stem cells and murine and human neuronal progenitors. We also present the results of the first single-molecule FISH application in a cellular model of polyglutamine disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. [Unconventional disease agents--a danger for humans and animals?].

    Science.gov (United States)

    Kaaden, O R

    1994-02-01

    The occurrence of bovine spongiform encephalopathy (BSE) in Great Britain in 1985/86, has focused again the public concern as well as scientific interest to the Scrapie disease of sheep and goat known more than 150 years. The agents of scrapie and BSE are characterized by unusual biological and physical-chemical properties, especially their high tenacity. Therefore, they are also designated "unconventional agents of viruses". Different theories have been proposed about their infectious characteristics--especially because of the apparent or real missing of an agent-specific nucleic acid--which are named Virinos, Prions or Nemavirus. The broad host range of Scrapie respective BSE, which includes domestic and wild ruminants, Suidae, Felidae, Mustelidae, small rodents, birds and non-primates, has created some concern since there might be an aetiological correlation between the transmissible spongiform encephalopathies of man (Creutzfeld-Jakob- and Gerstmann-Sträussler-Scheinker-Disease) and that of animals. Although at present neither epidemiological nor molecular biological evidence whatsoever was proved, the hypothesis cannot be completely disproved. The probability of infection through digestive tract seems to be rather unlikely but special precautions should be taken as far as production, investigation and application of human medicine drugs of animal origin. Furthermore, research about the aetiology of "unconventional agents" and pathogenesis of resulting diseases is necessary and should be intensified in Germany. Finally, only an early intra vitam-Diagnose and in vitro detection can avoid an further spread of this new category of diseases.

  1. Involution of categorical thinking processes in Alzheimer's disease: Preliminary results

    Directory of Open Access Journals (Sweden)

    Claudia Berlim de Mello

    Full Text Available Abstract Alzheimer's disease (AD is a degenerative brain disorder characterized by progressive losses in cognitive functions, including memory. The sequence of these losses may correspond to the inverse order of the normal sequence of ontogenetic cognitive acquisitions, a process named retrogenesis. One of the acquisitions that improve in normal development is the ability to retrieve previously acquired categorical knowledge from semantic memory in order to guide associative thinking and memory processes; consequently, children become able to associate verbal stimuli in more complex taxonomic ways and to use this knowledge to improve their recall. Objective: In this study, we investigated if AD-related deterioration of semantic memory involves a decrease in categorical thinking processes with progression of the disease, according to the retrogenesis hypothesis. Methods: We compared the performance of AD patients at mild and moderate stages, and of groups of 7, 10 and 14-year-old children in tasks of free association along with recall tasks of perceptually and semantically related stimuli. Results: ANOVAS showed a decrease in taxonomic associations and an increase in diffuse associations between mild and moderate stages, corresponding to the inverse order shown by the child groups. At the moderate AD stage, the pattern was similar to that of 7-year-old children. Both groups of patients performed worse than child groups in recall tasks. Conclusions: These results corroborate the hypothesis of an involution of the processes of categorical associative thinking in the course of the disease.

  2. Emerging role of mitophagy in human diseases and physiology.

    Science.gov (United States)

    Um, Jee-Hyun; Yun, Jeanho

    2017-06-01

    Mitophagy is a process of selective removal of damaged or unnecessary mitochondria using autophagic machinery. Mitophagy plays an essential role in maintaining mitochondrial quality control and homeostasis. Mitochondrial dysfunctions and defective mitophagy in neurodegenerative diseases, cancer, and metabolic diseases indicate a close link between human disease and mitophagy. Furthermore, recent studies showing the involvement of mitophagy in differentiation and development, suggest that mitophagy may play a more active role in controlling cellular functions. A better understanding of mitophagy will provide insights about human disease and offer novel chance for treatment. This review mainly focuses on the recent implications for mitophagy in human diseases and normal physiology. [BMB Reports 2017; 50(6): 299-307].

  3. Economic Burden of Human Papillomavirus-Related Diseases in Italy

    Science.gov (United States)

    Baio, Gianluca; Capone, Alessandro; Marcellusi, Andrea; Mennini, Francesco Saverio; Favato, Giampiero

    2012-01-01

    Introduction Human papilloma virus (HPV) genotypes 6, 11, 16, and 18 impose a substantial burden of direct costs on the Italian National Health Service that has never been quantified fully. The main objective of the present study was to address this gap: (1) by estimating the total direct medical costs associated with nine major HPV-related diseases, namely invasive cervical cancer, cervical dysplasia, cancer of the vulva, vagina, anus, penis, and head and neck, anogenital warts, and recurrent respiratory papillomatosis, and (2) by providing an aggregate measure of the total economic burden attributable to HPV 6, 11, 16, and 18 infection. Methods For each of the nine conditions, we used available Italian secondary data to estimate the lifetime cost per case, the number of incident cases of each disease, the total economic burden, and the relative prevalence of HPV types 6, 11, 16, and 18, in order to estimate the aggregate fraction of the total economic burden attributable to HPV infection. Results The total direct costs (expressed in 2011 Euro) associated with the annual incident cases of the nine HPV-related conditions included in the analysis were estimated to be €528.6 million, with a plausible range of €480.1–686.2 million. The fraction attributable to HPV 6, 11, 16, and 18 was €291.0 (range €274.5–315.7 million), accounting for approximately 55% of the total annual burden of HPV-related disease in Italy. Conclusions The results provided a plausible estimate of the significant economic burden imposed by the most prevalent HPV-related diseases on the Italian welfare system. The fraction of the total direct lifetime costs attributable to HPV 6, 11, 16, and 18 infections, and the economic burden of noncervical HPV-related diseases carried by men, were found to be cost drivers relevant to the making of informed decisions about future investments in programmes of HPV prevention. PMID:23185412

  4. Human glia can both induce and rescue aspects of disease phenotype in Huntington disease

    DEFF Research Database (Denmark)

    Benraiss, Abdellatif; Wang, Su; Herrlinger, Stephanie

    2016-01-01

    The causal contribution of glial pathology to Huntington disease (HD) has not been heavily explored. To define the contribution of glia to HD, we established human HD glial chimeras by neonatally engrafting immunodeficient mice with mutant huntingtin (mHTT)-expressing human glial progenitor cells...... chimeras are hyperexcitable. Conversely, normal glia can ameliorate disease phenotype in transgenic HD mice, as striatal transplantation of normal glia rescues aspects of electrophysiological and behavioural phenotype, restores interstitial potassium homeostasis, slows disease progression and extends...

  5. Vitamins in the prevention of human diseases

    National Research Council Canada - National Science Library

    Herrmann, Wolfgang, Prof; Obeid, Rima

    2011-01-01

    ... in ancient Egypt. One-sided nutrition, smoking, alcohol, genetic factors, and even geographical origin interfere with our dietary intake of the vitamins. Insufficient vitamin intake can impact our health and contribute significantly to the development of diseases. This book offers expert reviews and judgements on the role of vitamins in health and ...

  6. Long term results of radiotherapy of degenerative joint diseases

    Energy Technology Data Exchange (ETDEWEB)

    Lindner, H; Freislederer, R

    1982-04-01

    At the Radiologic Department of the Staedt. Krankenhaus Passau, 473 patients with degenerative diseases in the big joints and the spine were irradiated with the caesium unit between 1971 and 1979. Among these patients, 249 could be followed up during a prolonged period (1/2 to 9 years, i.e. 4.2 years on an average). According to the categories of v. Pannewitz, 11% were pain-free at this moment, 21% showed an essential improvement, 29% showed an improvement, and 39% were not influenced by the treatment. 13.5% showed recurrent pains; these were mentioned as 'not influenced' in the statistical analysis. It is proved that the relief of pain does not depend on the age of the patients, but on the anamnesis period, the results of the X-ray examiantion, and the degree of the restriction of mobility. Due to the delay of irradiation, a preliminary treatment mostly produces a less favorable radiotherapeutic result. Compared with other therapeutic methods, the long term results of radiotherapy of degenerative joint diseases are generally favorable. This conclusion is also confirmed by the results of patients checked up more than five years after the treatment.

  7. Exposure to Human Immunodeficiency Disease. What Precautions ...

    African Journals Online (AJOL)

    Background: The Human Immunodeficiency Virus (HIV) epidemic is more pronounced in sub-Saharan Africa. The ever-increasing prevalence of HIV infection and the continued improvement in clinical management has increased the likelihood of these patients being managed by healthcare workers. The aim of the review ...

  8. Mutations that Cause Human Disease: A Computational/Experimental Approach

    Energy Technology Data Exchange (ETDEWEB)

    Beernink, P; Barsky, D; Pesavento, B

    2006-01-11

    International genome sequencing projects have produced billions of nucleotides (letters) of DNA sequence data, including the complete genome sequences of 74 organisms. These genome sequences have created many new scientific opportunities, including the ability to identify sequence variations among individuals within a species. These genetic differences, which are known as single nucleotide polymorphisms (SNPs), are particularly important in understanding the genetic basis for disease susceptibility. Since the report of the complete human genome sequence, over two million human SNPs have been identified, including a large-scale comparison of an entire chromosome from twenty individuals. Of the protein coding SNPs (cSNPs), approximately half leads to a single amino acid change in the encoded protein (non-synonymous coding SNPs). Most of these changes are functionally silent, while the remainder negatively impact the protein and sometimes cause human disease. To date, over 550 SNPs have been found to cause single locus (monogenic) diseases and many others have been associated with polygenic diseases. SNPs have been linked to specific human diseases, including late-onset Parkinson disease, autism, rheumatoid arthritis and cancer. The ability to predict accurately the effects of these SNPs on protein function would represent a major advance toward understanding these diseases. To date several attempts have been made toward predicting the effects of such mutations. The most successful of these is a computational approach called ''Sorting Intolerant From Tolerant'' (SIFT). This method uses sequence conservation among many similar proteins to predict which residues in a protein are functionally important. However, this method suffers from several limitations. First, a query sequence must have a sufficient number of relatives to infer sequence conservation. Second, this method does not make use of or provide any information on protein structure, which

  9. Skin Diseases: Cross-section of human skin

    Science.gov (United States)

    Skip Navigation Bar Home Current Issue Past Issues Skin Diseases Cross-section of human skin Past Issues / Fall 2008 Table of Contents For ... Logical Images, Inc. I n the areas of skin health and skin diseases, the NIH's National Institute ...

  10. Mosquitoes as vectors of human disease in South Africa | Jupp ...

    African Journals Online (AJOL)

    While malaria is the most important mosquito-borne disease in South Africa, there are also several mosquito-borne viruses that also cause human disease. The most significant are chikungunya, West Nile, Sindbis and Rift Valley fever viruses. In this review these are compared with malaria, mainly in regard to their ecology ...

  11. A murine model of human myeloma bone disease

    NARCIS (Netherlands)

    Garrett, I.R.; Dallas, S.; Radl, J.; Mundy, G.R.

    1997-01-01

    Myeloma causes a devastating and unique form of osteolytic bone disease. Although osteoclast activation is responsible for bone destruction, the precise mechanisms by which myeloma cells increase osteoclast activity have not been defined. An animal model of human myeloma bone disease mould help in

  12. Animal models of human respiratory syncytial virus disease

    NARCIS (Netherlands)

    Bem, Reinout A.; Domachowske, Joseph B.; Rosenberg, Helene F.

    2011-01-01

    Infection with the human pneumovirus pathogen, respiratory syncytial virus (hRSV), causes a wide spectrum of respiratory disease, notably among infants and the elderly. Laboratory animal studies permit detailed experimental modeling of hRSV disease and are therefore indispensable in the search for

  13. The DNA-damage response in human biology and disease

    DEFF Research Database (Denmark)

    Jackson, Stephen P; Bartek, Jiri

    2009-01-01

    , signal its presence and mediate its repair. Such responses, which have an impact on a wide range of cellular events, are biologically significant because they prevent diverse human diseases. Our improving understanding of DNA-damage responses is providing new avenues for disease management....

  14. Positions of human dwellings affect few tropical diseases near ...

    African Journals Online (AJOL)

    user

    Some factors that possibly affect tropical disease distribution was investigated in about 500 randomize human dwellings. The studied factors include wild animals, domestic animals, wild plants, cultivated plants, nature of soil, nature of water, positions of human dwellings, nature of building material and position of animal ...

  15. Animal models for human genetic diseases | Sharif | African Journal ...

    African Journals Online (AJOL)

    The study of human genetic diseases can be greatly aided by animal models because of their similarity to humans in terms of genetics. In addition to understand diverse aspects of basic biology, model organisms are extensively used in applied research in agriculture, industry, and also in medicine, where they are used to ...

  16. Human drivers of ecological and evolutionary dynamics in emerging and disappearing infectious disease systems.

    Science.gov (United States)

    Rogalski, Mary A; Gowler, Camden D; Shaw, Clara L; Hufbauer, Ruth A; Duffy, Meghan A

    2017-01-19

    Humans have contributed to the increased frequency and severity of emerging infectious diseases, which pose a significant threat to wild and domestic species, as well as human health. This review examines major pathways by which humans influence parasitism by altering (co)evolutionary interactions between hosts and parasites on ecological timescales. There is still much to learn about these interactions, but a few well-studied cases show that humans influence disease emergence every step of the way. Human actions significantly increase dispersal of host, parasite and vector species, enabling greater frequency of infection in naive host populations and host switches. Very dense host populations resulting from urbanization and agriculture can drive the evolution of more virulent parasites and, in some cases, more resistant host populations. Human activities that reduce host genetic diversity or impose abiotic stress can impair the ability of hosts to adapt to disease threats. Further, evolutionary responses of hosts and parasites can thwart disease management and biocontrol efforts. Finally, in rare cases, humans influence evolution by eradicating an infectious disease. If we hope to fully understand the factors driving disease emergence and potentially control these epidemics we must consider the widespread influence of humans on host and parasite evolutionary trajectories.This article is part of the themed issue 'Human influences on evolution, and the ecological and societal consequences'. © 2016 The Author(s).

  17. Control of human parasitic diseases: Context and overview.

    Science.gov (United States)

    Molyneux, David H

    2006-01-01

    The control of parasitic diseases of humans has been undertaken since the aetiology and natural history of the infections was recognized and the deleterious effects on human health and well-being appreciated by policy makers, medical practitioners and public health specialists. However, while some parasitic infections such as malaria have proved difficult to control, as defined by a sustained reduction in incidence, others, particularly helminth infections can be effectively controlled. The different approaches to control from diagnosis, to treatment and cure of the clinically sick patient, to control the transmission within the community by preventative chemotherapy and vector control are outlined. The concepts of eradication, elimination and control are defined and examples of success summarized. Overviews of the health policy and financing environment in which programmes to control or eliminate parasitic diseases are positioned and the development of public-private partnerships as vehicles for product development or access to drugs for parasite disease control are discussed. Failure to sustain control of parasites may be due to development of drug resistance or the failure to implement proven strategies as a result of decreased resources within the health system, decentralization of health management through health-sector reform and the lack of financial and human resources in settings where per capita government expenditure on health may be less than $US 5 per year. However, success has been achieved in several large-scale programmes through sustained national government investment and/or committed donor support. It is also widely accepted that the level of investment in drug development for the parasitic diseases of poor populations is an unattractive option for pharmaceutical companies. The development of partnerships to specifically address this need provides some hope that the intractable problems of the treatment regimens for the trypanosomiases and

  18. Multifractal Detrended Fluctuation Analysis of Human gait Diseases

    Directory of Open Access Journals (Sweden)

    Srimonti eDutta

    2013-10-01

    Full Text Available IIn this paper multifractal detrended fluctuation analysis is used to study the human gait time series for normal and diseased sets. It is observed that long range correlation is primarily responsible for the origin of multifractality. The study reveals that the degree of multifractality is more for normal set compared to diseased set. However the method fails to distinguish between the two diseased sets.

  19. [Bartonellosis. II. Other Bartonella responsible for human diseases].

    Science.gov (United States)

    Piémont, Y; Heller, R

    1999-01-01

    In addition to Bartonella henselae, five other Bartonella species were involved in human pathology. As for B. henselae, ectoparasites seem to be responsible for the transmission of most or all these bacterial species. B. bacilliformis is responsible for Carrion's disease that occurs in some valleys of Colombia, Ecuador and Peru. This disease is transmitted by biting of infected sandflies. The bacterial reservoir is constituted by humans only. That disease occurs either as an acute form with severe infectious hemolytic anemia (or Oroya fever), or as benign cutaneous tumors, also called verruga peruana. Healthy blood carriers of the bacterium exist. Trench fever was described during the First World War. This non-lethal disease is constituted of recurrent febrile attacks associated particularly with osseous pains. The causative agent of the disease is B. quintana, transmitted by the body louse. Humans seem to be the reservoir of that bacterium. In some patients, B. quintana can be responsible for endocarditis, bacillary angiomatosis and chronic or recurrent bacteremia. Other human infections due to Bartonella sp. have been described: B. vinsonii, isolated from blood of small rodents, and B. elizabethae, the reservoir of which is currently unknown, can be responsible for endocardites. B. clarridgeiae (isolated from blood of 5% of pet cats and 17% of stray cats) may be responsible for human cat scratch disease. All these bartonelloses are diagnosed by non-standard blood culture or by in vitro DNA amplification or by serological testing. Their treatment requires tetracyclines or chloramphenicol or macrolides.

  20. Impacts of Gut Bacteria on Human Health and Diseases

    Science.gov (United States)

    Zhang, Yu-Jie; Li, Sha; Gan, Ren-You; Zhou, Tong; Xu, Dong-Ping; Li, Hua-Bin

    2015-01-01

    Gut bacteria are an important component of the microbiota ecosystem in the human gut, which is colonized by 1014 microbes, ten times more than the human cells. Gut bacteria play an important role in human health, such as supplying essential nutrients, synthesizing vitamin K, aiding in the digestion of cellulose, and promoting angiogenesis and enteric nerve function. However, they can also be potentially harmful due to the change of their composition when the gut ecosystem undergoes abnormal changes in the light of the use of antibiotics, illness, stress, aging, bad dietary habits, and lifestyle. Dysbiosis of the gut bacteria communities can cause many chronic diseases, such as inflammatory bowel disease, obesity, cancer, and autism. This review summarizes and discusses the roles and potential mechanisms of gut bacteria in human health and diseases. PMID:25849657

  1. Human genetics of infectious diseases: between proof of principle and paradigm.

    Science.gov (United States)

    Alcaïs, Alexandre; Abel, Laurent; Casanova, Jean-Laurent

    2009-09-01

    The observation that only a fraction of individuals infected by infectious agents develop clinical disease raises fundamental questions about the actual pathogenesis of infectious diseases. Epidemiological and experimental evidence is accumulating to suggest that human genetics plays a major role in this process. As we discuss here, human predisposition to infectious diseases seems to cover a continuous spectrum from monogenic to polygenic inheritance. Although many studies have provided proof of principle that infectious diseases may result from various types of inborn errors of immunity, the genetic determinism of most infectious diseases in most patients remains unclear. However, in the future, studies in human genetics are likely to establish a new paradigm for infectious diseases.

  2. G protein-coupled receptor mutations and human genetic disease.

    Science.gov (United States)

    Thompson, Miles D; Hendy, Geoffrey N; Percy, Maire E; Bichet, Daniel G; Cole, David E C

    2014-01-01

    Genetic variations in G protein-coupled receptor genes (GPCRs) disrupt GPCR function in a wide variety of human genetic diseases. In vitro strategies and animal models have been used to identify the molecular pathologies underlying naturally occurring GPCR mutations. Inactive, overactive, or constitutively active receptors have been identified that result in pathology. These receptor variants may alter ligand binding, G protein coupling, receptor desensitization and receptor recycling. Receptor systems discussed include rhodopsin, thyrotropin, parathyroid hormone, melanocortin, follicle-stimulating hormone (FSH), luteinizing hormone, gonadotropin-releasing hormone (GNRHR), adrenocorticotropic hormone, vasopressin, endothelin-β, purinergic, and the G protein associated with asthma (GPRA or neuropeptide S receptor 1 (NPSR1)). The role of activating and inactivating calcium-sensing receptor (CaSR) mutations is discussed in detail with respect to familial hypocalciuric hypercalcemia (FHH) and autosomal dominant hypocalemia (ADH). The CASR mutations have been associated with epilepsy. Diseases caused by the genetic disruption of GPCR functions are discussed in the context of their potential to be selectively targeted by drugs that rescue altered receptors. Examples of drugs developed as a result of targeting GPCRs mutated in disease include: calcimimetics and calcilytics, therapeutics targeting melanocortin receptors in obesity, interventions that alter GNRHR loss from the cell surface in idiopathic hypogonadotropic hypogonadism and novel drugs that might rescue the P2RY12 receptor congenital bleeding phenotype. De-orphanization projects have identified novel disease-associated receptors, such as NPSR1 and GPR35. The identification of variants in these receptors provides genetic reagents useful in drug screens. Discussion of the variety of GPCRs that are disrupted in monogenic Mendelian disorders provides the basis for examining the significance of common

  3. Proteome analysis of human substantia nigra in Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Werner Cornelius J

    2008-02-01

    Full Text Available Abstract Background Parkinson's disease (PD is the most common neurodegenerative disorder involving the motor system. Although not being the only region involved in PD, affection of the substantia nigra and its projections is responsible for some of the most debilitating features of the disease. To further advance a comprehensive understanding of nigral pathology, we conducted a tissue based comparative proteome study of healthy and diseased human substantia nigra. Results The gross number of differentially regulated proteins in PD was 221. In total, we identified 37 proteins, of which 16 were differentially expressed. Identified differential proteins comprised elements of iron metabolism (H-ferritin and glutathione-related redox metabolism (GST M3, GST P1, GST O1, including novel redox proteins (SH3BGRL. Additionally, many glial or related proteins were found to be differentially regulated in PD (GFAP, GMFB, galectin-1, sorcin, as well as proteins belonging to metabolic pathways sparsely described in PD, such as adenosyl homocysteinase (methylation, aldehyde dehydrogenase 1 and cellular retinol-binding protein 1 (aldehyde metabolism. Further differentially regulated proteins included annexin V, beta-tubulin cofactor A, coactosin-like protein and V-type ATPase subunit 1. Proteins that were similarly expressed in healthy or diseased substantia nigra comprised housekeeping proteins such as COX5A, Rho GDI alpha, actin gamma 1, creatin-kinase B, lactate dehydrogenase B, disulfide isomerase ER-60, Rab GDI beta, methyl glyoxalase 1 (AGE metabolism and glutamine synthetase. Interestingly, also DJ-1 and UCH-L1 were expressed similarly. Furthermore, proteins believed to serve as internal standards were found to be expressed in a constant manner, such as 14-3-3 epsilon and hCRMP-2, thus lending further validity to our results. Conclusion Using an approach encompassing high sensitivity and high resolution, we show that alterations of SN in PD include many

  4. Human borna disease virus infection impacts host proteome and histone lysine acetylation in human oligodendroglia cells

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xia [Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Department of Neurology, The Fifth People' s Hospital of Shanghai, School of Medicine, Fudan University, Shanghai, 200240 (China); Zhao, Libo [Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Department of Neurology, The Third People' s Hospital of Chongqing, 400014 (China); Yang, Yongtao [Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, 400016 (China); Institute of Neuroscience, Chongqing Medical University, Chongqing, 400016 (China); Bode, Liv [Bornavirus Research Group affiliated to the Free University of Berlin, Berlin (Germany); Huang, Hua [Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, 400016 (China); Institute of Neuroscience, Chongqing Medical University, Chongqing, 400016 (China); Liu, Chengyu [Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, 400016 (China); Institute of Neuroscience, Chongqing Medical University, Chongqing, 400016 (China); Huang, Rongzhong [Department of Rehabilitative Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010 (China); Zhang, Liang [Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, 400016 (China); Institute of Neuroscience, Chongqing Medical University, Chongqing, 400016 (China); and others

    2014-09-15

    Background: Borna disease virus (BDV) replicates in the nucleus and establishes persistent infections in mammalian hosts. A human BDV strain was used to address the first time, how BDV infection impacts the proteome and histone lysine acetylation (Kac) of human oligodendroglial (OL) cells, thus allowing a better understanding of infection-driven pathophysiology in vitro. Methods: Proteome and histone lysine acetylation were profiled through stable isotope labeling for cell culture (SILAC)-based quantitative proteomics. The quantifiable proteome was annotated using bioinformatics. Histone acetylation changes were validated by biochemistry assays. Results: Post BDV infection, 4383 quantifiable differential proteins were identified and functionally annotated to metabolism pathways, immune response, DNA replication, DNA repair, and transcriptional regulation. Sixteen of the thirty identified Kac sites in core histones presented altered acetylation levels post infection. Conclusions: BDV infection using a human strain impacted the whole proteome and histone lysine acetylation in OL cells. - Highlights: • A human strain of BDV (BDV Hu-H1) was used to infect human oligodendroglial cells (OL cells). • This study is the first to reveal the host proteomic and histone Kac profiles in BDV-infected OL cells. • BDV infection affected the expression of many transcription factors and several HATs and HDACs.

  5. Human borna disease virus infection impacts host proteome and histone lysine acetylation in human oligodendroglia cells

    International Nuclear Information System (INIS)

    Liu, Xia; Zhao, Libo; Yang, Yongtao; Bode, Liv; Huang, Hua; Liu, Chengyu; Huang, Rongzhong; Zhang, Liang

    2014-01-01

    Background: Borna disease virus (BDV) replicates in the nucleus and establishes persistent infections in mammalian hosts. A human BDV strain was used to address the first time, how BDV infection impacts the proteome and histone lysine acetylation (Kac) of human oligodendroglial (OL) cells, thus allowing a better understanding of infection-driven pathophysiology in vitro. Methods: Proteome and histone lysine acetylation were profiled through stable isotope labeling for cell culture (SILAC)-based quantitative proteomics. The quantifiable proteome was annotated using bioinformatics. Histone acetylation changes were validated by biochemistry assays. Results: Post BDV infection, 4383 quantifiable differential proteins were identified and functionally annotated to metabolism pathways, immune response, DNA replication, DNA repair, and transcriptional regulation. Sixteen of the thirty identified Kac sites in core histones presented altered acetylation levels post infection. Conclusions: BDV infection using a human strain impacted the whole proteome and histone lysine acetylation in OL cells. - Highlights: • A human strain of BDV (BDV Hu-H1) was used to infect human oligodendroglial cells (OL cells). • This study is the first to reveal the host proteomic and histone Kac profiles in BDV-infected OL cells. • BDV infection affected the expression of many transcription factors and several HATs and HDACs

  6. Disease induction by human microbial pathogens in plant-model systems: potential, problems and prospects.

    Science.gov (United States)

    van Baarlen, Peter; van Belkum, Alex; Thomma, Bart P H J

    2007-02-01

    Relatively simple eukaryotic model organisms such as the genetic model weed plant Arabidopsis thaliana possess an innate immune system that shares important similarities with its mammalian counterpart. In fact, some human pathogens infect Arabidopsis and cause overt disease with human symptomology. In such cases, decisive elements of the plant's immune system are likely to be targeted by the same microbial factors that are necessary for causing disease in humans. These similarities can be exploited to identify elementary microbial pathogenicity factors and their corresponding targets in a green host. This circumvents important cost aspects that often frustrate studies in humans or animal models and, in addition, results in facile ethical clearance.

  7. NMR relaxation times in human brain tumors (preliminary results)

    International Nuclear Information System (INIS)

    Benoist, L.; Certaines, J. de; Chatel, M.; Menault, F.

    1981-01-01

    Since the early work of Damadian in 1971, proton NMR studies of tumors has been well documented. Present study concerns the spin-lattice T 1 and spin-spin T 2 relaxation times of normal dog brain according to the histological differentiation and of 35 human benignant or malignant tumors. The results principally show T 2 important variations between white and gray substance in normal brain but no discrimination between malignant and benignant tumors [fr

  8. FISH CONSUMPTION, METHYLMERCURY, AND HUMAN HEART DISEASE.

    Energy Technology Data Exchange (ETDEWEB)

    LIPFERT, F.W.; SULLIVAN, T.M.

    2005-09-21

    Environmental mercury continues to be of concern to public health advocates, both in the U.S. and abroad, and new research continues to be published. A recent analysis of potential health benefits of reduced mercury emissions has opened a new area of public health concern: adverse effects on the cardiovascular system, which could account for the bulk of the potential economic benefits. The authors were careful to include caveats about the uncertainties of such impacts, but they cited only a fraction of the applicable health effects literature. That literature includes studies of the potentially harmful ingredient (methylmercury, MeHg) in fish, as well as of a beneficial ingredient, omega-3 fatty acids or ''fish oils''. The U.S. Food and Drug Administration (FDA) recently certified that some of these fat compounds that are primarily found in fish ''may be beneficial in reducing coronary heart disease''. This paper briefly summarizes and categorizes the extensive literature on both adverse and beneficial links between fish consumption and cardiovascular health, which are typically based on studies of selected groups of individuals (cohorts). Such studies tend to comprise the ''gold standard'' of epidemiology, but cohorts tend to exhibit a great deal of variability, in part because of the limited numbers of individuals involved and in part because of interactions with other dietary and lifestyle considerations. Note that eating fish will involve exposure to both the beneficial effects of fatty acids and the potentially harmful effects of contaminants like Hg or PCBs, all of which depend on the type of fish but tend to be correlated within a population. As a group, the cohort studies show that eating fish tends to reduce mortality, especially due to heart disease, for consumption rates up to about twice weekly, above which the benefits tend to level off. A Finnish cohort study showed increased mortality risks

  9. Modeling cognition and disease using human glial chimeric mice

    DEFF Research Database (Denmark)

    Goldman, Steven A.; Nedergaard, Maiken; Windrem, Martha S.

    2015-01-01

    , oligodendrocytes as well. As a result, the recipient brains may become inexorably humanized with regards to their resident glial populations, yielding human glial chimeric mouse brains. These brains provide us a fundamentally new tool by which to assess the species-specific attributes of glia in modulating human...... for studying the human-specific contributions of glia to psychopathology, as well as to higher cognition. As such, the assessment of human glial chimeric mice may provide us new insight into the species-specific contributions of glia to human cognitive evolution, as well as to the pathogenesis of human...

  10. Human resource leadership: the key to improved results in health

    Directory of Open Access Journals (Sweden)

    O'Neil Mary L

    2008-06-01

    Full Text Available Abstract This article is the lead article in the Human Resources for Health journal's first quarterly feature. The series of seven articles has been contributed by Management Sciences for Health (MSH under the theme of leadership and management in public health and will be published article by article over the next few weeks. The journal has invited Dr Manuel M. Dayrit, Director of the WHO Department of Human Resources for Health and former Minister of Health for the Philippines to launch the feature with an opening editorial to be found in the journal's blog. This opening article describes the human resource challenges that managers around the world report and analyses why solutions often fail to be implemented. Despite rising attention to the acute shortage of health care workers, solutions to the human resource (HR crisis are difficult to achieve, especially in the poorest countries. Although we are aware of the issues and have developed HR strategies, the problem is that some old systems of leading and managing human resources for health do not work in today's context. The Leadership Development Program (LDP is grounded on the belief that good leadership and management can be learned and practiced at all levels. The case studies in this issue were chosen to illustrate results from using the LDP at different levels of the health sector. The LDP makes a profound difference in health managers' attitudes towards their work. Rather than feeling defeated by a workplace climate that lacks motivation, hope, and commitment to change, people report that they are mobilized to take action to change the status quo. The lesson is that without this capacity at all levels, global policy and national HR strategies will fail to make a difference.

  11. Human genomic disease variants: a neutral evolutionary explanation.

    Science.gov (United States)

    Dudley, Joel T; Kim, Yuseob; Liu, Li; Markov, Glenn J; Gerold, Kristyn; Chen, Rong; Butte, Atul J; Kumar, Sudhir

    2012-08-01

    Many perspectives on the role of evolution in human health include nonempirical assumptions concerning the adaptive evolutionary origins of human diseases. Evolutionary analyses of the increasing wealth of clinical and population genomic data have begun to challenge these presumptions. In order to systematically evaluate such claims, the time has come to build a common framework for an empirical and intellectual unification of evolution and modern medicine. We review the emerging evidence and provide a supporting conceptual framework that establishes the classical neutral theory of molecular evolution (NTME) as the basis for evaluating disease- associated genomic variations in health and medicine. For over a decade, the NTME has already explained the origins and distribution of variants implicated in diseases and has illuminated the power of evolutionary thinking in genomic medicine. We suggest that a majority of disease variants in modern populations will have neutral evolutionary origins (previously neutral), with a relatively smaller fraction exhibiting adaptive evolutionary origins (previously adaptive). This pattern is expected to hold true for common as well as rare disease variants. Ultimately, a neutral evolutionary perspective will provide medicine with an informative and actionable framework that enables objective clinical assessment beyond convenient tendencies to invoke past adaptive events in human history as a root cause of human disease.

  12. Drosophila tools and assays for the study of human diseases

    Directory of Open Access Journals (Sweden)

    Berrak Ugur

    2016-03-01

    Full Text Available Many of the internal organ systems of Drosophila melanogaster are functionally analogous to those in vertebrates, including humans. Although humans and flies differ greatly in terms of their gross morphological and cellular features, many of the molecular mechanisms that govern development and drive cellular and physiological processes are conserved between both organisms. The morphological differences are deceiving and have led researchers to undervalue the study of invertebrate organs in unraveling pathogenic mechanisms of diseases. In this review and accompanying poster, we highlight the physiological and molecular parallels between fly and human organs that validate the use of Drosophila to study the molecular pathogenesis underlying human diseases. We discuss assays that have been developed in flies to study the function of specific genes in the central nervous system, heart, liver and kidney, and provide examples of the use of these assays to address questions related to human diseases. These assays provide us with simple yet powerful tools to study the pathogenic mechanisms associated with human disease-causing genes.

  13. Research priorities for Chagas disease, human African trypanosomiasis and leishmaniasis.

    Science.gov (United States)

    2012-01-01

    This report provides a review and analysis of the research landscape for three diseases - Chagas disease, human African trypanosomiasis and leishmaniasis - that disproportionately afflict poor and remote populations with limited access to health services. It represents the work of the disease reference group on Chagas Disease, Human African Trypanosomiasis and Leishmaniasis (DRG3) which was established to identify key research priorities through review of research evidence and input from stakeholders' consultations. The diseases, which are caused by related protozoan parasites, are described in terms of their epidemiology and diseases burden, clinical forms and pathogenesis, HIV coinfection, diagnosis, drugs and drug resistance, vaccines, vector control, and health-care interventions. Priority areas for research are identified based on criteria such as public health relevance, benefit and impact on poor populations and equity, and feasibility. The priorities are found in the areas of diagnostics, drugs, vector control, asymptomatic infection, economic analysis of treatment and vector control methods, and in some specific issues such as surveillance methods or transmission-blocking vaccines for particular diseases. This report will be useful to researchers, policy and decision-makers, funding bodies, implementation organizations, and civil society. This is one of ten disease and thematic reference group reports that have come out of the TDR Think Tank, all of which have contributed to the development of the Global Report for Research on Infectious Diseases of Poverty, available at: www.who.int/tdr/stewardship/global_report/en/index.html.

  14. Disease modeling using human induced pluripotent stem cells: lessons from the liver.

    Science.gov (United States)

    Gieseck, Richard L; Colquhoun, Jennifer; Hannan, Nicholas R F

    2015-01-01

    Human pluripotent stem cells (hPSCs) have the capacity to differentiate into any of the hundreds of distinct cell types that comprise the human body. This unique characteristic has resulted in considerable interest in the field of regenerative medicine, given the potential for these cells to be used to protect, repair, or replace diseased, injured, and aged cells within the human body. In addition to their potential in therapeutics, hPSCs can be used to study the earliest stages of human development and to provide a platform for both drug screening and disease modeling using human cells. Recently, the description of human induced pluripotent stem cells (hIPSCs) has allowed the field of disease modeling to become far more accessible and physiologically relevant, as pluripotent cells can be generated from patients of any genetic background. Disease models derived from hIPSCs that manifest cellular disease phenotypes have been established to study several monogenic diseases; furthermore, hIPSCs can be used for phenotype-based drug screens to investigate complex diseases for which the underlying genetic mechanism is unknown. As a result, the use of stem cells as research tools has seen an unprecedented growth within the last decade as researchers look for in vitro disease models which closely mimic in vivo responses in humans. Here, we discuss the beginnings of hPSCs, starting with isolation of human embryonic stem cells, moving into the development and optimization of hIPSC technology, and ending with the application of hIPSCs towards disease modeling and drug screening applications, with specific examples highlighting the modeling of inherited metabolic disorders of the liver. This article is part of a Special Issue entitled Linking transcription to physiology in lipodomics. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

  15. Polycystins, calcium signaling, and human diseases

    International Nuclear Information System (INIS)

    Delmas, Patrick; Padilla, Francoise; Osorio, Nancy; Coste, Bertrand; Raoux, Matthieu; Crest, Marcel

    2004-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is a major, inherited nephropathy affecting over 1:1000 of the worldwide population. It is a systemic condition with frequent hepatic and cardiovascular manifestations in addition to the progressive development of fluid-filled cysts from the tubules and collecting ducts of affected kidneys. The pathogenesis of cyst formation is currently thought to involve increased proliferation of epithelial cells, mild dedifferentiation, and fluid accumulation. In the past decade, study of ADPKD led to the discovery of a unique family of highly complex proteins, the polycystins. Loss-of-function mutations in either of two polycystin proteins, polycystin-1 or polycystin-2, give rise to ADPKD. These proteins are thought to function together as part of a multiprotein complex that may initiate Ca 2+ signals, directing attention to the regulation of intracellular Ca 2+ as a possible misstep that participates in cyst formation. Here we review what is known about the Ca 2+ signaling functions of polycystin proteins and focus on findings that have significantly advanced our physiological insight. Special attention is paid to the recently discovered role of these proteins in the mechanotransduction of the renal primary cilium and the model it suggests

  16. Rare human diseases: 9p deletion syndrome

    Directory of Open Access Journals (Sweden)

    Galagan V.O.

    2014-09-01

    Full Text Available Objective of the study was to review the anamnesis, pheno - and genotype in patients with rare chromosome disorders such as 9p deletion syndrome. Genetic methods of investigation (clinical and genealogical, cytogenetic, FISH- method, paraclinical and instrumental methods of examination were used. Karyotyping was performed by the G-method of differential staining of chromosomes. Only three cases of pathology were diagnosed in the Medical Genetics Center over the last 10 years. By anamnesis data nobody in the probands’ families had bad habits, was exposed to occupational hazards, took part in the elimination of the Chernobyl accident or lived in contaminated areas. Clinical signs of diseases have not been identified in probands’ parents. All probands had trigonocephaly, bilateral epicanthal folds, ocular hypertelorism, downslanting palpebral fissures, long philtrum, flat face and nasal bridge, low set ears with malformed auricles. Two patients of three ones had exophthalmos, contracture of the second and third fingers, abnormal external genitalia. In all three cases there was monosomy of chromosome 9 of critical segment p 24. Normal karyotypes were seen in all parents, so there were three cases of new mutations of 9p deletion syndrome. Retardation of physical, psycho-spech, mental development in proband with or without congenital anomalies requires medical genetic counseling in a specialized institution. Cases of reproductive loss in anamnesis require cytogenetic investigation of fetal membranes and amniotic fluid.

  17. Spiral Form of the Human Cochlea Results from Spatial Constraints.

    Science.gov (United States)

    Pietsch, M; Aguirre Dávila, L; Erfurt, P; Avci, E; Lenarz, T; Kral, A

    2017-08-08

    The human inner ear has an intricate spiral shape often compared to shells of mollusks, particularly to the nautilus shell. It has inspired many functional hearing theories. The reasons for this complex geometry remain unresolved. We digitized 138 human cochleae at microscopic resolution and observed an astonishing interindividual variability in the shape. A 3D analytical cochlear model was developed that fits the analyzed data with high precision. The cochlear geometry neither matched a proposed function, namely sound focusing similar to a whispering gallery, nor did it have the form of a nautilus. Instead, the innate cochlear blueprint and its actual ontogenetic variants were determined by spatial constraints and resulted from an efficient packing of the cochlear duct within the petrous bone. The analytical model predicts well the individual 3D cochlear geometry from few clinical measures and represents a clinical tool for an individualized approach to neurosensory restoration with cochlear implants.

  18. Revascularization experience and results in ischaemic cerebrovascular disease: Moyamoya disease and carotid occlusion.

    Science.gov (United States)

    Arikan, Fuat; Rubiera, Marta; Serena, Joaquín; Rodríguez-Hernández, Ana; Gándara, Darío; Lorenzo-Bosquet, Carles; Tomasello, Alejandro; Chocrón, Ivette; Quintana-Corvalan, Maximiliano; Sahuquillo, Juan

    2018-03-14

    Cerebral revascularization techniques are an indispensable tool in the current armamentarium of vascular neurosurgeons. We present revascularization surgery experience and results in both moyamoya disease and occlusive cerebral ischaemia. Patients with ischaemic occlusive disease and moyamoya disease who underwent microsurgical revascularization between October 2014 and September 2017 were analysed. In the study period, 23 patients with occlusive ischaemic disease underwent microsurgical revascularization. Three patients presented with serious postoperative complications (2 intraparenchymal haemorrhages in the immediate postoperative period and one thrombosis of the femoral artery). All patients, except one, achieved normalization of the cerebral hemodynamic reserve (CHR) in the SPECT study. Twenty patients had a good neurological result, with no ischaemic recurrence of the revascularized territory. Among patients with moyamoya, 20 had moyamoya disease and 5 had moyamoya syndrome with unilateral involvement. Five patients were treated at paediatric age. Haemorrhagic onset occurred in 2 patients. The CHR study showed hemodynamic compromise in all patients. Cerebral SPECT at one year showed resolution of the hemodynamic failure in all patients. There have been 4 postoperative complications (acute subdural hematoma, two subdural collections and one dehiscence of the surgical wound). No patient presented with neurological worsening at 6 and 12months of follow-up. Cerebral revascularization through end-to-side anastomosis between the superficial temporal artery and a cortical branch of the middle cerebral artery is an indisputable technique in the treatment of moyamoya disease and possibly in a subgroup of patients with symptomatic occlusive ischaemic cerebrovascular disease. Copyright © 2018 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. Human lipodystrophies: genetic and acquired diseases of adipose tissue

    Science.gov (United States)

    Capeau, Jacqueline; Magré, Jocelyne; Caron-Debarle, Martine; Lagathu, Claire; Antoine, Bénédicte; Béréziat, Véronique; Lascols, Olivier; Bastard, Jean-Philippe; Vigouroux, Corinne

    2010-01-01

    Human lipodystrophies represent a heterogeneous group of diseases characterized by generalized or partial fat loss, with fat hypertrophy in other depots when partial. Insulin resistance, dyslipidemia and diabetes are generally associated, leading to early complications. Genetic forms are uncommon: recessive generalized congenital lipodystrophies result in most cases from mutations in the genes encoding seipin or the 1-acyl-glycerol-3-phosphate-acyltransferase 2 (AGPAT2). Dominant partial familial lipodystrophies result from mutations in genes encoding the nuclear protein lamin A/C or the adipose transcription factor PPARγ. Importantly, lamin A/C mutations are also responsible for metabolic laminopathies, resembling the metabolic syndrome and progeria, a syndrome of premature aging. A number of lipodystrophic patients remain undiagnosed at the genetic level. Acquired lipodystrophy can be generalized, resembling congenital forms, or partial, as the Barraquer-Simons syndrome, with loss of fat in the upper part of the body contrasting with accumulation in the lower part. Although their aetiology is generally unknown, they could be associated with signs of auto-immunity. The most common forms of lipodystrophies are iatrogenic. In human immunodeficiency virus-infected patients, some first generation antiretroviral drugs were strongly related with peripheral lipoatrophy and metabolic alterations. Partial lipodystrophy also characterize patients with endogenous or exogenous long-term corticoid excess. Treatment of fat redistribution can sometimes benefit from plastic surgery. Lipid and glucose alterations are difficult to control leading to early occurrence of diabetic, cardio-vascular and hepatic complications. PMID:20551664

  20. Infectious prion diseases in humans: cannibalism, iatrogenicity and zoonoses.

    Science.gov (United States)

    Haïk, Stéphane; Brandel, Jean-Philippe

    2014-08-01

    In contrast with other neurodegenerative disorders associated to protein misfolding, human prion diseases include infectious forms (also called transmitted forms) such as kuru, iatrogenic Creutzfeldt-Jakob disease and variant Creutzfeldt-Jakob disease. The transmissible agent is thought to be solely composed of the abnormal isoform (PrP(Sc)) of the host-encoded prion protein that accumulated in the central nervous system of affected individuals. Compared to its normal counterpart, PrP(Sc) is β-sheet enriched and aggregated and its propagation is based on an autocatalytic conversion process. Increasing evidence supports the view that conformational variations of PrP(Sc) encoded the biological properties of the various prion strains that have been isolated by transmission studies in experimental models. Infectious forms of human prion diseases played a pivotal role in the emergence of the prion concept and in the characterization of the very unconventional properties of prions. They provide a unique model to understand how prion strains are selected and propagate in humans. Here, we review and discuss how genetic factors interplay with strain properties and route of transmission to influence disease susceptibility, incubation period and phenotypic expression in the light of the kuru epidemics due to ritual endocannibalism, the various series iatrogenic diseases secondary to extractive growth hormone treatment or dura mater graft and the epidemics of variant Creutzfeldt-Jakob disease linked to dietary exposure to the agent of bovine spongiform encephalopathy. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Modelling Neurodegenerative Diseases Using Human Pluripotent Stem Cells

    DEFF Research Database (Denmark)

    Hall, Vanessa Jane

    2016-01-01

    Neurodegenerative diseases are being modelled in-vitro using human patient-specific, induced pluripotent stem cells and transgenic embryonic stem cells to determine more about disease mechanisms, as well as to discover new treatments for patients. Current research in modelling Alzheimer’s disease......, frontotemporal dementia and Parkinson’s disease using pluripotent stem cells is described, along with the advent of gene-editing, which has been the complimentary tool for the field. Current methods used to model these diseases are predominantly dependent on 2D cell culture methods. Outcomes reveal that only...... that includes studying more complex 3D cell cultures, as well as accelerating aging of the neurons, may help to yield stronger phenotypes in the cultured cells. Thus, the use and application of pluripotent stem cells for modelling disease have already shown to be a powerful approach for discovering more about...

  2. Direct Lineage Reprogramming Reveals Disease-Specific Phenotypes of Motor Neurons from Human ALS Patients

    Directory of Open Access Journals (Sweden)

    Meng-Lu Liu

    2016-01-01

    Full Text Available Subtype-specific neurons obtained from adult humans will be critical to modeling neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS. Here, we show that adult human skin fibroblasts can be directly and efficiently converted into highly pure motor neurons without passing through an induced pluripotent stem cell stage. These adult human induced motor neurons (hiMNs exhibit the cytological and electrophysiological features of spinal motor neurons and form functional neuromuscular junctions (NMJs with skeletal muscles. Importantly, hiMNs converted from ALS patient fibroblasts show disease-specific degeneration manifested through poor survival, soma shrinkage, hypoactivity, and an inability to form NMJs. A chemical screen revealed that the degenerative features of ALS hiMNs can be remarkably rescued by the small molecule kenpaullone. Taken together, our results define a direct and efficient strategy to obtain disease-relevant neuronal subtypes from adult human patients and reveal their promising value in disease modeling and drug identification.

  3. Genetic engineering in nonhuman primates for human disease modeling.

    Science.gov (United States)

    Sato, Kenya; Sasaki, Erika

    2018-02-01

    Nonhuman primate (NHP) experimental models have contributed greatly to human health research by assessing the safety and efficacy of newly developed drugs, due to their physiological and anatomical similarities to humans. To generate NHP disease models, drug-inducible methods, and surgical treatment methods have been employed. Recent developments in genetic and developmental engineering in NHPs offer new options for producing genetically modified disease models. Moreover, in recent years, genome-editing technology has emerged to further promote this trend and the generation of disease model NHPs has entered a new era. In this review, we summarize the generation of conventional disease model NHPs and discuss new solutions to the problem of mosaicism in genome-editing technology.

  4. Results of radioiodine therapy of benign thyroid disease

    International Nuclear Information System (INIS)

    Pronath, A.

    1982-01-01

    The goal of this work is the quantification of therapy results of a radioiodine therapy with Iodine 131 on 367 patients with the following benign thyroid diseases: euthyroidal struma, hyperthyroidism, hyperthyroidal struma and autonomous adenoma. 1. Euthyroidal struma - subjective improvement and objective diminution of the struma by 63%, subjective or objective improvement by 21% of the patients. Including the probable successful therapies the success rate was all together 90.1%. 2. Hyperthyroidism - after one-time/more-time (18.6%) radioiodine therapy the success rate was 71.5/85.7% including latent (8.6/10.0%) and manifest (7.1/8.5%) hypothroidism. 3. Hyperthyroidal struma - after one-time/more-time (16.9%) radioiodine therapy the success rate was 74.7/90.1% including latent (-/5.7%) and manifest (1.4/2.8%) hypothyroidism. 4. Autonomous adenoma - after one-time/two-time (5.2%) radioiodine therapy the success rate was 80.5/84.6% including 15.5% latent hypothyroidism. The results will be discussed in comparison to published data and to operation and thyrostatic treatment. (TRV) [de

  5. Natural selection and infectious disease in human populations

    Science.gov (United States)

    Karlsson, Elinor K.; Kwiatkowski, Dominic P.; Sabeti, Pardis C.

    2015-01-01

    The ancient biological 'arms race' between microbial pathogens and humans has shaped genetic variation in modern populations, and this has important implications for the growing field of medical genomics. As humans migrated throughout the world, populations encountered distinct pathogens, and natural selection increased the prevalence of alleles that are advantageous in the new ecosystems in both host and pathogens. This ancient history now influences human infectious disease susceptibility and microbiome homeostasis, and contributes to common diseases that show geographical disparities, such as autoimmune and metabolic disorders. Using new high-throughput technologies, analytical methods and expanding public data resources, the investigation of natural selection is leading to new insights into the function and dysfunction of human biology. PMID:24776769

  6. Human genetics of infectious diseases: a unified theory

    OpenAIRE

    Casanova, Jean-Laurent; Abel, Laurent

    2007-01-01

    Since the early 1950s, the dominant paradigm in the human genetics of infectious diseases postulates that rare monogenic immunodeficiencies confer vulnerability to multiple infectious diseases (one gene, multiple infections), whereas common infections are associated with the polygenic inheritance of multiple susceptibility genes (one infection, multiple genes). Recent studies, since 1996 in particular, have challenged this view. A newly recognised group of primary immunodeficiencies predispos...

  7. Genome editing of human pluripotent stem cells to generate human cellular disease models

    Directory of Open Access Journals (Sweden)

    Kiran Musunuru

    2013-07-01

    Full Text Available Disease modeling with human pluripotent stem cells has come into the public spotlight with the awarding of the Nobel Prize in Physiology or Medicine for 2012 to Drs John Gurdon and Shinya Yamanaka for the discovery that mature cells can be reprogrammed to become pluripotent. This discovery has opened the door for the generation of pluripotent stem cells from individuals with disease and the differentiation of these cells into somatic cell types for the study of disease pathophysiology. The emergence of genome-editing technology over the past few years has made it feasible to generate and investigate human cellular disease models with even greater speed and efficiency. Here, recent technological advances in genome editing, and its utility in human biology and disease studies, are reviewed.

  8. Linking adult hippocampal neurogenesis with human physiology and disease.

    Science.gov (United States)

    Bowers, Megan; Jessberger, Sebastian

    2016-07-01

    We here review the existing evidence linking adult hippocampal neurogenesis and human brain function in physiology and disease. Furthermore, we aim to point out where evidence is missing, highlight current promising avenues of investigation, and suggest future tools and approaches to foster the link between life-long neurogenesis and human brain function. Developmental Dynamics 245:702-709, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  9. Interconnectivity of human cellular metabolism and disease prevalence

    Science.gov (United States)

    Lee, Deok-Sun

    2010-12-01

    Fluctuations of metabolic reaction fluxes may cause abnormal concentrations of toxic or essential metabolites, possibly leading to metabolic diseases. The mutual binding of enzymatic proteins and ones involving common metabolites enforces distinct coupled reactions, by which local perturbations may spread through the cellular network. Such network effects at the molecular interaction level in human cellular metabolism can reappear in the patterns of disease occurrence. Here we construct the enzyme-reaction network and the metabolite-reaction network, capturing the flux coupling of metabolic reactions caused by the interacting enzymes and the shared metabolites, respectively. Diseases potentially caused by the failure of individual metabolic reactions can be identified by using the known disease-gene association, which allows us to derive the probability of an inactivated reaction causing diseases from the disease records at the population level. We find that the greater the number of proteins that catalyze a reaction, the higher the mean prevalence of its associated diseases. Moreover, the number of connected reactions and the mean size of the avalanches in the networks constructed are also shown to be positively correlated with the disease prevalence. These findings illuminate the impact of the cellular network topology on disease development, suggesting that the global organization of the molecular interaction network should be understood to assist in disease diagnosis, treatment, and drug discovery.

  10. [Results of anastomotic urethroplasty for male urethral stricture disease].

    Science.gov (United States)

    Fall, B; Zeondo, C; Sow, Y; Sarr, A; Sine, B; Thiam, A; Faye, S T; Sow, O; Traoré, A; Diao, B; Fall, P A; Ndoye, A K; Ba, M

    2018-04-04

    To report our experience with anastomotic uretroplasty (AU) due to male urethral stricture disease (USD) and to identify factors affecting the results. We conducted a retrospective study over a period of 4 years and 6 months (July 2012 to December 2016). Any subsequent use of endoscopic urethrotomy or new urethroplasty was considered a failure. Forty-eight cases were included. The mean age of patients was 53.5±17.3 years (23-87 years). Urinary retention was the reason for consultation in 42 cases (87.5%). The most common localization of USD was the bulbar urethra (n=45). The mean length of USD was 1.23±0.62cm (0.5-3cm) with a median length of 1cm. The etiology was post-infectious in 56.3% of cases. More than half (58.3%) of patients had already undergone at least one urethral manipulation. After an average follow-up of 21.1±12.6 months (1 to 52 months), the overall success rate was 77.1%. In univariate analysis, length, cause and location of the stricture, age of patient, the presenting symptoms of the stricture, previous urethral manipulation and surgeon experience did not significantly impact on the success rate of anastomotic urethroplasty at one and two years follow-up. The AU had provided good results in our practice. The infectious origin of the stricture and previous urethral manipulation did not significantly impact the result of this surgical technique. 4. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  11. Bowen's Disease Associated With Two Human Papilloma Virus Types.

    Science.gov (United States)

    Eftekhari, Hojat; Gharaei Nejad, Kaveh; Azimi, Seyyede Zeinab; Rafiei, Rana; Mesbah, Alireza

    2017-09-01

    Bowen's disease (BD) is an epidermal in-situ squamous cell carcinoma (SCC). Most Human Papilloma Viruses (HPV)-positive lesions in Bowen's disease are localized to the genital region or distal extremities (periungual sites) in which HPV type-16 is frequently detected. Patient was a 64-year-old construction worker for whom we detected 2 erythematous psoriasiform reticular scaly plaques on peri-umbilical and medial knee. Biopsy established the diagnosis of Bowen's disease and polymerase chain reaction assay showed HPV-6, -18 co-infection. Patient was referred for surgical excision.

  12. Human gene therapy and imaging in neurological diseases

    International Nuclear Information System (INIS)

    Jacobs, Andreas H.; Winkler, Alexandra; Castro, Maria G.; Lowenstein, Pedro

    2005-01-01

    Molecular imaging aims to assess non-invasively disease-specific biological and molecular processes in animal models and humans in vivo. Apart from precise anatomical localisation and quantification, the most intriguing advantage of such imaging is the opportunity it provides to investigate the time course (dynamics) of disease-specific molecular events in the intact organism. Further, molecular imaging can be used to address basic scientific questions, e.g. transcriptional regulation, signal transduction or protein/protein interaction, and will be essential in developing treatment strategies based on gene therapy. Most importantly, molecular imaging is a key technology in translational research, helping to develop experimental protocols which may later be applied to human patients. Over the past 20 years, imaging based on positron emission tomography (PET) and magnetic resonance imaging (MRI) has been employed for the assessment and ''phenotyping'' of various neurological diseases, including cerebral ischaemia, neurodegeneration and brain gliomas. While in the past neuro-anatomical studies had to be performed post mortem, molecular imaging has ushered in the era of in vivo functional neuro-anatomy by allowing neuroscience to image structure, function, metabolism and molecular processes of the central nervous system in vivo in both health and disease. Recently, PET and MRI have been successfully utilised together in the non-invasive assessment of gene transfer and gene therapy in humans. To assess the efficiency of gene transfer, the same markers are being used in animals and humans, and have been applied for phenotyping human disease. Here, we review the imaging hallmarks of focal and disseminated neurological diseases, such as cerebral ischaemia, neurodegeneration and glioblastoma multiforme, as well as the attempts to translate gene therapy's experimental knowledge into clinical applications and the way in which this process is being promoted through the use of

  13. Consent: a Cartesian ideal? Human neural transplantation in Parkinson's disease.

    Science.gov (United States)

    Lopes, Manuel; Meningaud, Jean-Paul; Behin, Anthony; Hervé, Christian

    2003-01-01

    The grafting of human embryonic cells in Parkinson's disease is an innovative and hopefully useful therapeutic approach. However, it still concerns a very small number of patients and is only suggested as a research protocol. We present here a study of the problems of information and consent to research within the framework of this disease in which the efficacy of medical treatment is shortlived. The only French center to use this treatment (Hôpital H. Mondor in Créteil) has received authorization from the Comité Consultatif National d'Ethique (Consultative National Committee on Ethics). Eleven patients were treated between 1991 and 1998. The study of the results of a questionnaire sent to those patients showed the difficulties met in evaluating the perception of information despite intact intellectual capacities in people "prepared to risk everything." In France, the duty to inform patients during research procedures is regulated by the Huriet Act. However, it is not easy to guarantee genuine consent when preliminary information is given to patients psychologically impaired by the slow and ineluctable course of their disease. In these borderline cases, a valid consent seems to be a myth in terms of pure autonomy when considered with the Cartesian aim of elimination of uncertainty. The relevance of this concept of genuine consent probably makes more sense as aiming at a Cartesian ideal which is perhaps more in the spirit rather than in the letter. It is in that same spirit that, from the outset, we propose to define t he practical ways of answering the patients' request for information, even sometimes after consent has been given.

  14. Effects of antibiotics on human microbiota and subsequent disease.

    Science.gov (United States)

    Keeney, Kristie M; Yurist-Doutsch, Sophie; Arrieta, Marie-Claire; Finlay, B Brett

    2014-01-01

    Although antibiotics have significantly improved human health and life expectancy, their disruption of the existing microbiota has been linked to significant side effects such as antibiotic-associated diarrhea, pseudomembranous colitis, and increased susceptibility to subsequent disease. By using antibiotics to break colonization resistance against Clostridium, Salmonella, and Citrobacter species, researchers are now exploring mechanisms for microbiota-mediated modulation against pathogenic infection, revealing potential roles for different phyla and family members as well as microbiota-liberated sugars, hormones, and short-chain fatty acids in regulating pathogenicity. Furthermore, connections are now being made between microbiota dysbiosis and a variety of different diseases such as rheumatoid arthritis, inflammatory bowel disease, type 1 diabetes, atopy, and obesity. Future advances in the rapidly developing field of microbial bioinformatics will enable researchers to further characterize the mechanisms of microbiota modulation of disease and potentially identify novel therapeutics against disease.

  15. Human heart disease : lessons from human pluripotent stem cell-derived cardiomyocytes

    NARCIS (Netherlands)

    Giacomelli, E.; Mummery, C.L.; Bellin, M.

    2017-01-01

    Technical advances in generating and phenotyping cardiomyocytes from human pluripotent stem cells (hPSC-CMs) are now driving their wider acceptance as in vitro models to understand human heart disease and discover therapeutic targets that may lead to new compounds for clinical use. Current

  16. Economic downturn results in tick-borne disease upsurge

    Directory of Open Access Journals (Sweden)

    Randolph Sarah E

    2011-03-01

    Full Text Available Abstract Background The emergence of zoonoses is due both to changes in human activities and to changes in their natural wildlife cycles. One of the most significant vector-borne zoonoses in Europe, tick-borne encephalitis (TBE, doubled in incidence in 1993, largely as a consequence of the socio-economic transition from communism to capitalism and associated environmental changes. Methods To test the effect of the current economic recession, unemployment in 2009 and various socio-economic indices were compared to weather indices (derived from principal component analyses as predictors for the change in TBE case numbers in 2009 relative to 2004-08, for 14 European countries. Results Greatest increases in TBE incidence occurred in Latvia, Lithuania and Poland (91, 79 and 45%, respectively. The weather was rejected as an explanatory variable. Indicators of high background levels of poverty, e.g. percent of household expenditure on food, were significant predictors. The increase in unemployment in 2009 relative to 2008 together with 'in-work risk of poverty' is the only case in which a multivariate model has a second significant term. Conclusion Background socio-economic conditions determine susceptibility to risk of TBE, while increased unemployment triggered a sudden increase in risk. Mechanisms behind this result may include reduced resistance to infection through stress; reduced uptake of costly vaccination; and more exposure of people to infected ticks in their forest habitat as they make greater use of wild forest foods, especially in those countries, Lithuania and Poland, with major marketing opportunities in such products. Recognition of these risk factors could allow more effective protection through education and a vaccination programme targeted at the economically most vulnerable.

  17. Interconnectivity of human cellular metabolism and disease prevalence

    International Nuclear Information System (INIS)

    Lee, Deok-Sun

    2010-01-01

    Fluctuations of metabolic reaction fluxes may cause abnormal concentrations of toxic or essential metabolites, possibly leading to metabolic diseases. The mutual binding of enzymatic proteins and ones involving common metabolites enforces distinct coupled reactions, by which local perturbations may spread through the cellular network. Such network effects at the molecular interaction level in human cellular metabolism can reappear in the patterns of disease occurrence. Here we construct the enzyme-reaction network and the metabolite-reaction network, capturing the flux coupling of metabolic reactions caused by the interacting enzymes and the shared metabolites, respectively. Diseases potentially caused by the failure of individual metabolic reactions can be identified by using the known disease–gene association, which allows us to derive the probability of an inactivated reaction causing diseases from the disease records at the population level. We find that the greater the number of proteins that catalyze a reaction, the higher the mean prevalence of its associated diseases. Moreover, the number of connected reactions and the mean size of the avalanches in the networks constructed are also shown to be positively correlated with the disease prevalence. These findings illuminate the impact of the cellular network topology on disease development, suggesting that the global organization of the molecular interaction network should be understood to assist in disease diagnosis, treatment, and drug discovery

  18. Cross-pollination of research findings, although uncommon, may accelerate discovery of human disease genes

    Directory of Open Access Journals (Sweden)

    Duda Marlena

    2012-11-01

    Full Text Available Abstract Background Technological leaps in genome sequencing have resulted in a surge in discovery of human disease genes. These discoveries have led to increased clarity on the molecular pathology of disease and have also demonstrated considerable overlap in the genetic roots of human diseases. In light of this large genetic overlap, we tested whether cross-disease research approaches lead to faster, more impactful discoveries. Methods We leveraged several gene-disease association databases to calculate a Mutual Citation Score (MCS for 10,853 pairs of genetically related diseases to measure the frequency of cross-citation between research fields. To assess the importance of cooperative research, we computed an Individual Disease Cooperation Score (ICS and the average publication rate for each disease. Results For all disease pairs with one gene in common, we found that the degree of genetic overlap was a poor predictor of cooperation (r2=0.3198 and that the vast majority of disease pairs (89.56% never cited previous discoveries of the same gene in a different disease, irrespective of the level of genetic similarity between the diseases. A fraction (0.25% of the pairs demonstrated cross-citation in greater than 5% of their published genetic discoveries and 0.037% cross-referenced discoveries more than 10% of the time. We found strong positive correlations between ICS and publication rate (r2=0.7931, and an even stronger correlation between the publication rate and the number of cross-referenced diseases (r2=0.8585. These results suggested that cross-disease research may have the potential to yield novel discoveries at a faster pace than singular disease research. Conclusions Our findings suggest that the frequency of cross-disease study is low despite the high level of genetic similarity among many human diseases, and that collaborative methods may accelerate and increase the impact of new genetic discoveries. Until we have a better

  19. Lipid metabolism in peroxisomes in relation to human disease

    NARCIS (Netherlands)

    Wanders, R. J.; Tager, J. M.

    1998-01-01

    Peroxisomes were long believed to play only a minor role in cellular metabolism but it is now clear that they catalyze a number of important functions. The importance of peroxisomes in humans is stressed by the existence of a group of genetic diseases in man in which one or more peroxisomal

  20. Gene therapy in nonhuman primate models of human autoimmune disease

    NARCIS (Netherlands)

    t'Hart, B. A.; Vervoordeldonk, M.; Heeney, J. L.; Tak, P. P.

    2003-01-01

    Before autoimmune diseases in humans can be treated with gene therapy, the safety and efficacy of the used vectors must be tested in valid experimental models. Monkeys, such as the rhesus macaque or the common marmoset, provide such models. This publication reviews the state of the art in monkey

  1. Foresight Infectious Diseases China Project--a novel approach to anticipating future trends in risk of infectious diseases in China: methodology and results from an initial application.

    Science.gov (United States)

    Nicoll, A; Huang, J; Xie, Z

    2009-07-09

    The project devised a simple but novel methodology for identifying possible future trends in infectious diseases in animals and humans in China, of priority concern to the Chinese authorities. It used a model of disease drivers (social, economic, biological or environmental factors that affect disease outcomes, by changing the behaviour of diseases, sources or pathways) devised for the Foresight Programme in the United Kingdom. Nine families of drivers were adapted to Chinese circumstances and matrices were constructed to identify the likely relationship of single infectious diseases or families of diseases to the drivers. The likely future trends in those drivers in China were determined by interviews with 36 independent Chinese experts. These trends included not only potentially adverse animal and human movements but also opportunities for innovative surveillance methods, more use of hospitals, antimicrobials and vaccines. Some human behaviours and social trends were expected to increase the risk of infections (in particular sexually transmitted and healthcare-associated infections) while at the same time the experts thought the awareness of risk in the Chinese population would increase. The results suggested a number of areas where the Chinese authorities may experience difficulties in the future, such as rising numbers of healthcare-associated infections, zoonoses and other emerging diseases and sexually transmitted infections (including HIV). Not making firm predictions, this work identifies priority disease groups requiring surveillance and consideration of countermeasures as well as recommending strengthening basic surveillance and response mechanisms for unanticipatable zoonoses and other emerging disease threats.

  2. [Leprosy, a pillar of human genetics of infectious diseases].

    Science.gov (United States)

    Gaschignard, J; Scurr, E; Alcaïs, A

    2013-06-01

    Despite a natural reservoir of Mycobacterium leprae limited to humans and free availability of an effective antibiotic treatment, more than 200,000 people develop leprosy each year. This disease remains a major cause of disability and social stigma worldwide. The cause of this constant incidence is currently unknown and indicates that important aspects of the complex relationship between the pathogen and its human host remain to be discovered. An important contribution of host genetics to susceptibility to leprosy has long been suggested to account for the considerable variability between individuals sustainably exposed to M. leprae. Given the inability to cultivate M. leprae in vitro and in the absence of relevant animal model, genetic epidemiology is the main strategy used to identify the genes and, consequently, the immunological pathways involved in protective immunity to M. leprae. Recent genome-wide studies have identified new pathophysiological pathways which importance is only beginning to be understood. In addition, the prism of human genetics placed leprosy at the crossroads of other common diseases such as Crohn's disease, asthma or myocardial infarction. Therefore, novel lights on the pathogenesis of many common diseases could eventually emerge from the detailed understanding of a disease of the shadows. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  3. Single-Domain Antibodies As Therapeutics against Human Viral Diseases

    Directory of Open Access Journals (Sweden)

    Yanling Wu

    2017-12-01

    Full Text Available In full-size formats, monoclonal antibodies have been highly successful as therapeutics against cancer and immune diseases. However, their large size leads to inaccessibility of some epitopes and relatively high production costs. As an alternative, single-domain antibodies (sdAbs offer special advantages compared to full-size antibodies, including smaller size, larger number of accessible epitopes, relatively low production costs and improved robustness. Currently, sdAbs are being developed against a number of viruses, including human immunodeficiency virus-1 (HIV-1, influenza viruses, hepatitis C virus (HCV, respiratory syncytial virus (RSV, and enteric viruses. Although sdAbs are very potent inhibitors of viral infections, no sdAbs have been approved for clinical use against virial infection or any other diseases. In this review, we discuss the current state of research on sdAbs against viruses and their potential as therapeutics against human viral diseases.

  4. Human genetics of infectious diseases: a unified theory

    Science.gov (United States)

    Casanova, Jean-Laurent; Abel, Laurent

    2007-01-01

    Since the early 1950s, the dominant paradigm in the human genetics of infectious diseases postulates that rare monogenic immunodeficiencies confer vulnerability to multiple infectious diseases (one gene, multiple infections), whereas common infections are associated with the polygenic inheritance of multiple susceptibility genes (one infection, multiple genes). Recent studies, since 1996 in particular, have challenged this view. A newly recognised group of primary immunodeficiencies predisposing the individual to a principal or single type of infection is emerging. In parallel, several common infections have been shown to reflect the inheritance of one major susceptibility gene, at least in some populations. This novel causal relationship (one gene, one infection) blurs the distinction between patient-based Mendelian genetics and population-based complex genetics, and provides a unified conceptual frame for exploring the molecular genetic basis of infectious diseases in humans. PMID:17255931

  5. Impact of climate change on human infectious diseases: Empirical evidence and human adaptation.

    Science.gov (United States)

    Wu, Xiaoxu; Lu, Yongmei; Zhou, Sen; Chen, Lifan; Xu, Bing

    2016-01-01

    Climate change refers to long-term shifts in weather conditions and patterns of extreme weather events. It may lead to changes in health threat to human beings, multiplying existing health problems. This review examines the scientific evidences on the impact of climate change on human infectious diseases. It identifies research progress and gaps on how human society may respond to, adapt to, and prepare for the related changes. Based on a survey of related publications between 1990 and 2015, the terms used for literature selection reflect three aspects--the components of infectious diseases, climate variables, and selected infectious diseases. Humans' vulnerability to the potential health impacts by climate change is evident in literature. As an active agent, human beings may control the related health effects that may be effectively controlled through adopting proactive measures, including better understanding of the climate change patterns and of the compound disease-specific health effects, and effective allocation of technologies and resources to promote healthy lifestyles and public awareness. The following adaptation measures are recommended: 1) to go beyond empirical observations of the association between climate change and infectious diseases and develop more scientific explanations, 2) to improve the prediction of spatial-temporal process of climate change and the associated shifts in infectious diseases at various spatial and temporal scales, and 3) to establish locally effective early warning systems for the health effects of predicated climate change. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Economic downturn results in tick-borne disease upsurge.

    Science.gov (United States)

    Godfrey, Elinor R; Randolph, Sarah E

    2011-03-15

    The emergence of zoonoses is due both to changes in human activities and to changes in their natural wildlife cycles. One of the most significant vector-borne zoonoses in Europe, tick-borne encephalitis (TBE), doubled in incidence in 1993, largely as a consequence of the socio-economic transition from communism to capitalism and associated environmental changes. To test the effect of the current economic recession, unemployment in 2009 and various socio-economic indices were compared to weather indices (derived from principal component analyses) as predictors for the change in TBE case numbers in 2009 relative to 2004-08, for 14 European countries. Greatest increases in TBE incidence occurred in Latvia, Lithuania and Poland (91, 79 and 45%, respectively). The weather was rejected as an explanatory variable. Indicators of high background levels of poverty, e.g. percent of household expenditure on food, were significant predictors. The increase in unemployment in 2009 relative to 2008 together with 'in-work risk of poverty' is the only case in which a multivariate model has a second significant term. Background socio-economic conditions determine susceptibility to risk of TBE, while increased unemployment triggered a sudden increase in risk. Mechanisms behind this result may include reduced resistance to infection through stress; reduced uptake of costly vaccination; and more exposure of people to infected ticks in their forest habitat as they make greater use of wild forest foods, especially in those countries, Lithuania and Poland, with major marketing opportunities in such products. Recognition of these risk factors could allow more effective protection through education and a vaccination programme targeted at the economically most vulnerable.

  7. Human brucellosis in France in the 21st century: Results from national surveillance 2004-2013.

    Science.gov (United States)

    Mailles, A; Garin-Bastuji, B; Lavigne, J P; Jay, M; Sotto, A; Maurin, M; Pelloux, I; O'Callaghan, D; Mick, V; Vaillant, V; De Valk, H

    2016-12-01

    Brucellosis is a bacterial zoonotic disease mainly transmitted to humans by ruminants. In France, brucellosis has disappeared from ruminants herds. Human brucellosis surveillance is performed through mandatory notification and the national reference center. We report the results of human brucellosis surveillance from 2004 to 2013 with regards to epidemiological, clinical and microbiological data. A total of 250 cases were notified, making an annual incidence of 0.3 cases per million inhabitants. Brucella melitensis biovar 3 was the most frequently identified bacterium (79% of isolated strains). In total, 213 (85%) cases had been contaminated abroad in endemic countries. In 2012, an episode of re-emergence of brucellosis in cattle occurred in Haute-Savoie, in the French Alps, and was responsible for 2 human cases. Brucellosis has become a disease of travelers in France. However, maintaining a stringent epidemiological surveillance is necessary to be able to early detect any local re-emergence in humans or animals. The multidisciplinary surveillance was implemented in France years ago and is a successful example of the One Health Concept. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  8. Vibrio cholerae Infection of Drosophilamelanogaster Mimics the Human Disease Cholera.

    Directory of Open Access Journals (Sweden)

    2005-09-01

    Full Text Available Cholera, the pandemic diarrheal disease caused by the gram-negative bacterium Vibrio cholerae, continues to be a major public health challenge in the developing world. Cholera toxin, which is responsible for the voluminous stools of cholera, causes constitutive activation of adenylyl cyclase, resulting in the export of ions into the intestinal lumen. Environmental studies have demonstrated a close association between V. cholerae and many species of arthropods including insects. Here we report the susceptibility of the fruit fly, Drosophila melanogaster, to oral V. cholerae infection through a process that exhibits many of the hallmarks of human disease: (i death of the fly is dependent on the presence of cholera toxin and is preceded by rapid weight loss; (ii flies harboring mutant alleles of either adenylyl cyclase, Gsalpha, or the Gardos K channel homolog SK are resistant to V. cholerae infection; and (iii ingestion of a K channel blocker along with V. cholerae protects wild-type flies against death. In mammals, ingestion of as little as 25 mug of cholera toxin results in massive diarrhea. In contrast, we found that ingestion of cholera toxin was not lethal to the fly. However, when cholera toxin was co-administered with a pathogenic strain of V. cholerae carrying a chromosomal deletion of the genes encoding cholera toxin, death of the fly ensued. These findings suggest that additional virulence factors are required for intoxication of the fly that may not be essential for intoxication of mammals. Furthermore, we demonstrate for the first time the mechanism of action of cholera toxin in a whole organism and the utility of D. melanogaster as an accurate, inexpensive model for elucidation of host susceptibility to cholera.

  9. Differential overexpression of SERPINA3 in human prion diseases.

    Science.gov (United States)

    Vanni, S; Moda, F; Zattoni, M; Bistaffa, E; De Cecco, E; Rossi, M; Giaccone, G; Tagliavini, F; Haïk, S; Deslys, J P; Zanusso, G; Ironside, J W; Ferrer, I; Kovacs, G G; Legname, G

    2017-11-15

    Prion diseases are fatal neurodegenerative disorders with sporadic, genetic or acquired etiologies. The molecular alterations leading to the onset and the spreading of these diseases are still unknown. In a previous work we identified a five-gene signature able to distinguish intracranially BSE-infected macaques from healthy ones, with SERPINA3 showing the most prominent dysregulation. We analyzed 128 suitable frontal cortex samples, from prion-affected patients (variant Creutzfeldt-Jakob disease (vCJD) n = 20, iatrogenic CJD (iCJD) n = 11, sporadic CJD (sCJD) n = 23, familial CJD (gCJD) n = 17, fatal familial insomnia (FFI) n = 9, Gerstmann-Sträussler-Scheinker syndrome (GSS)) n = 4), patients with Alzheimer disease (AD, n = 14) and age-matched controls (n = 30). Real Time-quantitative PCR was performed for SERPINA3 transcript, and ACTB, RPL19, GAPDH and B2M were used as reference genes. We report SERPINA3 to be strongly up-regulated in the brain of all human prion diseases, with only a mild up-regulation in AD. We show that this striking up-regulation, both at the mRNA and at the protein level, is present in all types of human prion diseases analyzed, although to a different extent for each specific disorder. Our data suggest that SERPINA3 may be involved in the pathogenesis and the progression of prion diseases, representing a valid tool for distinguishing different forms of these disorders in humans.

  10. Annotating Diseases Using Human Phenotype Ontology Improves Prediction of Disease-Associated Long Non-coding RNAs.

    Science.gov (United States)

    Le, Duc-Hau; Dao, Lan T M

    2018-05-23

    Recently, many long non-coding RNAs (lncRNAs) have been identified and their biological function has been characterized; however, our understanding of their underlying molecular mechanisms related to disease is still limited. To overcome the limitation in experimentally identifying disease-lncRNA associations, computational methods have been proposed as a powerful tool to predict such associations. These methods are usually based on the similarities between diseases or lncRNAs since it was reported that similar diseases are associated with functionally similar lncRNAs. Therefore, prediction performance is highly dependent on how well the similarities can be captured. Previous studies have calculated the similarity between two diseases by mapping exactly each disease to a single Disease Ontology (DO) term, and then use a semantic similarity measure to calculate the similarity between them. However, the problem of this approach is that a disease can be described by more than one DO terms. Until now, there is no annotation database of DO terms for diseases except for genes. In contrast, Human Phenotype Ontology (HPO) is designed to fully annotate human disease phenotypes. Therefore, in this study, we constructed disease similarity networks/matrices using HPO instead of DO. Then, we used these networks/matrices as inputs of two representative machine learning-based and network-based ranking algorithms, that is, regularized least square and heterogeneous graph-based inference, respectively. The results showed that the prediction performance of the two algorithms on HPO-based is better than that on DO-based networks/matrices. In addition, our method can predict 11 novel cancer-associated lncRNAs, which are supported by literature evidence. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. Human anthrax as a re-emerging disease.

    Science.gov (United States)

    Doganay, Mehmet; Demiraslan, Hayati

    2015-01-01

    Anthrax is primarily a disease of herbivores and the etiological agent is B. anthracis which is a gram-positive, aerobic, spore-forming, and rod shaped bacterium. Bacillus anthracis spores are highly resistant to heat, pressure, ultraviolet and ionizing radiation, chemical agents and disinfectants. For these reasons, B. anthracis spores are an attractive choice as biological agents for the use of bioweapon and/or bioterrorism. Soil is the main reservoir for the infectious agent. The disease most commonly affects wild and domestic mammals. Human are secondarily infected by contact with infected animals and contaminated animal products or directly expose to B. anthracis spores. Anthrax occurs worldwide. This infection is still endemic or hyperendemic in both animals and humans in some part of areas of the world; particularly in Middle East, West Africa, Central Asia, some part of India, South America. However, some countries are claiming free of anthrax, and anthrax has become a re-emerging disease in western countries with the intentional outbreak. Currently, anthrax is classified according to its setting as (1) naturally occurring anthrax, (2) bioterrorism-related anthrax. Vast majority of human anthrax are occurring as naturally occurring anthrax in the world. It is also a threaten disease for western countries. The aim of this paper is to review the relevant patents, short historical perspective, microbiological and epidemiological features, clinical presentations and treatment.

  12. [The German program for disease management guidelines. Results and perspectives].

    Science.gov (United States)

    Ollenschläger, Günter; Kopp, Ina

    2007-05-15

    The Program for National Disease Management Guidelines (German DM-CPG Program) is a joint initiative of the German Medical Association (umbrella organization of the German Chambers of Physicians), the Association of the Scientific Medical Societies (AWMF), and of the National Association of Statutory Health Insurance Physicians (NASHIP). The program aims at developing, implementing and continuously updating best-practice recommendations for countrywide and regional disease management programs in Germany. Since 2003 twelve national guidelines (topics: asthma, chronic obstructive pulmonary disease, HI (Chronic heart failure), CVD (Chronic coronary heart disease) back pain, depression, several aspects of diabetes) have been produced by use of a standardized procedure in accordance with internationally consented methodologies. For countrywide dissemination and implementation the program uses a wide range of specialist journals, continuous medical education and quality management programs. So far, 36 out of 150 national scientific medical associations, four allied health profession organizations, and twelve national consumer organizations have been participating in the DM-CPG Program. Studies to evaluate the program's effects on health-care providers' behavior and patients' outcomes are under way.

  13. Chronic kidney disease screening: Results of the 2013 World ...

    African Journals Online (AJOL)

    Background: Chronic kidney disease (CKD) is on the rise globally due to the increase in prevalence of common risk factors. Screening for CKD risk factors is important for early detection and institution of measures to retard its progression. This study aimed to determine the markers of CKD and its risk factors in a selected ...

  14. Mobile technologies for disease surveillance in humans and animals.

    Science.gov (United States)

    Mwabukusi, Mpoki; Karimuribo, Esron D; Rweyemamu, Mark M; Beda, Eric

    2014-04-23

    A paper-based disease reporting system has been associated with a number of challenges. These include difficulties to submit hard copies of the disease surveillance forms because of poor road infrastructure, weather conditions or challenging terrain, particularly in the developing countries. The system demands re-entry of the data at data processing and analysis points, thus making it prone to introduction of errors during this process. All these challenges contribute to delayed acquisition, processing and response to disease events occurring in remote hard to reach areas. Our study piloted the use of mobile phones in order to transmit near to real-time data from remote districts in Tanzania (Ngorongoro and Ngara), Burundi (Muyinga) and Zambia (Kazungula and Sesheke). Two technologies namely, digital and short messaging services were used to capture and transmit disease event data in the animal and human health sectors in the study areas based on a server-client model. Smart phones running the Android operating system (minimum required version: Android 1.6), and which supported open source application, Epicollect, as well as the Open Data Kit application, were used in the study. These phones allowed collection of geo-tagged data, with the opportunity of including static and moving images related to disease events. The project supported routine disease surveillance systems in the ministries responsible for animal and human health in Burundi, Tanzania and Zambia, as well as data collection for researchers at the Sokoine University of Agriculture, Tanzania. During the project implementation period between 2011 and 2013, a total number of 1651 diseases event-related forms were submitted, which allowed reporters to include GPS coordinates and photographs related to the events captured. It was concluded that the new technology-based surveillance system is useful in providing near to real-time data, with potential for enhancing timely response in rural remote areas of

  15. The human oral metaproteome reveals potential biomarkers for caries disease

    DEFF Research Database (Denmark)

    Belda-Ferre, Pedro; Williamson, James; Simón-Soro, Áurea

    2015-01-01

    metabolism and immune response. We applied multivariate analysis in order to find the minimum set of proteins that better allows discrimination of healthy and caries-affected dental plaque samples, detecting seven bacterial and five human protein functions that allow determining the health status......Tooth decay is considered the most prevalent human disease worldwide. We present the first metaproteomic study of the oral biofilm, using different mass spectrometry approaches that have allowed us to quantify individual peptides in healthy and caries-bearing individuals. A total of 7771 bacterial...... and 853 human proteins were identified in 17 individuals, which provide the first available protein repertoire of human dental plaque. Actinomyces and Coryneybacterium represent a large proportion of the protein activity followed by Rothia and Streptococcus. Those four genera account for 60-90% of total...

  16. Molecular epidemiology of human oral Chagas disease outbreaks in Colombia.

    Directory of Open Access Journals (Sweden)

    Juan David Ramírez

    Full Text Available BACKGROUND: Trypanosoma cruzi, the causative agent of Chagas disease, displays significant genetic variability revealed by six Discrete Typing Units (TcI-TcVI. In this pathology, oral transmission represents an emerging epidemiological scenario where different outbreaks associated to food/beverages consumption have been reported in Argentina, Bolivia, Brazil, Ecuador and Venezuela. In Colombia, six human oral outbreaks have been reported corroborating the importance of this transmission route. Molecular epidemiology of oral outbreaks is barely known observing the incrimination of TcI, TcII, TcIV and TcV genotypes. METHODOLOGY AND PRINCIPAL FINDINGS: High-throughput molecular characterization was conducted performing MLMT (Multilocus Microsatellite Typing and mtMLST (mitochondrial Multilocus Sequence Typing strategies on 50 clones from ten isolates. Results allowed observing the occurrence of TcI, TcIV and mixed infection of distinct TcI genotypes. Thus, a majority of specific mitochondrial haplotypes and allelic multilocus genotypes associated to the sylvatic cycle of transmission were detected in the dataset with the foreseen presence of mitochondrial haplotypes and allelic multilocus genotypes associated to the domestic cycle of transmission. CONCLUSIONS: These findings suggest the incrimination of sylvatic genotypes in the oral outbreaks occurred in Colombia. We observed patterns of super-infection and/or co-infection with a tailored association with the severe forms of myocarditis in the acute phase of the disease. The transmission dynamics of this infection route based on molecular epidemiology evidence was unraveled and the clinical and biological implications are discussed.

  17. Credit scores, cardiovascular disease risk, and human capital.

    Science.gov (United States)

    Israel, Salomon; Caspi, Avshalom; Belsky, Daniel W; Harrington, HonaLee; Hogan, Sean; Houts, Renate; Ramrakha, Sandhya; Sanders, Seth; Poulton, Richie; Moffitt, Terrie E

    2014-12-02

    Credit scores are the most widely used instruments to assess whether or not a person is a financial risk. Credit scoring has been so successful that it has expanded beyond lending and into our everyday lives, even to inform how insurers evaluate our health. The pervasive application of credit scoring has outpaced knowledge about why credit scores are such useful indicators of individual behavior. Here we test if the same factors that lead to poor credit scores also lead to poor health. Following the Dunedin (New Zealand) Longitudinal Study cohort of 1,037 study members, we examined the association between credit scores and cardiovascular disease risk and the underlying factors that account for this association. We find that credit scores are negatively correlated with cardiovascular disease risk. Variation in household income was not sufficient to account for this association. Rather, individual differences in human capital factors—educational attainment, cognitive ability, and self-control—predicted both credit scores and cardiovascular disease risk and accounted for ∼45% of the correlation between credit scores and cardiovascular disease risk. Tracing human capital factors back to their childhood antecedents revealed that the characteristic attitudes, behaviors, and competencies children develop in their first decade of life account for a significant portion (∼22%) of the link between credit scores and cardiovascular disease risk at midlife. We discuss the implications of these findings for policy debates about data privacy, financial literacy, and early childhood interventions.

  18. Limits to human enhancement: nature, disease, therapy or betterment?

    Science.gov (United States)

    Hofmann, Bjørn

    2017-10-10

    New technologies facilitate the enhancement of a wide range of human dispositions, capacities, or abilities. While it is argued that we need to set limits to human enhancement, it is unclear where we should find resources to set such limits. Traditional routes for setting limits, such as referring to nature, the therapy-enhancement distinction, and the health-disease distinction, turn out to have some shortcomings. However, upon closer scrutiny the concept of enhancement is based on vague conceptions of what is to be enhanced. Explaining why it is better to become older, stronger, and more intelligent presupposes a clear conception of goodness, which is seldom provided. In particular, the qualitative better is frequently confused with the quantitative more. We may therefore not need "external" measures for setting its limits - they are available in the concept of enhancement itself. While there may be shortcomings in traditional sources of limit setting to human enhancement, such as nature, therapy, and disease, such approaches may not be necessary. The specification-of-betterment problem inherent in the conception of human enhancement itself provides means to restrict its unwarranted proliferation. We only need to demand clear, sustainable, obtainable goals for enhancement that are based on evidence, and not on lofty speculations, hypes, analogies, or weak associations. Human enhancements that specify what will become better, and provide adequate evidence, are good and should be pursued. Others should not be accepted.

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

    Science.gov (United States)

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

    2015-01-01

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

  20. Early embryonic chromosome instability results in stable mosaic pattern in human tissues.

    Directory of Open Access Journals (Sweden)

    Hasmik Mkrtchyan

    Full Text Available The discovery of copy number variations (CNV in the human genome opened new perspectives on the study of the genetic causes of inherited disorders and the aetiology of common diseases. Here, a single-cell-level investigation of CNV in different human tissues led us to uncover the phenomenon of mitotically derived genomic mosaicism, which is stable in different cell types of one individual. The CNV mosaic ratios were different between the 10 individuals studied. However, they were stable in the T lymphocytes, immortalized B lymphoblastoid cells, and skin fibroblasts analyzed in each individual. Because these cell types have a common origin in the connective tissues, we suggest that mitotic changes in CNV regions may happen early during embryonic development and occur only once, after which the stable mosaic ratio is maintained throughout the differentiated tissues. This concept is further supported by a unique study of immortalized B lymphoblastoid cell lines obtained with 20 year difference from two subjects. We provide the first evidence of somatic mosaicism for CNV, with stable variation ratios in different cell types of one individual leading to the hypothesis of early embryonic chromosome instability resulting in stable mosaic pattern in human tissues. This concept has the potential to open new perspectives in personalized genetic diagnostics and can explain genetic phenomena like diminished penetrance in autosomal dominant diseases. We propose that further genomic studies should focus on the single-cell level, to better understand the aetiology of aging and diseases mediated by somatic mutations.

  1. Are human endogenous retroviruses triggers of autoimmune diseases?

    DEFF Research Database (Denmark)

    Nexø, Bjørn A; Villesen, Palle; Nissen, Kari K

    2016-01-01

    factors. Viruses including human endogenous retroviruses have long been linked to the occurrence of autoimmunity, but never proven to be causative factors. Endogenous viruses are retroviral sequences embedded in the host germline DNA and transmitted vertically through successive generations in a Mendelian...... manner. In this study by means of genetic epidemiology, we have searched for the involvement of endogenous retroviruses in three selected autoimmune diseases: multiple sclerosis, type 1 diabetes mellitus, and rheumatoid arthritis. We found that at least one human endogenous retroviral locus...

  2. 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.

  3. Human Ebola virus infection results in substantial immune activation.

    Science.gov (United States)

    McElroy, Anita K; Akondy, Rama S; Davis, Carl W; Ellebedy, Ali H; Mehta, Aneesh K; Kraft, Colleen S; Lyon, G Marshall; Ribner, Bruce S; Varkey, Jay; Sidney, John; Sette, Alessandro; Campbell, Shelley; Ströher, Ute; Damon, Inger; Nichol, Stuart T; Spiropoulou, Christina F; Ahmed, Rafi

    2015-04-14

    Four Ebola patients received care at Emory University Hospital, presenting a unique opportunity to examine the cellular immune responses during acute Ebola virus infection. We found striking activation of both B and T cells in all four patients. Plasmablast frequencies were 10-50% of B cells, compared with less than 1% in healthy individuals. Many of these proliferating plasmablasts were IgG-positive, and this finding coincided with the presence of Ebola virus-specific IgG in the serum. Activated CD4 T cells ranged from 5 to 30%, compared with 1-2% in healthy controls. The most pronounced responses were seen in CD8 T cells, with over 50% of the CD8 T cells expressing markers of activation and proliferation. Taken together, these results suggest that all four patients developed robust immune responses during the acute phase of Ebola virus infection, a finding that would not have been predicted based on our current assumptions about the highly immunosuppressive nature of Ebola virus. Also, quite surprisingly, we found sustained immune activation after the virus was cleared from the plasma, observed most strikingly in the persistence of activated CD8 T cells, even 1 mo after the patients' discharge from the hospital. These results suggest continued antigen stimulation after resolution of the disease. From these convalescent time points, we identified CD4 and CD8 T-cell responses to several Ebola virus proteins, most notably the viral nucleoprotein. Knowledge of the viral proteins targeted by T cells during natural infection should be useful in designing vaccines against Ebola virus.

  4. Comparative Study of Human Liver Ferritin and Chicken Liver by Moessbauer Spectroscopy. Preliminary Results

    Energy Technology Data Exchange (ETDEWEB)

    Oshtrakh, M. I. [Ural State Technical University - UPI, Division of Applied Biophysics, Faculty of Physical Techniques and Devices for Quality Control (Russian Federation); Milder, O. B.; Semionkin, V. A. [Ural State Technical University - UPI, Faculty of Experimental Physics (Russian Federation); Prokopenko, P. G. [Russian State Medical University, Faculty of Biochemistry (Russian Federation); Malakheeva, L. I. [Simbio Holding, Science Consultation Department (Russian Federation)

    2004-12-15

    A comparative study of normal human liver ferritin and livers from normal chicken and chicken with Marek disease was made by Moessbauer spectroscopy. Small differences of quadrupole splitting and isomer shift were found for human liver ferritin and chicken liver. Moessbauer parameters for liver from normal chicken and chicken with Marek disease were the same.

  5. Comparative Study of Human Liver Ferritin and Chicken Liver by Moessbauer Spectroscopy. Preliminary Results

    International Nuclear Information System (INIS)

    Oshtrakh, M. I.; Milder, O. B.; Semionkin, V. A.; Prokopenko, P. G.; Malakheeva, L. I.

    2004-01-01

    A comparative study of normal human liver ferritin and livers from normal chicken and chicken with Marek disease was made by Moessbauer spectroscopy. Small differences of quadrupole splitting and isomer shift were found for human liver ferritin and chicken liver. Moessbauer parameters for liver from normal chicken and chicken with Marek disease were the same.

  6. Molecular clocks and the human condition: approaching their characterization in human physiology and disease.

    Science.gov (United States)

    Fitzgerald, G A; Yang, G; Paschos, G K; Liang, X; Skarke, C

    2015-09-01

    Molecular clockworks knit together diverse biological networks and compelling evidence from model systems infers their importance in metabolism, immunological and cardiovascular function. Despite this and the diurnal variation in many aspects of human physiology and the phenotypic expression of disease, our understanding of the role and importance of clock function and dysfunction in humans is modest. There are tantalizing hints of connection across the translational divide and some correlative evidence of gene variation and human disease but most of what we know derives from forced desynchrony protocols in controlled environments. We now have the ability to monitor quantitatively ex vivo or in vivo the genome, metabolome, proteome and microbiome of humans in the wild. Combining this capability, with the power of mobile telephony and the evolution of remote sensing, affords a new opportunity for deep phenotyping, including the characterization of diurnal behaviour and the assessment of the impact of the clock on approved drug function. © 2015 John Wiley & Sons Ltd.

  7. Under the lash: Demodex mites in human diseases.

    Science.gov (United States)

    Lacey, Noreen; Kavanagh, Kevin; Tseng, Scheffer C G

    2009-08-01

    Demodex mites, class Arachnida and subclass Acarina, are elongated mites with clear cephalothorax and abdomens, the former with four pairs of legs. There are more than 100 species of Demodex mite, many of which are obligatory commensals of the pilosebaceous unit of mammals including cats, dogs, sheep, cattle, pigs, goats, deer, bats, hamsters, rats and mice. Among them, Demodex canis, which is found ubiquitously in dogs, is the most documented and investigated. In excessive numbers D. canis causes the inflammatory disease termed demodicosis (demodectic mange, follicular mange or red mange), which is more common in purebred dogs and has a hereditary predisposition in breeding kennels1. Two distinct Demodex species have been confirmed as the most common ectoparasite in man. The larger Demodex folliculorum, about 0.3-0.4 mm long, is primarily found as a cluster in the hair follicle (Figure 1a), while the smaller Demodex brevis, about 0.2-0.3 mm long with a spindle shape and stubby legs, resides solitarily in the sebaceous gland (Figure 1b). These two species are also ubiquitously found in all human races without gender preference. The pathogenic role of Demodex mites in veterinary medicine is not as greatly disputed as in human diseases. In this article, we review the key literature and our joint research experience regarding the pathogenic potential of these two mites in causing inflammatory diseases of human skin and eye. We hope that the evidence summarized herein will invite readers to take a different look at the life of Demodex mites in several common human diseases.

  8. Does biodiversity protect humans against infectious disease? Reply

    Science.gov (United States)

    Wood, Chelsea L.; Lafferty, Kevin D.; DeLeo, Giulio; Young, Hillary S.; Hudson, Peter J.; Kuris, Armand M.

    2016-01-01

    The dilution effect is the sort of idea that everyone wants to be true. If nature protects humans against infectious disease, imagine the implications: nature's value could be tallied in terms of human suffering avoided. This makes a potent argument for conservation, convincing even to those who would otherwise be disinclined to support conservation initiatives. The appeal of the dilution effect has been recognized by others: “the desire to make the case for conservation has led to broad claims regarding the benefits of nature conservation for human health” (Bauch et al. 2015). Randolph and Dobson (2012) were among the first to critique these claims, making the case that promotion of conservation to reduce Lyme disease risk, although well intentioned, was flawed. Along with Randolph and Dobson's critique, there have been several calls for a more nuanced scientific assessment of the relationship between biodiversity and disease transmission (Dunn 2010, Salkeld et al. 2013, Wood and Lafferty 2013, Young et al. 2013). In response, supporters of the dilution effect have instead increased the scope of their generalizations with review papers, press releases, and, like Levi et al. (2015), letters. These responses have been successful; it is not uncommon to read papers that repeat the assertion that biodiversity generally interferes with disease transmission and that conservation will therefore generally benefit human health. Here, we explain how Levi et al. (2015) and other, similar commentaries use selective interpretation and shifting definitions to argue for the generality of the dilution effect hypothesis.

  9. Systematic review of brucellosis in Kenya: disease frequency in humans and animals and risk factors for human infection

    Directory of Open Access Journals (Sweden)

    J. Njeru

    2016-08-01

    Full Text Available Abstract Background Brucellosis is a debilitating zoonotic disease affecting humans and animals. A comprehensive, evidence-based assessment of literature and officially available data on animal and human brucellosis for Kenya are missing. The aim of the current review is to provide frequency estimates of brucellosis in humans, animals and risk factors for human infection, and help to understand the current situation in Kenya. Methods A total of accessible 36 national and international publications on brucellosis from 1916 to 2016 were reviewed to estimate the frequency of brucellosis in humans and animals, and strength of associations between potential risk factors and seropositivity in humans in Kenya. Results The conducted studies revealed only few and fragmented evidence of the disease spatial and temporal distribution in an epidemiological context. Bacteriological evidence revealed the presence of Brucella (B. abortus and B. melitensis in cattle and human patients, whilst B. suis was isolated from wild rodents only. Similar evidence for Brucella spp infection in small ruminants and other animal species is unavailable. The early and most recent serological studies revealed that animal brucellosis is widespread in all animal production systems. The animal infection pressure in these systems has remained strong due to mixing of large numbers of animals from different geographical regions, movement of livestock in search of pasture, communal sharing of grazing land, and the concentration of animals around water points. Human cases are more likely seen in groups occupationally or domestically exposed to livestock or practicing risky social-cultural activities such as consumption of raw blood and dairy products, and slaughtering of animals within the homesteads. Many brucellosis patients are misdiagnosed and probably mistreated due to lack of reliable laboratory diagnostic support resulting to adverse health outcomes of the patients and routine

  10. Small particle aerosol inoculation of cowpox Brighton Red in rhesus monkeys results in a severe respiratory disease

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Reed F. [Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702 (United States); Hammoud, Dima A. [Center for Infectious Disease Imaging, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD 20892 (United States); Lackemeyer, Matthew G.; Yellayi, Srikanth [Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702 (United States); Solomon, Jeffrey [Center for Infectious Disease Imaging, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD 20892 (United States); Bohannon, Jordan K.; Janosko, Krisztina B.; Jett, Catherine; Cooper, Kurt [Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702 (United States); Blaney, Joseph E. [Office of the Scientific Director, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 (United States); Jahrling, Peter B. [Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702 (United States); Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702 (United States)

    2015-07-15

    Cowpox virus (CPXV) inoculation of nonhuman primates (NHPs) has been suggested as an alternate model for smallpox (Kramski et al., 2010, PLoS One, 5, e10412). Previously, we have demonstrated that intrabronchial inoculation of CPXV-Brighton Red (CPXV-BR) into cynomolgus monkeys resulted in a disease that shared many similarities to smallpox; however, severe respiratory tract disease was observed (Smith et al., 2011, J. Gen. Virol.). Here we describe the course of disease after small particle aerosol exposure of rhesus monkeys using computed tomography (CT) to monitor respiratory disease progression. Subjects developed a severe respiratory disease that was uniformly lethal at 5.7 log{sub 10} PFU of CPXV-BR. CT indicated changes in lung architecture that correlated with changes in peripheral blood monocytes and peripheral oxygen saturation. While the small particle aerosol inoculation route does not accurately mimic human smallpox, the data suggest that CT can be used as a tool to monitor real-time disease progression for evaluation of animal models for human diseases. - Highlights: • Small particle aerosol exposure of rhesus results in a severe respiratory disease. • CT findings correlated with peripheral oxygen saturation and monocyte increases. • Virus dissemination was limited and mainly confined to the respiratory tract. • CT provides insight into pathogenesis to aid development of animal models of disease.

  11. Small particle aerosol inoculation of cowpox Brighton Red in rhesus monkeys results in a severe respiratory disease

    International Nuclear Information System (INIS)

    Johnson, Reed F.; Hammoud, Dima A.; Lackemeyer, Matthew G.; Yellayi, Srikanth; Solomon, Jeffrey; Bohannon, Jordan K.; Janosko, Krisztina B.; Jett, Catherine; Cooper, Kurt; Blaney, Joseph E.; Jahrling, Peter B.

    2015-01-01

    Cowpox virus (CPXV) inoculation of nonhuman primates (NHPs) has been suggested as an alternate model for smallpox (Kramski et al., 2010, PLoS One, 5, e10412). Previously, we have demonstrated that intrabronchial inoculation of CPXV-Brighton Red (CPXV-BR) into cynomolgus monkeys resulted in a disease that shared many similarities to smallpox; however, severe respiratory tract disease was observed (Smith et al., 2011, J. Gen. Virol.). Here we describe the course of disease after small particle aerosol exposure of rhesus monkeys using computed tomography (CT) to monitor respiratory disease progression. Subjects developed a severe respiratory disease that was uniformly lethal at 5.7 log 10 PFU of CPXV-BR. CT indicated changes in lung architecture that correlated with changes in peripheral blood monocytes and peripheral oxygen saturation. While the small particle aerosol inoculation route does not accurately mimic human smallpox, the data suggest that CT can be used as a tool to monitor real-time disease progression for evaluation of animal models for human diseases. - Highlights: • Small particle aerosol exposure of rhesus results in a severe respiratory disease. • CT findings correlated with peripheral oxygen saturation and monocyte increases. • Virus dissemination was limited and mainly confined to the respiratory tract. • CT provides insight into pathogenesis to aid development of animal models of disease

  12. Human hereditary diseases associated with elevated frequency of chromosome aberrations

    International Nuclear Information System (INIS)

    Ejima, Yosuke

    1988-01-01

    Human recessive diseases collectively known as chromosome breakage syndromes include Fanconi's anemia, Bloom's syndrome and ataxia telangiectasia. Cells from these patients show chromosome instabilities both spontaneously and following treatments with radiations or certain chemicals, where defects in DNA metabolisms are supposed to be involved. Cells from patients with ataxia telangiectasia are hypersensitive to ionizing radiations, though DNA replication is less affected than in normal cells. Chromatid-type as well as chromosom-type aberrations are induced in cells irradiated in G 0 or G 1 phases. These unusual responses to radiations may provide clues for understanding the link between DNA replicative response and cellular radiosensitivity. Alterations in cellular radiosensitivity or spontaneous chromosome instabilities are observed in some patients with congenital chromosome anomalies or dominant diseases, where underlying defects may be different from those in recessive diseases. (author)

  13. Human hereditary diseases associated with elevated frequency of chromosome aberrations

    Energy Technology Data Exchange (ETDEWEB)

    Ejima, Yosuke; Ikushima, Takaji (ed.)

    1988-07-01

    Human recessive diseases collectively known as chromosome breakage syndromes include Fanconi's anemia, Bloom's syndrome and ataxia telangiectasia. Cells from these patients show chromosome instabilities both spontaneously and following treatments with radiations or certain chemicals, where defects in DNA metabolisms are supposed to be involved. Cells from patients with ataxia telangiectasia are hypersensitive to ionizing radiations, though DNA replication is less affected than in normal cells. Chromatid-type as well as chromosom-type aberrations are induced in cells irradiated in G/sub 0/ or G/sub 1/ phases. These unusual responses to radiations may provide clues for understanding the link between DNA replicative response and cellular radiosensitivity. Alterations in cellular radiosensitivity or spontaneous chromosome instabilities are observed in some patients with congenital chromosome anomalies or dominant diseases, where underlying defects may be different from those in recessive diseases.

  14. Pulmonary disease in patients with human immunodeficiency virus infection

    DEFF Research Database (Denmark)

    Lundgren, J D; Orholm, Marianne; Lundgren, B

    1989-01-01

    cause pulmonary disease alone or in combination. Bilateral interstitial infiltrates are the most frequent chest x-ray abnormality and are most frequently caused by infection with Pneumocystis carinii. Cytomegalovirus, Mycobacterium tuberculosis, nonspecific interstitial pneumonitis and pulmonary Kaposi......Pulmonary disease is the most important cause of morbidity and mortality in patients infected with human immunodeficiency virus (HIV). All parts of the hospital system are expected to be involved in the diagnosis and treatment of HIV infected patients in the coming years. Many different processes......'s sarcoma are the most important parts of the differential diagnosis. An aggressive approach to the diagnosis of pulmonary disease in this patient population is indicated in order to provide optimal care and assess new therapies....

  15. Reverse engineering human neurodegenerative disease using pluripotent stem cell technology.

    Science.gov (United States)

    Liu, Ying; Deng, Wenbin

    2016-05-01

    With the technology of reprogramming somatic cells by introducing defined transcription factors that enables the generation of "induced pluripotent stem cells (iPSCs)" with pluripotency comparable to that of embryonic stem cells (ESCs), it has become possible to use this technology to produce various cells and tissues that have been difficult to obtain from living bodies. This advancement is bringing forth rapid progress in iPSC-based disease modeling, drug screening, and regenerative medicine. More and more studies have demonstrated that phenotypes of adult-onset neurodegenerative disorders could be rather faithfully recapitulated in iPSC-derived neural cell cultures. Moreover, despite the adult-onset nature of the diseases, pathogenic phenotypes and cellular abnormalities often exist in early developmental stages, providing new "windows of opportunity" for understanding mechanisms underlying neurodegenerative disorders and for discovering new medicines. The cell reprogramming technology enables a reverse engineering approach for modeling the cellular degenerative phenotypes of a wide range of human disorders. An excellent example is the study of the human neurodegenerative disease amyotrophic lateral sclerosis (ALS) using iPSCs. ALS is a progressive neurodegenerative disease characterized by the loss of upper and lower motor neurons (MNs), culminating in muscle wasting and death from respiratory failure. The iPSC approach provides innovative cell culture platforms to serve as ALS patient-derived model systems. Researchers have converted iPSCs derived from ALS patients into MNs and various types of glial cells, all of which are involved in ALS, to study the disease. The iPSC technology could be used to determine the role of specific genetic factors to track down what's wrong in the neurodegenerative disease process in the "disease-in-a-dish" model. Meanwhile, parallel experiments of targeting the same specific genes in human ESCs could also be performed to control

  16. Proteomic approach in human health and disease: Preventive and cure studies

    Directory of Open Access Journals (Sweden)

    Khaled MM Koriem

    2018-01-01

    Full Text Available Proteomic is a branch of science that deals with various numbers of proteins where proteins are essential human constituents. Proteomic has a lot of functions inside the human and animal living organisms. This review helps to make a thought on the importance of proteomic application in human health and disease with special reference to preventive and cure studies. The human health can be divided into physical and mental health. The physical health relates to keeping human body state in a good health and to nutritional type and environmental factors. The mental health correlates to human psychological state. The main factors that affect the status of human health are human diet, exercise and sleep. The healthy diet is very important and needs to maintain the human health. The training program exercise improves human fitness and overall health and wellness. The sleep is a vital factor to sustain the human health. The human disease indicates abnormal human condition which influences the specific human part or the whole human body. There are external and internal factors which induce human disease. The external factors include pathogens while internal factors include allergies and autoimmunity. There are 4 principle types of human diseases: (1 infectious disease, (2 deficiency disease, (3 genetic disease and (4 physiological disease. There are many and various external microbes' factors that induce human infectious disease and these agents include viruses, bacteria, fungi and protozoa. The lack of necessary and vital dietary rudiments such as vitamins and minerals is the main cause of human deficiency disease. The genetic disease is initiated by hereditary disturbances that occur in the human genetic map. The physiological disease occurs when the normal human function body is affected due to human organs become malfunction. In conclusion, proteomic plays a vital and significant role in human health and disease.

  17. DRUMS: a human disease related unique gene mutation search engine.

    Science.gov (United States)

    Li, Zuofeng; Liu, Xingnan; Wen, Jingran; Xu, Ye; Zhao, Xin; Li, Xuan; Liu, Lei; Zhang, Xiaoyan

    2011-10-01

    With the completion of the human genome project and the development of new methods for gene variant detection, the integration of mutation data and its phenotypic consequences has become more important than ever. Among all available resources, locus-specific databases (LSDBs) curate one or more specific genes' mutation data along with high-quality phenotypes. Although some genotype-phenotype data from LSDB have been integrated into central databases little effort has been made to integrate all these data by a search engine approach. In this work, we have developed disease related unique gene mutation search engine (DRUMS), a search engine for human disease related unique gene mutation as a convenient tool for biologists or physicians to retrieve gene variant and related phenotype information. Gene variant and phenotype information were stored in a gene-centred relational database. Moreover, the relationships between mutations and diseases were indexed by the uniform resource identifier from LSDB, or another central database. By querying DRUMS, users can access the most popular mutation databases under one interface. DRUMS could be treated as a domain specific search engine. By using web crawling, indexing, and searching technologies, it provides a competitively efficient interface for searching and retrieving mutation data and their relationships to diseases. The present system is freely accessible at http://www.scbit.org/glif/new/drums/index.html. © 2011 Wiley-Liss, Inc.

  18. Global and disease-associated genetic variation in the human Fanconi anemia gene family

    OpenAIRE

    Rogers, Kai J.; Fu, Wenqing; Akey, Joshua M.; Monnat, Raymond J.

    2014-01-01

    Fanconi anemia (FA) is a human recessive genetic disease resulting from inactivating mutations in any of 16 FANC (Fanconi) genes. Individuals with FA are at high risk of developmental abnormalities, early bone marrow failure and leukemia. These are followed in the second and subsequent decades by a very high risk of carcinomas of the head and neck and anogenital region, and a small continuing risk of leukemia. In order to characterize base pair-level disease-associated (DA) and population gen...

  19. IgY antibodies in human nutrition for disease prevention.

    Science.gov (United States)

    Müller, Sandra; Schubert, Andreas; Zajac, Julia; Dyck, Terry; Oelkrug, Christopher

    2015-10-20

    Oral administration of preformed specific antibodies is an attractive approach against infections of the digestive system in humans and animals in times of increasing antibiotic resistances. Previous studies showed a positive effect of egg yolk IgY antibodies on bacterial intoxications in animals and humans. Immunization of chickens with specific antigens offers the possibility to create various forms of antibodies. Research shows that orally applied IgY's isolated from egg yolks can passively cure or prevent diseases of the digestive system. The use of these alternative therapeutic drugs provides further advantages: (1) The production of IgY's is a non-invasive alternative to current methods; (2) The keeping of chickens is inexpensive; (3) The animals are easy to handle; (4) It avoids repetitive bleeding of laboratory animals; (5) It is also very cost effective regarding the high IgY concentration within the egg yolk. Novel targets of these antigen specific antibodies are Helicobacter pylori and also molecules involved in signaling pathways in gastric cancer. Furthermore, also dental caries causing bacteria like Streptococcus mutans or opportunistic Pseudomonas aeruginosa in cystic fibrosis patients are possible targets. Therefore, IgY's included in food for human consumption may be able to prevent or cure human diseases.

  20. Systematic review of brucellosis in Kenya: disease frequency in humans and animals and risk factors for human infection.

    Science.gov (United States)

    Njeru, J; Wareth, G; Melzer, F; Henning, K; Pletz, M W; Heller, R; Neubauer, H

    2016-08-22

    Brucellosis is a debilitating zoonotic disease affecting humans and animals. A comprehensive, evidence-based assessment of literature and officially available data on animal and human brucellosis for Kenya are missing. The aim of the current review is to provide frequency estimates of brucellosis in humans, animals and risk factors for human infection, and help to understand the current situation in Kenya. A total of accessible 36 national and international publications on brucellosis from 1916 to 2016 were reviewed to estimate the frequency of brucellosis in humans and animals, and strength of associations between potential risk factors and seropositivity in humans in Kenya. The conducted studies revealed only few and fragmented evidence of the disease spatial and temporal distribution in an epidemiological context. Bacteriological evidence revealed the presence of Brucella (B.) abortus and B. melitensis in cattle and human patients, whilst B. suis was isolated from wild rodents only. Similar evidence for Brucella spp infection in small ruminants and other animal species is unavailable. The early and most recent serological studies revealed that animal brucellosis is widespread in all animal production systems. The animal infection pressure in these systems has remained strong due to mixing of large numbers of animals from different geographical regions, movement of livestock in search of pasture, communal sharing of grazing land, and the concentration of animals around water points. Human cases are more likely seen in groups occupationally or domestically exposed to livestock or practicing risky social-cultural activities such as consumption of raw blood and dairy products, and slaughtering of animals within the homesteads. Many brucellosis patients are misdiagnosed and probably mistreated due to lack of reliable laboratory diagnostic support resulting to adverse health outcomes of the patients and routine disease underreporting. We found no studies of disease

  1. Automation Diagnosis of Skin Disease in Humans using Dempster-Shafer Method

    Science.gov (United States)

    Khairina, Dyna Marisa; Hatta, Heliza Rahmania; Rustam; Maharani, Septya

    2018-02-01

    Skin disease is an infectious disease that is common in people of all ages. Disorders of the skin often occur because there are factors, among others, are climate, environment, shelter, unhealthy living habits, allergies and others. Skin diseases in Indonesia are mostly caused by bacterial, fungal, parasitic, and allergies. The objective of the research is to diagnose skin diseases in humans by using the method of making decision tree then performing the search by forward chaining and calculating the probability value of Dempster-Shafer method. The results of research in the form of an automated system that can resemble an expert in diagnosing skin disease accurately and can help in overcoming the problem of skin diseases.

  2. Imaging neuroreceptors in the human brain in health and disease

    International Nuclear Information System (INIS)

    Wagner, H.N. Jr.; Dannals, R.F.; Frost, J.J.

    1985-01-01

    For nearly a century it has been known that chemical activity accompanies mental activity, but only recently has it been possible to begin to examine its exact nature. Positron-emitting radioactive tracers have made it possible to study the chemistry of the human brain in health and disease, using chiefly cyclotron-produced radionuclides, carbon-11, fluorine-18 and oxygen-15. It is now well established that measurable increases in regional cerebral blood flow, and glucose and oxygen metabolism accompany the mental functions of perception, cognition, emotion and motion. On 25 May 1983 the first imaging of a neuroreceptor in the human brain was accomplished with carbon-11 N-methyl spiperone, a ligand that binds preferentially to dopamine-2 receptors, 80% of which are located in the caudate nucleus and putamen. Quantitative imaging of serotonin-2, opiate, benzodiazapine and muscarinic cholinergic receptors has subsequently been accomplished. In studies of normal men and women, it has been found that dopamine and serotonin receptor activity decreases dramatically with age, such a decrease being more pronounced in men than in women and greater in the case of dopamine-2 receptors than in serotonin-2 receptors. Preliminary studies of patients with neuropsychiatric disorders suggest that dopamine-2 receptor activity is diminished in the caudate nucleus of patients with Huntington's disease. Positron tomography permits a quantitative assay of picomolar quantities of neuroreceptors within the living human brain. Studies of patients with Parkinson's disease, Alzheimer's disease, depression, anxiety, schizophrenia, acute and chronic pain states and drug addiction are now in progress. (author)

  3. Drosophila as an In Vivo Model for Human Neurodegenerative Disease

    Science.gov (United States)

    McGurk, Leeanne; Berson, Amit; Bonini, Nancy M.

    2015-01-01

    With the increase in the ageing population, neurodegenerative disease is devastating to families and poses a huge burden on society. The brain and spinal cord are extraordinarily complex: they consist of a highly organized network of neuronal and support cells that communicate in a highly specialized manner. One approach to tackling problems of such complexity is to address the scientific questions in simpler, yet analogous, systems. The fruit fly, Drosophila melanogaster, has been proven tremendously valuable as a model organism, enabling many major discoveries in neuroscientific disease research. The plethora of genetic tools available in Drosophila allows for exquisite targeted manipulation of the genome. Due to its relatively short lifespan, complex questions of brain function can be addressed more rapidly than in other model organisms, such as the mouse. Here we discuss features of the fly as a model for human neurodegenerative disease. There are many distinct fly models for a range of neurodegenerative diseases; we focus on select studies from models of polyglutamine disease and amyotrophic lateral sclerosis that illustrate the type and range of insights that can be gleaned. In discussion of these models, we underscore strengths of the fly in providing understanding into mechanisms and pathways, as a foundation for translational and therapeutic research. PMID:26447127

  4. Environmental and human exposure as a result of radioactive discharges

    International Nuclear Information System (INIS)

    2010-02-01

    Nuclear accidents can lead to the discharge of radioactive particulates, gases, and liquid effluents into the environment. Effluents are characterized by their composition, duration and by other characteristics which can influence the dispersion of radioactivity in the environment. Populations can be exposed directly or through the contamination of the terrestrial and aquatic environments. Therefore, it is necessary to take into consideration both the environmental contamination pathways and the human contamination pathways through the environment. This document summarizes these different pathways: contamination by atmospheric discharge (surface contamination, surface waters, terrestrial fauna and flora); contamination by liquid discharge; spreading of contaminated areas; human contamination pathways (external irradiation, internal contamination, skin contamination). (J.S.)

  5. Human Gut Microbiota: Toward an Ecology of Disease

    Directory of Open Access Journals (Sweden)

    Susannah Selber-Hnatiw

    2017-07-01

    Full Text Available Composed of trillions of individual microbes, the human gut microbiota has adapted to the uniquely diverse environments found in the human intestine. Quickly responding to the variances in the ingested food, the microbiota interacts with the host via reciprocal biochemical signaling to coordinate the exchange of nutrients and proper immune function. Host and microbiota function as a unit which guards its balance against invasion by potential pathogens and which undergoes natural selection. Disturbance of the microbiota composition, or dysbiosis, is often associated with human disease, indicating that, while there seems to be no unique optimal composition of the gut microbiota, a balanced community is crucial for human health. Emerging knowledge of the ecology of the microbiota-host synergy will have an impact on how we implement antibiotic treatment in therapeutics and prophylaxis and how we will consider alternative strategies of global remodeling of the microbiota such as fecal transplants. Here we examine the microbiota-human host relationship from the perspective of the microbial community dynamics.

  6. Human Gut Microbiota: Toward an Ecology of Disease

    Science.gov (United States)

    Selber-Hnatiw, Susannah; Rukundo, Belise; Ahmadi, Masoumeh; Akoubi, Hayfa; Al-Bizri, Hend; Aliu, Adelekan F.; Ambeaghen, Tanyi U.; Avetisyan, Lilit; Bahar, Irmak; Baird, Alexandra; Begum, Fatema; Ben Soussan, Hélène; Blondeau-Éthier, Virginie; Bordaries, Roxane; Bramwell, Helene; Briggs, Alicia; Bui, Richard; Carnevale, Matthew; Chancharoen, Marisa; Chevassus, Talia; Choi, Jin H.; Coulombe, Karyne; Couvrette, Florence; D'Abreau, Samantha; Davies, Meghan; Desbiens, Marie-Pier; Di Maulo, Tamara; Di Paolo, Sean-Anthony; Do Ponte, Sabrina; dos Santos Ribeiro, Priscyla; Dubuc-Kanary, Laure-Anne; Duncan, Paola K.; Dupuis, Frédérique; El-Nounou, Sara; Eyangos, Christina N.; Ferguson, Natasha K.; Flores-Chinchilla, Nancy R.; Fotakis, Tanya; Gado Oumarou H D, Mariam; Georgiev, Metodi; Ghiassy, Seyedehnazanin; Glibetic, Natalija; Grégoire Bouchard, Julien; Hassan, Tazkia; Huseen, Iman; Ibuna Quilatan, Marlon-Francis; Iozzo, Tania; Islam, Safina; Jaunky, Dilan B.; Jeyasegaram, Aniththa; Johnston, Marc-André; Kahler, Matthew R.; Kaler, Kiranpreet; Kamani, Cedric; Karimian Rad, Hessam; Konidis, Elisavet; Konieczny, Filip; Kurianowicz, Sandra; Lamothe, Philippe; Legros, Karina; Leroux, Sebastien; Li, Jun; Lozano Rodriguez, Monica E.; Luponio-Yoffe, Sean; Maalouf, Yara; Mantha, Jessica; McCormick, Melissa; Mondragon, Pamela; Narayana, Thivaedee; Neretin, Elizaveta; Nguyen, Thi T. T.; Niu, Ian; Nkemazem, Romeo B.; O'Donovan, Martin; Oueis, Matthew; Paquette, Stevens; Patel, Nehal; Pecsi, Emily; Peters, Jackie; Pettorelli, Annie; Poirier, Cassandra; Pompa, Victoria R.; Rajen, Harshvardhan; Ralph, Reginald-Olivier; Rosales-Vasquez, Josué; Rubinshtein, Daria; Sakr, Surya; Sebai, Mohammad S.; Serravalle, Lisa; Sidibe, Fily; Sinnathurai, Ahnjana; Soho, Dominique; Sundarakrishnan, Adithi; Svistkova, Veronika; Ugbeye, Tsolaye E.; Vasconcelos, Megan S.; Vincelli, Michael; Voitovich, Olga; Vrabel, Pamela; Wang, Lu; Wasfi, Maryse; Zha, Cong Y.; Gamberi, Chiara

    2017-01-01

    Composed of trillions of individual microbes, the human gut microbiota has adapted to the uniquely diverse environments found in the human intestine. Quickly responding to the variances in the ingested food, the microbiota interacts with the host via reciprocal biochemical signaling to coordinate the exchange of nutrients and proper immune function. Host and microbiota function as a unit which guards its balance against invasion by potential pathogens and which undergoes natural selection. Disturbance of the microbiota composition, or dysbiosis, is often associated with human disease, indicating that, while there seems to be no unique optimal composition of the gut microbiota, a balanced community is crucial for human health. Emerging knowledge of the ecology of the microbiota-host synergy will have an impact on how we implement antibiotic treatment in therapeutics and prophylaxis and how we will consider alternative strategies of global remodeling of the microbiota such as fecal transplants. Here we examine the microbiota-human host relationship from the perspective of the microbial community dynamics. PMID:28769880

  7. Mobile technologies for disease surveillance in humans and animals

    Directory of Open Access Journals (Sweden)

    Mpoki Mwabukusi

    2014-04-01

    Full Text Available A paper-based disease reporting system has been associated with a number of challenges. These include difficulties to submit hard copies of the disease surveillance forms because of poor road infrastructure, weather conditions or challenging terrain, particularly in the developing countries. The system demands re-entry of the data at data processing and analysis points, thus making it prone to introduction of errors during this process. All these challenges contribute to delayed acquisition, processing and response to disease events occurring in remote hard to reach areas. Our study piloted the use of mobile phones in order to transmit near to real-time data from remote districts in Tanzania (Ngorongoro and Ngara, Burundi (Muyinga and Zambia (Kazungula and Sesheke. Two technologies namely, digital and short messaging services were used to capture and transmit disease event data in the animal and human health sectors in the study areas based on a server–client model. Smart phones running the Android operating system (minimum required version: Android 1.6, and which supported open source application, Epicollect, as well as the Open Data Kit application, were used in the study. These phones allowed collection of geo-tagged data, with the opportunity of including static and moving images related to disease events. The project supported routine disease surveillance systems in the ministries responsible for animal and human health in Burundi, Tanzania and Zambia, as well as data collection for researchers at the Sokoine University of Agriculture, Tanzania. During the project implementation period between 2011 and 2013, a total number of 1651 diseases event-related forms were submitted, which allowed reporters to include GPS coordinates and photographs related to the events captured. It was concluded that the new technology-based surveillance system is useful in providing near to real-time data, with potential for enhancing

  8. From Human to Artificial Mouth, From Basics to Results

    International Nuclear Information System (INIS)

    Mielle, Patrick; Tarrega, Amparo; Salles, Christian; Gorria, Patrick; Liodenot, Jean Jacques; Liaboeuf, Joeel; Andrejewski, Jean-Luc

    2009-01-01

    Sensory perception of the flavor release during the eating of a food piece is highly dependent upon mouth parameters. Major limitations have been reported during in-vivo flavor release studies, such as marked intra- and inter-individual variability. To overcome these limitations, a chewing simulator has been developed to mimic the human mastication of food samples. The device faithfully reproduces most of the functions of the human mouth. The active cell comprises several mobile parts that can accurately reproduce shear and compression strengths and tongue functions in real-time, according to data previously collected in-vivo. The mechanical functionalities of the system were validated using peanuts, with a fair agreement with the human data. Flavor release can be monitored on-line using either API-MS or chemical sensors, or off-line using HPLC for non-volatile compounds. Couplings with API-MS detectors have shown differences in the kinetics of flavour release, as a function of the cheeses composition. Data were also collected for the analysis of taste compounds released during the human chewing but are not available yet for the Artificial Mouth.

  9. Is Autism a Member of a Family of Diseases Resulting from Genetic/Cultural Mismatches? Implications for Treatment and Prevention

    Directory of Open Access Journals (Sweden)

    Staci D. Bilbo

    2012-01-01

    Full Text Available Several lines of evidence support the view that autism is a typical member of a large family of immune-related, noninfectious, chronic diseases associated with postindustrial society. This family of diseases includes a wide range of inflammatory, allergic, and autoimmune diseases and results from consequences of genetic/culture mismatches which profoundly destabilize the immune system. Principle among these consequences is depletion of important components, particularly helminths, from the ecosystem of the human body, the human biome. Autism shares a wide range of features in common with this family of diseases, including the contribution of genetics/epigenetics, the identification of disease-inducing triggers, the apparent role of immunity in pathogenesis, high prevalence, complex etiologies and manifestations, and potentially some aspects of epidemiology. Fortunately, using available resources and technology, modern medicine has the potential to effectively reconstitute the human biome, thus treating or even avoiding altogether the consequences of genetic/cultural mismatches which underpin this entire family of disease. Thus, if indeed autism is an epidemic of postindustrial society associated with immune hypersensitivity, we can expect that the disease is readily preventable.

  10. Functional modules, mutational load and human genetic disease.

    Science.gov (United States)

    Zaghloul, Norann A; Katsanis, Nicholas

    2010-04-01

    The ability to generate a massive amount of sequencing and genotyping data is transforming the study of human genetic disorders. Driven by such innovation, it is likely that whole exome and whole-genome resequencing will replace regionally focused approaches for gene discovery and clinical testing in the next few years. However, this opportunity brings a significant interpretative challenge to assigning function and phenotypic variance to common and rare alleles. Understanding the effect of individual mutations in the context of the remaining genomic variation represents a major challenge to our interpretation of disease. Here, we discuss the challenges of assigning mutation functionality and, drawing from the examples of ciliopathies as well as cohesinopathies and channelopathies, discuss possibilities for the functional modularization of the human genome. Functional modularization in addition to the development of physiologically relevant assays to test allele functionality will accelerate our understanding of disease architecture and enable the use of genome-wide sequence data for disease diagnosis and phenotypic prediction in individuals. Copyright 2010 Elsevier Ltd. All rights reserved.

  11. Role of Lactobacillus reuteri in Human Health and Diseases

    Directory of Open Access Journals (Sweden)

    Qinghui Mu

    2018-04-01

    Full Text Available Lactobacillus reuteri (L. reuteri is a well-studied probiotic bacterium that can colonize a large number of mammals. In humans, L. reuteri is found in different body sites, including the gastrointestinal tract, urinary tract, skin, and breast milk. The abundance of L. reuteri varies among different individuals. Several beneficial effects of L. reuteri have been noted. First, L. reuteri can produce antimicrobial molecules, such as organic acids, ethanol, and reuterin. Due to its antimicrobial activity, L. reuteri is able to inhibit the colonization of pathogenic microbes and remodel the commensal microbiota composition in the host. Second, L. reuteri can benefit the host immune system. For instance, some L. reuteri strains can reduce the production of pro-inflammatory cytokines while promoting regulatory T cell development and function. Third, bearing the ability to strengthen the intestinal barrier, the colonization of L. reuteri may decrease the microbial translocation from the gut lumen to the tissues. Microbial translocation across the intestinal epithelium has been hypothesized as an initiator of inflammation. Therefore, inflammatory diseases, including those located in the gut as well as in remote tissues, may be ameliorated by increasing the colonization of L. reuteri. Notably, the decrease in the abundance of L. reuteri in humans in the past decades is correlated with an increase in the incidences of inflammatory diseases over the same period of time. Direct supplementation or prebiotic modulation of L. reuteri may be an attractive preventive and/or therapeutic avenue against inflammatory diseases.

  12. Transcriptome Profiling in Human Diseases: New Advances and Perspectives

    Directory of Open Access Journals (Sweden)

    Amelia Casamassimi

    2017-07-01

    Full Text Available In the last decades, transcriptome profiling has been one of the most utilized approaches to investigate human diseases at the molecular level. Through expression studies, many molecular biomarkers and therapeutic targets have been found for several human pathologies. This number is continuously increasing thanks to total RNA sequencing. Indeed, this new technology has completely revolutionized transcriptome analysis allowing the quantification of gene expression levels and allele-specific expression in a single experiment, as well as to identify novel genes, splice isoforms, fusion transcripts, and to investigate the world of non-coding RNA at an unprecedented level. RNA sequencing has also been employed in important projects, like ENCODE (Encyclopedia of the regulatory elements and TCGA (The Cancer Genome Atlas, to provide a snapshot of the transcriptome of dozens of cell lines and thousands of primary tumor specimens. Moreover, these studies have also paved the way to the development of data integration approaches in order to facilitate management and analysis of data and to identify novel disease markers and molecular targets to use in the clinics. In this scenario, several ongoing clinical trials utilize transcriptome profiling through RNA sequencing strategies as an important instrument in the diagnosis of numerous human pathologies.

  13. Transcriptome Profiling in Human Diseases: New Advances and Perspectives.

    Science.gov (United States)

    Casamassimi, Amelia; Federico, Antonio; Rienzo, Monica; Esposito, Sabrina; Ciccodicola, Alfredo

    2017-07-29

    In the last decades, transcriptome profiling has been one of the most utilized approaches to investigate human diseases at the molecular level. Through expression studies, many molecular biomarkers and therapeutic targets have been found for several human pathologies. This number is continuously increasing thanks to total RNA sequencing. Indeed, this new technology has completely revolutionized transcriptome analysis allowing the quantification of gene expression levels and allele-specific expression in a single experiment, as well as to identify novel genes, splice isoforms, fusion transcripts, and to investigate the world of non-coding RNA at an unprecedented level. RNA sequencing has also been employed in important projects, like ENCODE (Encyclopedia of the regulatory elements) and TCGA (The Cancer Genome Atlas), to provide a snapshot of the transcriptome of dozens of cell lines and thousands of primary tumor specimens. Moreover, these studies have also paved the way to the development of data integration approaches in order to facilitate management and analysis of data and to identify novel disease markers and molecular targets to use in the clinics. In this scenario, several ongoing clinical trials utilize transcriptome profiling through RNA sequencing strategies as an important instrument in the diagnosis of numerous human pathologies.

  14. Serological prevalence of human parvovirus B19 in diseases or disordersrelated to different human body systems.

    Science.gov (United States)

    Aktaş, Osman; Aydin, Hakan; Uslu, Hakan

    2016-02-17

    Human parvovirus B19 is a pathogen that affects different parts of the body. We planned this study because of the lack of data on B19 seroprevalence based on different body-system diseases. The prevalence of parvovirus B19 antibodies was investigated retrospectively in 1239 patients by review of medical records from 2009-2012, according to their diseases classified under general titles in compliance with the International Classification of Diseases (ICD-10). Parvovirus B19-specific antibodies were detected by quantitative enzyme immunoassays. The positivity rate was 27.8% for only IgG, 8.5% for only IgM, and 2.6% for both IgG and IgM. The highest positivity for IgG alone was found in musculoskeletal system and connective tissue diseases (55.9%), while the highest positivity for IgM was found in neoplasms (16.4%). The highest positivity for IgG was seen in rheumatoid arthritis (72.2%) and pregnancy (52.6%), and the highest positivity for total IgM was found in upper respiratory tract disease (21.0%) and hepatic failure (17.1%). Parvovirus B19 seroprevalence was relatively low in northeastern Anatolia compared to most serological studies conducted in other regions. We think that this study has provided the first wide-ranging information on the seroprevalence of B19 in diseases and disorders of the major human body systems.

  15. 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.

  16. HSC extrinsic sex-related and intrinsic autoimmune disease-related human B-cell variation is recapitulated in humanized mice.

    Science.gov (United States)

    Borsotti, Chiara; Danzl, Nichole M; Nauman, Grace; Hölzl, Markus A; French, Clare; Chavez, Estefania; Khosravi-Maharlooei, Mohsen; Glauzy, Salome; Delmotte, Fabien R; Meffre, Eric; Savage, David G; Campbell, Sean R; Goland, Robin; Greenberg, Ellen; Bi, Jing; Satwani, Prakash; Yang, Suxiao; Bathon, Joan; Winchester, Robert; Sykes, Megan

    2017-10-24

    B cells play a major role in antigen presentation and antibody production in the development of autoimmune diseases, and some of these diseases disproportionally occur in females. Moreover, immune responses tend to be stronger in female vs male humans and mice. Because it is challenging to distinguish intrinsic from extrinsic influences on human immune responses, we used a personalized immune (PI) humanized mouse model, in which immune systems were generated de novo from adult human hematopoietic stem cells (HSCs) in immunodeficient mice. We assessed the effect of recipient sex and of donor autoimmune diseases (type 1 diabetes [T1D] and rheumatoid arthritis [RA]) on human B-cell development in PI mice. We observed that human B-cell levels were increased in female recipients regardless of the source of human HSCs or the strain of immunodeficient recipient mice. Moreover, mice injected with T1D- or RA-derived HSCs displayed B-cell abnormalities compared with healthy control HSC-derived mice, including altered B-cell levels, increased proportions of mature B cells and reduced CD19 expression. Our study revealed an HSC-extrinsic effect of recipient sex on human B-cell reconstitution. Moreover, the PI humanized mouse model revealed HSC-intrinsic defects in central B-cell tolerance that recapitulated those in patients with autoimmune diseases. These results demonstrate the utility of humanized mouse models as a tool to better understand human immune cell development and regulation.

  17. Mitochondrial regulation of epigenetics and its role in human diseases

    DEFF Research Database (Denmark)

    Minocherhomji, Sheroy; Tollefsbol, Trygve O; Singh, Keshav K

    2012-01-01

    as the sole pathogenic factor suggesting that additional mechanisms contribute to lack of genotype and clinical phenotype correlationship. An increasing number of studies have identified a possible effect on the epigenetic landscape of the nuclear genome as a consequence of mitochondrial dysfunction....... In particular, these studies demonstrate reversible or irreversible changes in genomic DNA methylation profiles of the nuclear genome. Here we review how mitochondria damage checkpoint (mitocheckpoint) induces epigenetic changes in the nucleus. Persistent pathogenic mutations in mtDNA may also lead...... to epigenetic changes causing genomic instability in the nuclear genome. We propose that "mitocheckpoint" mediated epigenetic and genetic changes may play key roles in phenotypic variation related to mitochondrial diseases or host of human diseases in which mitochondrial defect plays a primary role....

  18. Crossed wires: 3D genome misfolding in human disease.

    Science.gov (United States)

    Norton, Heidi K; Phillips-Cremins, Jennifer E

    2017-11-06

    Mammalian genomes are folded into unique topological structures that undergo precise spatiotemporal restructuring during healthy development. Here, we highlight recent advances in our understanding of how the genome folds inside the 3D nucleus and how these folding patterns are miswired during the onset and progression of mammalian disease states. We discuss potential mechanisms underlying the link among genome misfolding, genome dysregulation, and aberrant cellular phenotypes. We also discuss cases in which the endogenous 3D genome configurations in healthy cells might be particularly susceptible to mutation or translocation. Together, these data support an emerging model in which genome folding and misfolding is critically linked to the onset and progression of a broad range of human diseases. © 2017 Norton and Phillips-Cremins.

  19. Use of rodents as models of human diseases

    Directory of Open Access Journals (Sweden)

    Thierry F Vandamme

    2014-01-01

    Full Text Available Advances in molecular biology have significantly increased the understanding of the biology of different diseases. However, these discoveries have not yet been fully translated into improved treatments for patients with diseases such as cancers. One of the factors limiting the translation of knowledge from preclinical studies to the clinic has been the limitations of in vivo diseases models. In this brief review, we will discuss the advantages and disadvantages of rodent models that have been developed to simulate human pathologies, focusing in models that employ xenografts and genetic modification. Within the framework of genetically engineered mouse (GEM models, we will review some of the current genetic strategies for modeling diseases in the mouse and the preclinical studies that have already been undertaken. We will also discuss how recent improvements in imaging technologies may increase the information derived from using these GEMs during early assessments of potential therapeutic pathways. Furthermore, it is interesting to note that one of the values of using a mouse model is the very rapid turnover rate of the animal, going through the process of birth to death in a very short timeframe relative to that of larger mammalian species.

  20. Molecular mechanisms of acrolein toxicity: relevance to human disease.

    Science.gov (United States)

    Moghe, Akshata; Ghare, Smita; Lamoreau, Bryan; Mohammad, Mohammad; Barve, Shirish; McClain, Craig; Joshi-Barve, Swati

    2015-02-01

    Acrolein, a highly reactive unsaturated aldehyde, is a ubiquitous environmental pollutant and its potential as a serious environmental health threat is beginning to be recognized. Humans are exposed to acrolein per oral (food and water), respiratory (cigarette smoke, automobile exhaust, and biocide use) and dermal routes, in addition to endogenous generation (metabolism and lipid peroxidation). Acrolein has been suggested to play a role in several disease states including spinal cord injury, multiple sclerosis, Alzheimer's disease, cardiovascular disease, diabetes mellitus, and neuro-, hepato-, and nephro-toxicity. On the cellular level, acrolein exposure has diverse toxic effects, including DNA and protein adduction, oxidative stress, mitochondrial disruption, membrane damage, endoplasmic reticulum stress, and immune dysfunction. This review addresses our current understanding of each pathogenic mechanism of acrolein toxicity, with emphasis on the known and anticipated contribution to clinical disease, and potential therapies. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  1. Bioprinted three dimensional human tissues for toxicology and disease modeling.

    Science.gov (United States)

    Nguyen, Deborah G; Pentoney, Stephen L

    2017-03-01

    The high rate of attrition among clinical-stage therapies, due largely to an inability to predict human toxicity and/or efficacy, underscores the need for in vitro models that better recapitulate in vivo human biology. In much the same way that additive manufacturing has revolutionized the production of solid objects, three-dimensional (3D) bioprinting is enabling the automated production of more architecturally and functionally accurate in vitro tissue culture models. Here, we provide an overview of the most commonly used bioprinting approaches and how they are being used to generate complex in vitro tissues for use in toxicology and disease modeling research. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Enhanced vulnerability of human proteins towards disease-associated inactivation through divergent evolution.

    Science.gov (United States)

    Medina-Carmona, Encarnación; Fuchs, Julian E; Gavira, Jose A; Mesa-Torres, Noel; Neira, Jose L; Salido, Eduardo; Palomino-Morales, Rogelio; Burgos, Miguel; Timson, David J; Pey, Angel L

    2017-09-15

    Human proteins are vulnerable towards disease-associated single amino acid replacements affecting protein stability and function. Interestingly, a few studies have shown that consensus amino acids from mammals or vertebrates can enhance protein stability when incorporated into human proteins. Here, we investigate yet unexplored relationships between the high vulnerability of human proteins towards disease-associated inactivation and recent evolutionary site-specific divergence of stabilizing amino acids. Using phylogenetic, structural and experimental analyses, we show that divergence from the consensus amino acids at several sites during mammalian evolution has caused local protein destabilization in two human proteins linked to disease: cancer-associated NQO1 and alanine:glyoxylate aminotransferase, mutated in primary hyperoxaluria type I. We demonstrate that a single consensus mutation (H80R) acts as a disease suppressor on the most common cancer-associated polymorphism in NQO1 (P187S). The H80R mutation reactivates P187S by enhancing FAD binding affinity through local and dynamic stabilization of its binding site. Furthermore, we show how a second suppressor mutation (E247Q) cooperates with H80R in protecting the P187S polymorphism towards inactivation through long-range allosteric communication within the structural ensemble of the protein. Our results support that recent divergence of consensus amino acids may have occurred with neutral effects on many functional and regulatory traits of wild-type human proteins. However, divergence at certain sites may have increased the propensity of some human proteins towards inactivation due to disease-associated mutations and polymorphisms. Consensus mutations also emerge as a potential strategy to identify structural hot-spots in proteins as targets for pharmacological rescue in loss-of-function genetic diseases. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please

  3. Melanopsin-expressing retinal ganglion cells: implications for human diseases

    DEFF Research Database (Denmark)

    La Morgia, Chiara; Ross-Cisneros, Fred N; Hannibal, Jens

    2011-01-01

    In the last decade, there was the seminal discovery of melanopsin-expressing retinal ganglion cells (mRGCs) as a new class of photoreceptors that subserve the photoentrainment of circadian rhythms and other non-image forming functions of the eye. Since then, there has been a growing research...... interest on these cells, mainly focused on animal models. Only recently, a few studies have started to address the relevance of the mRGC system in humans and related diseases. We recently discovered that mRGCs resist neurodegeneration in two inherited mitochondrial disorders that cause blindness, i...

  4. Decrease in Hurst exponent of human gait with aging and neurodegenerative diseases

    International Nuclear Information System (INIS)

    Zhauang Jianjun; Ning Xinbao; Yang Xiaodong; Huo Chengyu; Hou Fengzhen

    2008-01-01

    In this paper the decrease in the Hurst exponent of human gait with aging and neurodegenerative diseases was observed by using an improved rescaled range (R/S) analysis method. It indicates that the long-range correlations of gait rhythm from young healthy people are stronger than those from the healthy elderly and the diseased. The result further implies that fractal dynamics in human gait will be altered due to weakening or impairment of neural control on locomotion resulting from aging and neurodegenerative diseases. Due to analysing short-term data sequences rather than long datasets required by most nonlinear methods, the algorithm has the characteristics of simplicity and sensitivity, most importantly, fast calculation as well as powerful anti-noise capacities. These findings have implications for modelling locomotor control and also for quantifying gait dynamics in varying physiologic and pathologic states

  5. Regulatory Role of Small Nucleolar RNAs in Human Diseases

    Directory of Open Access Journals (Sweden)

    Grigory A. Stepanov

    2015-01-01

    Full Text Available Small nucleolar RNAs (snoRNAs are appreciable players in gene expression regulation in human cells. The canonical function of box C/D and box H/ACA snoRNAs is posttranscriptional modification of ribosomal RNAs (rRNAs, namely, 2′-O-methylation and pseudouridylation, respectively. A series of independent studies demonstrated that snoRNAs, as well as other noncoding RNAs, serve as the source of various short regulatory RNAs. Some snoRNAs and their fragments can also participate in the regulation of alternative splicing and posttranscriptional modification of mRNA. Alterations in snoRNA expression in human cells can affect numerous vital cellular processes. SnoRNA level in human cells, blood serum, and plasma presents a promising target for diagnostics and treatment of human pathologies. Here we discuss the relation between snoRNAs and oncological, neurodegenerative, and viral diseases and also describe changes in snoRNA level in response to artificial stress and some drugs.

  6. A Nonhuman Primate Model of Human Radiation-Induced Venocclusive Liver Disease and Hepatocyte Injury

    Energy Technology Data Exchange (ETDEWEB)

    Yannam, Govardhana Rao [Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska (United States); Han, Bing [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi' an Jiaotong University, Xi' an, Shaanxi (China); Setoyama, Kentaro [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Yamamoto, Toshiyuki [Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska (United States); Ito, Ryotaro; Brooks, Jenna M. [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Guzman-Lepe, Jorge [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Department of Pathology, Children' s Hospital of Pittsburgh, Pittsburgh, Pennsylvania (United States); Galambos, Csaba [Department of Pathology, Children' s Hospital of Pittsburgh, Pittsburgh, Pennsylvania (United States); Fong, Jason V. [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Deutsch, Melvin; Quader, Mubina A. [Department of Radiation Oncology, Children' s Hospital of Pittsburgh, Pittsburgh, Pennsylvania (United States); Yamanouchi, Kosho [Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York (United States); Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, New York (United States); Kabarriti, Rafi; Mehta, Keyur [Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York (United States); Soto-Gutierrez, Alejandro [Department of Pathology, Children' s Hospital of Pittsburgh, Pittsburgh, Pennsylvania (United States); McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); and others

    2014-02-01

    Background: Human liver has an unusual sensitivity to radiation that limits its use in cancer therapy or in preconditioning for hepatocyte transplantation. Because the characteristic veno-occlusive lesions of radiation-induced liver disease do not occur in rodents, there has been no experimental model to investigate the limits of safe radiation therapy or explore the pathogenesis of hepatic veno-occlusive disease. Methods and Materials: We performed a dose-escalation study in a primate, the cynomolgus monkey, using hypofractionated stereotactic body radiotherapy in 13 animals. Results: At doses ≥40 Gy, animals developed a systemic syndrome resembling human radiation-induced liver disease, consisting of decreased albumin, elevated alkaline phosphatase, loss of appetite, ascites, and normal bilirubin. Higher radiation doses were lethal, causing severe disease that required euthanasia approximately 10 weeks after radiation. Even at lower doses in which radiation-induced liver disease was mild or nonexistent, latent and significant injury to hepatocytes was demonstrated by asialoglycoprotein-mediated functional imaging. These monkeys developed hepatic failure with encephalopathy when they received parenteral nutrition containing high concentrations of glucose. Histologically, livers showed central obstruction via an unusual intimal swelling that progressed to central fibrosis. Conclusions: The cynomolgus monkey, as the first animal model of human veno-occlusive radiation-induced liver disease, provides a resource for characterizing the early changes and pathogenesis of venocclusion, for establishing nonlethal therapeutic dosages, and for examining experimental therapies to minimize radiation injury.

  7. A Nonhuman Primate Model of Human Radiation-Induced Venocclusive Liver Disease and Hepatocyte Injury

    International Nuclear Information System (INIS)

    Yannam, Govardhana Rao; Han, Bing; Setoyama, Kentaro; Yamamoto, Toshiyuki; Ito, Ryotaro; Brooks, Jenna M.; Guzman-Lepe, Jorge; Galambos, Csaba; Fong, Jason V.; Deutsch, Melvin; Quader, Mubina A.; Yamanouchi, Kosho; Kabarriti, Rafi; Mehta, Keyur; Soto-Gutierrez, Alejandro

    2014-01-01

    Background: Human liver has an unusual sensitivity to radiation that limits its use in cancer therapy or in preconditioning for hepatocyte transplantation. Because the characteristic veno-occlusive lesions of radiation-induced liver disease do not occur in rodents, there has been no experimental model to investigate the limits of safe radiation therapy or explore the pathogenesis of hepatic veno-occlusive disease. Methods and Materials: We performed a dose-escalation study in a primate, the cynomolgus monkey, using hypofractionated stereotactic body radiotherapy in 13 animals. Results: At doses ≥40 Gy, animals developed a systemic syndrome resembling human radiation-induced liver disease, consisting of decreased albumin, elevated alkaline phosphatase, loss of appetite, ascites, and normal bilirubin. Higher radiation doses were lethal, causing severe disease that required euthanasia approximately 10 weeks after radiation. Even at lower doses in which radiation-induced liver disease was mild or nonexistent, latent and significant injury to hepatocytes was demonstrated by asialoglycoprotein-mediated functional imaging. These monkeys developed hepatic failure with encephalopathy when they received parenteral nutrition containing high concentrations of glucose. Histologically, livers showed central obstruction via an unusual intimal swelling that progressed to central fibrosis. Conclusions: The cynomolgus monkey, as the first animal model of human veno-occlusive radiation-induced liver disease, provides a resource for characterizing the early changes and pathogenesis of venocclusion, for establishing nonlethal therapeutic dosages, and for examining experimental therapies to minimize radiation injury

  8. Evaluating Human T-Cell Therapy of Cytomegalovirus Organ Disease in HLA-Transgenic Mice.

    Directory of Open Access Journals (Sweden)

    Simone Thomas

    2015-07-01

    Full Text Available Reactivation of human cytomegalovirus (HCMV can cause severe disease in recipients of hematopoietic stem cell transplantation. Although preclinical research in murine models as well as clinical trials have provided 'proof of concept' for infection control by pre-emptive CD8 T-cell immunotherapy, there exists no predictive model to experimentally evaluate parameters that determine antiviral efficacy of human T cells in terms of virus control in functional organs, prevention of organ disease, and host survival benefit. We here introduce a novel mouse model for testing HCMV epitope-specific human T cells. The HCMV UL83/pp65-derived NLV-peptide was presented by transgenic HLA-A2.1 in the context of a lethal infection of NOD/SCID/IL-2rg-/- mice with a chimeric murine CMV, mCMV-NLV. Scenarios of HCMV-seropositive and -seronegative human T-cell donors were modeled by testing peptide-restimulated and T-cell receptor-transduced human T cells, respectively. Upon transfer, the T cells infiltrated host tissues in an epitope-specific manner, confining the infection to nodular inflammatory foci. This resulted in a significant reduction of viral load, diminished organ pathology, and prolonged survival. The model has thus proven its potential for a preclinical testing of the protective antiviral efficacy of HCMV epitope-specific human T cells in the evaluation of new approaches to an immunotherapy of CMV disease.

  9. Can the silkworm (Bombyx mori) be used as a human disease model?

    Science.gov (United States)

    Tabunoki, Hiroko; Bono, Hidemasa; Ito, Katsuhiko; Yokoyama, Takeshi

    2016-02-01

    Bombyx mori (silkworm) is the most famous lepidopteran in Japan. B. mori has long been used in the silk industry and also as a model insect for agricultural research. In recent years, B. mori has attracted interest in its potential for use in pathological analysis of model animals. For example, the human macular carotenoid transporter was discovered using information of B. mori carotenoid transporter derived from yellow-cocoon strain. The B. mori carotenoid transport system is useful in human studies. To develop a human disease model, we characterized the human homologs of B. mori, and by constructing KAIKO functional annotation pipeline, and to analyze gene expression profile of a unique B. mori mutant strain using microarray analysis. As a result, we identified a novel molecular network involved in Parkinson's disease. Here we describe the potential use of a spontaneous mutant silkworm strain as a human disease model. We also summarize recent progress in the application of genomic information for annotation of human homologs in B. mori. The B. mori mutant will provide a clue to pathological mechanisms, and the findings will be helpful for the development of therapies and for medical drug discovery.

  10. DISEASES

    DEFF Research Database (Denmark)

    Pletscher-Frankild, Sune; Pallejà, Albert; Tsafou, Kalliopi

    2015-01-01

    Text mining is a flexible technology that can be applied to numerous different tasks in biology and medicine. We present a system for extracting disease-gene associations from biomedical abstracts. The system consists of a highly efficient dictionary-based tagger for named entity recognition...... of human genes and diseases, which we combine with a scoring scheme that takes into account co-occurrences both within and between sentences. We show that this approach is able to extract half of all manually curated associations with a false positive rate of only 0.16%. Nonetheless, text mining should...... not stand alone, but be combined with other types of evidence. For this reason, we have developed the DISEASES resource, which integrates the results from text mining with manually curated disease-gene associations, cancer mutation data, and genome-wide association studies from existing databases...

  11. Prevalence of Hookworm infection and Strongyloidiasis in Cats and Potential Risk Factor of Human Diseases

    Science.gov (United States)

    Sedionoto, Blego; Anamnart, Witthaya

    2018-02-01

    Hookworm infection and Stronyloidiasis are public health problem in the worldwide which both of them could infective in human by penetrated on skin and they have potential risk from Gastrointestinal zoonotic helminths of pets, including cats. We investigated the prevalence soil transmitted helminths infection in human and cats used modified Formal-Ether Concentration and agar plate culture. Fecal samples of 23 cats and human from Naitung and Subua Villages (area study 1), and fecal samples of 15 cats and 17 humans from Thasala Beach villages (area study 2) were collected. Result of study in area study 1 showed prevalence of infection in human was not hookworm and strongyloidiasis but 10% humans have infected Ascaris and Tricuris, and in cats have infected by hookworm 75.2% and S. strercoralis 8.5%, toxocara 13%, spirometra 13% and overall prevalence 82.5%. In area study 2 showed in human has infected by Trichuris 100% and S. stercoralis 29.4% and in cats have infected by hookworm 100% and S. strercoralis 40%, toxocora 20%, and spirometra 20%. Helminth infection found in both humans in two areas study are S. strercoralis. Hookworms were the most common helminth in cats but did not connection with infection in human, while S. strercoralis was helminth infection in cats which has potential zoonotic disease to human.

  12. Modeling human diseases: an education in interactions and interdisciplinary approaches

    Directory of Open Access Journals (Sweden)

    Leonard Zon

    2016-06-01

    Full Text Available Traditionally, most investigators in the biomedical arena exploit one model system in the course of their careers. Occasionally, an investigator will switch models. The selection of a suitable model system is a crucial step in research design. Factors to consider include the accuracy of the model as a reflection of the human disease under investigation, the numbers of animals needed and ease of husbandry, its physiology and developmental biology, and the ability to apply genetics and harness the model for drug discovery. In my lab, we have primarily used the zebrafish but combined it with other animal models and provided a framework for others to consider the application of developmental biology for therapeutic discovery. Our interdisciplinary approach has led to many insights into human diseases and to the advancement of candidate drugs to clinical trials. Here, I draw on my experiences to highlight the importance of combining multiple models, establishing infrastructure and genetic tools, forming collaborations, and interfacing with the medical community for successful translation of basic findings to the clinic.

  13. Hepatic cholesterol ester hydrolase in human liver disease.

    Science.gov (United States)

    Simon, J B; Poon, R W

    1978-09-01

    Human liver contains an acid cholesterol ester hydrolase (CEH) of presumed lysosomal origin, but its significance is unknown. We developed a modified CEH radioassay suitable for needle biopsy specimens and measured hepatic activity of this enzyme in 69 patients undergoing percutaneous liver biopsy. Histologically normal livers hydrolyzed 5.80 +/- 0.78 SEM mumoles of cholesterol ester per hr per g of liver protein (n, 10). Values were similar in alcoholic liver disease (n, 17), obstructive jaundice (n, 9), and miscellaneous hepatic disorders (n, 21). In contrast, mean hepatic CEH activity was more than 3-fold elevated in 12 patients with acute hepatitis, 21.05 +/- 2.45 SEM mumoles per hr per g of protein (P less than 0.01). In 2 patients studied serially, CEH returned to normal as hepatitis resolved. CEH activity in all patients paralleled SGOT levels (r, 0.84; P less than 0.01). There was no correlation with serum levels of free or esterified cholesterol nor with serum activity of lecithin-cholesterol acyltransferase, the enzyme responsible for cholesterol esterification in plasma. These studies confirm the presence of CEH activity in human liver and show markedly increased activity in acute hepatitis. The pathogenesis and clinical significance of altered hepatic CEH activity in liver disease require further study.

  14. Characterization of RNA isolated from eighteen different human tissues: results from a rapid human autopsy program.

    Science.gov (United States)

    Walker, Douglas G; Whetzel, Alexis M; Serrano, Geidy; Sue, Lucia I; Lue, Lih-Fen; Beach, Thomas G

    2016-09-01

    Many factors affect the integrity of messenger RNA from human autopsy tissues including postmortem interval (PMI) between death and tissue preservation and the pre-mortem agonal and disease states. In this communication, we describe RNA isolation and characterization of 389 samples from 18 different tissues from elderly donors who were participants in a rapid whole-body autopsy program located in Sun City, Arizona ( www.brainandbodydonationprogram.org ). Most tissues were collected within a PMI of 2-6 h (median 3.15 h; N = 455), but for this study, tissue from cases with longer PMIs (1.25-29.25 h) were included. RNA quality was assessed by RNA integrity number (RIN) and total yield (ng RNA/mg tissue). RIN correlated with PMI for heart (r = -0.531, p = 0.009) and liver (r = -558, p = 0.0017), while RNA yield correlated with PMI for colon (r = -485, p = 0.016) and skin (r = -0.460, p = 0.031). RNAs with the lowest integrity were from skin and cervix where 22.7 and 31.4 % of samples respectively failed to produce intact RNA; by contrast all samples from esophagus, lymph node, jejunum, lung, stomach, submandibular gland and kidney produced RNA with measurable RINs. Expression levels in heart RNA of 4 common housekeeping normalization genes showed significant correlations of Ct values with RIN, but only one gene, glyceraldehyde-3 phosphate dehydrogenase, showed a correlation of Ct with PMI. There were no correlations between RIN values obtained for liver, adrenal, cervix, esophagus and lymph node and those obtained from corresponding brain samples. We show that high quality RNA can be produced from most human autopsy tissues, though with significant differences between tissues and donors. The RNA stability and yield did not depend solely on PMI; other undetermined factors are involved, but these do not include the age of the donor.

  15. Prioritizing Zoonotic Diseases: Differences in Perspectives Between Human and Animal Health Professionals in North America.

    Science.gov (United States)

    Ng, V; Sargeant, J M

    2016-05-01

    Zoonoses pose a significant burden of illness in North America. Zoonoses represent an additional threat to public health because the natural reservoirs are often animals, particularly wildlife, thus eluding control efforts such as quarantine, vaccination and social distancing. As there are limited resources available, it is necessary to prioritize diseases in order to allocate resources to those posing the greatest public health threat. Many studies have attempted to prioritize zoonoses, but challenges exist. This study uses a quantitative approach, conjoint analysis (CA), to overcome some limitations of traditional disease prioritization exercises. We used CA to conduct a zoonoses prioritization study involving a range of human and animal health professionals across North America; these included epidemiologists, public health practitioners, research scientists, physicians, veterinarians, laboratory technicians and nurses. A total of 699 human health professionals (HHP) and 585 animal health professionals (AHP) participated in this study. We used CA to prioritize 62 zoonotic diseases using 21 criteria. Our findings suggest CA can be used to produce reasonable criteria scores for disease prioritization. The fitted models were satisfactory for both groups with a slightly better fit for AHP compared to HHP (84.4% certainty fit versus 83.6%). Human-related criteria were more influential for HHP in their decision to prioritize zoonoses, while animal-related criteria were more influential for AHP resulting in different disease priority lists. While the differences were not statistically significant, a difference of one or two ranks could be considered important for some individuals. A potential solution to address the varying opinions is discussed. The scientific framework for disease prioritization presented can be revised on a regular basis by updating disease criteria to reflect diseases as they evolve over time; such a framework is of value allowing diseases of

  16. The Spanish biology/disease initiative within the human proteome project: Application to rheumatic diseases.

    Science.gov (United States)

    Ruiz-Romero, Cristina; Calamia, Valentina; Albar, Juan Pablo; Casal, José Ignacio; Corrales, Fernando J; Fernández-Puente, Patricia; Gil, Concha; Mateos, Jesús; Vivanco, Fernando; Blanco, Francisco J

    2015-09-08

    The Spanish Chromosome 16 consortium is integrated in the global initiative Human Proteome Project, which aims to develop an entire map of the proteins encoded following a gene-centric strategy (C-HPP) in order to make progress in the understanding of human biology in health and disease (B/D-HPP). Chromosome 16 contains many genes encoding proteins involved in the development of a broad range of diseases, which have a significant impact on the health care system. The Spanish HPP consortium has developed a B/D platform with five programs focused on selected medical areas: cancer, obesity, cardiovascular, infectious and rheumatic diseases. Each of these areas has a clinical leader associated to a proteomic investigator with the responsibility to get a comprehensive understanding of the proteins encoded by Chromosome 16 genes. Proteomics strategies have enabled great advances in the area of rheumatic diseases, particularly in osteoarthritis, with studies performed on joint cells, tissues and fluids. In this manuscript we describe how the Spanish HPP-16 consortium has developed a B/D platform with five programs focused on selected medical areas: cancer, obesity, cardiovascular, infectious and rheumatic diseases. Each of these areas has a clinical leader associated to a proteomic investigator with the responsibility to get a comprehensive understanding of the proteins encoded by Chromosome 16 genes. We show how the Proteomic strategy has enabled great advances in the area of rheumatic diseases, particularly in osteoarthritis, with studies performed on joint cells, tissues and fluids. This article is part of a Special Issue entitled: HUPO 2014. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Being human: The role of pluripotent stem cells in regenerative medicine and humanizing Alzheimer's disease models.

    Science.gov (United States)

    Sproul, Andrew A

    2015-01-01

    Human pluripotent stem cells (PSCs) have the capacity to revolutionize medicine by allowing the generation of functional cell types such as neurons for cell replacement therapy. However, the more immediate impact of PSCs on treatment of Alzheimer's disease (AD) will be through improved human AD model systems for mechanistic studies and therapeutic screening. This review will first briefly discuss different types of PSCs and genome-editing techniques that can be used to modify PSCs for disease modeling or for personalized medicine. This will be followed by a more in depth analysis of current AD iPSC models and a discussion of the need for more complex multicellular models, including cell types such as microglia. It will finish with a discussion on current clinical trials using PSC-derived cells and the long-term potential of such strategies for treating AD. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. RAS signalling in energy metabolism and rare human diseases.

    Science.gov (United States)

    Dard, L; Bellance, N; Lacombe, D; Rossignol, R

    2018-05-08

    The RAS pathway is a highly conserved cascade of protein-protein interactions and phosphorylation that is at the heart of signalling networks that govern proliferation, differentiation and cell survival. Recent findings indicate that the RAS pathway plays a role in the regulation of energy metabolism via the control of mitochondrial form and function but little is known on the participation of this effect in RAS-related rare human genetic diseases. Germline mutations that hyperactivate the RAS pathway have been discovered and linked to human developmental disorders that are known as RASopathies. Individuals with RASopathies, which are estimated to affect approximately 1/1000 human birth, share many overlapping characteristics, including cardiac malformations, short stature, neurocognitive impairment, craniofacial dysmorphy, cutaneous, musculoskeletal, and ocular abnormalities, hypotonia and a predisposition to developing cancer. Since the identification of the first RASopathy, type 1 neurofibromatosis (NF1), which is caused by the inactivation of neurofibromin 1, several other syndromes have been associated with mutations in the core components of the RAS-MAPK pathway. These syndromes include Noonan syndrome (NS), Noonan syndrome with multiple lentigines (NSML), which was formerly called LEOPARD syndrome, Costello syndrome (CS), cardio-facio-cutaneous syndrome (CFC), Legius syndrome (LS) and capillary malformation-arteriovenous malformation syndrome (CM-AVM). Here, we review current knowledge about the bioenergetics of the RASopathies and discuss the molecular control of energy homeostasis and mitochondrial physiology by the RAS pathway. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Quadrivalent human papillomavirus vaccination in boys and risk of autoimmune diseases, neurological diseases and venous thromboembolism

    DEFF Research Database (Denmark)

    Frisch, Morten; Besson, Andréa; Clemmensen, Kim Katrine Bjerring

    2018-01-01

    following HPV vaccination in this group. We investigated if quadrivalent HPV (qHPV) vaccination of 10-17-year-old boys is associated with any unusual risk of autoimmune diseases, neurological diseases or venous thromboembolism. Methods: We conducted a national cohort study of 568 410 boys born in Denmark...... 1988-2006 and followed for 4 million person-years during 2006-16, using nationwide registers to obtain individual-level information about received doses of the qHPV vaccine and hospital records for 39 autoimmune diseases, 12 neurological diseases and venous thromboembolism. For each outcome, we...... estimated incidence rate ratios (RRs) with 95% confidence intervals (CIs) according to qHPV vaccination status. Results: Altogether 7384 boys received at least one dose of the qHPV vaccine at age 10-17 years. Overall, RRs were close to unity for the combined groups of autoimmune diseases (RR = 0.96; 95% CI...

  20. Food safety. [chemical contaminants and human toxic diseases

    Science.gov (United States)

    Pier, S. M.; Valentine, J. L.

    1975-01-01

    Illness induced by unsafe food is a problem of great public health significance. This study relates exclusively to the occurrence of chemical agents which will result in food unsafe for human consumption since the matter of food safety is of paramount importance in the mission and operation of the manned spacecraft program of the National Aeronautics and Space Administration.

  1. Possible roles of transglutaminases in molecular mechanisms responsible for human neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Nicola Gaetano Gatta

    2016-11-01

    Full Text Available Transglutaminases are a family of Ca2+-dependent enzymes which catalyze post-translational modifications of proteins. The main activity of these enzymes is the cross-linking of glutaminyl residues of a protein/peptide substrate to lysyl residues of a protein/peptide co-substrate. In addition to lysyl residues, other second nucleophilic co-substrates may include monoamines or polyamines (to form mono- or bi-substituted/crosslinked adducts or –OH groups (to form ester linkages. In absence of co-substrates, the nucleophile may be water, resulting in the net deamidation of the glutaminyl residue. Transglutaminase activity has been suggested to be involved in molecular mechanisms responsible for both physiological or pathological processes. In particular, transglutaminase activity has been shown to be responsible for human autoimmune diseases, Celiac Disease is just one of them. Interestingly, neurodegenerative diseases, such as Alzheimer’s Disease, Parkinson’s Disease, supranuclear palsy, Huntington’s Disease and other polyglutamine diseases, are characterized in part by aberrant cerebral transglutaminase activity and by increased cross-linked proteins in affected brains. This review describes the possible molecular mechanisms by which these enzymes could be responsible for such diseases and the possible use of transglutaminase inhibitors for patients with diseases characterized by aberrant transglutaminase activity.

  2. Type 2 diabetes risk alleles demonstrate extreme directional differentiation among human populations, compared to other diseases.

    Directory of Open Access Journals (Sweden)

    Rong Chen

    Full Text Available Many disease-susceptible SNPs exhibit significant disparity in ancestral and derived allele frequencies across worldwide populations. While previous studies have examined population differentiation of alleles at specific SNPs, global ethnic patterns of ensembles of disease risk alleles across human diseases are unexamined. To examine these patterns, we manually curated ethnic disease association data from 5,065 papers on human genetic studies representing 1,495 diseases, recording the precise risk alleles and their measured population frequencies and estimated effect sizes. We systematically compared the population frequencies of cross-ethnic risk alleles for each disease across 1,397 individuals from 11 HapMap populations, 1,064 individuals from 53 HGDP populations, and 49 individuals with whole-genome sequences from 10 populations. Type 2 diabetes (T2D demonstrated extreme directional differentiation of risk allele frequencies across human populations, compared with null distributions of European-frequency matched control genomic alleles and risk alleles for other diseases. Most T2D risk alleles share a consistent pattern of decreasing frequencies along human migration into East Asia. Furthermore, we show that these patterns contribute to disparities in predicted genetic risk across 1,397 HapMap individuals, T2D genetic risk being consistently higher for individuals in the African populations and lower in the Asian populations, irrespective of the ethnicity considered in the initial discovery of risk alleles. We observed a similar pattern in the distribution of T2D Genetic Risk Scores, which are associated with an increased risk of developing diabetes in the Diabetes Prevention Program cohort, for the same individuals. This disparity may be attributable to the promotion of energy storage and usage appropriate to environments and inconsistent energy intake. Our results indicate that the differential frequencies of T2D risk alleles may

  3. Human Papillomavirus Vaccine Uptake among Individuals with Systemic Inflammatory Diseases

    Science.gov (United States)

    Feldman, Candace H.; Hiraki, Linda T.; Lii, Huichuan; Seeger, John D.; Kim, Seoyoung C.

    2015-01-01

    Objectives The human papillomavirus (HPV) vaccine is safe and efficacious in patients with systemic inflammatory diseases (SID) who have higher rates of persistent HPV infection. We compared HPV vaccine uptake among SID and non-SID patients. Methods Using a U.S. insurance claims database (2006–2012), we identified individuals 9–26 years with ≥2 SID diagnosis codes ≥7 days apart with ≥12 months of continuous enrollment prior to the second code (index date). We matched SID patients by age, sex and index date to randomly selected non-SID subjects and selected those with ≥24 months of post-index date continuous follow-up. We also identified a non-SID subcohort with ≥1 diagnosis code for asthma. We defined initiation as ≥1 HPV vaccination claim after 2007, and completion as 3 claims. We used multivariable logistic regression to assess uptake in females 11–26 years comparing SID, non-SID and asthma cohorts, adjusting for demographics, region, comorbidities, and healthcare utilization. Results We identified 5,642 patients 9–26 years with SID and 20,643 without. The mean age was 18.1 years (SD 4.9). We identified 1,083 patients with asthma; the mean age was 17.2 (SD 5.1). Among females, 20.6% with SID, 23.1% without SID and 22.9% with asthma, received ≥1 HPV vaccine. In our adjusted models, the odds of receipt of ≥1 vaccine was 0.87 times lower in SID (95% CI 0.77–0.98) compared to non-SID and did not differ for 3 vaccines (OR 1.03, 95% CI 0.83–1.26). The odds of initiation and completion were not statistically different between SID and non-SID asthma cohorts. Conclusions In this nationwide cohort, HPV vaccine uptake was extremely low. Despite the heightened risk of persistent HPV infection among those with SID, no increase in HPV vaccine uptake was observed. Public health efforts to promote HPV vaccination overall are needed, and may be particularly beneficial for those at higher risk. PMID:25692470

  4. Profiles of microbial fatty acids in the human metabolome are disease-specific

    Directory of Open Access Journals (Sweden)

    Zhanna A Ktsoyan

    2011-01-01

    Full Text Available The human gastrointestinal tract is inhabited by a diverse and dense symbiotic microbiota, the composition of which is the result of host-microbe co-evolution and co-adaptation. This tight integration creates intense crosstalk and signalling between the host and microbiota at the cellular and metabolic levels. In many genetic or infectious diseases the balance between host and microbiota may be compromised resulting in erroneous communication. Consequently, the composition of the human metabolome, which includes the gut metabolome, may be different in health and disease states in terms of microbial products and metabolites entering systemic circulation. To test this hypothesis, we measured the level of hydroxy, branched, cyclopropyl and unsaturated fatty acids, aldehydes, and phenyl derivatives in blood of patients with a hereditary autoinflammatory disorder, familial Mediterranean fever (FMF, and in patients with peptic ulceration (PU resulting from Helicobacter pylori infection. Discriminant function analysis of a data matrix consisting of 94 cases as statistical units (37 FMF patients, 14 PU patients, and 43 healthy controls and the concentration of 35 microbial products in the blood as statistical variables revealed a high accuracy of the proposed model (all cases were correctly classified. This suggests that the profile of microbial products and metabolites in the human metabolome is specific for a given disease and may potentially serve as a biomarker for disease.

  5. Human pathogen shown to cause disease in the threatened eklhorn coral Acropora palmata.

    Directory of Open Access Journals (Sweden)

    Kathryn Patterson Sutherland

    Full Text Available Coral reefs are in severe decline. Infections by the human pathogen Serratia marcescens have contributed to precipitous losses in the common Caribbean elkhorn coral, Acropora palmata, culminating in its listing under the United States Endangered Species Act. During a 2003 outbreak of this coral disease, called acroporid serratiosis (APS, a unique strain of the pathogen, Serratia marcescens strain PDR60, was identified from diseased A. palmata, human wastewater, the non-host coral Siderastrea siderea and the corallivorous snail Coralliophila abbreviata. In order to examine humans as a source and other marine invertebrates as vectors and/or reservoirs of the APS pathogen, challenge experiments were conducted with A. palmata maintained in closed aquaria to determine infectivity of strain PDR60 from reef and wastewater sources. Strain PDR60 from wastewater and diseased A. palmata caused disease signs in elkhorn coral in as little as four and five days, respectively, demonstrating that wastewater is a definitive source of APS and identifying human strain PDR60 as a coral pathogen through fulfillment of Koch's postulates. A. palmata inoculated with strain PDR60 from C. abbreviata showed limited virulence, with one of three inoculated fragments developing APS signs within 13 days. Strain PDR60 from non-host coral S. siderea showed a delayed pathogenic effect, with disease signs developing within an average of 20 days. These results suggest that C. abbreviata and non-host corals may function as reservoirs or vectors of the APS pathogen. Our results provide the first example of a marine "reverse zoonosis" involving the transmission of a human pathogen (S. marcescens to a marine invertebrate (A. palmata. These findings underscore the interaction between public health practices and environmental health indices such as coral reef survival.

  6. Human pathogen shown to cause disease in the threatened eklhorn coral Acropora palmata.

    Science.gov (United States)

    Sutherland, Kathryn Patterson; Shaban, Sameera; Joyner, Jessica L; Porter, James W; Lipp, Erin K

    2011-01-01

    Coral reefs are in severe decline. Infections by the human pathogen Serratia marcescens have contributed to precipitous losses in the common Caribbean elkhorn coral, Acropora palmata, culminating in its listing under the United States Endangered Species Act. During a 2003 outbreak of this coral disease, called acroporid serratiosis (APS), a unique strain of the pathogen, Serratia marcescens strain PDR60, was identified from diseased A. palmata, human wastewater, the non-host coral Siderastrea siderea and the corallivorous snail Coralliophila abbreviata. In order to examine humans as a source and other marine invertebrates as vectors and/or reservoirs of the APS pathogen, challenge experiments were conducted with A. palmata maintained in closed aquaria to determine infectivity of strain PDR60 from reef and wastewater sources. Strain PDR60 from wastewater and diseased A. palmata caused disease signs in elkhorn coral in as little as four and five days, respectively, demonstrating that wastewater is a definitive source of APS and identifying human strain PDR60 as a coral pathogen through fulfillment of Koch's postulates. A. palmata inoculated with strain PDR60 from C. abbreviata showed limited virulence, with one of three inoculated fragments developing APS signs within 13 days. Strain PDR60 from non-host coral S. siderea showed a delayed pathogenic effect, with disease signs developing within an average of 20 days. These results suggest that C. abbreviata and non-host corals may function as reservoirs or vectors of the APS pathogen. Our results provide the first example of a marine "reverse zoonosis" involving the transmission of a human pathogen (S. marcescens) to a marine invertebrate (A. palmata). These findings underscore the interaction between public health practices and environmental health indices such as coral reef survival.

  7. Classifying oxidative stress by F2-isoprostane levels across human diseases: A meta-analysis.

    Science.gov (United States)

    van 't Erve, Thomas J; Kadiiska, Maria B; London, Stephanie J; Mason, Ronald P

    2017-08-01

    The notion that oxidative stress plays a role in virtually every human disease and environmental exposure has become ingrained in everyday knowledge. However, mounting evidence regarding the lack of specificity of biomarkers traditionally used as indicators of oxidative stress in human disease and exposures now necessitates re-evaluation. To prioritize these re-evaluations, published literature was comprehensively analyzed in a meta-analysis to quantitatively classify the levels of systemic oxidative damage across human disease and in response to environmental exposures. In this meta-analysis, the F 2 -isoprostane, 8-iso-PGF 2α , was specifically chosen as the representative marker of oxidative damage. To combine published values across measurement methods and specimens, the standardized mean differences (Hedges' g) in 8-iso-PGF 2α levels between affected and control populations were calculated. The meta-analysis resulted in a classification of oxidative damage levels as measured by 8-iso-PGF 2α across 50 human health outcomes and exposures from 242 distinct publications. Relatively small increases in 8-iso-PGF 2α levels (ganalysis of published data. This analysis provides knowledge on the true involvement of oxidative damage across human health outcomes as well as utilizes past research to prioritize those conditions requiring further scrutiny on the mechanisms of biomarker generation. Copyright © 2017. Published by Elsevier B.V.

  8. Monkey-based research on human disease: the implications of genetic differences.

    Science.gov (United States)

    Bailey, Jarrod

    2014-11-01

    Assertions that the use of monkeys to investigate human diseases is valid scientifically are frequently based on a reported 90-93% genetic similarity between the species. Critical analyses of the relevance of monkey studies to human biology, however, indicate that this genetic similarity does not result in sufficient physiological similarity for monkeys to constitute good models for research, and that monkey data do not translate well to progress in clinical practice for humans. Salient examples include the failure of new drugs in clinical trials, the highly different infectivity and pathology of SIV/HIV, and poor extrapolation of research on Alzheimer's disease, Parkinson's disease and stroke. The major molecular differences underlying these inter-species phenotypic disparities have been revealed by comparative genomics and molecular biology - there are key differences in all aspects of gene expression and protein function, from chromosome and chromatin structure to post-translational modification. The collective effects of these differences are striking, extensive and widespread, and they show that the superficial similarity between human and monkey genetic sequences is of little benefit for biomedical research. The extrapolation of biomedical data from monkeys to humans is therefore highly unreliable, and the use of monkeys must be considered of questionable value, particularly given the breadth and potential of alternative methods of enquiry that are currently available to scientists. 2014 FRAME.

  9. Impacts of environment on human diseases: a web service for the human exposome

    Science.gov (United States)

    Karssenberg, Derek; Vaartjes, Ilonca; Kamphuis, Carlijn; Strak, Maciek; Schmitz, Oliver; Soenario, Ivan; de Jong, Kor

    2017-04-01

    The exposome is the totality of human environmental exposures from conception onwards. Identifying the contribution of the exposome to human diseases and health is a key issue in health research. Examples include the effect of air pollution exposure on cardiovascular diseases, the impact of disease vectors (mosquitos) and surface hydrology exposure on malaria, and the effect of fast food restaurant exposure on obesity. Essential to health research is to disentangle the effects of the exposome and genome on health. Ultimately this requires quantifying the totality of all human exposures, for each individual in the studied human population. This poses a massive challenge to geoscientists, as environmental data are required at a high spatial and temporal resolution, with a large spatial and temporal coverage representing the area inhabited by the population studied and the time span representing several decades. Then, these data need to be combined with space-time paths of individuals to calculate personal exposures for each individual in the population. The Global and Geo Health Data Centre is taking this challenge by providing a web service capable of enriching population data with exposome information. Our web service can generate environmental information either from archived national (up to 5 m spatial and 1 h temporal resolution) and global environmental information or generated on the fly using environmental models running as microservices. On top of these environmental data services runs an individual exposure service enabling health researchers to select different spatial and temporal aggregation methods and to upload space-time paths of individuals. These are then enriched with personal exposures and eventually returned to the user. We illustrate the service in an example of individual exposures to air pollutants calculated from hyper resolution air pollution data and various approaches to estimate space-time paths of individuals.

  10. Host control of human papillomavirus infection and disease.

    Science.gov (United States)

    Doorbar, John

    2018-02-01

    Most human papillomaviruses cause inapparent infections, subtly affecting epithelial homeostasis, to ensure genome persistence in the epithelial basal layer. As with conspicuous papillomas, these self-limiting lesions shed viral particles to ensure population level maintenance and depend on a balance between viral gene expression, immune cell stimulation and immune surveillance for persistence. The complex immune evasion strategies, characteristic of high-risk HPV types, also allow the deregulated viral gene expression that underlies neoplasia. Neoplasia occurs at particular epithelial sites where vulnerable cells such as the reserve or cuboidal cells of the cervical transformation zone are found. Beta papillomavirus infection can also predispose an individual with immune deficiencies to the development of cancers. The host control of HPV infections thus involves local interactions between keratinocytes and the adaptive immune response. Effective immune detection and surveillance limits overt disease, leading to HPV persistence as productive microlesions or in a true latent state. Copyright © 2017. Published by Elsevier Ltd.

  11. The role of airborne mineral dusts in human disease

    Science.gov (United States)

    Morman, Suzette A.; Plumlee, Geoffrey S.

    2013-01-01

    Exposure to fine particulate matter (PM) is generally acknowledged to increase risk for human morbidity and mortality. However, particulate matter (PM) research has generally examined anthropogenic (industry and combustion by-products) sources with few studies considering contributions from geogenic PM (produced from the Earth by natural processes, e.g., volcanic ash, windborne ash from wildfires, and mineral dusts) or geoanthropogenic PM (produced from natural sources by processes that are modified or enhanced by human activities, e.g., dusts from lakebeds dried by human removal of water, dusts produced from areas that have undergone desertification as a result of human practices). Globally, public health concerns are mounting, related to potential increases in dust emission from climate related changes such as desertification and the associated long range as well as local health effects. Recent epidemiological studies have identified associations between far-traveled dusts from primary sources and increased morbidity and mortality in Europe and Asia. This paper provides an outline of public health research and history as it relates to naturally occurring inorganic mineral dusts. We summarize results of current public health research and describe some of the many challenges related to understanding health effects from exposures to dust aerosols.

  12. The impact of Fusarium mycotoxins on human and animal host susceptibility to infectious diseases.

    Science.gov (United States)

    Antonissen, Gunther; Martel, An; Pasmans, Frank; Ducatelle, Richard; Verbrugghe, Elin; Vandenbroucke, Virginie; Li, Shaoji; Haesebrouck, Freddy; Van Immerseel, Filip; Croubels, Siska

    2014-01-28

    Contamination of food and feed with mycotoxins is a worldwide problem. At present, acute mycotoxicosis caused by high doses is rare in humans and animals. Ingestion of low to moderate amounts of Fusarium mycotoxins is common and generally does not result in obvious intoxication. However, these low amounts may impair intestinal health, immune function and/or pathogen fitness, resulting in altered host pathogen interactions and thus a different outcome of infection. This review summarizes the current state of knowledge about the impact of Fusarium mycotoxin exposure on human and animal host susceptibility to infectious diseases. On the one hand, exposure to deoxynivalenol and other Fusarium mycotoxins generally exacerbates infections with parasites, bacteria and viruses across a wide range of animal host species. Well-known examples include coccidiosis in poultry, salmonellosis in pigs and mice, colibacillosis in pigs, necrotic enteritis in poultry, enteric septicemia of catfish, swine respiratory disease, aspergillosis in poultry and rabbits, reovirus infection in mice and Porcine Reproductive and Respiratory Syndrome Virus infection in pigs. However, on the other hand, T-2 toxin has been shown to markedly decrease the colonization capacity of Salmonella in the pig intestine. Although the impact of the exposure of humans to Fusarium toxins on infectious diseases is less well known, extrapolation from animal models suggests possible exacerbation of, for instance, colibacillosis and salmonellosis in humans, as well.

  13. Three-dimensional genome architecture influences partner selection for chromosomal translocations in human disease.

    Directory of Open Access Journals (Sweden)

    Jesse M Engreitz

    Full Text Available Chromosomal translocations are frequent features of cancer genomes that contribute to disease progression. These rearrangements result from formation and illegitimate repair of DNA double-strand breaks (DSBs, a process that requires spatial colocalization of chromosomal breakpoints. The "contact first" hypothesis suggests that translocation partners colocalize in the nuclei of normal cells, prior to rearrangement. It is unclear, however, the extent to which spatial interactions based on three-dimensional genome architecture contribute to chromosomal rearrangements in human disease. Here we intersect Hi-C maps of three-dimensional chromosome conformation with collections of 1,533 chromosomal translocations from cancer and germline genomes. We show that many translocation-prone pairs of regions genome-wide, including the cancer translocation partners BCR-ABL and MYC-IGH, display elevated Hi-C contact frequencies in normal human cells. Considering tissue specificity, we find that translocation breakpoints reported in human hematologic malignancies have higher Hi-C contact frequencies in lymphoid cells than those reported in sarcomas and epithelial tumors. However, translocations from multiple tissue types show significant correlation with Hi-C contact frequencies, suggesting that both tissue-specific and universal features of chromatin structure contribute to chromosomal alterations. Our results demonstrate that three-dimensional genome architecture shapes the landscape of rearrangements directly observed in human disease and establish Hi-C as a key method for dissecting these effects.

  14. Comprehensive Control of Human Papillomavirus Infections and Related Diseases

    Science.gov (United States)

    Bosch, F. Xavier; Broker, Thomas R.; Forman, David; Moscicki, Anna-Barbara; Gillison, Maura L.; Doorbar, John; Stern, Peter L.; Stanley, Margaret; Arbyn, Marc; Poljak, Mario; Cuzick, Jack; Castle, Philip E.; Schiller, John T.; Markowitz, Lauri E.; Fisher, William A.; Canfell, Karen; Denny, Lynette A.; Franco, Eduardo L.; Steben, Marc; Kane, Mark A.; Schiffman, Mark; Meijer, Chris J.L.M.; Sankaranarayanan, Rengaswamy; Castellsagué, Xavier; Kim, Jane J.; Brotons, Maria; Alemany, Laia; Albero, Ginesa; Diaz, Mireia; de Sanjosé, Silvia

    2014-01-01

    Infection with human papillomavirus (HPV) is recognized as one of the major causes of infection-related cancer worldwide, as well as the causal factor in other diseases. Strong evidence for a causal etiology with HPV has been stated by the International Agency for Research on Cancer for cancers of the cervix uteri, penis, vulva, vagina, anus and oropharynx (including base of the tongue and tonsils). Of the estimated 12.7 million new cancers occurring in 2008 worldwide, 4.8% were attributable to HPV infection, with substantially higher incidence and mortality rates seen in developing versus developed countries. In recent years, we have gained tremendous knowledge about HPVs and their interactions with host cells, tissues and the immune system; have validated and implemented strategies for safe and efficacious prophylactic vaccination against HPV infections; have developed increasingly sensitive and specific molecular diagnostic tools for HPV detection for use in cervical cancer screening; and have substantially increased global awareness of HPV and its many associated diseases in women, men, and children. While these achievements exemplify the success of biomedical research in generating important public health interventions, they also generate new and daunting challenges: costs of HPV prevention and medical care, the implementation of what is technically possible, socio-political resistance to prevention opportunities, and the very wide ranges of national economic capabilities and health care systems. Gains and challenges faced in the quest for comprehensive control of HPV infection and HPV-related cancers and other disease are summarized in this review. The information presented may be viewed in terms of a reframed paradigm of prevention of cervical cancer and other HPV-related diseases that will include strategic combinations of at least four major components: 1) routine introduction of HPV vaccines to women in all countries, 2) extension and simplification of

  15. Human diseases with genetically altered DNA repair processes

    International Nuclear Information System (INIS)

    Cleaver, J.E.; Bootsma, D.; Friedberg, E.

    1975-01-01

    DNA repair of single-strand breaks (produced by ionizing radiation) and of base damage (produced by ultraviolet (uv) light) are two repair mechanisms that most mammalian cells possess. Genetic defects in these repair mechanisms are exemplified by cells from the human premature-aging disease, progeria, which fail to rejoin single-strand breaks, and the skin disease, xeroderma pigmentosum (XP), which exhibits high actinic carcinogenesis and involves failure to repair base damage. In terms of the response of XP cells, many chemical carcinogens can be classified as either x-ray-like (i.e., they cause damage that XP cells can repair) or uv-like (i.e., they cause damage that XP cells cannot repair). The first group contains some of the more strongly carcinogenic chemicals (e.g., alkylating agents). XP occurs in at least two clinical forms, and somatic cell hybridization indicates at least three complementation groups. In order to identify cell lines from various different laboratories unambiguously, a modified nomenclature of XP lines is proposed. (U.S.)

  16. Human diseases with genetically altered DNA repair processes

    International Nuclear Information System (INIS)

    Cleaver, J.E.; Bootsma, D.; Friedberg, E.

    1975-01-01

    DNA repair of single-strand breaks (produced by ionizing radiation) and of base damage (produced by ultraviolet (UV) light) are two repair mechanisms that most mammalian cells possess. Genetic defects in these repair mechanisms are exemplified by cells from the human premature-aging disease, progeria, which fail to rejoin single-strand breaks, and the skin disease, xeroderma pigmentosum (XP), which exhibits high actinic carcinogenesis and involves failure to repair base damage. In terms of the response of XP cells, many chemical carcinogens can be classified as either X-ray-like (i.e., they cause damage that XP cells can repair) or UV-like (i.e., they cause damage that XP cells cannot repair). The first group contains some of the more strongly carcinogenic chemicals (e.g., alkylating agents). XP occurs in at least two clinical forms, and somatic cell hybridization indicates at least three complementation groups. In order to identify cell lines from various different laboratories unambiguously, a modified nomenclature of XP lines is proposed

  17. [Demyelinating disease and vaccination of the human papillomavirus].

    Science.gov (United States)

    Álvarez-Soria, M Josefa; Hernández-González, Amalia; Carrasco-García de León, Sira; del Real-Francia, M Ángeles; Gallardo-Alcañiz, M José; López-Gómez, José L

    2011-04-16

    Primary prevention by prophylactic vaccination against the major cause of cervical cancer, the carcinogenic human papillomavirus (HPV) types 16 and 18, is now available worldwide. Postlicensure adverse neurological effects have been described. The studies realized after the license are descriptive and limited by the difficulty to obtain the information, despite most of the statistical indexes show that the adverse effects by the vaccine of the HPV are not upper compared with other vaccines, the substimation must be considered. We describe the cases of four young women that developed demyelinating disease after the vaccination of the HPV, with a rank of time between the administration of the dose and the development of the clinical of seven days to a month, with similar symptoms with the successive doses. We have described six episodes coinciding after the vaccination. Have been described seizures, autoimmune disorders such as Guillain-Barre syndrome, transverse myelitis, or motor neuron disease, probably adverse effects following immunization by HPV vaccine. So we suggest that vaccine may trigger an immunological mechanism leading to demyelinating events, perhaps in predisposed young.

  18. Alkaptonuria is a novel human secondary amyloidogenic disease.

    Science.gov (United States)

    Millucci, Lia; Spreafico, Adriano; Tinti, Laura; Braconi, Daniela; Ghezzi, Lorenzo; Paccagnini, Eugenio; Bernardini, Giulia; Amato, Loredana; Laschi, Marcella; Selvi, Enrico; Galeazzi, Mauro; Mannoni, Alessandro; Benucci, Maurizio; Lupetti, Pietro; Chellini, Federico; Orlandini, Maurizio; Santucci, Annalisa

    2012-11-01

    Alkaptonuria (AKU) is an ultra-rare disease developed from the lack of homogentisic acid oxidase activity, causing homogentisic acid (HGA) accumulation that produces a HGA-melanin ochronotic pigment, of unknown composition. There is no therapy for AKU. Our aim was to verify if AKU implied a secondary amyloidosis. Congo Red, Thioflavin-T staining and TEM were performed to assess amyloid presence in AKU specimens (cartilage, synovia, periumbelical fat, salivary gland) and in HGA-treated human chondrocytes and cartilage. SAA and SAP deposition was examined using immunofluorescence and their levels were evaluated in the patients' plasma by ELISA. 2D electrophoresis was undertaken in AKU cells to evaluate the levels of proteins involved in amyloidogenesis. AKU osteoarticular tissues contained SAA-amyloid in 7/7 patients. Ochronotic pigment and amyloid co-localized in AKU osteoarticular tissues. SAA and SAP composition of the deposits assessed secondary type of amyloidosis. High levels of SAA and SAP were found in AKU patients' plasma. Systemic amyloidosis was assessed by Congo Red staining of patients' abdominal fat and salivary gland. AKU is the second pathology after Parkinson's disease where amyloid is associated with a form of melanin. Aberrant expression of proteins involved in amyloidogenesis has been found in AKU cells. Our findings on alkaptonuria as a novel type II AA amyloidosis open new important perspectives for its therapy, since methotrexate treatment proved to significantly reduce in vitro HGA-induced A-amyloid aggregates. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Linking disease associations with regulatory information in the human genome

    KAUST Repository

    Schaub, M. A.; Boyle, A. P.; Kundaje, A.; Batzoglou, S.; Snyder, M.

    2012-01-01

    Genome-wide association studies have been successful in identifying single nucleotide polymorphisms (SNPs) associated with a large number of phenotypes. However, an associated SNP is likely part of a larger region of linkage disequilibrium. This makes it difficult to precisely identify the SNPs that have a biological link with the phenotype. We have systematically investigated the association of multiple types of ENCODE data with disease-associated SNPs and show that there is significant enrichment for functional SNPs among the currently identified associations. This enrichment is strongest when integrating multiple sources of functional information and when highest confidence disease-associated SNPs are used. We propose an approach that integrates multiple types of functional data generated by the ENCODE Consortium to help identify "functional SNPs" that may be associated with the disease phenotype. Our approach generates putative functional annotations for up to 80% of all previously reported associations. We show that for most associations, the functional SNP most strongly supported by experimental evidence is a SNP in linkage disequilibrium with the reported association rather than the reported SNP itself. Our results show that the experimental data sets generated by the ENCODE Consortium can be successfully used to suggest functional hypotheses for variants associated with diseases and other phenotypes.

  20. Serum Inflammatory Mediators as Markers of Human Lyme Disease Activity

    Science.gov (United States)

    Soloski, Mark J.; Crowder, Lauren A.; Lahey, Lauren J.; Wagner, Catriona A.

    2014-01-01

    Chemokines and cytokines are key signaling molecules that orchestrate the trafficking of immune cells, direct them to sites of tissue injury and inflammation and modulate their states of activation and effector cell function. We have measured, using a multiplex-based approach, the levels of 58 immune mediators and 7 acute phase markers in sera derived from of a cohort of patients diagnosed with acute Lyme disease and matched controls. This analysis identified a cytokine signature associated with the early stages of infection and allowed us to identify two subsets (mediator-high and mediator-low) of acute Lyme patients with distinct cytokine signatures that also differed significantly (pLyme disease (p = 0.01) and the decrease correlates with chemokine levels (p = 0.0375). The levels of CXCL9/10 did not relate to the size or number of skin lesions but elevated levels of serum CXCL9/CXCL10 were associated with elevated liver enzymes levels. Collectively these results indicate that the levels of serum chemokines and the levels of expression of their respective chemokine receptors on T cell subsets may prove to be informative biomarkers for Lyme disease and related to specific disease manifestations. PMID:24740099

  1. Linking disease associations with regulatory information in the human genome

    KAUST Repository

    Schaub, M. A.

    2012-09-01

    Genome-wide association studies have been successful in identifying single nucleotide polymorphisms (SNPs) associated with a large number of phenotypes. However, an associated SNP is likely part of a larger region of linkage disequilibrium. This makes it difficult to precisely identify the SNPs that have a biological link with the phenotype. We have systematically investigated the association of multiple types of ENCODE data with disease-associated SNPs and show that there is significant enrichment for functional SNPs among the currently identified associations. This enrichment is strongest when integrating multiple sources of functional information and when highest confidence disease-associated SNPs are used. We propose an approach that integrates multiple types of functional data generated by the ENCODE Consortium to help identify "functional SNPs" that may be associated with the disease phenotype. Our approach generates putative functional annotations for up to 80% of all previously reported associations. We show that for most associations, the functional SNP most strongly supported by experimental evidence is a SNP in linkage disequilibrium with the reported association rather than the reported SNP itself. Our results show that the experimental data sets generated by the ENCODE Consortium can be successfully used to suggest functional hypotheses for variants associated with diseases and other phenotypes.

  2. Latent physiological factors of complex human diseases revealed by independent component analysis of clinarrays

    Directory of Open Access Journals (Sweden)

    Chen David P

    2010-10-01

    Full Text Available Abstract Background Diagnosis and treatment of patients in the clinical setting is often driven by known symptomatic factors that distinguish one particular condition from another. Treatment based on noticeable symptoms, however, is limited to the types of clinical biomarkers collected, and is prone to overlooking dysfunctions in physiological factors not easily evident to medical practitioners. We used a vector-based representation of patient clinical biomarkers, or clinarrays, to search for latent physiological factors that underlie human diseases directly from clinical laboratory data. Knowledge of these factors could be used to improve assessment of disease severity and help to refine strategies for diagnosis and monitoring disease progression. Results Applying Independent Component Analysis on clinarrays built from patient laboratory measurements revealed both known and novel concomitant physiological factors for asthma, types 1 and 2 diabetes, cystic fibrosis, and Duchenne muscular dystrophy. Serum sodium was found to be the most significant factor for both type 1 and type 2 diabetes, and was also significant in asthma. TSH3, a measure of thyroid function, and blood urea nitrogen, indicative of kidney function, were factors unique to type 1 diabetes respective to type 2 diabetes. Platelet count was significant across all the diseases analyzed. Conclusions The results demonstrate that large-scale analyses of clinical biomarkers using unsupervised methods can offer novel insights into the pathophysiological basis of human disease, and suggest novel clinical utility of established laboratory measurements.

  3. [Synthetic human calcitonin in Paget's disease of bone and osteoporosis (author's transl)].

    Science.gov (United States)

    Nuti, R; Vattimo, A

    1981-01-30

    Synthetic human calcitonin was used in the treatment of 26 patients over a period of 1-14 months. 17 patients had Paget's disease of the bone, 6 postmenopausal osteoporosis and 3 Sudeck's syndrome. Subjective improvement (reduction of pain, improvement of mobility) was found in 15 patients with Paget's disease, in 4 females with postmenopausal osteoporosis and in all 3 patients with Sudeck's syndrome. Radiographic improvement of bone changes developed only very slowly. These results were confirmed by diminution of the exchangeable calcium pool indicating reduction of rates of osseous degradation. Calcitonin tolerance was acceptable. Transitory nausea and occasional vomiting occurred in 3 patients.

  4. Functional Echomyography of the human denervated muscle: first results

    Directory of Open Access Journals (Sweden)

    Riccardo Zanato

    2011-03-01

    Full Text Available In this study we followed with ultrasound three patients with permanent denervation to evaluate changes in morphology, thickness, contraction and vascularisation of muscles undergoing the home-based electrical stimulation program of the Rise2-Italy project. During a period of 1 year for the first subject, 6 months for the second subject and 3 months for the third subject we studied with ultrasound the denervated muscle comparing it (if possible to the contralateral normal muscle. We evaluated: 1. Changes in morphology and sonographic structure of the pathologic muscle; 2. Muscular thickness in response to the electrical stimulation therapy; 3. Short-term modifications in muscle perfusion and arterial flow patterns after stimulation; 4. Contraction-relaxation kinetic induced by volitional activity or electrical stimulation. Morphology and ultrasonographic structure of the denervated muscles changed during the period of stimulation from a pattern typical of complete muscular atrophy to a pattern which might be considered “normal” when detected in an old patient. Thickness improved significantly more in the middle third than in the proximal and distal third of the denervated muscle, reaching in the last measurements of the first subject approximately the same thickness as the contralateral normal muscle. In all the measurements done within this study, arterial flow of the denervated muscle showed at rest a low-resistance pattern with Doppler Ultra Sound (US, and a pulsed pattern after electrical stimulation. The stimulation- induced pattern is similar to the trifasic high-resistance pattern of the normal muscle. Contraction- relaxation kinetic, measured by recording the muscular movements during electrical stimulation, showed an abnormal behaviour of the denervated muscle during the relaxation phase, which resulted to be significantly longer than in normal muscle (880 msec in the denervated muscle vs 240 msec in the contralateral normal one

  5. Hygiene pests as vectors for parasitic and bacterial diseases in humans

    Science.gov (United States)

    Cholewiński, Marcin; Derda, Monika; Hadaś, Edward

    Diseases transmitted by hygiene pests remain a very serious problem in spite of fast developments in science and medicine. The present study focuses on pests carrying germs that pose a threat to human health and life. The quick pace of life, the need to satisfy human needs and mass production of food sometimes result in flagrant sanitary, hygienic and epidemiological deficiencies. These irregularities are conducive to hygiene pests, which, when not held in check by proper control measures, may act more efficiently and quickly.

  6. Human inflammatory bowel disease does not associate with Lawsonia intracellularis infection

    Directory of Open Access Journals (Sweden)

    Giese Thomas

    2006-09-01

    Full Text Available Abstract Background There is increasing evidence that bacterial infection of the intestinal mucosa may contribute to the pathogenesis of inflammatory bowel diseases (IBD. In pigs, an obligate intracellular bacterium, Lawsonia intracellularis (LI, was shown to cause proliferative enteropathy (PE of which some forms display histological and clinical similarities to human IBD. Since LI-similar Desulfovibrio spp. may infect human cells, we hypothesized that LI might be associated with the development of human IBD. Results In human intestinal tissue samples, PCR using LLG, 50SL27, LSA and strictly LI-specific 16SII primers, yielded either no amplicons or products with weak homology to human genomic sequences. Sequencing of these amplicons revealed no specificity for LI. However, amplification of DNA with less specific 16SI primers resulted in products bearing homology to certain Streptococcus species. These 16SI-amplified products were present in healthy and diseased specimens, without obvious prevalence. Conclusion LI is not associated with the pathogenesis of UC or CD. Whether an immunologic response to commensal bacteria such as streptococci may contribute to the chronic inflammatory condition in IBD, remained to be determined.

  7. A transgenic rat expressing human APP with the Swedish Alzheimer's disease mutation

    DEFF Research Database (Denmark)

    Folkesson, Ronnie; Malkiewicz, Katarzyna; Kloskowska, Ewa

    2007-01-01

    In recent years, transgenic mice have become valuable tools for studying mechanisms of Alzheimer's disease (AD). With the aim of developing an animal model better for memory and neurobehavioural testing, we have generated a transgenic rat model of AD. These animals express human amyloid precursor...... in cerebrovascular blood vessels with very rare diffuse plaques. We believe that crossing these animals with mutant PS1 transgenic rats will result in accelerated plaque formation similar to that seen in transgenic mice....

  8. Identification of human disease genes from interactome network using graphlet interaction.

    Directory of Open Access Journals (Sweden)

    Xiao-Dong Wang

    Full Text Available Identifying genes related to human diseases, such as cancer and cardiovascular disease, etc., is an important task in biomedical research because of its applications in disease diagnosis and treatment. Interactome networks, especially protein-protein interaction networks, had been used to disease genes identification based on the hypothesis that strong candidate genes tend to closely relate to each other in some kinds of measure on the network. We proposed a new measure to analyze the relationship between network nodes which was called graphlet interaction. The graphlet interaction contained 28 different isomers. The results showed that the numbers of the graphlet interaction isomers between disease genes in interactome networks were significantly larger than random picked genes, while graphlet signatures were not. Then, we designed a new type of score, based on the network properties, to identify disease genes using graphlet interaction. The genes with higher scores were more likely to be disease genes, and all candidate genes were ranked according to their scores. Then the approach was evaluated by leave-one-out cross-validation. The precision of the current approach achieved 90% at about 10% recall, which was apparently higher than the previous three predominant algorithms, random walk, Endeavour and neighborhood based method. Finally, the approach was applied to predict new disease genes related to 4 common diseases, most of which were identified by other independent experimental researches. In conclusion, we demonstrate that the graphlet interaction is an effective tool to analyze the network properties of disease genes, and the scores calculated by graphlet interaction is more precise in identifying disease genes.

  9. Identification of Human Disease Genes from Interactome Network Using Graphlet Interaction

    Science.gov (United States)

    Yang, Lun; Wei, Dong-Qing; Qi, Ying-Xin; Jiang, Zong-Lai

    2014-01-01

    Identifying genes related to human diseases, such as cancer and cardiovascular disease, etc., is an important task in biomedical research because of its applications in disease diagnosis and treatment. Interactome networks, especially protein-protein interaction networks, had been used to disease genes identification based on the hypothesis that strong candidate genes tend to closely relate to each other in some kinds of measure on the network. We proposed a new measure to analyze the relationship between network nodes which was called graphlet interaction. The graphlet interaction contained 28 different isomers. The results showed that the numbers of the graphlet interaction isomers between disease genes in interactome networks were significantly larger than random picked genes, while graphlet signatures were not. Then, we designed a new type of score, based on the network properties, to identify disease genes using graphlet interaction. The genes with higher scores were more likely to be disease genes, and all candidate genes were ranked according to their scores. Then the approach was evaluated by leave-one-out cross-validation. The precision of the current approach achieved 90% at about 10% recall, which was apparently higher than the previous three predominant algorithms, random walk, Endeavour and neighborhood based method. Finally, the approach was applied to predict new disease genes related to 4 common diseases, most of which were identified by other independent experimental researches. In conclusion, we demonstrate that the graphlet interaction is an effective tool to analyze the network properties of disease genes, and the scores calculated by graphlet interaction is more precise in identifying disease genes. PMID:24465923

  10. Significance of functional disease-causal/susceptible variants identified by whole-genome analyses for the understanding of human diseases.

    Science.gov (United States)

    Hitomi, Yuki; Tokunaga, Katsushi

    2017-01-01

    Human genome variation may cause differences in traits and disease risks. Disease-causal/susceptible genes and variants for both common and rare diseases can be detected by comprehensive whole-genome analyses, such as whole-genome sequencing (WGS), using next-generation sequencing (NGS) technology and genome-wide association studies (GWAS). Here, in addition to the application of an NGS as a whole-genome analysis method, we summarize approaches for the identification of functional disease-causal/susceptible variants from abundant genetic variants in the human genome and methods for evaluating their functional effects in human diseases, using an NGS and in silico and in vitro functional analyses. We also discuss the clinical applications of the functional disease causal/susceptible variants to personalized medicine.

  11. Acetylome in Human Fibroblasts From Parkinson's Disease Patients

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    Sokhna M. S. Yakhine-Diop

    2018-04-01

    Full Text Available Parkinson's disease (PD is a multifactorial neurodegenerative disorder. The pathogenesis of this disease is associated with gene and environmental factors. Mutations in leucine-rich repeat kinase 2 (LRRK2 are the most frequent genetic cause of familial and sporadic PD. Moreover, posttranslational modifications, including protein acetylation, are involved in the molecular mechanism of PD. Acetylation of lysine proteins is a dynamic process that is modulated in PD. In this descriptive study, we characterized the acetylated proteins and peptides in primary fibroblasts from idiopathic PD (IPD and genetic PD harboring G2019S or R1441G LRRK2 mutations. Identified acetylated peptides are modulated between individuals' groups. Although acetylated nuclear proteins are the most represented in cells, they are hypoacetylated in IPD. Results display that the level of hyperacetylated and hypoacetylated peptides are, respectively, enhanced in genetic PD and in IPD cells.

  12. Can Neglected Tropical Diseases Compromise Human Wellbeing in Sex-, Age-, and Trait-Specific Ways?

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    David C Geary

    2016-04-01

    Full Text Available Traits that facilitate competition for reproductive resources or that influence mate choice have evolved to signal resilience to infectious disease and other stressors. As a result, the dynamics of competition and choice can, in theory, be used to generate predictions about sex-, age-, and trait-specific vulnerabilities for any sexually reproducing species, including humans. These dynamics and associated vulnerabilities are reviewed for nonhuman species, focusing on traits that are compromised by exposure to parasites. Using the same approach, sex-, age-, and trait-specific vulnerabilities to parasitic disease are illustrated for children's and adolescent's physical growth and fitness. Suggestions are then provided for widening the assessment of human vulnerabilities to include age-appropriate measures of behavioral (e.g., children's play and cognitive (e.g., language fluency traits. These are traits that are likely to be compromised by infection in age- and sex-specific ways. Inclusion of these types of measures in studies of neglected tropic diseases has the potential to provide a more nuanced understanding of how these diseases undermine human wellbeing and may provide a useful means to study the efficacy of associated treatments.

  13. Systematic detection of positive selection in the human-pathogen interactome and lasting effects on infectious disease susceptibility.

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    Erik Corona

    Full Text Available Infectious disease has shaped the natural genetic diversity of humans throughout the world. A new approach to capture positive selection driven by pathogens would provide information regarding pathogen exposure in distinct human populations and the constantly evolving arms race between host and disease-causing agents. We created a human pathogen interaction database and used the integrated haplotype score (iHS to detect recent positive selection in genes that interact with proteins from 26 different pathogens. We used the Human Genome Diversity Panel to identify specific populations harboring pathogen-interacting genes that have undergone positive selection. We found that human genes that interact with 9 pathogen species show evidence of recent positive selection. These pathogens are Yersenia pestis, human immunodeficiency virus (HIV 1, Zaire ebolavirus, Francisella tularensis, dengue virus, human respiratory syncytial virus, measles virus, Rubella virus, and Bacillus anthracis. For HIV-1, GWAS demonstrate that some naturally selected variants in the host-pathogen protein interaction networks continue to have functional consequences for susceptibility to these pathogens. We show that selected human genes were enriched for HIV susceptibility variants (identified through GWAS, providing further support for the hypothesis that ancient humans were exposed to lentivirus pandemics. Human genes in the Italian, Miao, and Biaka Pygmy populations that interact with Y. pestis show significant signs of selection. These results reveal some of the genetic footprints created by pathogens in the human genome that may have left lasting marks on susceptibility to infectious disease.

  14. Most of rare missense alleles in humans are deleterious:implications for evolution of complex disease and associationstudies

    Energy Technology Data Exchange (ETDEWEB)

    Kryukov, Gregory V.; Pennacchio, Len A.; Sunyaev, Shamil R.

    2006-10-24

    The accumulation of mildly deleterious missense mutations inindividual human genomes has been proposed to be a genetic basis forcomplex diseases. The plausibility of this hypothesis depends onquantitative estimates of the prevalence of mildly deleterious de novomutations and polymorphic variants in humans and on the intensity ofselective pressure against them. We combined analysis of mutationscausing human Mendelian diseases, human-chimpanzee divergence andsystematic data on human SNPs and found that about 20 percent of newmissense mutations in humans result in a loss of function, while about 27percent are effectively neutral. Thus, more than half of new missensemutations have mildly deleterious effects. These mutations give rise tomany low frequency deleterious allelic variants in the human populationas evident from a new dataset of 37 genes sequenced in over 1,500individual human chromosomes. Surprisingly, up to 70 percent of lowfrequency missense alleles are mildly deleterious and associated with aheterozygous fitness loss in the range 0.001-0.003. Thus, the low allelefrequency of an amino acid variant can by itself serve as a predictor ofits functional significance. Several recent studies have reported asignificant excess of rare missense variants in disease populationscompared to controls in candidate genes or pathways. These studies wouldbe unlikely to work if most rare variants were neutral or if rarevariants were not a significant contributor to the genetic component ofphenotypic inheritance. Our results provide a justification for thesetypes of candidate gene (pathway) association studies and imply thatmutation-selection balance may be a feasible mechanism for evolution ofsome common diseases.

  15. Effects of environmental pollutants on cellular iron homeostasis and ultimate links to human disease

    Science.gov (United States)

    Chronic disease has increased in the last several decades, and environmental pollutants have been implicated. The magnitude and variety of diseases indicate the malfunctioning of some basic mechanism underlying human health. Environmental pollutants demonstrate a capability to co...

  16. Human prion diseases in The Netherlands : clinico-pathological, genetic and molecular aspects

    NARCIS (Netherlands)

    Jansen, C.

    2011-01-01

    Prion diseases, or transmissible spongiform encephalopathies (TSEs), are invariably fatal neurodegenerative disorders that can be sporadic, inherited or acquired by infection. In humans, TSEs comprise three major groups showing a wide phenotypic heterogeneity: Creutzfeldt-Jakob disease (CJD),

  17. Holistic approach to human health and disease: life circumstances and inner processing.

    Science.gov (United States)

    Tomljenović, Andrea

    2014-06-01

    Human body is dinamic, energetic system under the influences of food intake, environment, interpersonal relationships, inheritance, culture and human activities. The environmental and psychosocioeconomic factors affect the individual's health altering the performance of biological systems effecting disease risk and disease progression. The concerns in modern society are more and more devoted to stress and its influences on health. Life span is extended but the quality of life, well-being and productivity usually do not follow that extention. Body is a flow of energy and dynamic communications with inside and outside environment. The way to improve health is to address its social determinants. Only in sinergy the questions about disease and health could be better understood. It is not enough to diagnose illness, important is to diagnose circumstances and environmental influences that consequently lead to disease. Emotional disruptions make base for physical disruptions. Social gradient and stress involving personal life and work is a significant factor in physical and mental illness. The best indicator of the successful social policy result is the sense of well-being of the inhabitants. Holistic approach to a patient and discussions about the influences in patient's life can lead to a better health outcome. Anthropology studies people's habits, means and conditions of life and can be the bridge between the medicine and the life circumstances that put people's health at risk providing important insights into health and disease and assist in public health policies, preventive measures and health improvement of the populations.

  18. Defining the Human Macula Transcriptome and Candidate Retinal Disease Genes UsingEyeSAGE

    Science.gov (United States)

    Rickman, Catherine Bowes; Ebright, Jessica N.; Zavodni, Zachary J.; Yu, Ling; Wang, Tianyuan; Daiger, Stephen P.; Wistow, Graeme; Boon, Kathy; Hauser, Michael A.

    2009-01-01

    Purpose To develop large-scale, high-throughput annotation of the human macula transcriptome and to identify and prioritize candidate genes for inherited retinal dystrophies, based on ocular-expression profiles using serial analysis of gene expression (SAGE). Methods Two human retina and two retinal pigment epithelium (RPE)/choroid SAGE libraries made from matched macula or midperipheral retina and adjacent RPE/choroid of morphologically normal 28- to 66-year-old donors and a human central retina longSAGE library made from 41- to 66-year-old donors were generated. Their transcription profiles were entered into a relational database, EyeSAGE, including microarray expression profiles of retina and publicly available normal human tissue SAGE libraries. EyeSAGE was used to identify retina- and RPE-specific and -associated genes, and candidate genes for retina and RPE disease loci. Differential and/or cell-type specific expression was validated by quantitative and single-cell RT-PCR. Results Cone photoreceptor-associated gene expression was elevated in the macula transcription profiles. Analysis of the longSAGE retina tags enhanced tag-to-gene mapping and revealed alternatively spliced genes. Analysis of candidate gene expression tables for the identified Bardet-Biedl syndrome disease gene (BBS5) in the BBS5 disease region table yielded BBS5 as the top candidate. Compelling candidates for inherited retina diseases were identified. Conclusions The EyeSAGE database, combining three different gene-profiling platforms including the authors’ multidonor-derived retina/RPE SAGE libraries and existing single-donor retina/RPE libraries, is a powerful resource for definition of the retina and RPE transcriptomes. It can be used to identify retina-specific genes, including alternatively spliced transcripts and to prioritize candidate genes within mapped retinal disease regions. PMID:16723438

  19. Novel association strategy with copy number variation for identifying new risk Loci of human diseases.

    Directory of Open Access Journals (Sweden)

    Xianfeng Chen

    2010-08-01

    Full Text Available Copy number variations (CNV are important causal genetic variations for human disease; however, the lack of a statistical model has impeded the systematic testing of CNVs associated with disease in large-scale cohort.Here, we developed a novel integrated strategy to test CNV-association in genome-wide case-control studies. We converted the single-nucleotide polymorphism (SNP signal to copy number states using a well-trained hidden Markov model. We mapped the susceptible CNV-loci through SNP site-specific testing to cope with the physiological complexity of CNVs. We also ensured the credibility of the associated CNVs through further window-based CNV-pattern clustering. Genome-wide data with seven diseases were used to test our strategy and, in total, we identified 36 new susceptible loci that are associated with CNVs for the seven diseases: 5 with bipolar disorder, 4 with coronary artery disease, 1 with Crohn's disease, 7 with hypertension, 9 with rheumatoid arthritis, 7 with type 1 diabetes and 3 with type 2 diabetes. Fifteen of these identified loci were validated through genotype-association and physiological function from previous studies, which provide further confidence for our results. Notably, the genes associated with bipolar disorder converged in the phosphoinositide/calcium signaling, a well-known affected pathway in bipolar disorder, which further supports that CNVs have impact on bipolar disorder.Our results demonstrated the effectiveness and robustness of our CNV-association analysis and provided an alternative avenue for discovering new associated loci of human diseases.

  20. EML proteins in microtubule regulation and human disease.

    Science.gov (United States)

    Fry, Andrew M; O'Regan, Laura; Montgomery, Jessica; Adib, Rozita; Bayliss, Richard

    2016-10-15

    The EMLs are a conserved family of microtubule-associated proteins (MAPs). The founding member was discovered in sea urchins as a 77-kDa polypeptide that co-purified with microtubules. This protein, termed EMAP for echinoderm MAP, was the major non-tubulin component present in purified microtubule preparations made from unfertilized sea urchin eggs [J. Cell Sci. (1993) 104: , 445-450; J. Cell Sci. (1987) 87: (Pt 1), 71-84]. Orthologues of EMAP were subsequently identified in other echinoderms, such as starfish and sand dollar, and then in more distant eukaryotes, including flies, worms and vertebrates, where the name of ELP or EML (both for EMAP-like protein) has been adopted [BMC Dev. Biol. (2008) 8: , 110; Dev. Genes Evol. (2000) 210: , 2-10]. The common property of these proteins is their ability to decorate microtubules. However, whether they are associated with particular microtubule populations or exercise specific functions in different microtubule-dependent processes remains unknown. Furthermore, although there is limited evidence that they regulate microtubule dynamics, the biochemical mechanisms of their molecular activity have yet to be explored. Nevertheless, interest in these proteins has grown substantially because of the identification of EML mutations in neuronal disorders and oncogenic fusions in human cancers. Here, we summarize our current knowledge of the expression, localization and structure of what is proving to be an interesting and important class of MAPs. We also speculate about their function in microtubule regulation and highlight how the studies of EMLs in human diseases may open up novel avenues for patient therapy. © 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  1. Dog and human inflammatory bowel disease rely on overlapping yet distinct dysbiosis networks.

    Science.gov (United States)

    Vázquez-Baeza, Yoshiki; Hyde, Embriette R; Suchodolski, Jan S; Knight, Rob

    2016-10-03

    Inflammatory bowel disease (IBD) is an autoimmune condition that is difficult to diagnose, and animal models of this disease have questionable human relevance 1 . Here, we show that the dysbiosis network underlying IBD in dogs differs from that in humans, with some bacteria such as Fusobacterium switching roles between the two species (as Bacteroides fragilis switches roles between humans and mice) 2 . For example, a dysbiosis index trained on humans fails when applied to dogs, but a dog-specific dysbiosis index achieves high correlations with the overall dog microbial community diversity patterns. In addition, a random forest classifier trained on dog-specific samples achieves high discriminatory power, even when using stool samples rather than the mucosal biopsies required for high discriminatory power in humans 2 . These relationships were not detected in previously published dog IBD data sets due to their limited sample size and statistical power 3 . Taken together, these results reveal the need to train host-specific dysbiosis networks and point the way towards a generalized understanding of IBD across different mammalian models.

  2. Serum inflammatory mediators as markers of human Lyme disease activity.

    Directory of Open Access Journals (Sweden)

    Mark J Soloski

    Full Text Available Chemokines and cytokines are key signaling molecules that orchestrate the trafficking of immune cells, direct them to sites of tissue injury and inflammation and modulate their states of activation and effector cell function. We have measured, using a multiplex-based approach, the levels of 58 immune mediators and 7 acute phase markers in sera derived from of a cohort of patients diagnosed with acute Lyme disease and matched controls. This analysis identified a cytokine signature associated with the early stages of infection and allowed us to identify two subsets (mediator-high and mediator-low of acute Lyme patients with distinct cytokine signatures that also differed significantly (p<0.0005 in symptom presentation. In particular, the T cell chemokines CXCL9 (MIG, CXCL10 (IP-10 and CCL19 (MIP3B were coordinately increased in the mediator-high group and levels of these chemokines could be associated with seroconversion status and elevated liver function tests (p = 0.027 and p = 0.021 respectively. There was also upregulation of acute phase proteins including CRP and serum amyloid A. Consistent with the role of CXCL9/CXCL10 in attracting immune cells to the site of infection, CXCR3+ CD4 T cells are reduced in the blood of early acute Lyme disease (p = 0.01 and the decrease correlates with chemokine levels (p = 0.0375. The levels of CXCL9/10 did not relate to the size or number of skin lesions but elevated levels of serum CXCL9/CXCL10 were associated with elevated liver enzymes levels. Collectively these results indicate that the levels of serum chemokines and the levels of expression of their respective chemokine receptors on T cell subsets may prove to be informative biomarkers for Lyme disease and related to specific disease manifestations.

  3. Using the mouse to model human disease: increasing validity and reproducibility

    Directory of Open Access Journals (Sweden)

    Monica J. Justice

    2016-02-01

    Full Text Available Experiments that use the mouse as a model for disease have recently come under scrutiny because of the repeated failure of data, particularly derived from preclinical studies, to be replicated or translated to humans. The usefulness of mouse models has been questioned because of irreproducibility and poor recapitulation of human conditions. Newer studies, however, point to bias in reporting results and improper data analysis as key factors that limit reproducibility and validity of preclinical mouse research. Inaccurate and incomplete descriptions of experimental conditions also contribute. Here, we provide guidance on best practice in mouse experimentation, focusing on appropriate selection and validation of the model, sources of variation and their influence on phenotypic outcomes, minimum requirements for control sets, and the importance of rigorous statistics. Our goal is to raise the standards in mouse disease modeling to enhance reproducibility, reliability and clinical translation of findings.

  4. Interstitial lung disease associated with human papillomavirus vaccination

    Directory of Open Access Journals (Sweden)

    Yasushi Yamamoto

    2015-01-01

    Full Text Available Vaccinations against the human papillomavirus (HPV have been recommended for the prevention of cervical cancer. HPV-16/18 AS04-adjuvanted vaccines (Cervarix are said to have favourable safety profiles. Interstitial lung diseases (ILDs can occur following exposure to a drug or a biological agent. We report a case of ILD associated with a Cervarix vaccination. A woman in her 40's, with a history of conisation, received three inoculations of Cervarix. Three months later, she presented with a cough and shortness of breath. Findings from a computed tomography of the chest and a transbronchial lung biopsy were consistent with non-specific interstitial pneumonia. Workup eliminated all other causes of the ILD, except for the vaccination. Over the 11 months of the follow-up period, her symptoms resolved without steroid therapy. The onset and spontaneous resolution of the ILD showed a chronological association with the HPV vaccination. The semi-quantitative algorithm revealed that the likelihood of an adverse drug reaction to Cervarix was “Probable”. The outcome was relatively good, but more attention should be paid to a potential risk for HPV vaccinations to cause ILDs. Wherever possible, chest radiographic examinations should be performed in order not to overlook any ILDs.

  5. Chlamydophila spp. infection in horses with recurrent airway obstruction: similarities to human chronic obstructive disease

    Directory of Open Access Journals (Sweden)

    Hotzel Helmut

    2008-01-01

    Full Text Available Abstract Background Recurrent airway obstruction (RAO in horses is a naturally occurring dust-induced disease mainly characterized by bronchiolitis which shows histological and pathophysiological similarities to human chronic obstructive pulmonary disease (COPD. In human COPD previous investigations indicated an association with Chlamydophila psittaci infection. The present study was designed (1 to clarify a possible role of this infectious agent in RAO and (2 to investigate the suitability of this equine disorder as a model for human COPD. Methods Clinico-pathological parameters of a total of 45 horses (25 horses with clinical signs of RAO and 20 clinically healthy controls were compared to histological findings in lung tissue samples and infection by Chlamydiaceae using light microscopy, immunohistochemistry, and PCR. Results Horses with clinical signs of RAO vs. controls revealed more inflammatory changes in histology (p = 0.01, and a higher detection rate of Chlamydia psittaci antigens in all cells (p OmpA sequencing identified Chlamydophila psittaci (n = 9 and Chlamydophila abortus (n = 13 in both groups with no significant differences. Within the group of clinically healthy horses subgroups with no changes (n = 15 and slight inflammation of the small airways (n = 5 were identified. Also in the group of animals with RAO subgroups with slight (n = 16 and severe (n = 9 bronchiolitis could be formed. These four subgroups can be separated in parts by the number of cells positive for Chlamydia psittaci antigens. Conclusion Chlamydophila psittaci or abortus were present in the lung of both clinically healthy horses and those with RAO. Immunohistochemistry revealed acute chlamydial infections with inflammation in RAO horses, whereas in clinically healthy animals mostly persistent chlamydial infection and no inflammatory reactions were seen. Stable dust as the known fundamental abiotic factor in RAO is comparable to smoking in human disease. These

  6. Comparative Transcriptomic Profiling and Gene Expression for Myxomatous Mitral Valve Disease in the Dog and Human

    Directory of Open Access Journals (Sweden)

    Greg R. Markby

    2017-07-01

    Full Text Available Myxomatous mitral valve disease is the single most important mitral valve disease in both dogs and humans. In the case of the dog it is ubiquitous, such that all aged dogs will have some evidence of the disease, and for humans it is known as Barlow’s disease and affects up to 3% of the population, with an expected increase in prevalence as the population ages. Disease in the two species show many similarities and while both have the classic myxomatous degeneration only in humans is there extensive fibrosis. This dual pathology of the human disease markedly affects the valve transcriptome and the difference between the dog and human is dominated by changes in genes associated with fibrosis. This review will briefly examine the comparative valve pathology and then, in more detail, the transcriptomic profiling and gene expression reported so far for both species.

  7. A study on the air pollution related human diseases in Thiruvananthapuram City, Kerala

    Energy Technology Data Exchange (ETDEWEB)

    Bency, K.T.; Jansy, J.; Thakappan, B.; Kumar, B.; Sreelekha, T.T.; Hareendran, N.K.; Nair, P.K.K.; Krishnan Nair, M. [National Inst. of Environmental Health, Thiruvananthapuram, Kerala (India). Regional Cancer Centre

    2005-07-01

    This paper contains the results of a study that examined the impacts of air pollution on human health in Thiruvananthapuram City, India. The study compared health impacts arising from air pollution in three different zones including residential, commercial, and industrial. The paper presents the findings from the study according to each of these zones and presents conclusions.The study found that each zone had its individual environmental problems which were characterized by specific diseases. In the residential zone, there was a prevalence of diseases such as breast cancer and cardiac-related problems as well as dietary problems linked to obesity. In the industrial zone, respiratory illnesses related to air pollution were prevalent. Cardiac and vector-borne diseases, related to environmental hazards like waste water stagnation, dust and solid waste problem, were high in the commercial zone. 14 refs., 3 figs.

  8. Estimating the global burden of thalassogenic diseases: human infectious diseases caused by wastewater pollution of the marine environment.

    Science.gov (United States)

    Shuval, Hillel

    2003-06-01

    bathing in wastewater-polluted coastal waters. Filter-feeding shellfish/bivalves, which are often harvested from wastewater-polluted areas of the sea, can effectively filter out and concentrate the microbial pathogens in the seawater. It can be roughly estimated that annually there are some 4 million cases of infectious hepatitis A and E (HAV/HEV), with some 40 thousand deaths and 40 thousand cases of long-term disability, mainly chronic liver damage, from consuming raw or lightly steamed filter-feeding shellfish/molluscs harvested globally from polluted coastal waters. The total global health impact of the thalassogenic diseases--human infectious diseases associated with pathogenic microorganisms from land-based wastewater pollution of the seas--is estimated to be about 3 million 'disability-adjusted life years' (DALY)/year, with an estimated economic loss of some 12 billion dollars per year. Due to the preliminary nature of the estimates in this study it is appropriate to assume that all of the above figures are no more than first approximations and that the true figures may be 50% higher or lower. Nevertheless, it is the author's belief that this study indicates that wastewater pollution of the sea results in a multi-billion dollar per year health burden and that preventing wastewater pollution of the sea is worthy of inclusion on the global agenda of marine pollution prevention and control.

  9. Information to prevent human exposure to disease agents associated with wildlife—U.S. Geological Survey circulars on zoonotic disease

    Science.gov (United States)

    Meteyer, Carol U.; Moede Rogall, Gail

    2018-03-05

    The U.S. Geological Survey in collaboration with the U.S. Fish and Wildlife Service and others have published reports with information about geographic distribution, specific pathogens, disease ecology, and strategies to avoid exposure and infection for a selection of zoonotic diseases. Zoonotic diseases are diseases that can be passed from animals to humans, such as rabies and plague. This summary factsheet highlights the reports on plague, bat rabies, and raccoon roundworm with links to all seven zoonotic diseases covered in this series.

  10. Recombinant Newcastle disease virus-vectored vaccines against human and animal infectious diseases.

    Science.gov (United States)

    Duan, Zhiqiang; Xu, Houqiang; Ji, Xinqin; Zhao, Jiafu

    2015-01-01

    Recent advances in recombinant genetic engineering techniques have brought forward a leap in designing new vaccines in modern medicine. One attractive strategy is the application of reverse genetics technology to make recombinant Newcastle disease virus (rNDV) deliver protective antigens of pathogens. In recent years, numerous studies have demonstrated that rNDV-vectored vaccines can induce quicker and better humoral and mucosal immune responses than conventional vaccines and are protective against pathogen challenges. With deeper understanding of NDV molecular biology, it is feasible to develop gene-modified rNDV vaccines accompanied by good safety, high efficacy, low toxicity and better immunogenicity. This review summarizes the development of reverse genetics technology in using NDV as a promising vaccine vector to design new vaccines for human and animal use.

  11. Analysis of the robustness of network-based disease-gene prioritization methods reveals redundancy in the human interactome and functional diversity of disease-genes.

    Directory of Open Access Journals (Sweden)

    Emre Guney

    Full Text Available Complex biological systems usually pose a trade-off between robustness and fragility where a small number of perturbations can substantially disrupt the system. Although biological systems are robust against changes in many external and internal conditions, even a single mutation can perturb the system substantially, giving rise to a pathophenotype. Recent advances in identifying and analyzing the sequential variations beneath human disorders help to comprehend a systemic view of the mechanisms underlying various disease phenotypes. Network-based disease-gene prioritization methods rank the relevance of genes in a disease under the hypothesis that genes whose proteins interact with each other tend to exhibit similar phenotypes. In this study, we have tested the robustness of several network-based disease-gene prioritization methods with respect to the perturbations of the system using various disease phenotypes from the Online Mendelian Inheritance in Man database. These perturbations have been introduced either in the protein-protein interaction network or in the set of known disease-gene associations. As the network-based disease-gene prioritization methods are based on the connectivity between known disease-gene associations, we have further used these methods to categorize the pathophenotypes with respect to the recoverability of hidden disease-genes. Our results have suggested that, in general, disease-genes are connected through multiple paths in the human interactome. Moreover, even when these paths are disturbed, network-based prioritization can reveal hidden disease-gene associations in some pathophenotypes such as breast cancer, cardiomyopathy, diabetes, leukemia, parkinson disease and obesity to a greater extend compared to the rest of the pathophenotypes tested in this study. Gene Ontology (GO analysis highlighted the role of functional diversity for such diseases.

  12. Qualitative and quantitative methods for human factor analysis and assessment in NPP. Investigations and results

    International Nuclear Information System (INIS)

    Hristova, R.; Kalchev, B.; Atanasov, D.

    2005-01-01

    We consider here two basic groups of methods for analysis and assessment of the human factor in the NPP area and give some results from performed analyses as well. The human factor is the human interaction with the design equipment, with the working environment and takes into account the human capabilities and limits. In the frame of the qualitative methods for analysis of the human factor are considered concepts and structural methods for classifying of the information, connected with the human factor. Emphasize is given to the HPES method for human factor analysis in NPP. Methods for quantitative assessment of the human reliability are considered. These methods allow assigning of probabilities to the elements of the already structured information about human performance. This part includes overview of classical methods for human reliability assessment (HRA, THERP), and methods taking into account specific information about human capabilities and limits and about the man-machine interface (CHR, HEART, ATHEANA). Quantitative and qualitative results concerning human factor influence in the initiating events occurrences in the Kozloduy NPP are presented. (authors)

  13. Developmental Immunotoxicity, Perinatal Programming, and Noncommunicable Diseases: Focus on Human Studies

    Science.gov (United States)

    Dietert, Rodney R.

    2014-01-01

    Developmental immunotoxicity (DIT) is a term given to encompass the environmentally induced disruption of normal immune development resulting in adverse outcomes. A myriad of chemical, physical, and psychological factors can all contribute to DIT. As a core component of the developmental origins of adult disease, DIT is interlinked with three important concepts surrounding health risks across a lifetime: (1) the Barker Hypothesis, which connects prenatal development to later-life diseases, (2) the hygiene hypothesis, which connects newborns and infants to risk of later-life diseases and, (3) fetal programming and epigenetic alterations, which may exert effects both in later life and across future generations. This review of DIT considers: (1) the history and context of DIT research, (2) the fundamental features of DIT, (3) the emerging role of DIT in risk of noncommunicable diseases (NCDs) and (4) the range of risk factors that have been investigated through human research. The emphasis on the human DIT-related literature is significant since most prior reviews of DIT have largely focused on animal research and considerations of specific categories of risk factors (e.g., heavy metals). Risk factors considered in this review include air pollution, aluminum, antibiotics, arsenic, bisphenol A, ethanol, lead (Pb), maternal smoking and environmental tobacco smoke, paracetamol (acetaminophen), pesticides, polychlorinated biphenyls, and polyfluorinated compounds. PMID:26556429

  14. Mouse Models of Diet-Induced Nonalcoholic Steatohepatitis Reproduce the Heterogeneity of the Human Disease

    Science.gov (United States)

    Machado, Mariana Verdelho; Michelotti, Gregory Alexander; Xie, Guanhua; de Almeida, Thiago Pereira; Boursier, Jerome; Bohnic, Brittany; Guy, Cynthia D.; Diehl, Anna Mae

    2015-01-01

    Background and aims Non-alcoholic steatohepatitis (NASH), the potentially progressive form of nonalcoholic fatty liver disease (NAFLD), is the pandemic liver disease of our time. Although there are several animal models of NASH, consensus regarding the optimal model is lacking. We aimed to compare features of NASH in the two most widely-used mouse models: methionine-choline deficient (MCD) diet and Western diet. Methods Mice were fed standard chow, MCD diet for 8 weeks, or Western diet (45% energy from fat, predominantly saturated fat, with 0.2% cholesterol, plus drinking water supplemented with fructose and glucose) for 16 weeks. Liver pathology and metabolic profile were compared. Results The metabolic profile associated with human NASH was better mimicked by Western diet. Although hepatic steatosis (i.e., triglyceride accumulation) was also more severe, liver non-esterified fatty acid content was lower than in the MCD diet group. NASH was also less severe and less reproducible in the Western diet model, as evidenced by less liver cell death/apoptosis, inflammation, ductular reaction, and fibrosis. Various mechanisms implicated in human NASH pathogenesis/progression were also less robust in the Western diet model, including oxidative stress, ER stress, autophagy deregulation, and hedgehog pathway activation. Conclusion Feeding mice a Western diet models metabolic perturbations that are common in humans with mild NASH, whereas administration of a MCD diet better models the pathobiological mechanisms that cause human NAFLD to progress to advanced NASH. PMID:26017539

  15. Attributing the human disease burden of foodborne infections to specific sources.

    NARCIS (Netherlands)

    Pires, S.M.; Evers, E.G.; van Pelt, W.; Ayers, T.; Scallan, E.; Angulo, F.J.; Havelaar, A.H.; Hald, T.

    2009-01-01

    Foodborne diseases are an important cause of human illness worldwide. Humans acquire these infections from a variety of sources and routes of transmission. Many efforts have been made in the last decades to prevent and control foodborne diseases, particularly foodborne zoonoses. However, information

  16. Attributing the Human Disease Burden of Foodborne Infections to Specific Sources

    DEFF Research Database (Denmark)

    Pires, Sara Monteiro; Evers, Eric E.; Van Pely, Wilfrid

    2009-01-01

    Foodborne diseases are an important cause of human illness worldwide. Humans acquire these infections from a variety of sources and routes of transmission. Many efforts have been made in the last decades to prevent and control foodborne diseases, particularly foodborne zoonoses. However...

  17. Global burden of human papillomavirus and related diseases.

    Science.gov (United States)

    Forman, David; de Martel, Catherine; Lacey, Charles J; Soerjomataram, Isabelle; Lortet-Tieulent, Joannie; Bruni, Laia; Vignat, Jerome; Ferlay, Jacques; Bray, Freddie; Plummer, Martyn; Franceschi, Silvia

    2012-11-20

    The worldwide prevalence of infection with human papillomavirus (HPV) in women without cervical abnormalities is 11-12% with higher rates in sub-Saharan Africa (24%), Eastern Europe (21%) and Latin America (16%). The two most prevalent types are HPV16 (3.2%) and HPV18 (1.4%). Prevalence increases in women with cervical pathology in proportion to the severity of the lesion reaching around 90% in women with grade 3 cervical intraepithelial neoplasia and invasive cancer. HPV infection has been identified as a definite human carcinogen for six types of cancer: cervix, penis, vulva, vagina, anus and oropharynx (including the base of the tongue and tonsils). Estimates of the incidence of these cancers for 2008 due to HPV infection have been calculated globally. Of the estimated 12.7 million cancers occurring in 2008, 610,000 (Population Attributable Fraction [PAF]=4.8%) could be attributed to HPV infection. The PAF varies substantially by geographic region and level of development, increasing to 6.9% in less developed regions of the world, 14.2% in sub-Saharan Africa and 15.5% in India, compared with 2.1% in more developed regions, 1.6% in Northern America and 1.2% in Australia/New Zealand. Cervical cancer, for which the PAF is estimated to be 100%, accounted for 530,000 (86.9%) of the HPV attributable cases with the other five cancer types accounting for the residual 80,000 cancers. Cervical cancer is the third most common female malignancy and shows a strong association with level of development, rates being at least four-fold higher in countries defined within the low ranking of the Human Development Index (HDI) compared with those in the very high category. Similar disparities are evident for 5-year survival-less than 20% in low HDI countries and more than 65% in very high countries. There are five-fold or greater differences in incidence between world regions. In those countries for which reliable temporal data are available, incidence rates appear to be

  18. 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.

  19. Early Components of the Complement Classical Activation Pathway in Human Systemic Autoimmune Diseases

    Science.gov (United States)

    Lintner, Katherine E.; Wu, Yee Ling; Yang, Yan; Spencer, Charles H.; Hauptmann, Georges; Hebert, Lee A.; Atkinson, John P.; Yu, C. Yung

    2016-01-01

    The complement system consists of effector proteins, regulators, and receptors that participate in host defense against pathogens. Activation of the complement system, via the classical pathway (CP), has long been recognized in immune complex-mediated tissue injury, most notably systemic lupus erythematosus (SLE). Paradoxically, a complete deficiency of an early component of the CP, as evidenced by homozygous genetic deficiencies reported in human, are strongly associated with the risk of developing SLE or a lupus-like disease. Similarly, isotype deficiency attributable to a gene copy-number (GCN) variation and/or the presence of autoantibodies directed against a CP component or a regulatory protein that result in an acquired deficiency are relatively common in SLE patients. Applying accurate assay methodologies with rigorous data validations, low GCNs of total C4, and heterozygous and homozygous deficiencies of C4A have been shown as medium to large effect size risk factors, while high copy numbers of total C4 or C4A as prevalent protective factors, of European and East-Asian SLE. Here, we summarize the current knowledge related to genetic deficiency and insufficiency, and acquired protein deficiencies for C1q, C1r, C1s, C4A/C4B, and C2 in disease pathogenesis and prognosis of SLE, and, briefly, for other systemic autoimmune diseases. As the complement system is increasingly found to be associated with autoimmune diseases and immune-mediated diseases, it has become an attractive therapeutic target. We highlight the recent developments and offer a balanced perspective concerning future investigations and therapeutic applications with a focus on early components of the CP in human systemic autoimmune diseases. PMID:26913032

  20. 1st International Symposium on Stress-Associated RNA Granules in Human Disease and Viral Infection

    Directory of Open Access Journals (Sweden)

    Bruce W. Banfield

    2014-09-01

    Full Text Available In recent years, important linkages have been made between RNA granules and human disease processes. On June 8-10 of this year, we hosted a new symposium, dubbed the 1st International Symposium on Stress-Associated RNA Granules in Human Disease and Viral Infection. This symposium brought together experts from diverse research disciplines ranging from cancer and neuroscience to infectious disease. This report summarizes speaker presentations and highlights current challenges in the field.

  1. Transplantation of Human Embryonic Stem Cells in Patients with Multiple Sclerosis and Lyme Disease

    OpenAIRE

    Shroff, Geeta

    2016-01-01

    Case series Patient: Male, 42 ? Female, 30 Final Diagnosis: Human embryonic stem cells showed good therapeutic potential for treatment of multiple sclerosis with lyme disease Symptoms: Fatigue ? weakness in limbs Medication: ? Clinical Procedure: Human embryonic stem cells transplantation Specialty: Transplantology Objective: Rare disease Background: Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease in which the myelin sheath of nerve cells is damaged. It can cause dela...

  2. Human genetics of infectious diseases: between proof of principle and paradigm

    OpenAIRE

    Alcaïs, Alexandre; Abel, Laurent; Casanova, Jean-Laurent

    2009-01-01

    The observation that only a fraction of individuals infected by infectious agents develop clinical disease raises fundamental questions about the actual pathogenesis of infectious diseases. Epidemiological and experimental evidence is accumulating to suggest that human genetics plays a major role in this process. As we discuss here, human predisposition to infectious diseases seems to cover a continuous spectrum from monogenic to polygenic inheritance. Although many studies have provided proo...

  3. The consequences of human actions on risks for infectious diseases: a review

    OpenAIRE

    Lindahl, Johanna F.; Grace, Delia

    2015-01-01

    The human population is growing, requiring more space for food production, and needing more animals to feed it. Emerging infectious diseases are increasing, causing losses in both human and animal lives, as well as large costs to society. Many factors are contributing to disease emergence, including climate change, globalization and urbanization, and most of these factors are to some extent caused by humans. Pathogens may be more or less prone to emergence in themselves, and rapidly mutating ...

  4. [Assessment of invalidity as a result of infectious diseases].

    Science.gov (United States)

    Čeledová, L; Čevela, R; Bosák, M

    2016-01-01

    The article features the new medical assessment paradigm for invalidity as a result of infectious disease which is applied as of 1 January 2010. The invalidity assessment criteria are regulated specifically by Regulation No. 359/2009. Chapter I of the Annexe to the invalidity assessment regulation addresses the area of infectious diseases with respect to functional impairment and its impact on the quality of life. Since 2010, the invalidity has also been newly categorized into three groups. The new assessment approach makes it possible to evaluate a persons functional capacity, type of disability, and eligibility for compensation for reduced capacity for work. In 2010, a total of 170 375 invalidity cases were assessed, and in 2014, 147 121 invalidity assessments were made. Invalidity as a result of infectious disease was assessed in 177 persons in 2010, and 128 invalidity assessments were made in 2014. The most common causes of invalidity as a result of infectious disease are chronic viral hepatitis, other spirochetal infections, tuberculosis of the respiratory tract, tick-borne viral encephalitis, and HIV/AIDS. The number of assessments of invalidity as a result of infectious disease showed a declining trend between 2010 and 2014, similarly to the total of invalidity assessments. In spite of this fact, the cases of invalidity as a result of infectious disease account for approximately half percent of all invalidity assessments made in the above-mentioned period of time.

  5. Climate change and Ixodes tick-borne diseases of humans.

    Science.gov (United States)

    Ostfeld, Richard S; Brunner, Jesse L

    2015-04-05

    The evidence that climate warming is changing the distribution of Ixodes ticks and the pathogens they transmit is reviewed and evaluated. The primary approaches are either phenomenological, which typically assume that climate alone limits current and future distributions, or mechanistic, asking which tick-demographic parameters are affected by specific abiotic conditions. Both approaches have promise but are severely limited when applied separately. For instance, phenomenological approaches (e.g. climate envelope models) often select abiotic variables arbitrarily and produce results that can be hard to interpret biologically. On the other hand, although laboratory studies demonstrate strict temperature and humidity thresholds for tick survival, these limits rarely apply to field situations. Similarly, no studies address the influence of abiotic conditions on more than a few life stages, transitions or demographic processes, preventing comprehensive assessments. Nevertheless, despite their divergent approaches, both mechanistic and phenomenological models suggest dramatic range expansions of Ixodes ticks and tick-borne disease as the climate warms. The predicted distributions, however, vary strongly with the models' assumptions, which are rarely tested against reasonable alternatives. These inconsistencies, limited data about key tick-demographic and climatic processes and only limited incorporation of non-climatic processes have weakened the application of this rich area of research to public health policy or actions. We urge further investigation of the influence of climate on vertebrate hosts and tick-borne pathogen dynamics. In addition, testing model assumptions and mechanisms in a range of natural contexts and comparing their relative importance as competing models in a rigorous statistical framework will significantly advance our understanding of how climate change will alter the distribution, dynamics and risk of tick-borne disease.

  6. Identifying human disease genes through cross-species gene mapping of evolutionary conserved processes.

    Directory of Open Access Journals (Sweden)

    Martin Poot

    2011-05-01

    Full Text Available Understanding complex networks that modulate development in humans is hampered by genetic and phenotypic heterogeneity within and between populations. Here we present a method that exploits natural variation in highly diverse mouse genetic reference panels in which genetic and environmental factors can be tightly controlled. The aim of our study is to test a cross-species genetic mapping strategy, which compares data of gene mapping in human patients with functional data obtained by QTL mapping in recombinant inbred mouse strains in order to prioritize human disease candidate genes.We exploit evolutionary conservation of developmental phenotypes to discover gene variants that influence brain development in humans. We studied corpus callosum volume in a recombinant inbred mouse panel (C57BL/6J×DBA/2J, BXD strains using high-field strength MRI technology. We aligned mouse mapping results for this neuro-anatomical phenotype with genetic data from patients with abnormal corpus callosum (ACC development.From the 61 syndromes which involve an ACC, 51 human candidate genes have been identified. Through interval mapping, we identified a single significant QTL on mouse chromosome 7 for corpus callosum volume with a QTL peak located between 25.5 and 26.7 Mb. Comparing the genes in this mouse QTL region with those associated with human syndromes (involving ACC and those covered by copy number variations (CNV yielded a single overlap, namely HNRPU in humans and Hnrpul1 in mice. Further analysis of corpus callosum volume in BXD strains revealed that the corpus callosum was significantly larger in BXD mice with a B genotype at the Hnrpul1 locus than in BXD mice with a D genotype at Hnrpul1 (F = 22.48, p<9.87*10(-5.This approach that exploits highly diverse mouse strains provides an efficient and effective translational bridge to study the etiology of human developmental disorders, such as autism and schizophrenia.

  7. Human rabies: still a neglected preventable disease in Nigeria.

    Science.gov (United States)

    Eke, C B; Omotowo, I B; Ukoha, O M; Ibe, B C

    2015-01-01

    Adequate surveillance and monitoring of dog bite incidents are veritable tools in the determination of the epidemiology of human rabies infections. There is a paucity of data with regards to rabies in Nigeria. Hence, this study was aimed at describing the pattern and outcomes of dog bites and rabies infections among patients presenting to University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu. This was a 10-year (January 1, 2004 to December 31, 2013) observational retrospective study. Case definition of rabies was based on ICD 10 criteria, while relevant clinical data were retrieved from individual folders of registered victims using a semi-structured questionnaire. Data were analyzed using SPSS version 17.0 while the level of statistical significance was set at P cases of dog bites were reported during the period under review, of which 6 (4.0%) had confirmed rabies. Ninety-six (64.4%) cases presented more than 24 h after the bites. Majority of the offending dogs were stray dogs 86 (57.7%), which attacked their victims unprovoked, in 54.6% of cases. Furthermore, most of the bites were from dogs with unknown history of rabies vaccination 72 (52.3%), while the case fatality rate was 100%. All the cases of rabies reported were as a result of bites from stray dogs with unknown history of rabies vaccinations, and the outcome was 100% fatality in all cases. Efforts should be made to create and strengthen awareness campaigns on control of rabies infections through responsible dog ownership including their regular vaccinations as well as provision and use of prompt postexposure prophylaxis in human cases of dog bites at all levels of health care.

  8. [A brief history of the natural causes of human disease].

    Science.gov (United States)

    Lips-Castro, Walter

    2015-01-01

    In the study of the causes of disease that have arisen during the development of humankind, one can distinguish three major perspectives: the natural, the supernatural, and the artificial. In this paper we distinguish the rational natural causes of disease from the irrational natural causes. Within the natural and rational causal approaches of disease, we can highlight the Egyptian theory of putrid intestinal materials called "wechdu", the humoral theory, the atomistic theory, the contagious theory, the cellular theory, the molecular (genetic) theory, and the ecogenetic theory. Regarding the irrational, esoteric, and mystic causal approaches to disease, we highlight the astrological, the alchemical, the iatrochemical, the iatromechanical, and others (irritability, solidism, brownism, and mesmerism).

  9. Phenotypic concordance in familial inflammatory bowel disease (IBD). Results of a nationwide IBD Spanish database.

    Science.gov (United States)

    Cabré, Eduard; Mañosa, Míriam; García-Sánchez, Valle; Gutiérrez, Ana; Ricart, Elena; Esteve, Maria; Guardiola, Jordi; Aguas, Mariam; Merino, Olga; Ponferrada, Angel; Gisbert, Javier P; Garcia-Planella, Esther; Ceña, Gloria; Cabriada, José L; Montoro, Miguel; Domènech, Eugeni

    2014-07-01

    Disease outcome has been found to be poorer in familial inflammatory bowel disease (IBD) than in sporadic forms, but assessment of phenotypic concordance in familial IBD provided controversial results. We assessed the concordance for disease type and phenotypic features in IBD families. Patients with familial IBD were identified from the IBD Spanish database ENEIDA. Families in whom at least two members were in the database were selected for concordance analysis (κ index). Concordance for type of IBD [Crohn's disease (CD) vs. ulcerative colitis (UC)], as well as for disease extent, localization and behaviour, perianal disease, extraintestinal manifestations, and indicators of severe disease (i.e., need for immunosuppressors, biological agents, and surgery) for those pairs concordant for IBD type, were analyzed. 798 out of 11,905 IBD patients (7%) in ENEIDA had familial history of IBD. Complete data of 107 families (231 patients and 144 consanguineous pairs) were available for concordance analyses. The youngest members of the pairs were diagnosed with IBD at a significantly younger age (p<0.001) than the oldest ones. Seventy-six percent of pairs matched up for the IBD type (κ=0.58; 95%CI: 0.42-0.73, moderate concordance). There was no relevant concordance for any of the phenotypic items assessed in both diseases. Familial IBD is associated with diagnostic anticipation in younger individuals. Familial history does not allow predicting any phenotypic feature other than IBD type. Copyright © 2013 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

  10. Human papillomavirus vaccine uptake among individuals with systemic inflammatory diseases.

    Directory of Open Access Journals (Sweden)

    Candace H Feldman

    Full Text Available The human papillomavirus (HPV vaccine is safe and efficacious in patients with systemic inflammatory diseases (SID who have higher rates of persistent HPV infection. We compared HPV vaccine uptake among SID and non-SID patients.Using a U.S. insurance claims database (2006-2012, we identified individuals 9-26 years with ≥2 SID diagnosis codes ≥7 days apart with ≥12 months of continuous enrollment prior to the second code (index date. We matched SID patients by age, sex and index date to randomly selected non-SID subjects and selected those with ≥24 months of post-index date continuous follow-up. We also identified a non-SID subcohort with ≥1 diagnosis code for asthma. We defined initiation as ≥1 HPV vaccination claim after 2007, and completion as 3 claims. We used multivariable logistic regression to assess uptake in females 11-26 years comparing SID, non-SID and asthma cohorts, adjusting for demographics, region, comorbidities, and healthcare utilization.We identified 5,642 patients 9-26 years with SID and 20,643 without. The mean age was 18.1 years (SD 4.9. We identified 1,083 patients with asthma; the mean age was 17.2 (SD 5.1. Among females, 20.6% with SID, 23.1% without SID and 22.9% with asthma, received ≥1 HPV vaccine. In our adjusted models, the odds of receipt of ≥1 vaccine was 0.87 times lower in SID (95% CI 0.77-0.98 compared to non-SID and did not differ for 3 vaccines (OR 1.03, 95% CI 0.83-1.26. The odds of initiation and completion were not statistically different between SID and non-SID asthma cohorts.In this nationwide cohort, HPV vaccine uptake was extremely low. Despite the heightened risk of persistent HPV infection among those with SID, no increase in HPV vaccine uptake was observed. Public health efforts to promote HPV vaccination overall are needed, and may be particularly beneficial for those at higher risk.

  11. Epidemiological studies on Johne’s disease in ruminants and Crohn’s disease in humans in Egypt

    Directory of Open Access Journals (Sweden)

    A. Fawzy

    2013-12-01

    Full Text Available The correlation between Johne’s disease (JD and Crohn’s disease (CD in Egypt was investigated. A total of 371 human and 435 animal sera were collected from the same Egyptian governorates that had a known history of paratuberculosis infection and were subjected to screening for paratuberculosis using ELISA to assess the human/animal risk at a single time point. Five CD patients and five JD clinically infected dairy cattle were also included. Out of 435 animal serum samples, 196 (45.2% were MAP-ELISA positive. Twenty three (6.1% out of 371 human serum samples were MAP-ELISA positive, while 37 (9.9% were positive for anti-Saccharomyces cerevisiae antibodies (ASCA ELISAs. There was a very poor agreement between human MAP and ASCA ELISAs (0.036 by kappa statistics. The prevalence of MAP antibodies among humans is clearly lower than in animals. In conclusion there is an increase in Johne’s disease incidence in animals and a very weak relationship between MAP and Crohn’s disease in humans in Egypt.

  12. Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease

    International Nuclear Information System (INIS)

    Lake, April D.; Novak, Petr; Shipkova, Petia; Aranibar, Nelly; Robertson, Donald; Reily, Michael D.; Lu, Zhenqiang; Lehman-McKeeman, Lois D.; Cherrington, Nathan J.

    2013-01-01

    Bile acids (BAs) have many physiological roles and exhibit both toxic and protective influences within the liver. Alterations in the BA profile may be the result of disease induced liver injury. Nonalcoholic fatty liver disease (NAFLD) is a prevalent form of chronic liver disease characterized by the pathophysiological progression from simple steatosis to nonalcoholic steatohepatitis (NASH). The hypothesis of this study is that the ‘classical’ (neutral) and ‘alternative’ (acidic) BA synthesis pathways are altered together with hepatic BA composition during progression of human NAFLD. This study employed the use of transcriptomic and metabolomic assays to study the hepatic toxicologic BA profile in progressive human NAFLD. Individual human liver samples diagnosed as normal, steatosis, and NASH were utilized in the assays. The transcriptomic analysis of 70 BA genes revealed an enrichment of downregulated BA metabolism and transcription factor/receptor genes in livers diagnosed as NASH. Increased mRNA expression of BAAT and CYP7B1 was observed in contrast to decreased CYP8B1 expression in NASH samples. The BA metabolomic profile of NASH livers exhibited an increase in taurine together with elevated levels of conjugated BA species, taurocholic acid (TCA) and taurodeoxycholic acid (TDCA). Conversely, cholic acid (CA) and glycodeoxycholic acid (GDCA) were decreased in NASH liver. These findings reveal a potential shift toward the alternative pathway of BA synthesis during NASH, mediated by increased mRNA and protein expression of CYP7B1. Overall, the transcriptomic changes of BA synthesis pathway enzymes together with altered hepatic BA composition signify an attempt by the liver to reduce hepatotoxicity during disease progression to NASH. - Highlights: ► Altered hepatic bile acid composition is observed in progressive NAFLD. ► Bile acid synthesis enzymes are transcriptionally altered in NASH livers. ► Increased levels of taurine and conjugated bile acids

  13. Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Lake, April D. [University of Arizona, Department of Pharmacology and Toxicology, Tucson, AZ 85721 (United States); Novak, Petr [Biology Centre ASCR, Institute of Plant Molecular Biology, Ceske Budejovice 37001 (Czech Republic); Shipkova, Petia; Aranibar, Nelly; Robertson, Donald; Reily, Michael D. [Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Co., Princeton, NJ 08543 (United States); Lu, Zhenqiang [The Arizona Statistical Consulting Laboratory, University of Arizona, Tucson, AZ 85721 (United States); Lehman-McKeeman, Lois D. [Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Co., Princeton, NJ 08543 (United States); Cherrington, Nathan J., E-mail: cherrington@pharmacy.arizona.edu [University of Arizona, Department of Pharmacology and Toxicology, Tucson, AZ 85721 (United States)

    2013-04-15

    Bile acids (BAs) have many physiological roles and exhibit both toxic and protective influences within the liver. Alterations in the BA profile may be the result of disease induced liver injury. Nonalcoholic fatty liver disease (NAFLD) is a prevalent form of chronic liver disease characterized by the pathophysiological progression from simple steatosis to nonalcoholic steatohepatitis (NASH). The hypothesis of this study is that the ‘classical’ (neutral) and ‘alternative’ (acidic) BA synthesis pathways are altered together with hepatic BA composition during progression of human NAFLD. This study employed the use of transcriptomic and metabolomic assays to study the hepatic toxicologic BA profile in progressive human NAFLD. Individual human liver samples diagnosed as normal, steatosis, and NASH were utilized in the assays. The transcriptomic analysis of 70 BA genes revealed an enrichment of downregulated BA metabolism and transcription factor/receptor genes in livers diagnosed as NASH. Increased mRNA expression of BAAT and CYP7B1 was observed in contrast to decreased CYP8B1 expression in NASH samples. The BA metabolomic profile of NASH livers exhibited an increase in taurine together with elevated levels of conjugated BA species, taurocholic acid (TCA) and taurodeoxycholic acid (TDCA). Conversely, cholic acid (CA) and glycodeoxycholic acid (GDCA) were decreased in NASH liver. These findings reveal a potential shift toward the alternative pathway of BA synthesis during NASH, mediated by increased mRNA and protein expression of CYP7B1. Overall, the transcriptomic changes of BA synthesis pathway enzymes together with altered hepatic BA composition signify an attempt by the liver to reduce hepatotoxicity during disease progression to NASH. - Highlights: ► Altered hepatic bile acid composition is observed in progressive NAFLD. ► Bile acid synthesis enzymes are transcriptionally altered in NASH livers. ► Increased levels of taurine and conjugated bile acids

  14. Climate vs grapevine pests and diseases worldwide: the first results of a global survey

    Directory of Open Access Journals (Sweden)

    Benjamin Bois

    2017-05-01

    Methods and results: Based on the answer of respondent about the main reported diseases/pests in their region, a severity index was calculated. Each region was geolocalised and data were compared to the WorldClim gridded climate database to document the range of climate conditions (growing season temperature and rainfall associated to the main diseases/pests. The potential climatic-induced changes of grapevine disease and pest geography by 2050 are assessed using agro-climate projections from the ARPEGE CNRM model, using the RCP 4.5 scenario. The preliminary results allow to determine the distribution of diseases as function of agroclimatic indicators. Conclusion: While the distribution of diseases differs according to the region of the world, the current analysis suggests that mildews remain the major phytosanitary threat in most of the regions. Powdery mildew, trunk diseases and viruses were reported in extremely diverse climatic conditions, including intermediate and wet regions.  Significance and impact of the study: This paper present an original methodology to address the relationship between grapevine disease and pest occurrences and climate. Such documentation is scarce in the current literature. Further analysis is currently being performed, including additional survey answers, climate indices and supplementary data collected (spatial extension, frequency of treatments… to better depict the challenges of grapevine phytosanitary management in a changing climate.

  15. Experimental primates and non-human primate (NHP) models of human diseases in China: current status and progress.

    Science.gov (United States)

    Zhang, Xiao-Liang; Pang, Wei; Hu, Xin-Tian; Li, Jia-Li; Yao, Yong-Gang; Zheng, Yong-Tang

    2014-11-18

    Non-human primates (NHPs) are phylogenetically close to humans, with many similarities in terms of physiology, anatomy, immunology, as well as neurology, all of which make them excellent experimental models for biomedical research. Compared with developed countries in America and Europe, China has relatively rich primate resources and has continually aimed to develop NHPs resources. Currently, China is a leading producer and a major supplier of NHPs on the international market. However, there are some deficiencies in feeding and management that have hampered China's growth in NHP research and materials. Nonetheless, China has recently established a number of primate animal models for human diseases and achieved marked scientific progress on infectious diseases, cardiovascular diseases, endocrine diseases, reproductive diseases, neurological diseases, and ophthalmic diseases, etc. Advances in these fields via NHP models will undoubtedly further promote the development of China's life sciences and pharmaceutical industry, and enhance China's position as a leader in NHP research. This review covers the current status of NHPs in China and other areas, highlighting the latest developments in disease models using NHPs, as well as outlining basic problems and proposing effective countermeasures to better utilize NHP resources and further foster NHP research in China.

  16. Haemophilus influenzae genome evolution during persistence in the human airways in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Pettigrew, Melinda M; Ahearn, Christian P; Gent, Janneane F; Kong, Yong; Gallo, Mary C; Munro, James B; D'Mello, Adonis; Sethi, Sanjay; Tettelin, Hervé; Murphy, Timothy F

    2018-04-03

    Nontypeable Haemophilus influenzae (NTHi) exclusively colonize and infect humans and are critical to the pathogenesis of chronic obstructive pulmonary disease (COPD). In vitro and animal models do not accurately capture the complex environments encountered by NTHi during human infection. We conducted whole-genome sequencing of 269 longitudinally collected cleared and persistent NTHi from a 15-y prospective study of adults with COPD. Genome sequences were used to elucidate the phylogeny of NTHi isolates, identify genomic changes that occur with persistence in the human airways, and evaluate the effect of selective pressure on 12 candidate vaccine antigens. Strains persisted in individuals with COPD for as long as 1,422 d. Slipped-strand mispairing, mediated by changes in simple sequence repeats in multiple genes during persistence, regulates expression of critical virulence functions, including adherence, nutrient uptake, and modification of surface molecules, and is a major mechanism for survival in the hostile environment of the human airways. A subset of strains underwent a large 400-kb inversion during persistence. NTHi does not undergo significant gene gain or loss during persistence, in contrast to other persistent respiratory tract pathogens. Amino acid sequence changes occurred in 8 of 12 candidate vaccine antigens during persistence, an observation with important implications for vaccine development. These results indicate that NTHi alters its genome during persistence by regulation of critical virulence functions primarily by slipped-strand mispairing, advancing our understanding of how a bacterial pathogen that plays a critical role in COPD adapts to survival in the human respiratory tract.

  17. Neonatal screening for four lysosomal storage diseases with a digital microfluidics platform: Initial results in Brazil

    Directory of Open Access Journals (Sweden)

    Eurico Camargo Neto

    2018-06-01

    Full Text Available Abstract We describe the initial results of a neonatal screening program for four lysosomal storage diseases (MPS I, Pompe, Gaucher and Fabry using the digital microfluidics methodology. The method successfully identified patients previously diagnosed with these diseases and was used to test dried blood spot samples obtained from 10,527 newborns aged 2 to 14 days. The digital microfluidic technology shows potential for a simple, rapid and high-throughput screening for these four diseases in a standard neonatal screening laboratory.

  18. Prevalence estimates of chronic kidney disease in Canada: results of a nationally representative survey

    Science.gov (United States)

    Arora, Paul; Vasa, Priya; Brenner, Darren; Iglar, Karl; McFarlane, Phil; Morrison, Howard; Badawi, Alaa

    2013-01-01

    Background: Chronic kidney disease is an important risk factor for death and cardiovascular-related morbidity, but estimates to date of its prevalence in Canada have generally been extrapolated from the prevalence of end-stage renal disease. We used direct measures of kidney function collected from a nationally representative survey population to estimate the prevalence of chronic kidney disease among Canadian adults. Methods: We examined data for 3689 adult participants of cycle 1 of the Canadian Health Measures Survey (2007–2009) for the presence of chronic kidney disease. We also calculated the age-standardized prevalence of cardiovascular risk factors by chronic kidney disease group. We cross-tabulated the estimated glomerular filtration rate (eGFR) with albuminuria status. Results: The prevalence of chronic kidney disease during the period 2007–2009 was 12.5%, representing about 3 million Canadian adults. The estimated prevalence of stage 3–5 disease was 3.1% (0.73 million adults) and albuminuria 10.3% (2.4 million adults). The prevalence of diabetes, hypertension and hypertriglyceridemia were all significantly higher among adults with chronic kidney disease than among those without it. The prevalence of albuminuria was high, even among those whose eGFR was 90 mL/min per 1.73 m2 or greater (10.1%) and those without diabetes or hypertension (9.3%). Awareness of kidney dysfunction among adults with stage 3–5 chronic kidney disease was low (12.0%). Interpretation: The prevalence of kidney dysfunction was substantial in the survey population, including individuals without hypertension or diabetes, conditions most likely to prompt screening for kidney dysfunction. These findings highlight the potential for missed opportunities for early intervention and secondary prevention of chronic kidney disease. PMID:23649413

  19. Best Practices for Preventing Vector-Borne Diseases in Dogs and Humans.

    Science.gov (United States)

    Dantas-Torres, Filipe; Otranto, Domenico

    2016-01-01

    Vector-borne diseases constitute a diversified group of illnesses, which are caused by a multitude of pathogens transmitted by arthropod vectors, such as mosquitoes, fleas, ticks, and sand flies. Proper management of these diseases is important from both human and veterinary medicine standpoints, given that many of these pathogens are transmissible to humans and dogs, which often live in close contact. In this review, we summarize the most important vector-borne diseases of dogs and humans and the best practices for their prevention. The control of these diseases would ultimately improve animal and human health and wellbeing, particularly in developing countries in the tropics, where the risk of these diseases is high and access to health care is poor. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Use of genome editing tools in human stem cell-based disease modeling and precision medicine.

    Science.gov (United States)

    Wei, Yu-da; Li, Shuang; Liu, Gai-gai; Zhang, Yong-xian; Ding, Qiu-rong

    2015-10-01

    Precision medicine emerges as a new approach that takes into account individual variability. The successful conduct of precision medicine requires the use of precise disease models. Human pluripotent stem cells (hPSCs), as well as adult stem cells, can be differentiated into a variety of human somatic cell types that can be used for research and drug screening. The development of genome editing technology over the past few years, especially the CRISPR/Cas system, has made it feasible to precisely and efficiently edit the genetic background. Therefore, disease modeling by using a combination of human stem cells and genome editing technology has offered a new platform to generate " personalized " disease models, which allow the study of the contribution of individual genetic variabilities to disease progression and the development of precise treatments. In this review, recent advances in the use of genome editing in human stem cells and the generation of stem cell models for rare diseases and cancers are discussed.

  1. The Burden of Human Papillomavirus Infections and Related Diseases in Sub-Saharan Africa

    Science.gov (United States)

    De Vuyst, Hugo; Alemany, Laia; Lacey, Charles; Chibwesha, Carla J.; Sahasrabuddhe, Vikrant; Banura, Cecily; Denny, Lynette; Parham, Groesbeck P.

    2014-01-01

    Despite the scarcity of high quality cancer registries and lack of reliable mortality data, it is clear that human papillomavirus (HPV)-associated diseases, particularly cervical cancer, are major causes of morbidity and mortality in sub-Saharan Africa (SSA). Cervical cancer incidence rates in SSA are the highest in the world and the disease is the most common cause of cancer death among women in the region. The high incidence of cervical cancer is a consequence of the inability of most countries to either initiate or sustain cervical cancer prevention services. In addition, it appears that the prevalence of HPV in women with normal cytology is higher than in more developed areas of the world, at an average of 24%. There is, however, significant regional variation in SSA, with the highest incidence of HPV infection and cervical cancer found in Eastern and Western Africa. It is expected that, due to aging and growth of the population, but also to lack of access to appropriate prevention services and the concomitant human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) epidemic, cervical cancer incidence and mortality rates in SSA will rise over the next 20 years. HPV16 and 18 are the most common genotypes in cervical cancer in SSA, although other carcinogenic HPV types, such as HPV45 and 35, are also relatively more frequent compared with other world regions. Data on other HPV-related anogenital cancers including those of the vulva, vagina, anus, and penis, are limited. Genital warts are common and associated with HPV types 6 and 11. HIV infection increases incidence and prevalence of all HPV-associated diseases. Sociocultural determinants of HPV-related disease, as well as the impact of forces that result in social destabilization, demand further study. Strategies to reduce the excessive burden of HPV-related diseases in SSA include age-appropriate prophylactic HPV vaccination, cervical cancer prevention services for women of the reproductive

  2. Follicular Helper CD4+ T Cells in Human Neuroautoimmune Diseases and Their Animal Models

    Directory of Open Access Journals (Sweden)

    Xueli Fan

    2015-01-01

    Full Text Available Follicular helper CD4+ T (TFH cells play a fundamental role in humoral immunity deriving from their ability to provide help for germinal center (GC formation, B cell differentiation into plasma cells and memory cells, and antibody production in secondary lymphoid tissues. TFH cells can be identified by a combination of markers, including the chemokine receptor CXCR5, costimulatory molecules ICOS and PD-1, transcription repressor Bcl-6, and cytokine IL-21. It is difficult and impossible to get access to secondary lymphoid tissues in humans, so studies are usually performed with human peripheral blood samples as circulating counterparts of tissue TFH cells. A balance of TFH cell generation and function is critical for protective antibody response, whereas overactivation of TFH cells or overexpression of TFH-associated molecules may result in autoimmune diseases. Emerging data have shown that TFH cells and TFH-associated molecules may be involved in the pathogenesis of neuroautoimmune diseases including multiple sclerosis (MS, neuromyelitis optica (NMO/neuromyelitis optica spectrum disorders (NMOSD, and myasthenia gravis (MG. This review summarizes the features of TFH cells, including their development, function, and roles as well as TFH-associated molecules in neuroautoimmune diseases and their animal models.

  3. Molecular Mechanism of Adult Neurogenesis and its Association with Human Brain Diseases

    Directory of Open Access Journals (Sweden)

    He Liu

    2016-01-01

    Full Text Available Recent advances in neuroscience challenge the old dogma that neurogenesis occurs only during embryonic development. Mounting evidence suggests that functional neurogenesis occurs throughout adulthood. This review article discusses molecular factors that affect adult neurogenesis, including morphogens, growth factors, neurotransmitters, transcription factors, and epigenetic factors. Furthermore, we summarize and compare current evidence of associations between adult neurogenesis and human brain diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and brain tumors.

  4. Mitochondrial DNA sequence variation in human evolution and disease.

    Science.gov (United States)

    Wallace, D C

    1994-09-13

    Germ-line and somatic mtDNA mutations are hypothesized to act together to shape our history and our health. Germ-line mtDNA mutations, both ancient and recent, have been associated with a variety of degenerative diseases. Mildly to moderately deleterious germ-line mutations, like neutral polymorphisms, have become established in the distant past through genetic drift but now may predispose certain individuals to late-onset degenerative diseases. As an example, a homoplasmic, Caucasian, tRNA(Gln) mutation at nucleotide pair (np) 4336 has been observed in 5% of Alzheimer disease and Parkinson disease patients and may contribute to the multifactorial etiology of these diseases. Moderately to severely deleterious germ-line mutations, on the other hand, appear repeatedly but are eliminated by selection. Hence, all extant mutations of this class are recent and associated with more devastating diseases of young adults and children. Representative of these mutations is a heteroplasmic mutation in MTND6 at np 14459 whose clinical presentations range from adult-onset blindness to pediatric dystonia and basal ganglial degeneration. To the inherited mutations are added somatic mtDNA mutations which accumulate in random arrays within stable tissues. These mutations provide a molecular clock that measures our age and may cause a progressive decline in tissue energy output that could precipitate the onset of degenerative diseases in individuals harboring inherited deleterious mutations.

  5. Pathological alterations typical of human Tay-Sachs disease, in the retina of a deep-sea fish

    Science.gov (United States)

    Fishelson, L.; Delarea, Yacov; Galil, Bella S.

    Micrographs of retinas from the deep-sea fish Cataetyx laticeps revealed visual cells containing membranous whorls in the ellipsoids of the inner segments resulting from stretching and modifications of the mitochondria membranes and their cristae. These pathological structures seem to be homologous to the whorls observed in retinas of human carriers of Tay-Sachs disease. This disease, a genetic disorder, is found in humans and some mammals. Our findings in fish suggest that the gene responsible can be found throughout the vertebrate evolutionary tree, possibly dormant in most taxa.

  6. The scent of disease: human body odor contains an early chemosensory cue of sickness.

    Science.gov (United States)

    Olsson, Mats J; Lundström, Johan N; Kimball, Bruce A; Gordon, Amy R; Karshikoff, Bianka; Hosseini, Nishteman; Sorjonen, Kimmo; Olgart Höglund, Caroline; Solares, Carmen; Soop, Anne; Axelsson, John; Lekander, Mats

    2014-03-01

    Observational studies have suggested that with time, some diseases result in a characteristic odor emanating from different sources on the body of a sick individual. Evolutionarily, however, it would be more advantageous if the innate immune response were detectable by healthy individuals as a first line of defense against infection by various pathogens, to optimize avoidance of contagion. We activated the innate immune system in healthy individuals by injecting them with endotoxin (lipopolysaccharide). Within just a few hours, endotoxin-exposed individuals had a more aversive body odor relative to when they were exposed to a placebo. Moreover, this effect was statistically mediated by the individuals' level of immune activation. This chemosensory detection of the early innate immune response in humans represents the first experimental evidence that disease smells and supports the notion of a "behavioral immune response" that protects healthy individuals from sick ones by altering patterns of interpersonal contact.

  7. The Einstein Center for Epigenomics: studying the role of epigenomic dysregulation in human disease.

    Science.gov (United States)

    McLellan, Andrew S; Dubin, Robert A; Jing, Qiang; Maqbool, Shahina B; Olea, Raul; Westby, Gael; Broin, Pilib Ó; Fazzari, Melissa J; Zheng, Deyou; Suzuki, Masako; Greally, John M

    2009-10-01

    There is increasing interest in the role of epigenetic and transcriptional dysregulation in the pathogenesis of a range of human diseases, not just in the best-studied example of cancer. It is, however, quite difficult for an individual investigator to perform these studies, as they involve genome-wide molecular assays combined with sophisticated computational analytical approaches of very large datasets that may be generated from various resources and technologies. In 2008, the Albert Einstein College of Medicine in New York, USA established a Center for Epigenomics to facilitate the research programs of its investigators, providing shared resources for genome-wide assays and for data analysis. As a result, several avenues of research are now expanding, with cancer epigenomics being complemented by studies of the epigenomics of infectious disease and a neuroepigenomics program.

  8. Periodontal disease, tooth loss and colorectal cancer risk: Results from the Nurses' Health Study.

    Science.gov (United States)

    Momen-Heravi, Fatemeh; Babic, Ana; Tworoger, Shelley S; Zhang, Libin; Wu, Kana; Smith-Warner, Stephanie A; Ogino, Shuji; Chan, Andrew T; Meyerhardt, Jeffrey; Giovannucci, Edward; Fuchs, Charles; Cho, Eunyoung; Michaud, Dominique S; Stampfer, Meir J; Yu, Yau-Hua; Kim, David; Zhang, Xuehong

    2017-02-01

    Periodontal diseases including tooth loss might increase systemic inflammation, lead to immune dysregulation and alter gut microbiota, thereby possibly influencing colorectal carcinogenesis. Few epidemiological studies have examined the association between periodontal diseases and colorectal cancer (CRC) risk. We collected information on the periodontal disease (defined as history of periodontal bone loss) and number of natural teeth in the Nurses' Health Study. A total of 77,443 women were followed since 1992. We used Cox proportional hazard models to calculate multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) after adjustment for smoking and other known risk factors for CRC. We documented 1,165 incident CRC through 2010. Compared to women with 25-32 teeth, the multivariable HR (95% CI) for CRC for women with periodontal disease, HRs for CRC were 0.91 (95% CI 0.74-1.12) for periodontal disease, and 1.22 (95% CI 0.91-1.63) when limited to moderate to severe periodontal disease. The results were not modified by smoking status, body mass index or alcohol consumption. Women with fewer teeth, possibly moderate or severe periodontal disease, might be at a modest increased risk of developing CRC, suggesting a potential role of oral health in colorectal carcinogenesis. © 2016 UICC.

  9. Multi-platform ’Omics Analysis of Human Ebola Virus Disease Pathogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Eisfeld, Amie J.; Halfmann, Peter J.; Wendler, Jason P.; Kyle, Jennifer E.; Burnum-Johnson, Kristin E.; Peralta, Zuleyma; Maemura, Tadashi; Walters, Kevin B.; Watanabe, Tokiko; Fukuyama, Satoshi; Yamashita, Makoto; Jacobs, Jon M.; Kim, Young-Mo; Casey, Cameron P.; Stratton, Kelly G.; Webb-Robertson, Bobbie-Jo M.; Gritsenko, Marina A.; Monroe, Matthew E.; Weitz, Karl K.; Shukla, Anil K.; Tian, Mingyuan; Neumann, Gabriele; Reed, Jennifer L.; van Bakel, Harm; Metz, Thomas O.; Smith, Richard D.; Waters, Katrina M.; N' jai, Alhaji; Sahr, Foday; Kawaoka, Yoshihiro

    2017-12-01

    The pathogenesis of human Ebola virus disease (EVD) is complex. EVD is characterized by high levels of virus replication and dissemination, dysregulated immune responses, extensive virus- and host-mediated tissue damage, and disordered coagulation. To clarify how host responses contribute to EVD pathophysiology, we performed multi-platform ’omics analysis of peripheral blood mononuclear cells and plasma from EVD patients. Our results indicate that EVD molecular signatures overlap with those of sepsis, imply that pancreatic enzymes contribute to tissue damage in fatal EVD, and suggest that Ebola virus infection may induce aberrant neutrophils whose activity could explain hallmarks of fatal EVD. Moreover, integrated biomarker prediction identified putative biomarkers from different data platforms that differentiated survivors and fatalities early after infection. This work reveals insight into EVD pathogenesis, suggests an effective approach for biomarker identification, and provides an important community resource for further analysis of human EVD severity.

  10. How to become a top model: impact of animal experimentation on human Salmonella disease research.

    Science.gov (United States)

    Tsolis, Renée M; Xavier, Mariana N; Santos, Renato L; Bäumler, Andreas J

    2011-05-01

    Salmonella serotypes are a major cause of human morbidity and mortality worldwide. Over the past decades, a series of animal models have been developed to advance vaccine development, provide insights into immunity to infection, and study the pathogenesis of human Salmonella disease. The successive introduction of new animal models, each suited to interrogate previously neglected aspects of Salmonella disease, has ushered in important conceptual advances that continue to have a strong and sustained influence on the ideas driving research on Salmonella serotypes. This article reviews important milestones in the use of animal models to study human Salmonella disease and identify research needs to guide future work.

  11. Gene expression patterns associated with neurological disease in human HIV infection.

    Directory of Open Access Journals (Sweden)

    Pietro Paolo Sanna

    Full Text Available The pathogenesis and nosology of HIV-associated neurological disease (HAND remain incompletely understood. Here, to provide new insight into the molecular events leading to neurocognitive impairments (NCI in HIV infection, we analyzed pathway dysregulations in gene expression profiles of HIV-infected patients with or without NCI and HIV encephalitis (HIVE and control subjects. The Gene Set Enrichment Analysis (GSEA algorithm was used for pathway analyses in conjunction with the Molecular Signatures Database collection of canonical pathways (MSigDb. We analyzed pathway dysregulations in gene expression profiles of patients from the National NeuroAIDS Tissue Consortium (NNTC, which consists of samples from 3 different brain regions, including white matter, basal ganglia and frontal cortex of HIV-infected and control patients. While HIVE is characterized by widespread, uncontrolled inflammation and tissue damage, substantial gene expression evidence of induction of interferon (IFN, cytokines and tissue injury is apparent in all brain regions studied, even in the absence of NCI. Various degrees of white matter changes were present in all HIV-infected subjects and were the primary manifestation in patients with NCI in the absence of HIVE. In particular, NCI in patients without HIVE in the NNTC sample is associated with white matter expression of chemokines, cytokines and β-defensins, without significant activation of IFN. Altogether, the results identified distinct pathways differentially regulated over the course of neurological disease in HIV infection and provide a new perspective on the dynamics of pathogenic processes in the course of HIV neurological disease in humans. These results also demonstrate the power of the systems biology analyses and indicate that the establishment of larger human gene expression profile datasets will have the potential to provide novel mechanistic insight into the pathogenesis of neurological disease in HIV

  12. Insights into the human gut microbiome and cardiovascular diseases

    Directory of Open Access Journals (Sweden)

    Soumalya Sarkar

    2018-01-01

    Full Text Available The microbiome comprises all of the genetic materials within a microbiota. This can also be referred to as the metagenome of the microbiota. Dysbiosis, a change in the composition of the gut microbiota, has been associated with pathology, including cardiovascular diseases (CVDs. The recently discovered contribution of gut microbiota-derived molecules in the development of heart disease and its risk factors has significantly increased attention toward the connection between our gut and heart. The gut microbiome is virtually an endocrine organ, capable of contributing to and reacting to circulating signaling molecules within the host. Gut microbiota-host interactions occur through many pathways, including trimethylamine-N-oxide and short-chain fatty acids. These molecules and others have been linked to chronic kidney disease, atherosclerosis, and hypertension. Dysbiosis has been implicated in CVD as well as many aspects of obesity, hypertension, chronic kidney disease, and diabetes.

  13. An atlas of genetic correlations across human diseases and traits

    DEFF Research Database (Denmark)

    Bulik-Sullivan, Brendan; Finucane, Hilary K; Anttila, Verneri

    2015-01-01

    Identifying genetic correlations between complex traits and diseases can provide useful etiological insights and help prioritize likely causal relationships. The major challenges preventing estimation of genetic correlation from genome-wide association study (GWAS) data with current methods are t...

  14. Pesticides and human chronic diseases: Evidences, mechanisms, and perspectives

    International Nuclear Information System (INIS)

    Mostafalou, Sara; Abdollahi, Mohammad

    2013-01-01

    Along with the wide use of pesticides in the world, the concerns over their health impacts are rapidly growing. There is a huge body of evidence on the relation between exposure to pesticides and elevated rate of chronic diseases such as different types of cancers, diabetes, neurodegenerative disorders like Parkinson, Alzheimer, and amyotrophic lateral sclerosis (ALS), birth defects, and reproductive disorders. There is also circumstantial evidence on the association of exposure to pesticides with some other chronic diseases like respiratory problems, particularly asthma and chronic obstructive pulmonary disease (COPD), cardiovascular disease such as atherosclerosis and coronary artery disease, chronic nephropathies, autoimmune diseases like systemic lupus erythematous and rheumatoid arthritis, chronic fatigue syndrome, and aging. The common feature of chronic disorders is a disturbance in cellular homeostasis, which can be induced via pesticides' primary action like perturbation of ion channels, enzymes, receptors, etc., or can as well be mediated via pathways other than the main mechanism. In this review, we present the highlighted evidence on the association of pesticide's exposure with the incidence of chronic diseases and introduce genetic damages, epigenetic modifications, endocrine disruption, mitochondrial dysfunction, oxidative stress, endoplasmic reticulum stress and unfolded protein response (UPR), impairment of ubiquitin proteasome system, and defective autophagy as the effective mechanisms of action. - Highlights: ► There is a link between exposure to pesticides and incidence of chronic diseases. ► Genotoxicity and proteotoxicity are two main involved mechanisms. ► Epigenetic knowledge may help diagnose the relationships. ► Efficient policies on safe use of pesticides should be set up

  15. Pesticides and human chronic diseases: Evidences, mechanisms, and perspectives

    Energy Technology Data Exchange (ETDEWEB)

    Mostafalou, Sara; Abdollahi, Mohammad, E-mail: Mohammad.Abdollahi@UToronto.Ca

    2013-04-15

    Along with the wide use of pesticides in the world, the concerns over their health impacts are rapidly growing. There is a huge body of evidence on the relation between exposure to pesticides and elevated rate of chronic diseases such as different types of cancers, diabetes, neurodegenerative disorders like Parkinson, Alzheimer, and amyotrophic lateral sclerosis (ALS), birth defects, and reproductive disorders. There is also circumstantial evidence on the association of exposure to pesticides with some other chronic diseases like respiratory problems, particularly asthma and chronic obstructive pulmonary disease (COPD), cardiovascular disease such as atherosclerosis and coronary artery disease, chronic nephropathies, autoimmune diseases like systemic lupus erythematous and rheumatoid arthritis, chronic fatigue syndrome, and aging. The common feature of chronic disorders is a disturbance in cellular homeostasis, which can be induced via pesticides' primary action like perturbation of ion channels, enzymes, receptors, etc., or can as well be mediated via pathways other than the main mechanism. In this review, we present the highlighted evidence on the association of pesticide's exposure with the incidence of chronic diseases and introduce genetic damages, epigenetic modifications, endocrine disruption, mitochondrial dysfunction, oxidative stress, endoplasmic reticulum stress and unfolded protein response (UPR), impairment of ubiquitin proteasome system, and defective autophagy as the effective mechanisms of action. - Highlights: ► There is a link between exposure to pesticides and incidence of chronic diseases. ► Genotoxicity and proteotoxicity are two main involved mechanisms. ► Epigenetic knowledge may help diagnose the relationships. ► Efficient policies on safe use of pesticides should be set up.

  16. Proteomics analyses for the global proteins in the brain tissues of different human prion diseases.

    Science.gov (United States)

    Shi, Qi; Chen, Li-Na; Zhang, Bao-Yun; Xiao, Kang; Zhou, Wei; Chen, Cao; Zhang, Xiao-Mei; Tian, Chan; Gao, Chen; Wang, Jing; Han, Jun; Dong, Xiao-Ping

    2015-04-01

    Proteomics changes of brain tissues have been described in different neurodegenerative diseases including Alzheimer's disease and Parkinson's disease. However, the brain proteomics of human prion disease remains less understood. In the study, the proteomics patterns of cortex and cerebellum of brain tissues of sporadic Creutzfeldt-Jakob disease, fatal familial insomnia, and G114V genetic CJD were analyzed with isobaric tags for relative and absolute quantitation combined with multidimensional liquid chromatography and MS analysis, with the brains from three normal individuals as controls. Global protein profiling, significant pathway, and functional categories were analyzed. In total, 2287 proteins were identified with quantitative information both in cortex and cerebellum regions. Cerebellum tissues appeared to contain more up- and down-regulated proteins (727 proteins) than cortex regions (312 proteins) of Creutzfeldt-Jakob disease, fatal familial insomnia, and G114V genetic CJD. Viral myocarditis, Parkinson's disease, Alzheimer's disease, lysosome, oxidative phosphorylation, protein export, and drug metabolism-cytochrome P450 were the most commonly affected pathways of the three kinds of diseases. Almost coincident biological functions were identified in the brain tissues of the three diseases. In all, data here demonstrate that the brain tissues of Creutzfeldt-Jakob disease, fatal familial insomnia, and G114V genetic CJD have obvious proteomics changes at their terminal stages, which show the similarities not only among human prion diseases but also with other neurodegeneration diseases. This is the first study to provide a reference proteome map for human prion diseases and will be helpful for future studies focused on potential biomarkers for the diagnosis and therapy of human prion diseases. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Mineral density volume gradients in normal and diseased human tissues.

    Directory of Open Access Journals (Sweden)

    Sabra I Djomehri

    Full Text Available Clinical computed tomography provides a single mineral density (MD value for heterogeneous calcified tissues containing early and late stage pathologic formations. The novel aspect of this study is that, it extends current quantitative methods of mapping mineral density gradients to three dimensions, discretizes early and late mineralized stages, identifies elemental distribution in discretized volumes, and correlates measured MD with respective calcium (Ca to phosphorus (P and Ca to zinc (Zn elemental ratios. To accomplish this, MD variations identified using polychromatic radiation from a high resolution micro-computed tomography (micro-CT benchtop unit were correlated with elemental mapping obtained from a microprobe X-ray fluorescence (XRF using synchrotron monochromatic radiation. Digital segmentation of tomograms from normal and diseased tissues (N=5 per group; 40-60 year old males contained significant mineral density variations (enamel: 2820-3095 mg/cc, bone: 570-1415 mg/cc, cementum: 1240-1340 mg/cc, dentin: 1480-1590 mg/cc, cementum affected by periodontitis: 1100-1220 mg/cc, hypomineralized carious dentin: 345-1450 mg/cc, hypermineralized carious dentin: 1815-2740 mg/cc, and dental calculus: 1290-1770 mg/cc. A plausible linear correlation between segmented MD volumes and elemental ratios within these volumes was established, and Ca/P ratios for dentin (1.49, hypomineralized dentin (0.32-0.46, cementum (1.51, and bone (1.68 were observed. Furthermore, varying Ca/Zn ratios were distinguished in adapted compared to normal tissues, such as in bone (855-2765 and in cementum (595-990, highlighting Zn as an influential element in prompting observed adaptive properties. Hence, results provide insights on mineral density gradients with elemental concentrations and elemental footprints that in turn could aid in elucidating mechanistic processes for pathologic formations.

  18. Mineral Density Volume Gradients in Normal and Diseased Human Tissues

    Science.gov (United States)

    Djomehri, Sabra I.; Candell, Susan; Case, Thomas; Browning, Alyssa; Marshall, Grayson W.; Yun, Wenbing; Lau, S. H.; Webb, Samuel; Ho, Sunita P.

    2015-01-01

    Clinical computed tomography provides a single mineral density (MD) value for heterogeneous calcified tissues containing early and late stage pathologic formations. The novel aspect of this study is that, it extends current quantitative methods of mapping mineral density gradients to three dimensions, discretizes early and late mineralized stages, identifies elemental distribution in discretized volumes, and correlates measured MD with respective calcium (Ca) to phosphorus (P) and Ca to zinc (Zn) elemental ratios. To accomplish this, MD variations identified using polychromatic radiation from a high resolution micro-computed tomography (micro-CT) benchtop unit were correlated with elemental mapping obtained from a microprobe X-ray fluorescence (XRF) using synchrotron monochromatic radiation. Digital segmentation of tomograms from normal and diseased tissues (N=5 per group; 40-60 year old males) contained significant mineral density variations (enamel: 2820-3095mg/cc, bone: 570-1415mg/cc, cementum: 1240-1340mg/cc, dentin: 1480-1590mg/cc, cementum affected by periodontitis: 1100-1220mg/cc, hypomineralized carious dentin: 345-1450mg/cc, hypermineralized carious dentin: 1815-2740mg/cc, and dental calculus: 1290-1770mg/cc). A plausible linear correlation between segmented MD volumes and elemental ratios within these volumes was established, and Ca/P ratios for dentin (1.49), hypomineralized dentin (0.32-0.46), cementum (1.51), and bone (1.68) were observed. Furthermore, varying Ca/Zn ratios were distinguished in adapted compared to normal tissues, such as in bone (855-2765) and in cementum (595-990), highlighting Zn as an influential element in prompting observed adaptive properties. Hence, results provide insights on mineral density gradients with elemental concentrations and elemental footprints that in turn could aid in elucidating mechanistic processes for pathologic formations. PMID:25856386

  19. Diseases of poverty and lifestyle, well-being and human development.

    Science.gov (United States)

    Singh, Ajai R; Singh, Shakuntala A

    2008-01-01

    The problems of the haves differ substantially from those of the have-nots. Individuals in developing societies have to fight mainly against infectious and communicable diseases, while in the developed world the battles are mainly against lifestyle diseases. Yet, at a very fundamental level, the problems are the same-the fight is against distress, disability, and premature death; against human exploitation and for human development and self-actualisation; against the callousness to critical concerns in regimes and scientific power centres.While there has been great progress in the treatment of individual diseases, human pathology continues to increase. Sicknesses are not decreasing in number, they are only changing in type.The primary diseases of poverty like TB, malaria, and HIV/AIDS-and the often co-morbid and ubiquitous malnutrition-take their toll on helpless populations in developing countries. Poverty is not just income deprivation but capability deprivation and optimism deprivation as well.While life expectancy may have increased in the haves, and infant and maternal mortality reduced, these gains have not necessarily ensured that well-being results. There are ever-multiplying numbers of individuals whose well-being is compromised due to lifestyle diseases. These diseases are the result of faulty lifestyles and the consequent crippling stress. But it serves no one's purpose to understand them as such. So, the prescription pad continues to prevail over lifestyle-change counselling or research.The struggle to achieve well-being and positive health, to ensure longevity, to combat lifestyle stress and professional burnout, and to reduce psychosomatic ailments continues unabated, with hardly an end in sight.WE THUS REALISE THAT MORBIDITY, DISABILITY, AND DEATH ASSAIL ALL THREE SOCIETIES: the ones with infectious diseases, the ones with diseases of poverty, and the ones with lifestyle diseases. If it is bacteria in their various forms that are the culprit in

  20. [Oral microbiota: a promising predictor of human oral and systemic diseases].

    Science.gov (United States)

    Xin, Xu; Junzhi, He; Xuedong, Zhou

    2015-12-01

    A human oral microbiota is the ecological community of commensal, symbiotic, and pathogenic microorganisms found in human oral cavity. Oral microbiota exists mostly in the form of a biofilm and maintains a dynamic ecological equilibrium with the host body. However, the disturbance of this ecological balance inevitably causes oral infectious diseases, such as dental caries, apical periodontitis, periodontal diseases, pericoronitis, and craniofacial bone osteomyelitis. Oral microbiota is also correlated with many systemic diseases, including cancer, diabetes mellitus, rheumatoid arthritis, cardiovascular diseases, and preterm birth. Hence, oral microbiota has been considered as a potential biomarker of human diseases. The "Human Microbiome Project" and other metagenomic projects worldwide have advanced our knowledge of the human oral microbiota. The integration of these metadata has been the frontier of oral microbiology to improve clinical translation. By reviewing recent progress on studies involving oral microbiota-related oral and systemic diseases, we aimed to propose the essential role of oral microbiota in the prediction of the onset, progression, and prognosis of oral and systemic diseases. An oral microbiota-based prediction model helps develop a new paradigm of personalized medicine and benefits the human health in the post-metagenomics era.

  1. Human Embryonic Stem Cell Therapy in Crohn’s Disease: A Case Report

    Science.gov (United States)

    Shroff, Geeta

    2016-01-01

    Patient: Male, 21 Final Diagnosis: Crohn’s disease Symptoms: Intolerance to specific foods • abdominal pain and diarrhea Medication: Human embryonic stem cell therapy Clinical Procedure: Human embryonic stem cell transplantation Specialty: Gastroenterology Objective: Unusual or unexpected effect of treatment Background: Crohn’s disease is a chronic inflammatory disease of the intestines, mainly the colon and ileum, related with ulcers and fistulae. It is estimated to affect 565 000 people in the United States. Currently available therapies, such as antibiotics, thiopurines, and anti-tumor necrosis factor-alpha agents, are only observed to reduce the complications associated with Crohn’s disease and to improve quality of life, but cannot cure the disease. Stem cell therapy appears to have certain advantages over conventional therapies. Our study aimed to evaluate the efficacy of human embryonic stem cell therapy in a patient with Crohn’s disease. Case Report: A 21-year-old male with chief complaints of intolerance to specific foods, abdominal pain, and diarrhea underwent human embryonic stem cell therapy for two months. After undergoing human embryonic stem cell therapy, the patient showed symptomatic relief. He had no complaints of back pain, abdominal pain, or diarrhea and had improved digestion. The patient had no signs and symptoms of skin infection, and had improved limb stamina, strength, and endurance. The condition of patient was stable after the therapy. Conclusions: Human embryonic stem cell therapy might serve as a new optimistic treatment approach for Crohn’s disease. PMID:26923312

  2. Complement component 5 contributes to poor disease outcome in humans and mice with pneumococcal meningitis

    Science.gov (United States)

    Woehrl, Bianca; Brouwer, Matthijs C.; Murr, Carmen; Heckenberg, Sebastiaan G.B.; Baas, Frank; Pfister, Hans W.; Zwinderman, Aeilko H.; Morgan, B. Paul; Barnum, Scott R.; van der Ende, Arie; Koedel, Uwe; van de Beek, Diederik

    2011-01-01

    Pneumococcal meningitis is the most common and severe form of bacterial meningitis. Fatality rates are substantial, and long-term sequelae develop in about half of survivors. Disease outcome has been related to the severity of the proinflammatory response in the subarachnoid space. The complement system, which mediates key inflammatory processes, has been implicated as a modulator of pneumococcal meningitis disease severity in animal studies. Additionally, SNPs in genes encoding complement pathway proteins have been linked to susceptibility to pneumococcal infection, although no associations with disease severity or outcome have been established. Here, we have performed a robust prospective nationwide genetic association study in patients with bacterial meningitis and found that a common nonsynonymous complement component 5 (C5) SNP (rs17611) is associated with unfavorable disease outcome. C5 fragment levels in cerebrospinal fluid (CSF) of patients with bacterial meningitis correlated with several clinical indicators of poor prognosis. Consistent with these human data, C5a receptor–deficient mice with pneumococcal meningitis had lower CSF wbc counts and decreased brain damage compared with WT mice. Adjuvant treatment with C5-specific monoclonal antibodies prevented death in all mice with pneumococcal meningitis. Thus, our results suggest C5-specific monoclonal antibodies could be a promising new antiinflammatory adjuvant therapy for pneumococcal meningitis. PMID:21926466

  3. Humanized Mouse Models of Epstein-Barr Virus Infection and Associated Diseases

    Science.gov (United States)

    Fujiwara, Shigeyoshi; Matsuda, Go; Imadome, Ken-Ichi

    2013-01-01

    Epstein-Barr virus (EBV) is a ubiquitous herpesvirus infecting more than 90% of the adult population of the world. EBV is associated with a variety of diseases including infectious mononucleosis, lymphoproliferative diseases, malignancies such as Burkitt lymphoma and nasopharyngeal carcinoma, and autoimmune diseases including rheumatoid arthritis (RA). EBV in nature infects only humans, but in an experimental setting, a limited species of new-world monkeys can be infected with the virus. Small animal models, suitable for evaluation of novel therapeutics and vaccines, have not been available. Humanized mice, defined here as mice harboring functioning human immune system components, are easily infected with EBV that targets cells of the hematoimmune system. Furthermore, humanized mice can mount both cellular and humoral immune responses to EBV. Thus, many aspects of human EBV infection, including associated diseases (e.g., lymphoproliferative disease, hemophagocytic lymphohistiocytosis and erosive arthritis resembling RA), latent infection, and T-cell-mediated and humoral immune responses have been successfully reproduced in humanized mice. Here we summarize recent achievements in the field of humanized mouse models of EBV infection and show how they have been utilized to analyze EBV pathogenesis and normal and aberrant human immune responses to the virus. PMID:25436886

  4. Human gingival fibroblasts are critical in sustaining inflammation in periodontal disease.

    Science.gov (United States)

    Ara, Toshiaki; Kurata, Kazuyuki; Hirai, Kaname; Uchihashi, Takayuki; Uematsu, Takashi; Imamura, Yasuhiro; Furusawa, Kiyohumi; Kurihara, Saburo; Wang, Pao-Li

    2009-02-01

    A major factor in the pathogenesis of periodontal disease, which is one of the biofilm infectious diseases, is thought to be lipopolysaccharide (LPS), owing to its ability to cause inflammation and promote tissue destruction. Moreover, the elimination of pathogens and their component LPSs is essential for the successful treatment of periodontal disease. Lipopolysaccharide tolerance is a mechanism that prevents excessive and prolonged responses of monocytes and macrophages to LPS. Since persistence of inflammation is necessary for inflammatory cytokine production, cells other than monocytes and macrophages are thought to maintain the production of cytokines in the presence of LPS. In this study, we investigated whether human gingival fibroblasts (HGFs), the most abundant structural cell in periodontal tissue, might be able to maintain inflammatory cytokine production in the presence of LPS bynot displaying LPS tolerance. Human gingival fibroblasts were pretreated with LPS (from Porphyromonas gingivalis and Escherichia coli) and then treated with LPS, and the amounts of interleukin (IL)-6 and IL-8 in the cell culture supernatants were measured. The expression of negative regulators of LPS signalling (suppressor of cytokine signalling-1, interleukin-1 receptor-associated-kinase M and SH2 domain-containing inositol-5-phosphatase-1) was also examined in LPS-treated HGFs. Human gingival fibroblasts did not display LPS tolerance but maintained production of IL-6 and IL-8 when pretreated with LPS, followed by secondary LPS treatment. Lipopolysaccharide-treated HGFs did not express negative regulators. These results demonstrate that HGFs do not show LPS tolerance and suggest that this characteristic of HGFs sustains the inflammatory response in the presence of virulence factors.

  5. Stressful life events and Graves' disease: Results of a case control study

    International Nuclear Information System (INIS)

    Pintor, A.B.; Barrenechea, E.A.; Laureta, E.G.; Ligon, R.A.

    2003-01-01

    Prolonged worry has generally been acknowledged as one of the main precipitating factors of the onset of Graves' disease. A review of literature reveals that emotional stresses of considerable severity precede the onset of hyperthyroidism in about 90% of cases. However, not everyone subscribes to the Stress/Graves' disease hypothesis. Attempts to resolve this issue have tended to focus on whether a correlation can be shown between the magnitude of antecedent life events and the disease. Hence the main objective of the present study was to identify the possible association between stressful life events and Graves' disease. This paper presents the results of a case-control study, involving patents and subjects from the Veterans Memorial Medical Centre of Manila. A total of 224 patients of Graves' disease, newly or previously diagnosed, representing the 'patient's' arm were interviewed. All patients were questioned regarding various stresses, which greatly affected their life style spanning over a 12-month period prior to the onset of the disease. Simultaneously, 224 control subjects were also interviewed, and their stresses spanning over a similar period preceding the dates of interviews were recorded in quantifiable terms. Different stresses were given different intensity scores based on a social readjustment scale taking into consideration the life situations, emotions and diseases. In cases of multiple stresses, intensity scores were added to obtain the total stress intensity. Results were expressed as mean, standard deviation, median, frequency and percent distribution. Scatter plot was also constructed for intensity of stressful life events. To determine association of different factors with Graves' disease, Students t-test and chi-square tests were applied to the data. Odds ratio (OR) was also computed to determine risk attributed to each factor. Since there was significant difference in gender distribution between the patients and controls, stratified Mantel

  6. Disease in the Society: Infectious Cadavers Result in Collapse of Ant Sub-Colonies

    Science.gov (United States)

    Loreto, Raquel G.; Hughes, David P.

    2016-01-01

    Despite the growing number of experimental studies on mechanisms of social immunity in ant societies, little is known about how social behavior relates to disease progression within the nests of ants. In fact, when empirically studying disease in ant societies, it is common to remove dead ants from experiments to confirm infection by the studied parasite. This unfortunately does not allow disease to progress within the nest as it may be assumed would happen under natural conditions. Therefore, the approach taken so far has resulted in a limited knowledge of diseases dynamics within the nest environment. Here we introduced a single infectious cadaver killed by the fungus Beauveria bassiana into small nests of the ant Camponotus castaneus. We then observed the natural progression of the disease by not removing the corpses of the ants that died following the first entry of the disease. Because some behaviors such as social isolation of sick individuals or the removal of cadavers by nestmates are considered social immune functions and thus adaptations at the colony level that reduce disease spread, we also experimentally confined some sub-colonies to one or two chamber nests to prevent the expression of such behaviors. Based on 51 small nests and survival studies in 1,003 ants we found that a single introduced infectious cadaver was able to transmit within the nest, and social immunity did not prevent the collapse of the small sub-colonies here tested. This was true whether ants did or did not have the option to remove the infectious cadaver. Therefore, we found no evidence that the typically studied social immunity behaviors can reduce disease spread in the conditions here tested. PMID:27529548

  7. Modeling human diseases with induced pluripotent stem cells: from 2D to 3D and beyond.

    Science.gov (United States)

    Liu, Chun; Oikonomopoulos, Angelos; Sayed, Nazish; Wu, Joseph C

    2018-03-08

    The advent of human induced pluripotent stem cells (iPSCs) presents unprecedented opportunities to model human diseases. Differentiated cells derived from iPSCs in two-dimensional (2D) monolayers have proven to be a relatively simple tool for exploring disease pathogenesis and underlying mechanisms. In this Spotlight article, we discuss the progress and limitations of the current 2D iPSC disease-modeling platform, as well as recent advancements in the development of human iPSC models that mimic in vivo tissues and organs at the three-dimensional (3D) level. Recent bioengineering approaches have begun to combine different 3D organoid types into a single '4D multi-organ system'. We summarize the advantages of this approach and speculate on the future role of 4D multi-organ systems in human disease modeling. © 2018. Published by The Company of Biologists Ltd.

  8. The draft genome sequence of the ferret (Mustela putorius furo) facilitates study of human respiratory disease.

    Science.gov (United States)

    Peng, Xinxia; Alföldi, Jessica; Gori, Kevin; Eisfeld, Amie J; Tyler, Scott R; Tisoncik-Go, Jennifer; Brawand, David; Law, G Lynn; Skunca, Nives; Hatta, Masato; Gasper, David J; Kelly, Sara M; Chang, Jean; Thomas, Matthew J; Johnson, Jeremy; Berlin, Aaron M; Lara, Marcia; Russell, Pamela; Swofford, Ross; Turner-Maier, Jason; Young, Sarah; Hourlier, Thibaut; Aken, Bronwen; Searle, Steve; Sun, Xingshen; Yi, Yaling; Suresh, M; Tumpey, Terrence M; Siepel, Adam; Wisely, Samantha M; Dessimoz, Christophe; Kawaoka, Yoshihiro; Birren, Bruce W; Lindblad-Toh, Kerstin; Di Palma, Federica; Engelhardt, John F; Palermo, Robert E; Katze, Michael G

    2014-12-01

    The domestic ferret (Mustela putorius furo) is an important animal model for multiple human respiratory diseases. It is considered the 'gold standard' for modeling human influenza virus infection and transmission. Here we describe the 2.41 Gb draft genome assembly of the domestic ferret, constituting 2.28 Gb of sequence plus gaps. We annotated 19,910 protein-coding genes on this assembly using RNA-seq data from 21 ferret tissues. We characterized the ferret host response to two influenza virus infections by RNA-seq analysis of 42 ferret samples from influenza time-course data and showed distinct signatures in ferret trachea and lung tissues specific to 1918 or 2009 human pandemic influenza virus infections. Using microarray data from 16 ferret samples reflecting cystic fibrosis disease progression, we showed that transcriptional changes in the CFTR-knockout ferret lung reflect pathways of early disease that cannot be readily studied in human infants with cystic fibrosis disease.

  9. Acute Myocardial Infarction and Pulmonary Diseases Result in Two Different Degradation Profiles of Elastin as Quantified by Two Novel ELISAs.

    Directory of Open Access Journals (Sweden)

    Helene Skjøt-Arkil

    Full Text Available Elastin is a signature protein of the arteries and lungs, thus it was hypothesized that elastin is subject to enzymatic degradation during cardiovascular and pulmonary diseases. The aim was to investigate if different fragments of the same protein entail different information associated to two different diseases and if these fragments have the potential of being diagnostic biomarkers.Monoclonal antibodies were raised against an identified fragment (the ELM-2 neoepitope generated at the amino acid position '552 in elastin by matrix metalloproteinase (MMP -9/-12. A newly identified ELM neoepitope was generated by the same proteases but at amino acid position '441. The distribution of ELM-2 and ELM, in human arterial plaques and fibrotic lung tissues were investigated by immunohistochemistry. A competitive ELISA for ELM-2 was developed. The clinical relevance of the ELM and ELM-2 ELISAs was evaluated in patients with acute myocardial infarction (AMI, no AMI, high coronary calcium, or low coronary calcium. The serological release of ELM-2 in patients with chronic obstructive pulmonary disease (COPD or idiopathic pulmonary fibrosis (IPF was compared to controls.ELM and ELM-2 neoepitopes were both localized in diseased carotid arteries and fibrotic lungs. In the cardiovascular cohort, ELM-2 levels were 66% higher in serum from AMI patients compared to patients with no AMI (p<0.01. Levels of ELM were not significantly increased in these patients and no correlation was observed between ELM-2 and ELM. ELM-2 was not elevated in the COPD and IPF patients and was not correlated to ELM. ELM was shown to be correlated with smoking habits (p<0.01.The ELM-2 neoepitope was related to AMI whereas the ELM neoepitope was related to pulmonary diseases. These results indicate that elastin neoepitopes generated by the same proteases but at different amino acid sites provide different tissue-related information depending on the disease in question.

  10. A naturally occurring variant of the human prion protein completely prevents prion disease.

    Science.gov (United States)

    Asante, Emmanuel A; Smidak, Michelle; Grimshaw, Andrew; Houghton, Richard; Tomlinson, Andrew; Jeelani, Asif; Jakubcova, Tatiana; Hamdan, Shyma; Richard-Londt, Angela; Linehan, Jacqueline M; Brandner, Sebastian; Alpers, Michael; Whitfield, Jerome; Mead, Simon; Wadsworth, Jonathan D F; Collinge, John

    2015-06-25

    Mammalian prions, transmissible agents causing lethal neurodegenerative diseases, are composed of assemblies of misfolded cellular prion protein (PrP). A novel PrP variant, G127V, was under positive evolutionary selection during the epidemic of kuru--an acquired prion disease epidemic of the Fore population in Papua New Guinea--and appeared to provide strong protection against disease in the heterozygous state. Here we have investigated the protective role of this variant and its interaction with the common, worldwide M129V PrP polymorphism. V127 was seen exclusively on a M129 PRNP allele. We demonstrate that transgenic mice expressing both variant and wild-type human PrP are completely resistant to both kuru and classical Creutzfeldt-Jakob disease (CJD) prions (which are closely similar) but can be infected with variant CJD prions, a human prion strain resulting from exposure to bovine spongiform encephalopathy prions to which the Fore were not exposed. Notably, mice expressing only PrP V127 were completely resistant to all prion strains, demonstrating a different molecular mechanism to M129V, which provides its relative protection against classical CJD and kuru in the heterozygous state. Indeed, this single amino acid substitution (G→V) at a residue invariant in vertebrate evolution is as protective as deletion of the protein. Further study in transgenic mice expressing different ratios of variant and wild-type PrP indicates that not only is PrP V127 completely refractory to prion conversion but acts as a potent dose-dependent inhibitor of wild-type prion propagation.

  11. Persistent human Borna disease virus infection modifies the acetylome of human oligodendroglia cells towards higher energy and transporter levels

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xia [Shanghai Key Laboratory of Forensic Medicine, Institute of Forensic Science, Ministry of Justice, Shanghai 200063 (China); Liu, Siwen [Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016 (China); Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016 (China); Bode, Liv [Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016 (China); Liu, Chengyu [Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016 (China); Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016 (China); Zhang, Liang [Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016 (China); Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016 (China); Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Wang, Xiao [Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016 (China); Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016 (China); Li, Dan [Department of Pathology, Faculty of Basic Medicine, Chongqing Medical University, Chongqing 400016 (China); Lei, Yang [Department of Internal Medicine, University-Town Hospital of Chongqing Medical University, Chongqing 400016 (China); Peng, Xiaojun [Jingjie PTM BioLab (Hangzhou) Co. Ltd, Hangzhou 310018 (China); Cheng, Zhongyi [Advanced Institute of Translational Medicine, Tongji University, Shanghai 200092 (China); and others

    2015-11-15

    Background: Borna disease virus (BDV) is a neurotropic RNA virus persistently infecting mammalian hosts including humans. Lysine acetylation (Kac) is a key protein post-translational modification (PTM). The unexpectedly broad regulatory scope of Kac let us to profile the entire acetylome upon BDV infection. Methods: The acetylome was profiled through stable isotope labeling for cell culture (SILAC)-based quantitative proteomics. The quantifiable proteome was annotated using bioinformatics. Results: We identified and quantified 791 Kac sites in 473 Kac proteins in human BDV Hu-H1-infected and non-infected oligodendroglial (OL) cells. Bioinformatic analysis revealed that BDV infection alters the acetylation of metabolic proteins, membrane-associated proteins and transmembrane transporter activity, and affects the acetylation of several lysine acetyltransferases (KAT). Conclusions: Upon BDV persistence the OL acetylome is manipulated towards higher energy and transporter levels necessary for shuttling BDV proteins to and from nuclear replication sites. - Highlights: • We used SILAC-based proteomics to analyze the acetylome of BDV infected OL cells. • We quantified 791Kac sites in 473 proteins. • Bioinformatic analysis revealed altered acetylation of metabolic proteins et al. • BDV manipulates the OL acetylome towards higher energy and transporter levels. • BDV infection is associated with enriched phosphate-associated metabolic processes.

  12. Persistent human Borna disease virus infection modifies the acetylome of human oligodendroglia cells towards higher energy and transporter levels

    International Nuclear Information System (INIS)

    Liu, Xia; Liu, Siwen; Bode, Liv; Liu, Chengyu; Zhang, Liang; Wang, Xiao; Li, Dan; Lei, Yang; Peng, Xiaojun; Cheng, Zhongyi

    2015-01-01

    Background: Borna disease virus (BDV) is a neurotropic RNA virus persistently infecting mammalian hosts including humans. Lysine acetylation (Kac) is a key protein post-translational modification (PTM). The unexpectedly broad regulatory scope of Kac let us to profile the entire acetylome upon BDV infection. Methods: The acetylome was profiled through stable isotope labeling for cell culture (SILAC)-based quantitative proteomics. The quantifiable proteome was annotated using bioinformatics. Results: We identified and quantified 791 Kac sites in 473 Kac proteins in human BDV Hu-H1-infected and non-infected oligodendroglial (OL) cells. Bioinformatic analysis revealed that BDV infection alters the acetylation of metabolic proteins, membrane-associated proteins and transmembrane transporter activity, and affects the acetylation of several lysine acetyltransferases (KAT). Conclusions: Upon BDV persistence the OL acetylome is manipulated towards higher energy and transporter levels necessary for shuttling BDV proteins to and from nuclear replication sites. - Highlights: • We used SILAC-based proteomics to analyze the acetylome of BDV infected OL cells. • We quantified 791Kac sites in 473 proteins. • Bioinformatic analysis revealed altered acetylation of metabolic proteins et al. • BDV manipulates the OL acetylome towards higher energy and transporter levels. • BDV infection is associated with enriched phosphate-associated metabolic processes.

  13. The potential usefulness of human leukocyte antigen typing for celiac disease screening: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Alicia Díaz-Redondo

    2015-07-01

    Full Text Available Background and aim: The presence of specific human leukocyte antigen-DQ2 and DQ8 seems to be necessary for celiac disease development, but the real contribution of its typing for screening is still uncertain. We aim to conduct a systematic review and meta-analysis of the diagnostic performance of human leukocyte antigen typing tests for celiac disease screening. Methods: Systematic review of published studies assessing accuracy of human leukocyte antigen DQ2 and DQ8 typing for the detection of celiac disease were selected. MEDLINE and EMBASE were searched from 1st January 2004 until 31st December 2013. Two independent researchers carried out selection and classification of studies, data extraction and analysis. Meta-analysis combining sensitivities, specificities and likelihood ratios of HLA-DQ2 and DQ8 for the diagnosis of celiac disease were carried out. Results: 6 studies including 1303 individuals were finally evaluated. Pooled sensitivity was 98% (95% confidence interval: 97-99. Overall specificity was 45% (95% confidence interval: 41-48. Regarding specificity, studies were heterogeneous and a subgroup analysis was done according to the type of population included. Overall negative likelihood ratio was 0.05 (0.03-0.09. Conclusions: Due to its great sensitivity and low negative likelihood ratio, human leukocyte antigen-DQ2/DQ8 typing would be an appropriate test for ruling out celiac disease in the general population suffering related symptoms, and even more in at risk population.

  14. Interstitial cells of Cajal in human gut and gastrointestinal disease

    DEFF Research Database (Denmark)

    Vanderwinden, J M; Rumessen, J J

    1999-01-01

    This paper reviews the distribution of interstitial cells of Cajal (ICC) in the human gastrointestinal (GI) tract, based on ultrastructural and immunohistochemical evidence. The distribution and morphology of ICC at each level of the normal GI tracts is addressed from the perspective of their fun......This paper reviews the distribution of interstitial cells of Cajal (ICC) in the human gastrointestinal (GI) tract, based on ultrastructural and immunohistochemical evidence. The distribution and morphology of ICC at each level of the normal GI tracts is addressed from the perspective...

  15. Evaluation of Human Adipose Tissue Stromal Heterogeneity in Metabolic Disease Using Single Cell RNA-Seq

    Science.gov (United States)

    2017-09-01

    AWARD NUMBER: W81XWH-15-1-0251 TITLE: “Evaluation of Human Adipose Tissue Stromal Heterogeneity in Metabolic Disease Using Single Cell RNA...Heterogeneity in Metabolic Disease Using Single- Cell RNA-Seq 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Linus Tzu-Yen...ABSTRACT We have developed a robust protocol to generate single cell transcriptional profiles from subcutaneous adipose tissue samples of both human

  16. Human Chagas Disease and Migration in the Context of Globalization: Some Particular Aspects

    Directory of Open Access Journals (Sweden)

    João Carlos Pinto Dias

    2013-01-01

    Full Text Available Human Chagas disease originated in Latin America, being spread around the world in relation with multiple bioecological, sociocultural, and political factors. The process of the disease production and dispersion is discussed, emphasizing the human migration and correlated aspects, in the context of globalization. Positive and negative consequences concern the future of this trypanosomiasis, mainly in terms of the ecologic and sociopolitical characteristics of the endemic and nonendemic countries.

  17. Soil, grain and water chemistry in relation to human selenium responsive diseases in Enshi District, China

    OpenAIRE

    Fordyce, F.M.; Zhang, Guangdi; Green, K.; Xinping, Liu

    2000-01-01

    Selenium deficiency (Keshan Disease) and toxicity diseases in humans occur within 20 km of each other in Enshi District in China and have been linked to environmental levels of Se. Low concentrations of Se are associated with Jurassic siltstones and sandstones, whereas high concentrations occur in areas underlain by Permian carbonaceous strata. Although these broad relationships between Se in the environment and the human population have been established previously, not all villages underlain...

  18. Diseases of Poverty and Lifestyle, Well-Being and Human Development

    OpenAIRE

    Singh, Ajai R.; Singh, Shakuntala A.

    2008-01-01

    The problems of the haves differ substantially from those of the have-nots. Individuals in developing societies have to fight mainly against infectious and communicable diseases, while in the developed world the battles are mainly against lifestyle diseases. Yet, at a very fundamental level, the problems are the same-the fight is against distress, disability, and premature death; against human exploitation and for human development and self-actualisation; against the callousness to critical c...

  19. Human methanogen diversity and incidence in healthy and diseased colonic groups using mcrA gene analysis

    Directory of Open Access Journals (Sweden)

    Scanlan Pauline D

    2008-05-01

    Full Text Available Abstract Background The incidence and diversity of human methanogens are insufficiently characterised in the gastrointestinal tract of both health and disease. A PCR and clone library methodology targeting the mcrA gene was adopted to facilitate the two-fold aim of surveying the relative incidence of methanogens in health and disease groups and also to provide an overview of methanogen diversity in the human gastrointestinal tract. Results DNA faecal extracts (207 in total from a group of healthy controls and five gastrointestinal disease groups were investigated. Colorectal cancer, polypectomised, irritable bowel syndrome and the control group had largely equivalent numbers of individuals positive for methanogens (range 45–50%. Methanogen incidence in the inflammatory bowel disease groups was reduced, 24% for ulcerative colitis and 30% for Crohn's disease. Four unique mcrA gene restriction fragment length polymorphism profiles were identified and bioinformatic analyses revealed that the majority of all sequences (94% retrieved from libraries were 100% identical to Methanobrevibacter smithii mcrA gene. In addition, mcrA gene sequences most closely related to Methanobrevibacter oralis and members of the order Methanosarcinales were also recovered. Conclusion The mcrA gene serves as a useful biomarker for methanogen detection in the human gut and the varying trends of methanogen incidence in the human gut could serve as important indicators of intestinal function. Although Methanobrevibacter smithii is the dominant methanogen in both the distal colon of individuals in health and disease, the diversity of methanogens is greater than previously reported. In conclusion, the low incidence of methanogens in Inflammatory Bowel Disease, the functionality of the methanogens and impact of methane production in addition to competitive interactions between methanogens and other microbial groups in the human gastrointestinal tract warrants further

  20. Vitamin D and clinical disease progression in HIV infection: results from the EuroSIDA study

    DEFF Research Database (Denmark)

    Viard, Jean-Paul; Souberbielle, Jean-Claude; Kirk, Ole

    2011-01-01

    BACKGROUND:: We examined the association between vitamin D [25(OH)D] level and disease progression in HIV infection. METHODS:: Within the EuroSIDA study, 2000 persons were randomly selected for 25(OH)D measurement in stored plasma samples closest to study entry. 25(OH)D results were stratified...

  1. Validation of celiac disease diagnoses recorded in the Danish National Patient Register using duodenal biopsies, celiac disease-specific antibodies, and human leukocyte-antigen genotypes

    DEFF Research Database (Denmark)

    Dydensborg Sander, Stine; Størdal, Ketil; Plato Hansen, Tine

    2016-01-01

    PURPOSE: The purpose of this study was to validate the celiac disease diagnoses recorded in the Danish National Patient Register. To validate the diagnoses, we used information on duodenal biopsies from a national register of pathology reports (the Patobank) and information on celiac disease......-specific antibodies and human leukocyte antigen (HLA) genotypes obtained from patient medical records. PATIENTS AND METHODS: We included all the children who were born from 1995 to 2012 and who were registered as having celiac disease in the Danish National Patient Register. We reviewed all the pathology reports...... on duodenal biopsies in the Patobank and the information in the medical records on celiac disease-specific antibodies (ie, anti-tissue transglutaminase 2 IgA and IgG, endomysial antibodies IgA, and anti-deamidated gliadin peptide IgG) and HLA genotypes. RESULTS: We identified 2,247 children who were...

  2. Sugars, obesity, and cardiovascular disease: results from recent randomized control trials.

    Science.gov (United States)

    Rippe, James M; Angelopoulos, Theodore J

    2016-11-01

    The relationship between sugar consumption and various health-related sequelas is controversial. Some investigators have argued that excessive sugar consumption is associated with increased risk of obesity, coronary heart disease, diabetes (T2D), metabolic syndrome, non-alcoholic fatty liver disease, and stimulation of reward pathways in the brain potentially causing excessive caloric consumption. These concerns have influenced organizations such as the World Health Organization, the Scientific Advisory Committee on Nutrition in England not to exceed 5 % of total energy and the Dietary Guidelines for Americans Advisory Committee 2015 to recommend upper limits of sugar consumption not to exceed 10 % of calories. Data from many randomized control trials (RCTs) do not support linkages between sugar consumption at normal levels within the human diet and various adverse metabolic and health-related effects. Fructose and glucose are typically consumed together in roughly equal proportions from high-fructose corn syrup (also known as isoglucose in Europe) or sucrose. The purpose of this review is to present data from recent RCTs and findings from recent systematic reviews and meta-analyses related to sugar consumption and its putative health effects. This review evaluates findings from recent randomized controlled trials, systematic reviews and meta-analyses into the relationship of sugar consumption and a range of health-related issues including energy-regulating hormones, obesity, cardiovascular disease, diabetes, and accumulation of liver fat and neurologic responses. Data from these sources do not support linkages between sugar consumption at normal levels within the human diet and various adverse metabolic and health-related effects.

  3. Kynurenine Pathway Metabolites in Humans: Disease and Healthy States

    Directory of Open Access Journals (Sweden)

    Yiquan Chen

    2009-01-01

    Full Text Available Tryptophan is an essential amino acid that can be metabolised through different pathways, a major route being the kynurenine pathway. The first enzyme of the pathway, indoleamine-2,3-dioxygenase, is strongly stimulated by inflammatory molecules, particularly interferon gamma. Thus, the kynurenine pathway is often systematically up-regulated when the immune response is activated. The biological significance is that 1 the depletion of tryptophan and generation of kynurenines play a key modulatory role in the immune response; and 2 some of the kynurenines, such as quinolinic acid, 3-hydroxykynurenine and kynurenic acid, are neuroactive. The kynurenine pathway has been demonstrated to be involved in many diseases and disorders, including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, AIDS dementia complex, malaria, cancer, depression and schizophrenia, where imbalances in tryptophan and kynurenines have been found. This review compiles most of these studies and provides an overview of how the kynurenine pathway might be contributing to disease development, and the concentrations of tryptophan and kynurenines in the serum, cerebrospinal fluid and brain tissues in control and patient subjects.

  4. Emerging human infectious diseases: anthroponoses, zoonoses, and sapronoses

    Czech Academy of Sciences Publication Activity Database

    Hubálek, Zdeněk

    2003-01-01

    Roč. 9, č. 3 (2003), s. 403-404 ISSN 1080-6040 R&D Projects: GA AV ČR KSK6005114 Keywords : zoonoses Subject RIV: FN - Epidemiology, Contagious Diseases ; Clinical Immunology Impact factor: 5.340, year: 2003 http://www.cdc.gov.ncidod/EID/vol9no3/02-0208-app.htm

  5. Effects of Forest Fragmentation on Human Risk of Lyme Disease

    Science.gov (United States)

    Percent forest-herbaceous edge repeatedly explained most of the variability in reported Lyme disease rates within a rural-to-urban study gradient across central Maryland and southeastern Pennsylvania. A one-percent increase in forest-herbaceous edge was associated with an increas...

  6. Positions of human dwellings affect few tropical diseases near ...

    African Journals Online (AJOL)

    user

    for the sandflies which is the vector of visceral leishmaniasis. It seems that the effect of microclimate was not on the considerations of villagers to build their dwellings as the very dense of date palms trees, vegetable farms and irrigation canals which are a determinant factors in the prevalence of diseases. Some dwellings ...

  7. The commensal microbiota and the development of human disease - an introduction.

    Science.gov (United States)

    Marsh, Philip D

    2015-01-01

    Humans have co-evolved with microorganisms, and both exist in a symbiotic or mutualistic relationship. We are colonised by a diverse, resident microbiota, which develop into structurally and functionally organised biofilms. The resident microorganisms gain a secure, warm, nutritious habitat from the host and, in return, contribute to the development of many important host functions. The resident microbiota of each habitat is natural and provides important benefits for the host including immunological priming, down-regulation of excessive pro-inflammatory responses, regulation of gastrointestinal and cardiovascular systems, and prevention of colonisation by exogenous microbes. The biological properties of each habitat determine which microorganisms can colonise and grow, and dictate which will be major or minor components of the resident microbiota of a site. This results in different surfaces having distinct but characteristic microbiotas. This relationship between the resident microbiota and the host is dynamic and, on occasions, this symbiotic relationship breaks down due to, for example, changes in lifestyle, immune status or following broad spectrum antibiotic therapy. This 'dysbiosis' can result in previously minor components of the microbiota out-competing the normally dominant and beneficial bacteria, thereby increasing the risk of disease. Such perturbations have been associated with a number of clinical disorders such as obesity, allergy, and a variety of inflammatory diseases, including periodontal diseases. A better understanding of the delicate balance between the host and its resident microbiota could lead to novel approaches to the promotion of health and the prevention of dysbiosis.

  8. The commensal microbiota and the development of human disease – an introduction

    Directory of Open Access Journals (Sweden)

    Philip D. Marsh

    2015-09-01

    Full Text Available Humans have co-evolved with microorganisms, and both exist in a symbiotic or mutualistic relationship. We are colonised by a diverse, resident microbiota, which develop into structurally and functionally organised biofilms. The resident microorganisms gain a secure, warm, nutritious habitat from the host and, in return, contribute to the development of many important host functions. The resident microbiota of each habitat is natural and provides important benefits for the host including immunological priming, down-regulation of excessive pro-inflammatory responses, regulation of gastrointestinal and cardiovascular systems, and prevention of colonisation by exogenous microbes. The biological properties of each habitat determine which microorganisms can colonise and grow, and dictate which will be major or minor components of the resident microbiota of a site. This results in different surfaces having distinct but characteristic microbiotas. This relationship between the resident microbiota and the host is dynamic and, on occasions, this symbiotic relationship breaks down due to, for example, changes in lifestyle, immune status or following broad spectrum antibiotic therapy. This ‘dysbiosis’ can result in previously minor components of the microbiota out-competing the normally dominant and beneficial bacteria, thereby increasing the risk of disease. Such perturbations have been associated with a number of clinical disorders such as obesity, allergy, and a variety of inflammatory diseases, including periodontal diseases. A better understanding of the delicate balance between the host and its resident microbiota could lead to novel approaches to the promotion of health and the prevention of dysbiosis.

  9. 111Indium-labelled leucocyte scintigraphy in the diagnosis of inflammatory disease - first results

    International Nuclear Information System (INIS)

    Rovekamp, M.H.; Hardeman, M.R.; Schoot, J.B. van der; Belfer, A.J.

    1981-01-01

    In 61 patients, 66 scans were performed with 111 In-labelled autologous leucocytes to evaluate this method in the diagnosis of inflammatory disease. All scintigraphic results were compared with clinical, operative or postmortem findings. In the first 20 examinations in 19 patients, 2 scintigrams were true positive, 9 true negative and none false positive, whereas 9 scintigrams had to be considered as false negative. These false negative results were probably due to loss of viability of the labelled cells. A modified labelling technique, in which a much lower concentration of oxine was used, was employed for a further 46 examinations in 42 patients. Twenty-four scintigrams were true positive and 22 true negative, while no false positive or false negative results were observed. These results suggest that this modified technique is useful in the diagnosis of inflammatory disease. (author)

  10. Teaching Methods in Nutrition: Free Radicals, Antioxidants, and Human Disease.

    Science.gov (United States)

    Janowiak, John J.

    This article presents a teaching methodology for free radical theory and discusses the role of antioxidants in human health. Free radicals are a normal byproduct of respiration, which allows the body to use oxygen, liberate energy, and dispose of harmful substances. The body's antioxidants and nutritional antioxidants quench most of the free…

  11. Integrated Human and Animal Disease Control for Tanzanian ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    The research focuses on two agro-ecological zones of the cattle corridor in Tanzania - Ngorongoro and Kibaha/Kilosa districts - and will be led by a regional scientific network, the ... They will look at interactions between human and animal health, environmental change, gender, and other socio-economic conditions.

  12. Human rabies: Still a neglected preventable disease in Nigeria | Eke ...

    African Journals Online (AJOL)

    Background/Objectives: Adequate surveillance and monitoring of dog bite incidents are veritable tools in the determination of the epidemiology of human rabies infections. There is a paucity of data with regards to rabies in Nigeria. Hence, this study was aimed at describing the pattern and outcomes of dog bites and rabies ...

  13. Are Serum Vitamin D Levels Associated With Dry Eye Disease? Results From the Study Group for Environmental Eye Disease

    Directory of Open Access Journals (Sweden)

    Da-Hye Jeon

    2017-11-01

    Full Text Available Objectives Dry eye disease (DED is an increasingly important public health problem in Korea. Previous studies conducted in Korea have reported inconsistent results regarding the protective effects of vitamin D on DED, and these discrepancies may be related to the relatively simple questionnaire that has been used. Thus, we evaluated the association of serum vitamin D levels with DED using the ocular surface disease index (OSDI. Methods The present study evaluated data from participants in the Study Group for Environmental Eye Disease (2014-2015. This group included data from 752 participants, and data from 740 participants (253 men and 487 women were analyzed in the present study. DED severity was evaluated using the OSDI. Results Higher serum vitamin D levels were associated with a non-significantly reduced risk of DED in the crude analysis (odds ratio [OR], 0.991; 95% confidence interval [CI], 0.971 to 1.011 and in the adjusted analysis (OR, 0.988; 95% CI, 0.966 to 1.010. In the crude analysis of no/mild DED vs. moderate/severe DED, men exhibited a decreased risk with increasing serum vitamin D levels (OR, 0.999; 95% CI, 0.950 to 1.051, while women exhibited an increased risk (OR, 1.003; 95% CI, 0.979 to 1.027. In these analyses, we found no significant associations. Conclusions The findings of the present study support previous reports that serum vitamin D levels are not associated with DED.

  14. Evaluation of Potential Infectivity of Alzheimer and Parkinson Disease Proteins in Recipients of Cadaver-Derived Human Growth Hormone

    Science.gov (United States)

    Irwin, David J.; Abrams, Joseph Y.; Schonberger, Lawrence B.; Leschek, Ellen Werber; Mills, James L.; Lee, Virginia M.-Y.; Trojanowski, John Q.

    2013-01-01

    Importance Growing evidence of cell-to-cell transmission of neurodegenerative disease (ND)–associated proteins (NDAPs) (ie, tau, Aβ, and α-synuclein) suggests possible similarities in the infectious prion protein (PrPsc) in spongiform encephalopathies. There are limited data on the potential human-to-human transmission of NDAPs associated with Alzheimer disease (AD) and other non-PrPsc ND. Objective To examine evidence for human-to-human transmission of AD, Parkinson disease (PD), and related NDAPs in cadaveric human growth hormone (c-hGH) recipients. Design We conducted a detailed immunohistochemical analysis of pathological NDAPs other than PrPsc in human pituitary glands. We also searched for ND in recipients of pituitary-derived c-hGH by reviewing the National Hormone and Pituitary Program (NHPP) cohort database and medical literature. Setting University-based academic center and agencies of the US Department of Health and Human Services. Participants Thirty-four routine autopsy subjects (10 non-ND controls and 24 patients with ND) and a US cohort of c-hGH recipients in the NHPP. Main Outcome Measures Detectable NDAPs in human pituitary sections and death certificate reports of non-PrPsc ND in the NHPP database. Results We found mild amounts of pathological tau, Aβ, and α-synuclein deposits in the adeno/neurohypophysis of patients with ND and control patients. No cases of AD or PD were identified, and 3 deaths attributed to amyotrophic lateral sclerosis (ALS) were found among US NHPP c-hGH recipients, including 2 of the 796 decedents in the originally confirmed NHPP c-hGH cohort database. Conclusions and Relevance Despite the likely frequent exposure of c-hGH recipients to NDAPs, and their markedly elevated risk of PrPsc-related disease, this population of NHPP c-hGH recipients does not appear to be at increased risk of AD or PD. We discovered 3 ALS cases of unclear significance among US c-hGH recipients despite the absence of pathological deposits of ALS

  15. Gender, body mass index and rheumatoid arthritis disease activity: results from the QUEST-RA Study.

    Science.gov (United States)

    Jawaheer, D; Olsen, J; Lahiff, M; Forsberg, S; Lähteenmäki, J; da Silveira, I G; Rocha, F A; Magalhães Laurindo, I M; Henrique da Mota, L M; Drosos, A A; Murphy, E; Sheehy, C; Quirke, E; Cutolo, M; Rexhepi, S; Dadoniene, J; Verstappen, S M M; Sokka, T

    2010-01-01

    To investigate whether body mass index (BMI), as a proxy for body fat, influences rheumatoid arthritis (RA) disease activity in a gender-specific manner. Consecutive patients with RA were enrolled from 25 countries into the QUEST-RA program between 2005 and 2008. Clinical and demographic data were collected by treating rheumatologists and by patient self-report. Distributions of Disease Activity Scores (DAS28), BMI, age, and disease duration were assessed for each country and for the entire dataset; mean values between genders were compared using Student's t-tests. An association between BMI and DAS28 was investigated using linear regression, adjusting for age, disease duration and country. A total of 5,161 RA patients (4,082 women and 1,079 men) were included in the analyses. Overall, women were younger, had longer disease duration, and higher DAS28 scores than men, but BMI was similar between genders. The mean DAS28 scores increased with increasing BMI from normal to overweight and obese, among women, whereas the opposite trend was observed among men. Regression results showed BMI (continuous or categorical) to be associated with DAS28. Compared to the normal BMI range, being obese was associated with a larger difference in mean DAS28 (0.23, 95% CI: 0.11, 0.34) than being overweight (0.12, 95% CI: 0.03, 0.21); being underweight was not associated with disease activity. These associations were more pronounced among women, and were not explained by any single component of the DAS28. BMI appears to be associated with RA disease activity in women, but not in men.

  16. Frequency and clinical relevance of human bocavirus infection in acute exacerbations of chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Felix C Ringshausen

    2009-02-01

    Full Text Available Felix C Ringshausen1, Ai-Yui M Tan1, Tobias Allander2, Irmgard Borg1, Umut Arinir1, Juliane Kronsbein1, Barbara M Hauptmeier1, Gerhard Schultze-Werninghaus1, Gernot Rohde11Clinical Research Group “Significance of viral infections in chronic respiratory diseases of children and adults,” University Hospital Bergmannsheil, Department of Internal Medicine III–Pneumology, Allergology and Sleep Medicine, Bochum, Germany; 2Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, and Department of Clinical Microbiology, Karolinska University Hospital, Stockholm, SwedenObjective: Human bocavirus (HBoV is a recently discovered parvovirus associated with acute respiratory tract infections in children. The objective of the present study was to determine the frequency and clinical relevance of HBoV infection in adult patients with acute exacerbation of chronic obstructive pulmonary disease (AE-COPD.Methods: We retrospectively tested 212 COPD patients, 141 (66.5% with AE-COPD and 71 (33.5% with stable disease, of whom nasal lavage and induced sputum had been obtained for the presence of HBoV deoxyribonucleic acid (DNA. The specificity of positive polymerase chain reaction results was confirmed by sequencing.Results: Two hundred two of 212 patients for whom PCR results were available both for nasal lavage and induced sputum samples were eligible for data analysis. HBoV DNA was detected in three patients (1.5%. Of those, only one patient had AE-COPD. Thus, the frequency of HBoV infection demonstrated to be low in both AE-COPD (0.8% and stable COPD (2.9%. HBoV was found in two sputum and one nasal lavage sample in different patients, respectively. Sequencing revealed >99% sequence identity with the reference strain.Conclusion: HBoV detection was infrequent. Since we detected HBoV in both upper and lower respiratory tract specimens and in AE-COPD as well as stable disease, a major role of HBoV infection in adults with AE-COPD is unlikely

  17. North Atlantic weather oscillation and human infectious diseases in the Czech Republic, 1951-2003

    Czech Academy of Sciences Publication Activity Database

    Hubálek, Zdeněk

    2005-01-01

    Roč. 20, č. 3 (2005), s. 263-270 ISSN 0393-2990 R&D Projects: GA ČR(CZ) GA206/03/0726 Institutional research plan: CEZ:AV0Z60930519 Keywords : climate change * cluster analysis * human infectious diseases Subject RIV: FN - Epidemiology, Contagious Diseases ; Clinical Immunology Impact factor: 1.361, year: 2005

  18. Barcoding heat shock proteins to human diseases : looking beyond the heat shock response

    NARCIS (Netherlands)

    Kakkar, Vaishali; Meister-Broekema, Melanie; Minoia, Melania; Carra, Serena; Kampinga, Harm H.

    There are numerous human diseases that are associated with protein misfolding and the formation of toxic protein aggregates. Activating the heat shock response (HSR) - and thus generally restoring the disturbed protein homeostasis associated with such diseases - has often been suggested as a

  19. Modelling the influence of human behaviour on the spread of infectious diseases: a review.

    Science.gov (United States)

    Funk, Sebastian; Salathé, Marcel; Jansen, Vincent A A

    2010-09-06

    Human behaviour plays an important role in the spread of infectious diseases, and understanding the influence of behaviour on the spread of diseases can be key to improving control efforts. While behavioural responses to the spread of a disease have often been reported anecdotally, there has been relatively little systematic investigation into how behavioural changes can affect disease dynamics. Mathematical models for the spread of infectious diseases are an important tool for investigating and quantifying such effects, not least because the spread of a disease among humans is not amenable to direct experimental study. Here, we review recent efforts to incorporate human behaviour into disease models, and propose that such models can be broadly classified according to the type and source of information which individuals are assumed to base their behaviour on, and according to the assumed effects of such behaviour. We highlight recent advances as well as gaps in our understanding of the interplay between infectious disease dynamics and human behaviour, and suggest what kind of data taking efforts would be helpful in filling these gaps.

  20. Human capital financial results of an enterprise – research on the best employers in poland

    Directory of Open Access Journals (Sweden)

    Anna Bagieńska

    2014-12-01

    Full Text Available In a modern economy human capital is the basic resource, directly influencing production and the financial results of the enterprise. Employee involvement determines their better job performance and the achievement of better financial results. The analysed companies – winners of the contest named Best Employer in Poland demonstrated increasing effectiveness and profitability of their activities which was shown by the calculated coefficients. The human capital coefficients based on the data from financial reports do not reflect the proper analysis of changes in return on investment and human capital productivity dependent on the level of employee involvement. A proper evaluation should concern not only financial results such as sales revenues, but also non-financial results.

  1. Validation and results of a questionnaire for functional bowel disease in out-patients

    Directory of Open Access Journals (Sweden)

    Skordilis Panagiotis

    2002-05-01

    Full Text Available Abstract Background The aim was to evaluate and validate a bowel disease questionnaire in patients attending an out-patient gastroenterology clinic in Greece. Methods This was a prospective study. Diagnosis was based on detailed clinical and laboratory evaluation. The questionnaire was tested on a pilot group of patients. Interviewer-administration technique was used. One-hundred-and-forty consecutive patients attending the out-patient clinic for the first time and fifty healthy controls selected randomly participated in the study. Reliability (kappa statistics and validity of the questionnaire were tested. We used logistic regression models and binary recursive partitioning for assessing distinguishing ability among irritable bowel syndrome (IBS, functional dyspepsia and organic disease patients. Results Mean time for questionnaire completion was 18 min. In test-retest procedure a good agreement was obtained (kappa statistics 0.82. There were 55 patients diagnosed as having IBS, 18 with functional dyspepsia (Rome I criteria, 38 with organic disease. Location of pain was a significant distinguishing factor, patients with functional dyspepsia having no lower abdominal pain (p Conclusions This questionnaire for functional bowel disease is a valid and reliable instrument that can distinguish satisfactorily between organic and functional disease in an out-patient setting.

  2. Bilateral Testicular Tumors Resulting in Recurrent Cushing Disease After Bilateral Adrenalectomy.

    Science.gov (United States)

    Puar, Troy; Engels, Manon; van Herwaarden, Antonius E; Sweep, Fred C G J; Hulsbergen-van de Kaa, Christina; Kamphuis-van Ulzen, Karin; Chortis, Vasileios; Arlt, Wiebke; Stikkelbroeck, Nike; Claahsen-van der Grinten, Hedi L; Hermus, Ad R M M

    2017-02-01

    Recurrence of hypercortisolism in patients after bilateral adrenalectomy for Cushing disease is extremely rare. We present a 27-year-old man who previously underwent bilateral adrenalectomy for Cushing disease with complete clinical resolution. Cushingoid features recurred 12 years later, with bilateral testicular enlargement. Hormonal tests confirmed adrenocorticotropic hormone (ACTH)-dependent Cushing disease. Surgical resection of the testicular tumors led to clinical and biochemical remission. Gene expression analysis of the tumor tissue by quantitative polymerase chain reaction showed high expression of all key steroidogenic enzymes. Adrenocortical-specific genes were 5.1 × 105 (CYP11B1), 1.8 × 102 (CYP11B2), and 6.3 × 104 (MC2R) times higher than nonsteroidogenic fibroblast control. This correlated with urine steroid metabolome profiling showing 2 fivefold increases in the excretion of the metabolites of 11-deoxycortisol, 21-deoxycortisol, and total glucocorticoids. Leydig-specific genes were 4.3 × 101 (LHCGR) and 9.3 × 100 (HSD17B3) times higher than control, and urinary steroid profiling showed twofold increased excretion of the major androgen metabolites androsterone and etiocholanolone. These distinctly increased steroid metabolites were suppressed by dexamethasone but unresponsive to human chorionic gonadotropin stimulation, supporting the role of ACTH, but not luteinizing hormone, in regulating tumor-specific steroid excess. We report bilateral testicular tumors occurring in a patient with recurrent Cushing disease 12 years after bilateral adrenalectomy. Using mRNA expression analysis and steroid metabolome profiling, the tumors demonstrated both adrenocortical and gonadal steroidogenic properties, similar to testicular adrenal rest tumors found in patients with congenital adrenal hyperplasia, suggesting the presence of pluripotent cells even in patients without congenital adrenal hyperplasia. Copyright © 2017 by the Endocrine Society

  3. Global and disease-associated genetic variation in the human Fanconi anemia gene family.

    Science.gov (United States)

    Rogers, Kai J; Fu, Wenqing; Akey, Joshua M; Monnat, Raymond J

    2014-12-20

    Fanconi anemia (FA) is a human recessive genetic disease resulting from inactivating mutations in any of 16 FANC (Fanconi) genes. Individuals with FA are at high risk of developmental abnormalities, early bone marrow failure and leukemia. These are followed in the second and subsequent decades by a very high risk of carcinomas of the head and neck and anogenital region, and a small continuing risk of leukemia. In order to characterize base pair-level disease-associated (DA) and population genetic variation in FANC genes and the segregation of this variation in the human population, we identified 2948 unique FANC gene variants including 493 FA DA variants across 57,240 potential base pair variation sites in the 16 FANC genes. We then analyzed the segregation of this variation in the 7578 subjects included in the Exome Sequencing Project (ESP) and the 1000 Genomes Project (1KGP). There was a remarkably high frequency of FA DA variants in ESP/1KGP subjects: at least 1 FA DA variant was identified in 78.5% (5950 of 7578) individuals included in these two studies. Six widely used functional prediction algorithms correctly identified only a third of the known, DA FANC missense variants. We also identified FA DA variants that may be good candidates for different types of mutation-specific therapies. Our results demonstrate the power of direct DNA sequencing to detect, estimate the frequency of and follow the segregation of deleterious genetic variation in human populations. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. Depletion of the ozone layer: consequences for non-infectious human diseases

    International Nuclear Information System (INIS)

    Bentham, G.

    1993-01-01

    Stratospheric ozone depletion threatens to increase exposure to ultraviolet (UV) radiation which is known to be a factor in a number of diseases. There is little doubt that cumulative exposure to UV radiation is important in the aetiology of non-melanoma skin cancers. Evidence is also strong for a link with cutaneous malignant melanoma, although here it appears to be intermittent intense exposure that is most damaging. More controversial is the view that exposure to solar radiation is a significant factor in ocular damage, particularly in the formation of cataracts. Earlier studies pointing to such an effect have been criticized and alternative aetiological hypotheses have been proposed. However, other studies do show an effect of UV exposure on cortical cataract. Concern is also growing that UV may be capable of activating viruses and have immunological effects that might exacerbate infectious disease. Very worrying is the possibility that UV exposure can activate the human immunodeficiency virus which might accelerate the onset AIDS. Any such health effects that have been observed in human populations are the result of exposure to existing, naturally occurring levels of UV radiation. There is, therefore, great concern about the possible exacerbation of these impacts as a result of increased exposure to UV radiation associated with stratospheric ozone depletion. However, any assessment of the nature and scale of such impacts on human health has to deal with several major problems and these are the focus of this paper. There are uncertainties about recent trends in stratospheric ozone and problems in the prediction of future changes

  5. DNA replication stress: from molecular mechanisms to human disease.

    Science.gov (United States)

    Muñoz, Sergio; Méndez, Juan

    2017-02-01

    The genome of proliferating cells must be precisely duplicated in each cell division cycle. Chromosomal replication entails risks such as the possibility of introducing breaks and/or mutations in the genome. Hence, DNA replication requires the coordinated action of multiple proteins and regulatory factors, whose deregulation causes severe developmental diseases and predisposes to cancer. In recent years, the concept of "replicative stress" (RS) has attracted much attention as it impinges directly on genomic stability and offers a promising new avenue to design anticancer therapies. In this review, we summarize recent progress in three areas: (1) endogenous and exogenous factors that contribute to RS, (2) molecular mechanisms that mediate the cellular responses to RS, and (3) the large list of diseases that are directly or indirectly linked to RS.

  6. Human Genetic Variation and Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Sun Ju Chung

    2010-05-01

    Full Text Available Parkinson’s disease (PD is a chronic neurodegenerative disorder with multifactorial etiology. In the past decade, the genetic causes of monogenic forms of familial PD have been defined. However, the etiology and pathogenesis of the majority of sporadic PD cases that occur in outbred populations have yet to be clarified. The recent development of resources such as the International HapMap Project and technological advances in high-throughput genotyping have provided new basis for genetic association studies of common complex diseases, including PD. A new generation of genome-wide association studies will soon offer a potentially powerful approach for mapping causal genes and will likely change treatment and alter our perception of the genetic determinants of PD. However, the execution and analysis of such studies will require great care.

  7. Application of high-throughput sequencing in understanding human oral microbiome related with health and disease

    OpenAIRE

    Chen, Hui; Jiang, Wen

    2014-01-01

    The oral microbiome is one of most diversity habitat in the human body and they are closely related with oral health and disease. As the technique developing,, high throughput sequencing has become a popular approach applied for oral microbial analysis. Oral bacterial profiles have been studied to explore the relationship between microbial diversity and oral diseases such as caries and periodontal disease. This review describes the application of high-throughput sequencing for characterizati...

  8. The dopamine transporter: role in neurotoxicity and human disease

    International Nuclear Information System (INIS)

    Bannon, Michael J.

    2005-01-01

    The dopamine transporter (DAT) is a plasma membrane transport protein expressed exclusively within a small subset of CNS neurons. It plays a crucial role in controlling dopamine-mediated neurotransmission and a number of associated behaviors. This review focuses on recent data elucidating the role of the dopamine transporter in neurotoxicity and a number of CNS disorders, including Parkinson disease, drug abuse, and attention deficit hyperactivity disorder (ADHD)

  9. The dopamine transporter: role in neurotoxicity and human disease

    Energy Technology Data Exchange (ETDEWEB)

    Bannon, Michael J [Department of Psychiatry and Behavioral Neuroscience, Pharmacology, and Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201 (United States)

    2005-05-01

    The dopamine transporter (DAT) is a plasma membrane transport protein expressed exclusively within a small subset of CNS neurons. It plays a crucial role in controlling dopamine-mediated neurotransmission and a number of associated behaviors. This review focuses on recent data elucidating the role of the dopamine transporter in neurotoxicity and a number of CNS disorders, including Parkinson disease, drug abuse, and attention deficit hyperactivity disorder (ADHD)

  10. Adalimumab in the induction of Crohn's disease remission: results of a Brazilian multicenter case series

    Directory of Open Access Journals (Sweden)

    Paulo Gustavo Kotze

    2011-09-01

    Full Text Available Introduction: Adalimumab (ADA is a subcutaneous fully-human anti-TNF antibody which has a significant role in the management of Crohn's disease (CD. Its efficacy has been demonstrated in several clinical trials. The main objective of this study was to evaluate the role of ADA in the induction of clinical remission in a Brazilian series of CD cases. Method: A retrospective analysis of CD patients treated with ADA was performed in three Brazilian inflammatory bowel diseases (IBD reference centers. The following characteristics were analyzed: gender, age, indication to ADA treatment, type of response, previous exposure to infliximab (IFX, concomitant use of immunomodulators and adverse events, among others. Results: 54 patients (29 females were included in this series, with mean age of 36.72 years (ranging from 15 to 62 years. After induction regimen, 26 patients (48.14% were in clinical remission, 26 (48.14% had partial response, and 2 (3.72% were primary non-responders. After a mean follow-up of 9.83 (2 to 28 months, 17 patients (31.48% presented adverse events. The most common event was pain on the injection site (7 patients - 12.96%. Conclusions: ADA was effective to induce CD remission in this Brazilian case series. The remission and response rates were similar to the literature, as well as the safety profile of this drug.Introdução: O adalimumabe (ADA é um anticorpo anti-fator de necrose tumoral alfa totalmente humano, de uso subcutâneo, com eficácia e perfil de segurança bem determinados na doença de Crohn (DC. O objetivo principal deste estudo foi determinar o papel do ADA na indução da remissão na DC, em uma série brasileira de casos. Método: Estudo retrospectivo, realizado em três centros de referência em doenças inflamatórias intestinais, com usuários do ADA para tratamento da DC. As variáveis analisadas foram: idade, sexo, indicação do tratamento, forma de apresentação da doença, tipo de resposta (total, parcial

  11. Human genetics of infectious diseases: Unique insights into immunological redundancy.

    Science.gov (United States)

    Casanova, Jean-Laurent; Abel, Laurent

    2018-04-01

    For almost any given human-tropic virus, bacterium, fungus, or parasite, the clinical outcome of primary infection is enormously variable, ranging from asymptomatic to lethal infection. This variability has long been thought to be largely determined by the germline genetics of the human host, and this is increasingly being demonstrated to be the case. The number and diversity of known inborn errors of immunity is continually increasing, and we focus here on autosomal and X-linked recessive traits underlying complete deficiencies of the encoded protein. Schematically, four types of infectious phenotype have been observed in individuals with such deficiencies, each providing information about the redundancy of the corresponding human gene, in terms of host defense in natural conditions. The lack of a protein can confer vulnerability to a broad range of microbes in most, if not all patients, through the disruption of a key immunological component. In such cases, the gene concerned is of low redundancy. However, the lack of a protein may also confer vulnerability to a narrow range of microbes, sometimes a single pathogen, and not necessarily in all patients. In such cases, the gene concerned is highly redundant. Conversely, the deficiency may be apparently neutral, conferring no detectable predisposition to infection in any individual. In such cases, the gene concerned is completely redundant. Finally, the lack of a protein may, paradoxically, be advantageous to the host, conferring resistance to one or more infections. In such cases, the gene is considered to display beneficial redundancy. These findings reflect the current state of evolution of humans and microbes, and should not be considered predictive of redundancy, or of a lack of redundancy, in the distant future. Nevertheless, these observations are of potential interest to present-day biologists testing immunological hypotheses experimentally and physicians managing patients with immunological or infectious

  12. Selection pressure on human STR loci and its relevance in repeat expansion disease

    KAUST Repository

    Shimada, Makoto K.

    2016-06-11

    Short Tandem Repeats (STRs) comprise repeats of one to several base pairs. Because of the high mutability due to strand slippage during DNA synthesis, rapid evolutionary change in the number of repeating units directly shapes the range of repeat-number variation according to selection pressure. However, the remaining questions include: Why are STRs causing repeat expansion diseases maintained in the human population; and why are these limited to neurodegenerative diseases? By evaluating the genome-wide selection pressure on STRs using the database we constructed, we identified two different patterns of relationship in repeat-number polymorphisms between DNA and amino-acid sequences, although both patterns are evolutionary consequences of avoiding the formation of harmful long STRs. First, a mixture of degenerate codons is represented in poly-proline (poly-P) repeats. Second, long poly-glutamine (poly-Q) repeats are favored at the protein level; however, at the DNA level, STRs encoding long poly-Qs are frequently divided by synonymous SNPs. Furthermore, significant enrichments of apoptosis and neurodevelopment were biological processes found specifically in genes encoding poly-Qs with repeat polymorphism. This suggests the existence of a specific molecular function for polymorphic and/or long poly-Q stretches. Given that the poly-Qs causing expansion diseases were longer than other poly-Qs, even in healthy subjects, our results indicate that the evolutionary benefits of long and/or polymorphic poly-Q stretches outweigh the risks of long CAG repeats predisposing to pathological hyper-expansions. Molecular pathways in neurodevelopment requiring long and polymorphic poly-Q stretches may provide a clue to understanding why poly-Q expansion diseases are limited to neurodegenerative diseases. © 2016, Springer-Verlag Berlin Heidelberg.

  13. Preventive and Therapeutic Role of Functional Ingredients of Barley Grass for Chronic Diseases in Human Beings

    Directory of Open Access Journals (Sweden)

    Yawen Zeng

    2018-01-01

    Full Text Available Barley grass powder is the best functional food that provides nutrition and eliminates toxins from cells in human beings; however, its functional ingredients have played an important role as health benefit. In order to better cognize the preventive and therapeutic role of barley grass for chronic diseases, we carried out the systematic strategies for functional ingredients of barley grass, based on the comprehensive databases, especially the PubMed, Baidu, ISI Web of Science, and CNKI, between 2008 and 2017. Barley grass is rich in functional ingredients, such as gamma-aminobutyric acid (GABA, flavonoids, saponarin, lutonarin, superoxide dismutase (SOD, K, Ca, Se, tryptophan, chlorophyll, vitamins (A, B1, C, and E, dietary fiber, polysaccharide, alkaloid, metallothioneins, and polyphenols. Barley grass promotes sleep; has antidiabetic effect; regulates blood pressure; enhances immunity; protects liver; has anti-acne/detoxifying and antidepressant effects; improves gastrointestinal function; has anticancer, anti-inflammatory, antioxidant, hypolipidemic, and antigout effects; reduces hyperuricemia; prevents hypoxia, cardiovascular diseases, fatigue, and constipation; alleviates atopic dermatitis; is a calcium supplement; improves cognition; and so on. These results support that barley grass may be one of the best functional foods for preventive chronic diseases and the best raw material of modern diet structure in promoting the development of large health industry and further reveal that GABA, flavonoids, SOD, K-Ca, vitamins, and tryptophan mechanism of barley grass have preventive and therapeutic role for chronic diseases. This paper can be used as a scientific evidence for developing functional foods and novel drugs for barley grass for preventive chronic diseases.

  14. 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.

  15. 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.

  16. Controversial results of therapy with mesenchymal stem cells in the acute phase of canine distemper disease.

    Science.gov (United States)

    Pinheiro, A O; Cardoso, M T; Vidane, A S; Casals, J B; Passarelli, D; Alencar, A L F; Sousa, R L M; Fantinato-Neto, P; Oliveira, V C; Lara, V M; Ambrósio, C E

    2016-05-23

    Distemper disease is an infectious disease reported in several species of domestic and wild carnivores. The high mortality rate of animals infected with canine distemper virus (CDV) treated with currently available therapies has driven the study of new efficacious treatments. Mesenchymal stem cell (MSC)-based therapy is a promising therapeutic option for many degenerative, hereditary, and inflammatory diseases. Therefore, the aim of this study was to characterize stem cells derived from the canine fetal olfactory epithelium and to assess the systemic response of animals infected with CDV to symptomatic therapy and treatment with MSCs. Eight domestic mongrel dogs (N = 8) were divided into two groups: support group (SG) (N = 5) and support group + cell therapy (SGCT) (N = 3), which were monitored over 15 days. Blood samples were collected on days 0, 6, 9, 12, and 15 to assess blood count and serum biochemistry (urea, creatinine, alanine transferase, alkaline phosphatase, gamma-glutamyl transferase, total protein, albumin, and globulin), and urine samples were obtained on days 0 and 15 for urinary evaluation (urine I). The results showed a high mortality rate (SG = 4 and SGCT = 2), providing inadequate data on the clinical course of CDV infection. MSC therapy resulted in no significant improvement when administered during the acute phase of canine distemper disease, and a prevalence of animals with high mortality rate was found in both groups due to the severity of symptoms.

  17. [Results of hematopoietic stem cell transplantation in hemoglobinopathies: thalassemia major and sickle cell disease].

    Science.gov (United States)

    Hladun, R; Elorza, I; Olivé, T; Dapena, J L; Llort, A; Sánchez de Toledo, J; Díaz de Heredia, C

    2013-08-01

    The prevalence of hemoglobinopathies in Spain is increasing as a result of immigration. Thalassemia major presents with chronic hemolytic anemia that requires regular red blood cell transfusions within the first year of life. Patients with sickle cell disease suffer from chronic anemia, vasculopathy and progressive damage in almost any organ. There is decreased life expectancy in both conditions. Allogeneic hematopoietic stem cell transplantation represents the only potentially curative option. Seventeen patients (fourteen thalassemia major, and three sickle cell disease) underwent allogeneic hematopoietic stem cell transplantations. In the thalassemia group, nine donors were HLA-geno-identical siblings, two were partially matched related donors (one HLA allele mismatch), and three unrelated donors. All three patients with sickle cell disease were transplanted from HLA-geno-identical siblings. The source of stem cells was bone marrow in sixteen cases. Median patient age at transplant was six years (range: 1-16) in the thalassemia group, and twelve years (range: 8-15) in the sickle cell disease group. The graft was successful in all patients. Secondary graft rejection was observed in two thalassemia patients rendering them dependent on blood transfusions. Complete chimerism was observed in thirteen patients and, although mixed chimerism occurred in two, with all of them showing normal hemoglobin levels after transplantation and not requiring further transfusion support. Patients affected by sickle cell disease did not present with new vaso-occlusive crises, and stabilization of pulmonary and neurological function was observed. Chronic graft-versus-host disease was detected in three patients affected by thalassemia, and hypogonadotrophic hypogonadism in five patients. We conclude that for thalassemia major and sickle cell disease, allogenic hematopoietic stem cell transplantation from HLA-geno-identical siblings offers a high probability of complication-free survival

  18. Climate teleconnections and recent patterns of human and animal disease outbreaks.

    Directory of Open Access Journals (Sweden)

    Assaf Anyamba

    2012-01-01

    that chikungunya outbreaks occurred under conditions of anomalously high temperatures and drought over Eastern Africa. However, in Southeast Asia, chikungunya outbreaks were negatively correlated (p<0.05 with drought conditions, but positively correlated with warmer-than-normal temperatures and rainfall.Extremes in climate conditions forced by the El Niño/Southern Oscillation (ENSO lead to severe droughts or floods, ideal ecological conditions for disease vectors to emerge, and may result in epizootics and epidemics of Rift Valley fever and chikungunya. However, the immune status of livestock (Rift Valley fever and human (chikungunya populations is a factor that is largely unknown but very likely plays a role in the spatial-temporal patterns of these disease outbreaks. As the frequency and severity of extremes in climate increase, the potential for globalization of vectors and disease is likely to accelerate. Understanding the underlying patterns of global and regional climate variability and their impacts on ecological drivers of vector-borne diseases is critical in long-range planning of appropriate disease and disease-vector response, control, and mitigation strategies.

  19. Metabolomics in plants and humans: applications in the prevention and diagnosis of diseases.

    Science.gov (United States)

    Gomez-Casati, Diego F; Zanor, Maria I; Busi, María V

    2013-01-01

    In the recent years, there has been an increase in the number of metabolomic approaches used, in parallel with proteomic and functional genomic studies. The wide variety of chemical types of metabolites available has also accelerated the use of different techniques in the investigation of the metabolome. At present, metabolomics is applied to investigate several human diseases, to improve their diagnosis and prevention, and to design better therapeutic strategies. In addition, metabolomic studies are also being carried out in areas such as toxicology and pharmacology, crop breeding, and plant biotechnology. In this review, we emphasize the use and application of metabolomics in human diseases and plant research to improve human health.

  20. TLR3 and TLR4 expression in healthy and diseased human endometrium

    Directory of Open Access Journals (Sweden)

    Kimmig Rainer

    2008-09-01

    Full Text Available Abstract Background Toll-like receptors (TLRs play an essential role in the innate immune system by initiating and directing immune response to pathogens. TLRs are expressed in the human endometrium and their regulation might be crucial for the pathogenesis of endometrial diseases. Methods TLR3 and TLR4 expression was investigated during the menstrual cycle and in postmenopausal endometrium considering peritoneal endometriosis, hyperplasia, and endometrial adenocarcinoma specimens (grade 1 to 3. The expression studies applied quantitative RT-PCR and immunolabelling of both proteins. Results TLR3 and TLR4 proteins were mostly localised to the glandular and luminal epithelium. In addition, TLR4 was present on endometrial dendritic cells, monocytes and macrophages. TLR3 and TLR4 mRNA levels did not show significant changes during the menstrual cycle. In patients with peritoneal endometriosis, TLR3 and TLR4 mRNA expression decreased significantly in proliferative diseased endometrium compared to controls. Interestingly, ectopic endometriotic lesions showed a significant increase of TLR3 und TLR4 mRNA expression compared to corresponding eutopic tissues, indicating a local gain of TLR expression. Endometrial hyperplasia and adenocarcinoma revealed significantly reduced receptor levels when compared with postmenopausal controls. The lowest TLR expression levels were determined in poor differentiated carcinoma (grade 3. Conclusion Our data suggest an involvement of TLR3 and TLR4 in endometrial diseases as demonstrated by altered expression levels in endometriosis and endometrial cancer.

  1. Advances in metal-induced oxidative stress and human disease

    International Nuclear Information System (INIS)

    Jomova, Klaudia; Valko, Marian

    2011-01-01

    Detailed studies in the past two decades have shown that redox active metals like iron (Fe), copper (Cu), chromium (Cr), cobalt (Co) and other metals undergo redox cycling reactions and possess the ability to produce reactive radicals such as superoxide anion radical and nitric oxide in biological systems. Disruption of metal ion homeostasis may lead to oxidative stress, a state where increased formation of reactive oxygen species (ROS) overwhelms body antioxidant protection and subsequently induces DNA damage, lipid peroxidation, protein modification and other effects, all symptomatic for numerous diseases, involving cancer, cardiovascular disease, diabetes, atherosclerosis, neurological disorders (Alzheimer's disease, Parkinson's disease), chronic inflammation and others. The underlying mechanism of action for all these metals involves formation of the superoxide radical, hydroxyl radical (mainly via Fenton reaction) and other ROS, finally producing mutagenic and carcinogenic malondialdehyde (MDA), 4-hydroxynonenal (HNE) and other exocyclic DNA adducts. On the other hand, the redox inactive metals, such as cadmium (Cd), arsenic (As) and lead (Pb) show their toxic effects via bonding to sulphydryl groups of proteins and depletion of glutathione. Interestingly, for arsenic an alternative mechanism of action based on the formation of hydrogen peroxide under physiological conditions has been proposed. A special position among metals is occupied by the redox inert metal zinc (Zn). Zn is an essential component of numerous proteins involved in the defense against oxidative stress. It has been shown, that depletion of Zn may enhance DNA damage via impairments of DNA repair mechanisms. In addition, Zn has an impact on the immune system and possesses neuroprotective properties. The mechanism of metal-induced formation of free radicals is tightly influenced by the action of cellular antioxidants. Many low-molecular weight antioxidants (ascorbic acid (vitamin C), alpha

  2. Human organoids: a model system for intestinal diseases

    OpenAIRE

    Wiegerinck, C.L.

    2015-01-01

    You are what you eat. A common saying that indicates that your physical or mental state can be influenced by your choice of food. Unfortunately, not all people have the luxury to choose what to eat; this can be related to place of birth, social, economic state, or the physical inability of the diseased intestine to take up certain food. A cell layer, the epithelium, covers the intestine, and harbors the main functions of the intestine: uptake, digestion of food, and a barrier against unwanted...

  3. X-ray diffraction evidence for myelin disorder in brain from humans with Alzheimer's disease.

    Science.gov (United States)

    Chia, L S; Thompson, J E; Moscarello, M A

    1984-09-05

    Wide-angle X-ray diffraction studies revealed that the lipid phase transition temperature of myelin from brain tissue of humans with Alzheimer's disease was about 12 degrees C lower than that of normal age-matched controls, indicating differences in the physical organization of the myelin lipid bilayer. Elevated levels of malondialdehyde and conjugated diene were found in brain tissue from humans with Alzheimer's disease, indicating an increased amount of lipid peroxidation over the controls. An increase in myelin disorder and in lipid peroxidation can both be correlated with aging in human brain, but the changes in myelin from humans with Alzheimer's disease are more pronounced than in normal aging. These changes might represent severe or accelerated aging.

  4. Trends in population-based studies of human genetics in infectious diseases.

    Science.gov (United States)

    Rowell, Jessica L; Dowling, Nicole F; Yu, Wei; Yesupriya, Ajay; Zhang, Lyna; Gwinn, Marta

    2012-01-01

    Pathogen genetics is already a mainstay of public health investigation and control efforts; now advances in technology make it possible to investigate the role of human genetic variation in the epidemiology of infectious diseases. To describe trends in this field, we analyzed articles that were published from 2001 through 2010 and indexed by the HuGE Navigator, a curated online database of PubMed abstracts in human genome epidemiology. We extracted the principal findings from all meta-analyses and genome-wide association studies (GWAS) with an infectious disease-related outcome. Finally, we compared the representation of diseases in HuGE Navigator with their contributions to morbidity worldwide. We identified 3,730 articles on infectious diseases, including 27 meta-analyses and 23 GWAS. The number published each year increased from 148 in 2001 to 543 in 2010 but remained a small fraction (about 7%) of all studies in human genome epidemiology. Most articles were by authors from developed countries, but the percentage by authors from resource-limited countries increased from 9% to 25% during the period studied. The most commonly studied diseases were HIV/AIDS, tuberculosis, hepatitis B infection, hepatitis C infection, sepsis, and malaria. As genomic research methods become more affordable and accessible, population-based research on infectious diseases will be able to examine the role of variation in human as well as pathogen genomes. This approach offers new opportunities for understanding infectious disease susceptibility, severity, treatment, control, and prevention.

  5. Human sewage identified as likely source of white pox disease of the threatened Caribbean elkhorn coral, Acropora palmata.

    Science.gov (United States)

    Sutherland, Kathryn Patterson; Porter, James W; Turner, Jeffrey W; Thomas, Brian J; Looney, Erin E; Luna, Trevor P; Meyers, Meredith K; Futch, J Carrie; Lipp, Erin K

    2010-05-01

    Caribbean elkhorn coral, Acropora palmata, has been decimated in recent years, resulting in the listing of this species as threatened under the United States Endangered Species Act. A major contributing factor in the decline of this iconic species is white pox disease. In 2002, we identified the faecal enterobacterium, Serratia marcescens, as an etiological agent for white pox. During outbreaks in 2003 a unique strain of S. marcescens was identified in both human sewage and white pox lesions. This strain (PDR60) was also identified from corallivorious snails (Coralliophila abbreviata), reef water, and two non-acroporid coral species, Siderastrea siderea and Solenastrea bournoni. Identification of PDR60 in sewage, diseased Acropora palmata and other reef invertebrates within a discrete time frame suggests a causal link between white pox and sewage contamination on reefs and supports the conclusion that humans are a likely source of this disease.

  6. The psychosocial burden of human papillomavirus related disease and screening interventions.

    Science.gov (United States)

    Pirotta, M; Ung, L; Stein, A; Conway, E L; Mast, T C; Fairley, C K; Garland, S

    2009-12-01

    (i) To assess the psychosocial burden of testing for human papillomavirus (HPV) related genital disease or of a HPV-related diagnosis; (ii) to compare an instrument specifically designed to measure HPV-related psychosocial burden with other generic quality of life (QoL) instruments. A cross-sectional design. Researchers recruited women from outpatient clinics at a major tertiary women's hospital and a sexual health centre who completed surveys within 3 months of receiving 331 women, 18-45 years, who had experienced a normal cervical Papanicolaou (Pap) result, an abnormal Pap result, biopsy confirmed cervical intraepithelial neoplasia (CIN) or external genital warts (EGW). The HPV impact profile (HIP) designed to assess the psychosocial impact of HPV; two general health-related QoL surveys-the EuroQoL VAS and the Sheehan disability scale; and a HPV knowledge survey. Response rate was 78%. Significant psychosocial impacts were found for women screened for, or having a diagnosis of, HPV-related genital disease. The largest impact was in women with CIN 2/3 and EGW. This HPV-related psychosocial impact was most sensitively detected with the HIP. Relative to generic measures of QoL, the HIP provided insight into the full range of psychosocial impacts of HPV testing and diagnoses. Clinicians need to be aware of the potential psychosocial impact of testing for or diagnosing HPV-related genital disease, in particular CIN 2/3 and EGW. The HIP survey is a more sensitive measure of the psychosocial impact of HPV-related genital disease than generic QoL surveys.

  7. MSDD: a manually curated database of experimentally supported associations among miRNAs, SNPs and human diseases.

    Science.gov (United States)

    Yue, Ming; Zhou, Dianshuang; Zhi, Hui; Wang, Peng; Zhang, Yan; Gao, Yue; Guo, Maoni; Li, Xin; Wang, Yanxia; Zhang, Yunpeng; Ning, Shangwei; Li, Xia

    2018-01-04

    The MiRNA SNP Disease Database (MSDD, http://www.bio-bigdata.com/msdd/) is a manually curated database that provides comprehensive experimentally supported associations among microRNAs (miRNAs), single nucleotide polymorphisms (SNPs) and human diseases. SNPs in miRNA-related functional regions such as mature miRNAs, promoter regions, pri-miRNAs, pre-miRNAs and target gene 3'-UTRs, collectively called 'miRSNPs', represent a novel category of functional molecules. miRSNPs can lead to miRNA and its target gene dysregulation, and resulting in susceptibility to or onset of human diseases. A curated collection and summary of miRSNP-associated diseases is essential for a thorough understanding of the mechanisms and functions of miRSNPs. Here, we describe MSDD, which currently documents 525 associations among 182 human miRNAs, 197 SNPs, 153 genes and 164 human diseases through a review of more than 2000 published papers. Each association incorporates information on the miRNAs, SNPs, miRNA target genes and disease names, SNP locations and alleles, the miRNA dysfunctional pattern, experimental techniques, a brief functional description, the original reference and additional annotation. MSDD provides a user-friendly interface to conveniently browse, retrieve, download and submit novel data. MSDD will significantly improve our understanding of miRNA dysfunction in disease, and thus, MSDD has the potential to serve as a timely and valuable resource. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  8. Mechanistic modeling of aberrant energy metabolism in human disease

    Directory of Open Access Journals (Sweden)

    Vineet eSangar

    2012-10-01

    Full Text Available Dysfunction in energy metabolism—including in pathways localized to the mitochondria—has been implicated in the pathogenesis of a wide array of disorders, ranging from cancer to neurodegenerative diseases to type II diabetes. The inherent complexities of energy and mitochondrial metabolism present a significant obstacle in the effort to understand the role that these molecular processes play in the development of disease. To help unravel these complexities, systems biology methods have been applied to develop an array of computational metabolic models, ranging from mitochondria-specific processes to genome-scale cellular networks. These constraint-based models can efficiently simulate aspects of normal and aberrant metabolism in various genetic and environmental conditions. Development of these models leverages—and also provides a powerful means to integrate and interpret—information from a wide range of sources including genomics, proteomics, metabolomics, and enzyme kinetics. Here, we review a variety of mechanistic modeling studies that explore metabolic functions, deficiency disorders, and aberrant biochemical pathways in mitochondria and related regions in the cell.

  9. Comparison of Scintigraphic and Radiological Results in the Diagnosis of Pancreatic Diseases

    Energy Technology Data Exchange (ETDEWEB)

    Deininger, H. K.; Sielaff, H. J. [Strahlenklinik der Staedt. Krankenanstalten Heilbronn, Heilbronn, Federal Republic of Germany (Germany)

    1969-05-15

    The results obtained by pancreas scanning and standard radiological diagnostic methods are compared. The roentgenographic examinations of the stomach, intestine, colon, biliary tract and kidneys were performed by standard X-ray methods and by abdominal tomography with pneumoretroperitoneum. Special methods of a radiological pancreatic diagnosis, e.g. selective angiography and intra-operative pancreatography, are intentionally not considered. So far 192 pancreas scans have been carried out after administration of {sup 75}Se-1 -selenomethionine. The patients were prepared either with a special diet or a fasting period. The quality of the pancreas scans depended on the functional state of the pancreatic tissue and a comparison with phantom studies allowed an approximate estimation of the extent of the parenchymatous lesions. Of the 87 cases with proven pancreatic diseases the results were compared with the scintigraphical and radiological findings. This comparative research illustrates the superiority of pancreas scanning over the conventional rontgenographic methods in the exclusion or detection of pancreatic diseases. (author)

  10. Protection of visual functions by human neural progenitors in a rat model of retinal disease.

    Directory of Open Access Journals (Sweden)

    David M Gamm

    2007-03-01

    Full Text Available A promising clinical application for stem and progenitor cell transplantation is in rescue therapy for degenerative diseases. This strategy seeks to preserve rather than restore host tissue function by taking advantage of unique properties often displayed by these versatile cells. In studies using different neurodegenerative disease models, transplanted human neural progenitor cells (hNPC protected dying host neurons within both the brain and spinal cord. Based on these reports, we explored the potential of hNPC transplantation to rescue visual function in an animal model of retinal degeneration, the Royal College of Surgeons rat.Animals received unilateral subretinal injections of hNPC or medium alone at an age preceding major photoreceptor loss. Principal outcomes were quantified using electroretinography, visual acuity measurements and luminance threshold recordings from the superior colliculus. At 90-100 days postnatal, a time point when untreated rats exhibit little or no retinal or visual function, hNPC-treated eyes retained substantial retinal electrical activity and visual field with near-normal visual acuity. Functional efficacy was further enhanced when hNPC were genetically engineered to secrete glial cell line-derived neurotrophic factor. Histological examination at 150 days postnatal showed hNPC had formed a nearly continuous pigmented layer between the neural retina and retinal pigment epithelium, as well as distributed within the inner retina. A concomitant preservation of host cone photoreceptors was also observed.Wild type and genetically modified human neural progenitor cells survive for prolonged periods, migrate extensively, secrete growth factors and rescue visual functions following subretinal transplantation in the Royal College of Surgeons rat. These results underscore the potential therapeutic utility of hNPC in the treatment of retinal degenerative diseases and suggest potential mechanisms underlying their effect in

  11. Borna disease virus and its role in the pathology of animals and humans

    Directory of Open Access Journals (Sweden)

    A. O. Mikheev

    2017-12-01

    Full Text Available Infectious diseases that are caused by numerous pathogenic microorganisms – bacteria, viruses, protozoa or fungi – can be transmitted from patients or carriers to healthy people or animals. A large group of infectious disease is caused by pathogens of animal infections – zoonoses. The issue of zoonoses is of great significance in human pathology and requires comprehensive study. This is of particular relevance to Ukraine, as the question of prevalence, level within the population and threats to human life and health from zoonoses, though highly important, has remained insufficiently studied. Information about many of these pathogens is absent in the existing scientific literature accessible in Ukraine – both veterinary and medical. This applies, in particular, to a causative agent of viral zoonoses the Borna disease virus or Bornavirus. For this purpose, an analysis of the literature concerning the role of the Bornavirus in the pathology of animals and humans was conducted. It is well known that a large number of pathogens of animal infections (zoonoses, including viral, pose a potential threat to human health. Among these potential threats is the Borna disease virus belonging to the family of Bornaviridae, order Mononegavirales. This order includes representatives of deadly human diseases like rabies (family Rhabdoviridae, Ebola virus (family Filoviridae and Nipah virus (family Paramyxoviridae. Borna virus disease affects mainly mammals, but can infect birds and even reptiles (Aspid bornavirus. It is established that Bornaviruses have a wide range of natural hosts (horses, sheeps, cats, bats and various birds, including domestic animals, which poses a potential threat to human health. This is evidenced by numerous, although contradictory, research into the role of the Borna disease virus in human pathologies such as schizophrenia, depression, prolonged fatigue syndrome, multiple sclerosis and others. Analysis of the literature clearly

  12. [Detection of human parvovirus B19, human bocavirus and human parvovirus 4 infections in blood samples among 95 patients with liver disease in Nanjing by nested PCR].

    Science.gov (United States)

    Tong, Rui; Zhou, Wei-Min; Liu, Xi-Jun; Wang, Yue; Lou, Yong-Liang; Tan, Wen-Jie

    2013-04-01

    To analyze the infection of human parvovirus B19, human bocavirus (HBoV) and human parvovirus 4 (PARV4) in blood samples among patients with liver disease in Nanjing by molecular detection. Nested PCR assays were designed and validated to detect B19, HBoV and PARV4, respectively. The assays were used to screen three parvoviruses in blood samples from 95 patients with different liver disease in Nanjing. The parvovirus infection was analyzed statistically. The detection limits were 10 copies of genomic DNA equivalents per reaction for each assays and the good specificity were observed. The frequency of B19 and HBoV were 2/95 (2.1%) and 9/95 (9.5%) in blood samples respectively. No PARV4 was detected. HBoV was detected in 3/5 patients with drug-induced hepatitis. Both B19 and HBoV infection were detected in blood from patients with liver disease.

  13. [ANALYSIS OF THE SURGICAL TREATMENT RESULTS IN THE THYROID GLAND DISEASES].

    Science.gov (United States)

    Tarashchenko, Yu N; Bolgov, M Yu

    2015-08-01

    The results of surgical treatment of the thyroid gland diseases were analyzed, including the specific morbidity rate, cosmetic effect of the operation, stationary treatment of patients duration, the operation radicalism. Improvement of the operation methods and introduction of modern electric surgical instruments have permitted to reduce the operation duration, the surgical access length, the rate of postoperative hypocalcaemia occurrence, duration of the patients stationary treatment.

  14. Results of treatment of Icenko-Cushing disease with proton beam irradiation of the pituitary gland

    International Nuclear Information System (INIS)

    Marova, E.I.; Starkova, N.T.; Kirpatovskaya, L.E.; Kolesnikova, G.S.; Bukhman, A.I.; Rozhinskaya, L.Ya.; Bel'chenko, L.V.

    1987-01-01

    Proton beam therapy was given to 98 patients with Icenko-Cushing disease aged 15 to 40. Mild cases were treated by proton beam irradiation only while severe cases were managed using proton beam therapy combined with unilateral adrenalectomy or ortho-para-DDD. Catamnesis duration varied from 3 to 5 years. In most cases the exposure dose was 80-90 Gy (50-110 Gy). The procedure was well tolerated by all the patients. A dynamic multipolar converting method with 15-20 entrance poles in the left temporal area was employed (with the beam energy of 200 MeV). Stabilization of the course of disease and some clinical improvement were observed in most of the patients 3-4 months after proton beam therapy. In 6-36 months after irradiation 90% of the patients showed normal biochemical indices and the absence of any clinical signs of the disease. Thus the results of proton beam therapy of 98 patients with Icenko-Cushing disease after a follow-up of 3-5 years showed a high efficacy of this type of treatment. The method can be used alone or in combination with unilateral adrenalectomy as well as with oral administration of ortho-para-DDD

  15. Using therapeutic cloning to fight human disease: a conundrum or reality?

    Science.gov (United States)

    Hall, Vanessa J; Stojkovic, Petra; Stojkovic, Miodrag

    2006-07-01

    The development and transplantation of autologous cells derived from nuclear transfer embryonic stem cell (NT-ESC) lines to treat patients suffering from disease has been termed therapeutic cloning. Human NT is still a developing field, with further research required to improve somatic cell NT and human embryonic stem cell differentiation to deliver safe and effective cell replacement therapies. Furthermore, the implications of transferring mitochondrial heteroplasmic cells, which may harbor aberrant epigenetic gene expression profiles, are of concern. The production of human NT-ESC lines also remains plagued by ethical dilemmas, societal concerns, and controversies. Recently, a number of alternate therapeutic strategies have been proposed to circumvent the moral implications surrounding human nuclear transfer. It will be critical to overcome these biological, legislative, and moral restraints to maximize the potential of this therapeutic strategy and to alleviate human disease.

  16. The human RNase MRP complex : composition, assembly and role in human disease

    NARCIS (Netherlands)

    Eenennaam, Hans van

    2002-01-01

    Not all RNA molecules in human cells are being translated into proteins. Some of them function in binding proteins, thereby forming so-called RNA-protein complexes. The RNase MRP complex is an example of such an RNA-protein complex. In this thesis two new protein components of the human RNase MRP

  17. Targeting ADAM12 in human disease: head, body or tail?

    DEFF Research Database (Denmark)

    Jacobsen, J; Wewer, U M

    2009-01-01

    ) and insulin-like growth factor receptor signaling. The body of the protein (consisting of the disintegrin, cysteine-rich, and EGF-like domains) is involved in contacts with the extracellular matrix and other cells through interactions with integrins and syndecans. Finally, the tail of the protein (consisting......ADAM12/meltrin alpha is a type I transmembrane multidomain protein involved in tumor progression and other severe diseases, including osteoarthritis, and as such could be considered as a potential drug target. In addition to protease activity, ADAM12 possesses cell binding and cell signaling...... properties. This functional trinity is reflected in the structure of ADAM12, which can be divided into head, body, and tail. The head of the protein (consisting of the pro and catalytic domains) mediates processing of growth factors and cytokines and has been implicated in epidermal growth factor (EGF...

  18. Rapidly progressive periodontal disease associated with human immunodeficiency virus

    International Nuclear Information System (INIS)

    Hezaim, K.A.; Javed, F.; Askar, A.; Rasheed, A.A.

    2012-01-01

    Severe periodontal inflammation with generalized dental plaque accumulation, spontaneous and severe gingival bleeding, fungal infection, and inter dental papillae necrosis are presented in a patient infected with human immunodeficiency virus (HIV). Bite-wing radiographs revealed a generalized horizontal alveolar bone loss of 7-8 millimetres in both arches. Erythematous patches were noted on the gingival mucosa in both jaws. DNA testing was performed to identify the periodontopathogens. The patient had no signs or symptoms of acquired immunodeficiency syndrome. This case-report presents the massive periodontal destruction that occurred in a patient infected with HIV. Therefore, it is highly recommended that patients infected with HIV should be regularly monitored to aid in early detection and to provide proper management of periodontal inflammatory conditions to minimize its destruction. (author)

  19. Human Fascioliasis: A Re-emerging Disease in Upper Egypt

    Science.gov (United States)

    Mekky, Mohamed A.; Tolba, Mohammed; Abdel-Malek, Mohamed O.; Abbas, Wael A.; Zidan, Mohamed

    2015-01-01

    In recent years, the number of humans infected with Fasciola has risen rapidly. Diagnosis is based mainly on detection of eggs in stool analysis. The rate of infection in Egypt is unknown. In this retrospective study, we describe 23 cases of hepatic fascioliasis, and only 2 of these cases showed eggs in stools. The symptoms of infection, such as pyrexia of unknown origin, epigastric pain, and abdominal distension, were suggestive. Imaging techniques, including abdominal ultrasonography and computed tomography, were very helpful in detecting hepatic changes. An indirect hemagglutination assay proved to be of value for diagnosis. Treatment using a 2-day triclabendazole regimen cured the infection and signs of hepatic involvement disappeared. Combining both imaging techniques and laboratory tests is essential for diagnosis of fascioliasis in the early stage. PMID:25870421

  20. Human fascioliasis: a re-emerging disease in upper Egypt.

    Science.gov (United States)

    Mekky, Mohamed A; Tolba, Mohammed; Abdel-Malek, Mohamed O; Abbas, Wael A; Zidan, Mohamed

    2015-07-01

    In recent years, the number of humans infected with Fasciola has risen rapidly. Diagnosis is based mainly on detection of eggs in stool analysis. The rate of infection in Egypt is unknown. In this retrospective study, we describe 23 cases of hepatic fascioliasis, and only 2 of these cases showed eggs in stools. The symptoms of infection, such as pyrexia of unknown origin, epigastric pain, and abdominal distension, were suggestive. Imaging techniques, including abdominal ultrasonography and computed tomography, were very helpful in detecting hepatic changes. An indirect hemagglutination assay proved to be of value for diagnosis. Treatment using a 2-day triclabendazole regimen cured the infection and signs of hepatic involvement disappeared. Combining both imaging techniques and laboratory tests is essential for diagnosis of fascioliasis in the early stage. © The American Society of Tropical Medicine and Hygiene.

  1. Limited accessibility to designs and results of Japanese large-scale clinical trials for cardiovascular diseases

    Directory of Open Access Journals (Sweden)

    Tsutani Kiichiro

    2011-04-01

    Full Text Available Abstract Background Clinical evidence is important for improving the treatment of patients by health care providers. In the study of cardiovascular diseases, large-scale clinical trials involving thousands of participants are required to evaluate the risks of cardiac events and/or death. The problems encountered in conducting the Japanese Acute Myocardial Infarction Prospective (JAMP study highlighted the difficulties involved in obtaining the financial and infrastructural resources necessary for conducting large-scale clinical trials. The objectives of the current study were: 1 to clarify the current funding and infrastructural environment surrounding large-scale clinical trials in cardiovascular and metabolic diseases in Japan, and 2 to find ways to improve the environment surrounding clinical trials in Japan more generally. Methods We examined clinical trials examining cardiovascular diseases that evaluated true endpoints and involved 300 or more participants using Pub-Med, Ichushi (by the Japan Medical Abstracts Society, a non-profit organization, websites of related medical societies, the University Hospital Medical Information Network (UMIN Clinical Trials Registry, and clinicaltrials.gov at three points in time: 30 November, 2004, 25 February, 2007 and 25 July, 2009. Results We found a total of 152 trials that met our criteria for 'large-scale clinical trials' examining cardiovascular diseases in Japan. Of these, 72.4% were randomized controlled trials (RCTs. Of 152 trials, 9.2% of the trials examined more than 10,000 participants, and 42.8% examined between 1,000 and 10,000 participants. The number of large-scale clinical trials markedly increased from 2001 to 2004, but suddenly decreased in 2007, then began to increase again. Ischemic heart disease (39.5% was the most common target disease. Most of the larger-scale trials were funded by private organizations such as pharmaceutical companies. The designs and results of 13 trials were not

  2. Synaptic Tau Seeding Precedes Tau Pathology in Human Alzheimer's Disease Brain

    Directory of Open Access Journals (Sweden)

    Sarah L. DeVos

    2018-04-01

    pathology, further suggesting that aggregated tau seeds move through the human brain along synaptically connected neurons. Together, these data provide further evidence that the spread of tau aggregates through the human brain along synaptically connected networks results in the pathogenesis of human Alzheimer's disease.

  3. Tribology of skin : review and analysis of experimental results for the friction coefficient of human skin

    NARCIS (Netherlands)

    Derler, S.; Gerhardt, L.C.

    2012-01-01

    In this review, we discuss the current knowledge on the tribology of human skin and present an analysis of the available experimental results for skin-friction coefficients. Starting with an overview on the factors influencing the friction behaviour of skin, we discuss the up-to-date existing

  4. Concordant testing results between various Human Papillomavirus assays in primary cervical cancer screening

    DEFF Research Database (Denmark)

    de Thurah, Lena; Bonde, Jesper; Hoa Lam, Janni Uyen

    2018-01-01

    OBJECTIVES: Human Papillomavirus (HPV) assays are increasingly used for primary cervical screening and HPV vaccination effect monitoring. We undertook a systematic literature review to determine the concordance in positive test results (i.e., detection of HPV infections) between Hybrid Capture 2 ...

  5. Isolation of primary human hepatocytes from normal and diseased liver tissue: a one hundred liver experience.

    Directory of Open Access Journals (Sweden)

    Ricky H Bhogal

    2011-03-01

    Full Text Available Successful and consistent isolation of primary human hepatocytes remains a challenge for both cell-based therapeutics/transplantation and laboratory research. Several centres around the world have extensive experience in the isolation of human hepatocytes from non-diseased livers obtained from donor liver surplus to surgical requirement or at hepatic resection for tumours. These livers are an important but limited source of cells for therapy or research. The capacity to isolate cells from diseased liver tissue removed at transplantation would substantially increase availability of cells for research. However no studies comparing the outcome of human hepatocytes isolation from diseased and non-diseased livers presently exist. Here we report our experience isolating human hepatocytes from organ donors, non-diseased resected liver and cirrhotic tissue. We report the cell yields and functional qualities of cells isolated from the different types of liver and demonstrate that a single rigorous protocol allows the routine harvest of good quality primary hepatocytes from the most commonly accessible human liver tissue samples.

  6. Genetic human prion disease modelled in PrP transgenic Drosophila.

    Science.gov (United States)

    Thackray, Alana M; Cardova, Alzbeta; Wolf, Hanna; Pradl, Lydia; Vorberg, Ina; Jackson, Walker S; Bujdoso, Raymond

    2017-09-20

    Inherited human prion diseases, such as fatal familial insomnia (FFI) and familial Creutzfeldt-Jakob disease (fCJD), are associated with autosomal dominant mutations in the human prion protein gene PRNP and accumulation of PrP Sc , an abnormal isomer of the normal host protein PrP C , in the brain of affected individuals. PrP Sc is the principal component of the transmissible neurotoxic prion agent. It is important to identify molecular pathways and cellular processes that regulate prion formation and prion-induced neurotoxicity. This will allow identification of possible therapeutic interventions for individuals with, or at risk from, genetic human prion disease. Increasingly, Drosophila has been used to model human neurodegenerative disease. An important unanswered question is whether genetic prion disease with concomitant spontaneous prion formation can be modelled in Drosophila We have used pUAST/PhiC31-mediated site-directed mutagenesis to generate Drosophila transgenic for murine or hamster PrP (prion protein) that carry single-codon mutations associated with genetic human prion disease. Mouse or hamster PrP harbouring an FFI (D178N) or fCJD (E200K) mutation showed mild Proteinase K resistance when expressed in Drosophila Adult Drosophila transgenic for FFI or fCJD variants of mouse or hamster PrP displayed a spontaneous decline in locomotor ability that increased in severity as the flies aged. Significantly, this mutant PrP-mediated neurotoxic fly phenotype was transferable to recipient Drosophila that expressed the wild-type form of the transgene. Collectively, our novel data are indicative of the spontaneous formation of a PrP-dependent neurotoxic phenotype in FFI- or CJD-PrP transgenic Drosophila and show that inherited human prion disease can be modelled in this invertebrate host. © 2017 The Author(s).

  7. Urinary Phthalate Concentrations in Mothers and Their Children in Ireland: Results of the DEMOCOPHES Human Biomonitoring Study.

    Science.gov (United States)

    Cullen, Elizabeth; Evans, David; Griffin, Chris; Burke, Padraig; Mannion, Rory; Burns, Damien; Flanagan, Andrew; Kellegher, Ann; Schoeters, Greet; Govarts, Eva; Biot, Pierre; Casteleyn, Ludwine; Castaño, Argelia; Kolossa-Gehring, Marike; Esteban, Marta; Schwedler, Gerda; Koch, Holger M; Angerer, Jürgen; Knudsen, Lisbeth E; Joas, Reinhard; Joas, Anke; Dumez, Birgit; Sepai, Ovnair; Exley, Karen; Aerts, Dominique

    2017-11-25

    Background : Phthalates are chemicals which are widespread in the environment. Although the impacts on health of such exposure are unclear, there is evidence of a possible impact on the incidence of a diverse range of diseases. Monitoring of human exposure to phthalates is therefore important. This study aimed to determine the extent of phthalate exposure among mothers and their children in both rural and urban areas in Ireland, and to identify factors associated with elevated concentrations. It formed part of the 'Demonstration of a study to Co-ordinate and Perform Human Biomonitoring on a European Scale' (DEMOCOPHES) pilot biomonitoring study. Methods : the concentration of phthalate metabolites were determined from a convenience sample of 120 mother/child pairs. The median age of the children was 8 years. A questionnaire was used to collect information regarding lifestyle and environmental conditions of the children and mothers. Rigorous quality assurance within DEMOCOPHES guaranteed the accuracy and international comparability of results. Results : Phthalate metabolites were detected in all of the samples from both children and mothers. Concentrations were significantly higher in respondents from families with lower educational attainment and in those exposed to such items as polyvinyl chloride (PVC), fast food and personal care products (PCP). Conclusions : The study demonstrates that human biomonitoring for assessing exposure to phthalates can be undertaken in Ireland and that the exposure of the population is widespread. Further work will be necessary before the consequences of this exposure are understood.

  8. Urinary Phthalate Concentrations in Mothers and Their Children in Ireland: Results of the DEMOCOPHES Human Biomonitoring Study.

    LENUS (Irish Health Repository)

    2017-11-25

    Background: Phthalates are chemicals which are widespread in the environment. Although the impacts on health of such exposure are unclear, there is evidence of a possible impact on the incidence of a diverse range of diseases. Monitoring of human exposure to phthalates is therefore important. This study aimed to determine the extent of phthalate exposure among mothers and their children in both rural and urban areas in Ireland, and to identify factors associated with elevated concentrations. It formed part of the \\'Demonstration of a study to Co-ordinate and Perform Human Biomonitoring on a European Scale\\' (DEMOCOPHES) pilot biomonitoring study. Methods: the concentration of phthalate metabolites were determined from a convenience sample of 120 mother\\/child pairs. The median age of the children was 8 years. A questionnaire was used to collect information regarding lifestyle and environmental conditions of the children and mothers. Rigorous quality assurance within DEMOCOPHES guaranteed the accuracy and international comparability of results. Results: Phthalate metabolites were detected in all of the samples from both children and mothers. Concentrations were significantly higher in respondents from families with lower educational attainment and in those exposed to such items as polyvinyl chloride (PVC), fast food and personal care products (PCP). Conclusions: The study demonstrates that human biomonitoring for assessing exposure to phthalates can be undertaken in Ireland and that the exposure of the population is widespread. Further work will be necessary before the consequences of this exposure are understood.

  9. Urinary Phthalate Concentrations in Mothers and Their Children in Ireland: Results of the DEMOCOPHES Human Biomonitoring Study

    Directory of Open Access Journals (Sweden)

    Elizabeth Cullen

    2017-11-01

    Full Text Available Background: Phthalates are chemicals which are widespread in the environment. Although the impacts on health of such exposure are unclear, there is evidence of a possible impact on the incidence of a diverse range of diseases. Monitoring of human exposure to phthalates is therefore important. This study aimed to determine the extent of phthalate exposure among mothers and their children in both rural and urban areas in Ireland, and to identify factors associated with elevated concentrations. It formed part of the ‘Demonstration of a study to Co-ordinate and Perform Human Biomonitoring on a European Scale’ (DEMOCOPHES pilot biomonitoring study. Methods: the concentration of phthalate metabolites were determined from a convenience sample of 120 mother/child pairs. The median age of the children was 8 years. A questionnaire was used to collect information regarding lifestyle and environmental conditions of the children and mothers. Rigorous quality assurance within DEMOCOPHES guaranteed the accuracy and international comparability of results. Results: Phthalate metabolites were detected in all of the samples from both children and mothers. Concentrations were significantly higher in respondents from families with lower educational attainment and in those exposed to such items as polyvinyl chloride (PVC, fast food and personal care products (PCP. Conclusions: The study demonstrates that human biomonitoring for assessing exposure to phthalates can be undertaken in Ireland and that the exposure of the population is widespread. Further work will be necessary before the consequences of this exposure are understood.

  10. Fluorescence-guided surgery of human colon cancer increases complete resection resulting in cures in an orthotopic nude mouse model.

    Science.gov (United States)

    Metildi, Cristina A; Kaushal, Sharmeela; Snyder, Cynthia S; Hoffman, Robert M; Bouvet, Michael

    2013-01-01

    We inquired if fluorescence-guided surgery (FGS) could improve surgical outcomes in fluorescent orthotopic nude mouse models of human colon cancer. We established fluorescent orthotopic mouse models of human colon cancer expressing a fluorescent protein. Tumors were resected under bright light surgery (BLS) or FGS. Pre- and post-operative images with the OV-100 Small Animal Imaging System (Olympus Corp, Tokyo Japan) were obtained to assess the extent of surgical resection. All mice with primary tumor that had undergone FGS had complete resection compared with 58% of mice in the BLS group (P = 0.001). FGS resulted in decreased recurrence compared with BLS (33% versus 62%, P = 0.049) and lengthened disease-free median survival from 9 to >36 wk. The median overall survival increased from 16 wk in the BLS group to 31 weeks in the FGS group. FGS resulted in a cure in 67% of mice (alive without evidence of tumor at >6 mo after surgery) compared with only 37% of mice that underwent BLS (P = 0.049). Surgical outcomes in orthotopic nude mouse models of human colon cancer were significantly improved with FGS. The present study can be translated to the clinic by various effective methods of fluorescently labeling tumors. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Human Embryonic Stem Cell Therapy in Crohn's Disease: A Case Report.

    Science.gov (United States)

    Shroff, Geeta

    2016-02-29

    Crohn's disease is a chronic inflammatory disease of the intestines, mainly the colon and ileum, related with ulcers and fistulae. It is estimated to affect 565,000 people in the United States. Currently available therapies, such as antibiotics, thiopurines, and anti-tumor necrosis factor-alpha agents, are only observed to reduce the complications associated with Crohn's disease and to improve quality of life, but cannot cure the disease. Stem cell therapy appears to have certain advantages over conventional therapies. Our study aimed to evaluate the efficacy of human embryonic stem cell therapy in a patient with Crohn's disease. A 21-year-old male with chief complaints of intolerance to specific foods, abdominal pain, and diarrhea underwent human embryonic stem cell therapy for two months. After undergoing human embryonic stem cell therapy, the patient showed symptomatic relief. He had no complaints of back pain, abdominal pain, or diarrhea and had improved digestion. The patient had no signs and symptoms of skin infection, and had improved limb stamina, strength, and endurance. The condition of patient was stable after the therapy. Human embryonic stem cell therapy might serve as a new optimistic treatment approach for Crohn's disease.

  12. New variant of Creutzfeldt-Jakob (vCJD) disease and other human prion diseases under epidemiological surveillance in Brazil

    OpenAIRE

    Gattás, Vera Lúcia; Lima Neto, Antonio Silva; Dimech, George Santiago; Mancini, Denise; Cantarino, Ligia Maria; Marins, José Ricardo Pio; Luna, Expedito José Albuquerque

    2007-01-01

    Abstract To increase the timeliness of detection of human cases of the new variant of Creutzfeldt-Jakob disease (vCJD) and to reduce the risk of transmission, the Brazilian Ministry of Health has established and standardized rules and control measures. These include the definition of criteria for suspect cases, reporting, monitoring, and control measures for illness prevention and transmission. Guidelines to be used by the team of health care staff were published and distributed to health wor...

  13. Human Metapneumovirus Infection in Jordanian Children: Epidemiology and Risk Factors for Severe Disease

    Science.gov (United States)

    Schuster, Jennifer E.; Khuri-Bulos, Najwa; Faouri, Samir; Shehabi, Asem; Johnson, Monika; Wang, Li; Fonnesbeck, Christopher; Williams, John V.; Halasa, Natasha

    2016-01-01

    Background Human metapneumovirus (HMPV) is a leading cause of acute respiratory tract infection (ARTI) in young children. Our objectives were to define HMPV epidemiology and circulating strains and determine markers of severe disease in Jordanian children. Methods We conducted a prospective study March 16, 2010-March 31, 2013 using quantitative RT-PCR to determine the frequency of HMPV infection among children <2 years old admitted with fever and/or acute respiratory illness to a major government hospital in Amman, Jordan. Results HMPV was present in 273/3168 (8.6%) of children presenting with ARTI. HMPV A2, B1, and B2, but not A1, were detected during the 3-year period. HMPV-infected children were older and more likely to be diagnosed with bronchopneumonia than HMPV-negative children. HMPV-infected children with lower respiratory tract infection (LRTI) had higher rates of cough and shortness of breath than children with LRTI infected with other or no identifiable viruses. Symptoms and severity were not different between children with HMPV only compared with HMPV co-infection. Children with HMPV subgroup A infection were more likely to require supplemental oxygen. In a multivariate analysis, HMPV subgroup A and age <6 months were independently associated with supplemental oxygen requirement. Conclusions HMPV is a leading cause of acute respiratory tract disease in Jordanian children <2 years old. HMPV A and young age were associated with severe disease. Ninety percent of HMPV-infected hospitalized children were full-term and otherwise healthy, in contrast to high-income nations; thus, factors contributing to disease severity likely vary depending on geographic and resource differences. PMID:26372450

  14. Identification of differential gene expression patterns in human arteries from patients with chronic kidney disease

    DEFF Research Database (Denmark)

    Stubbe, Jane; Skov, Vibe; Thiesson, Helle Charlotte

    2018-01-01

    BACKGROUND: Uremia accelerates atherosclerosis but little is known about affected pathways in human vasculature. This study aimed to identify differentially expressed arterial transcripts in patients with chronic kidney disease (CKD) Methods: Global mRNA expression was estimated by microarray...... hybridization in iliac arteries (n=14) from renal transplant recipients and compared with renal arteries from healthy living kidney donors (n=19) in study 1. Study 2 compared non-atherosclerotic internal mammary arteries (IMA) from five patients with elevated plasma creatinine levels and age and gender matched...... controls with normal levels. Western blotting and immunohistochemistry for selected proteins was performed on a subset of study 1 samples. RESULTS: 15 gene transcripts with fold changes (FC)>1.05 were significantly different between the two groups in study 1, with false discovery rates (FDR) of

  15. Drosophila as a Model for Human Diseases-Focus on Innate Immunity in Barrier Epithelia.

    Science.gov (United States)

    Bergman, P; Seyedoleslami Esfahani, S; Engström, Y

    2017-01-01

    Epithelial immunity protects the host from harmful microbial invaders but also controls the beneficial microbiota on epithelial surfaces. When this delicate balance between pathogen and symbiont is disturbed, clinical disease often occurs, such as in inflammatory bowel disease, cystic fibrosis, or atopic dermatitis, which all can be in part linked to impairment of barrier epithelia. Many innate immune receptors, signaling pathways, and effector molecules are evolutionarily conserved between human and Drosophila. This review describes the current knowledge on Drosophila as a model for human diseases, with a special focus on innate immune-related disorders of the gut, lung, and skin. The discovery of antimicrobial peptides, the crucial role of Toll and Toll-like receptors, and the evolutionary conservation of signaling to the immune systems of both human and Drosophila are described in a historical perspective. Similarities and differences between human and Drosophila are discussed; current knowledge on receptors, signaling pathways, and effectors are reviewed, including antimicrobial peptides, reactive oxygen species, as well as autophagy. We also give examples of human diseases for which Drosophila appears to be a useful model. In addition, the limitations of the Drosophila model are mentioned. Finally, we propose areas for future research, which include using the Drosophila model for drug screening, as a validation tool for novel genetic mutations in humans and for exploratory research of microbiota-host interactions, with relevance for infection, wound healing, and cancer. © 2017 Elsevier Inc. All rights reserved.

  16. Human Genome Epidemiology : A scientific foundation for using genetic information to improve health and prevent disease

    Directory of Open Access Journals (Sweden)

    Stefania Boccia

    2005-03-01

    Full Text Available

    Human health is determined by the interplay of genetic factors and the environment. In this context the recent advances in human genomics are expected to play a central role in medicine and public health by providing genetic information for disease prediction and prevention.

    After the completion of the human genome sequencing, a fundamental step will be represented by the translation of these discoveries into meaningful actions to improve health and prevent diseases, and the field of epidemiology plays a central role in this effort. These are some of the issues addressed by Human Genome Epidemiology –A scientific foundation for using genetic information to improve health and prevent disease, a volume edited by Prof. M. Khoury, Prof. J. Little, Prof.W. Burke and published by Oxford university Press 2004.

    This book describes the important role that epidemiological methods play in the continuum from gene discovery to the development and application of genetic tests. The Authors calls this continuum human genome epidemiology (HuGE to denote an evolving field of inquiry that uses systematic applications of epidemiological methods to assess the impact of human genetic variation on health and disease.

    The book is divided into four sections and it is structured to allow readers to proceed systematically from the fundamentals of genome technology and discovery, to the epidemiological approaches, to gene characterisation, to the evaluation of genetic tests and their use in health services and public health.

  17. 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

  18. Radiation dose to human and non-human biota in the republic of Korea resulting from the Fukushima nuclear accident

    International Nuclear Information System (INIS)

    Keum, Dong Kwon; Jun, In; Lim, Kwang Muk; Choi, Yong Ho

    2013-01-01

    This paper describes the radiation doses to human and non-human biota in the Republic of Korea, as a result of the Fukushima nuclear accident. By using the measured airborne activity and ground deposition, the effective and thyroid doses of five human age groups (infant, 5 years, 10 years, 15 years and adult) were estimated by the ECOSYS code, and the whole body absorbed dose rate of the eight Korean reference animals and plants (RAPs) was estimated by the K-BIOTA (the Korean computer code to assess the risk of radioactivity to wildlife). The first-year effective and thyroid human doses ranged from 5.7E-5 mSv in the infant group to 2.0E-4 mSv in the 5 years group, and from 5.0E-4 mSv in the infant group to 3.4E-3 mSv in the 5 years group, respectively. The life-time (70 years) effective and thyroid human doses ranged from 1.5E-4 mSv in the infant group to 3.0E-4 mSv in the 5 years group, and from 6.0E-4 mSv in the infant group to 3.5E-3 mSv in the 5 years group, respectively. The estimated maximum whole body absorbed dose rate to the Korean RAPs was 6.7E-7 mGy/d for a snake living in soil (terrestrial biota), and 2.0E-5 mGy/d for freshwater fish (aquatic biota), both of which were far less than the generic dose criteria to protect biota from ionizing radiation. Also, the screening level assessment for ERICA's (Environmental Risks from Ionizing Contaminants: Assessments and management) limiting organisms showed that the risk quotient (RQ) for the estimated maximum soil and water activity was significantly less than unity for both the terrestrial and freshwater organisms. Conclusively, the radiological risk of the radioactivity released into the environment by the Fukushima nuclear accident to the public and the non-human biota in the republic of Korea is considered negligible.

  19. Radiation dose to human and non-human biota in the republic of Korea resulting from the Fukushima nuclear accident

    Energy Technology Data Exchange (ETDEWEB)

    Keum, Dong Kwon; Jun, In; Lim, Kwang Muk; Choi, Yong Ho [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2013-02-15

    This paper describes the radiation doses to human and non-human biota in the Republic of Korea, as a result of the Fukushima nuclear accident. By using the measured airborne activity and ground deposition, the effective and thyroid doses of five human age groups (infant, 5 years, 10 years, 15 years and adult) were estimated by the ECOSYS code, and the whole body absorbed dose rate of the eight Korean reference animals and plants (RAPs) was estimated by the K-BIOTA (the Korean computer code to assess the risk of radioactivity to wildlife). The first-year effective and thyroid human doses ranged from 5.7E-5 mSv in the infant group to 2.0E-4 mSv in the 5 years group, and from 5.0E-4 mSv in the infant group to 3.4E-3 mSv in the 5 years group, respectively. The life-time (70 years) effective and thyroid human doses ranged from 1.5E-4 mSv in the infant group to 3.0E-4 mSv in the 5 years group, and from 6.0E-4 mSv in the infant group to 3.5E-3 mSv in the 5 years group, respectively. The estimated maximum whole body absorbed dose rate to the Korean RAPs was 6.7E-7 mGy/d for a snake living in soil (terrestrial biota), and 2.0E-5 mGy/d for freshwater fish (aquatic biota), both of which were far less than the generic dose criteria to protect biota from ionizing radiation. Also, the screening level assessment for ERICA's (Environmental Risks from Ionizing Contaminants: Assessments and management) limiting organisms showed that the risk quotient (RQ) for the estimated maximum soil and water activity was significantly less than unity for both the terrestrial and freshwater organisms. Conclusively, the radiological risk of the radioactivity released into the environment by the Fukushima nuclear accident to the public and the non-human biota in the republic of Korea is considered negligible.

  20. Limited accessibility to designs and results of Japanese large-scale clinical trials for cardiovascular diseases.

    Science.gov (United States)

    Sawata, Hiroshi; Ueshima, Kenji; Tsutani, Kiichiro

    2011-04-14

    Clinical evidence is important for improving the treatment of patients by health care providers. In the study of cardiovascular diseases, large-scale clinical trials involving thousands of participants are required to evaluate the risks of cardiac events and/or death. The problems encountered in conducting the Japanese Acute Myocardial Infarction Prospective (JAMP) study highlighted the difficulties involved in obtaining the financial and infrastructural resources necessary for conducting large-scale clinical trials. The objectives of the current study were: 1) to clarify the current funding and infrastructural environment surrounding large-scale clinical trials in cardiovascular and metabolic diseases in Japan, and 2) to find ways to improve the environment surrounding clinical trials in Japan more generally. We examined clinical trials examining cardiovascular diseases that evaluated true endpoints and involved 300 or more participants using Pub-Med, Ichushi (by the Japan Medical Abstracts Society, a non-profit organization), websites of related medical societies, the University Hospital Medical Information Network (UMIN) Clinical Trials Registry, and clinicaltrials.gov at three points in time: 30 November, 2004, 25 February, 2007 and 25 July, 2009. We found a total of 152 trials that met our criteria for 'large-scale clinical trials' examining cardiovascular diseases in Japan. Of these, 72.4% were randomized controlled trials (RCTs). Of 152 trials, 9.2% of the trials examined more than 10,000 participants, and 42.8% examined between 1,000 and 10,000 participants. The number of large-scale clinical trials markedly increased from 2001 to 2004, but suddenly decreased in 2007, then began to increase again. Ischemic heart disease (39.5%) was the most common target disease. Most of the larger-scale trials were funded by private organizations such as pharmaceutical companies. The designs and results of 13 trials were not disclosed. To improve the quality of clinical

  1. Clinical results of treating Graves's disease with percutaneous intrathyroidal ethanol injection

    International Nuclear Information System (INIS)

    Jiang Guoliang; Li Xiangguo; Qian Zhendong; Wang Cheng; Jiang Zhonglin; Zhang Dengbao; Cheng Qiang; Ye Xianci; Wu Dezhong; Chen Yingzhi; Zhu Shufang; Chen Yong

    2002-01-01

    Objective: To observe the effectiveness of percutaneous intrathyroidal ethanol injection in the treatment of Graves's disease. Methods: 42 patients with Graves' disease were given percutaneous intrathyroidal ethanol injection (PEI) for treatment. The control group consists of 47 patients given per-oral antithyroid drug (PATD). clinical response, levels of serum TT 3 , TT 4 , FT 3 , FT 4 , TSH and size of thyroid were observed and followed up for six months. Results: In PEI group, 17 cases were cured, 24 cases were improved and only one case had no response. Total effective rate was 97.6% with no significant difference from that of PATD (p > 0.05). The size of gland after treatment were significantly smaller in PEI than that of PATD (p < 0.01). No severe adverse effect occurred in the PEI group. Conclusion: PEI is a new way in treating GD which is simple economical and effective

  2. [Air-conditioner disease. Results of an industrial medicine survey (author's transl)].

    Science.gov (United States)

    Molina, C; Aiache, J M; Bedu, M; Menaut, P; Wahl, D; Brestowski, J; Grall, Y

    1982-07-03

    The results of a survey conducted in a company employing 1850 persons working in air-conditioned premises are reported. One hundred and five persons were examined, including 790 who mostly complained of respiratory disorders and 20 controls. Regular check-ups during the last two years have failed to reveal any serious disease. The most frequent complaints were rhinitis and tracheitis, especially among female employees. No alveolitis was observed. The finding of Bacillus subtilis in samples of ambient air and air-conditioner filters in conjunction with the presence of precipitating antibodies against crude extracts from these samples, suggested that the respiratory disorders might have been due to this microorganism. A multifactorial analysis demonstrated a statistically significant correlation between clinical symptoms and immunological disorders. The air-conditioner disease, therefore, may present as a benign condition.

  3. Steroid synthesis by primary human keratinocytes; implications for skin disease

    Energy Technology Data Exchange (ETDEWEB)

    Hannen, Rosalind F., E-mail: r.f.hannen@qmul.ac.uk [Centre for Cutaneous Research, Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT (United Kingdom); Michael, Anthony E. [Centre for Developmental and Endocrine Signalling, Academic Section of Obstetrics and Gynaecology, Division of Clinical Developmental Sciences, 3rd Floor, Lanesborough Wing, St. George' s, University of London, Cranmer Terrace, Tooting, London SW17 0RE (United Kingdom); Jaulim, Adil [Centre for Cutaneous Research, Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT (United Kingdom); Bhogal, Ranjit [Life Science, Unilever R and D Colworth House, Sharnbrook, Bedfordshire MK44 1LQ (United Kingdom); Burrin, Jacky M. [Centre for Endocrinology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ (United Kingdom); Philpott, Michael P. [Centre for Cutaneous Research, Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT (United Kingdom)

    2011-01-07

    Research highlights: {yields} Primary keratinocytes express the steroid enzymes required for cortisol synthesis. {yields} Normal primary human keratinocytes can synthesise cortisol. {yields} Steroidogenic regulators, StAR and MLN64, are expressed in normal epidermis. {yields} StAR expression is down regulated in eczema and psoriatic epidermis. -- Abstract: Cortisol-based therapy is one of the most potent anti-inflammatory treatments available for skin conditions including psoriasis and atopic dermatitis. Previous studies have investigated the steroidogenic capabilities of keratinocytes, though none have demonstrated that these skin cells, which form up to 90% of the epidermis are able to synthesise cortisol. Here we demonstrate that primary human keratinocytes (PHK) express all the elements required for cortisol steroidogenesis and metabolise pregnenolone through each intermediate steroid to cortisol. We show that normal epidermis and cultured PHK express each of the enzymes (CYP11A1, CYP17A1, 3{beta}HSD1, CYP21 and CYP11B1) that are required for cortisol synthesis. These enzymes were shown to be metabolically active for cortisol synthesis since radiometric conversion assays traced the metabolism of [7-{sup 3}H]-pregnenolone through each steroid intermediate to [7-{sup 3}H]-cortisol in cultured PHK. Trilostane (a 3{beta}HSD1 inhibitor) and ketoconazole (a CYP17A1 inhibitor) blocked the metabolism of both pregnenolone and progesterone. Finally, we show that normal skin expresses two cholesterol transporters, steroidogenic acute regulatory protein (StAR), regarded as the rate-determining protein for steroid synthesis, and metastatic lymph node 64 (MLN64) whose function has been linked to cholesterol transport in steroidogenesis. The expression of StAR and MLN64 was aberrant in two skin disorders, psoriasis and atopic dermatitis, that are commonly treated with cortisol, suggesting dysregulation of epidermal steroid synthesis in these patients. Collectively these data

  4. Steroid synthesis by primary human keratinocytes; implications for skin disease

    International Nuclear Information System (INIS)

    Hannen, Rosalind F.; Michael, Anthony E.; Jaulim, Adil; Bhogal, Ranjit; Burrin, Jacky M.; Philpott, Michael P.

    2011-01-01

    Research highlights: → Primary keratinocytes express the steroid enzymes required for cortisol synthesis. → Normal primary human keratinocytes can synthesise cortisol. → Steroidogenic regulators, StAR and MLN64, are expressed in normal epidermis. → StAR expression is down regulated in eczema and psoriatic epidermis. -- Abstract: Cortisol-based therapy is one of the most potent anti-inflammatory treatments available for skin conditions including psoriasis and atopic dermatitis. Previous studies have investigated the steroidogenic capabilities of keratinocytes, though none have demonstrated that these skin cells, which form up to 90% of the epidermis are able to synthesise cortisol. Here we demonstrate that primary human keratinocytes (PHK) express all the elements required for cortisol steroidogenesis and metabolise pregnenolone through each intermediate steroid to cortisol. We show that normal epidermis and cultured PHK express each of the enzymes (CYP11A1, CYP17A1, 3βHSD1, CYP21 and CYP11B1) that are required for cortisol synthesis. These enzymes were shown to be metabolically active for cortisol synthesis since radiometric conversion assays traced the metabolism of [7- 3 H]-pregnenolone through each steroid intermediate to [7- 3 H]-cortisol in cultured PHK. Trilostane (a 3βHSD1 inhibitor) and ketoconazole (a CYP17A1 inhibitor) blocked the metabolism of both pregnenolone and progesterone. Finally, we show that normal skin expresses two cholesterol transporters, steroidogenic acute regulatory protein (StAR), regarded as the rate-determining protein for steroid synthesis, and metastatic lymph node 64 (MLN64) whose function has been linked to cholesterol transport in steroidogenesis. The expression of StAR and MLN64 was aberrant in two skin disorders, psoriasis and atopic dermatitis, that are commonly treated with cortisol, suggesting dysregulation of epidermal steroid synthesis in these patients. Collectively these data show that PHK are capable of extra

  5. The Human Proteome Organization Chromosome 6 Consortium: integrating chromosome-centric and biology/disease driven strategies.

    Science.gov (United States)

    Borchers, C H; Kast, J; Foster, L J; Siu, K W M; Overall, C M; Binkowski, T A; Hildebrand, W H; Scherer, A; Mansoor, M; Keown, P A

    2014-04-04

    The Human Proteome Project (HPP) is designed to generate a comprehensive map of the protein-based molecular architecture of the human body, to provide a resource to help elucidate biological and molecular function, and to advance diagnosis and treatment of diseases. Within this framework, the chromosome-based HPP (C-HPP) has allocated responsibility for mapping individual chromosomes by country or region, while the biology/disease HPP (B/D-HPP) coordinates these teams in cross-functional disease-based groups. Chromosome 6 (Ch6) provides an excellent model for integration of these two tasks. This metacentric chromosome has a complement of 1002-1034 genes that code for known, novel or putative proteins. Ch6 is functionally associated with more than 120 major human diseases, many with high population prevalence, devastating clinical impact and profound societal consequences. The unique combination of genomic, proteomic, metabolomic, phenomic and health services data being drawn together within the Ch6 program has enormous potential to advance personalized medicine by promoting robust biomarkers, subunit vaccines and new drug targets. The strong liaison between the clinical and laboratory teams, and the structured framework for technology transfer and health policy decisions within Canada will increase the speed and efficacy of this transition, and the value of this translational research. Canada has been selected to play a leading role in the international Human Proteome Project, the global counterpart of the Human Genome Project designed to understand the structure and function of the human proteome in health and disease. Canada will lead an international team focusing on chromosome 6, which is functionally associated with more than 120 major human diseases, including immune and inflammatory disorders affecting the brain, skeletal system, heart and blood vessels, lungs, kidney, liver, gastrointestinal tract and endocrine system. Many of these chronic and persistent

  6. Postmortem study of stable carbon isotope ratios in human cerebellar DNA: preliminary results

    International Nuclear Information System (INIS)

    Slatkin, D.N.; Irsa, A.P.; Friedman, L.

    1978-01-01

    It is observed that 13 C/ 12 C ratios in tissue specimens removed postmortem in the United States and Canada are significantly different from corresponding ratios in European specimens. On the basis of this information, measurements of carbon isotope ratios in DNA isolated from cerebella of native-born and European-born North Americans are in progress with the goal of estimating the average lifetime rate of DNA turnover in human neurons. Preliminary results from twenty postmortem examinations are consistent with the hypothesis that a significant proportion of human cerebellar DNA is renewed during the lifetime of an individual

  7. [Conservative anal fistula treatment with collagenic plug and human fibrin sealant. Preliminary results].

    Science.gov (United States)

    Gubitosi, A; Moccia, G; Malinconico, F A; Docimo, G; Ruggiero, R; Iside, G; Avenia, N; Docimo, L; Foroni, F; Gilio, F; Sparavigna, L; Agresti, M

    2009-01-01

    The authors, on the basis of a long clinical experience with human fibrin glue in general surgery, compared two different extracellular matrix (collagen), Surgisis and TissueDura, with human fibrin glue, applied during the operation, and sometimes in postoperative, to obtain the healing of perianal fistulas. The collagenic extracellular matrix provides, according to the rationale suggested, an optimal three-dimensional structure for the fibroblastic implant and neoangiogenesis, hence for the fistula "fibrotizzation" and closure. The encouraging results for transphincteric fistulas and a simple and easy technique push to researchers on samples statistically significant.

  8. A polynomial based model for cell fate prediction in human diseases.

    Science.gov (United States)

    Ma, Lichun; Zheng, Jie

    2017-12-21

    Cell fate regulation directly affects tissue homeostasis and human health. Research on cell fate decision sheds light on key regulators, facilitates understanding the mechanisms, and suggests novel strategies to treat human diseases that are related to abnormal cell development. In this study, we proposed a polynomial based model to predict cell fate. This model was derived from Taylor series. As a case study, gene expression data of pancreatic cells were adopted to test and verify the model. As numerous features (genes) are available, we employed two kinds of feature selection methods, i.e. correlation based and apoptosis pathway based. Then polynomials of different degrees were used to refine the cell fate prediction function. 10-fold cross-validation was carried out to evaluate the performance of our model. In addition, we analyzed the stability of the resultant cell fate prediction model by evaluating the ranges of the parameters, as well as assessing the variances of the predicted values at randomly selected points. Results show that, within both the two considered gene selection methods, the prediction accuracies of polynomials of different degrees show little differences. Interestingly, the linear polynomial (degree 1 polynomial) is more stable than others. When comparing the linear polynomials based on the two gene selection methods, it shows that although the accuracy of the linear polynomial that uses correlation analysis outcomes is a little higher (achieves 86.62%), the one within genes of the apoptosis pathway is much more stable. Considering both the prediction accuracy and the stability of polynomial models of different degrees, the linear model is a preferred choice for cell fate prediction with gene expression data of pancreatic cells. The presented cell fate prediction model can be extended to other cells, which may be important for basic research as well as clinical study of cell development related diseases.

  9. Pathogenesis of human papillomavirus-associated mucosal disease.

    Science.gov (United States)

    Groves, Ian J; Coleman, Nicholas

    2015-03-01

    Human papillomaviruses (HPVs) are a necessary cause of carcinoma of the cervix and other mucosal epithelia. Key events in high-risk HPV (HRHPV)-associated neoplastic progression include persistent infection, deregulated expression of virus early genes in basal epithelial cells and genomic instability causing secondary host genomic imbalances. There are multiple mechanisms by which deregulated virus early gene expression may be achieved. Integration of virus DNA into host chromosomes is observed in the majority of cervical squamous cell carcinomas (SCCs), although in ∼15% of cases the virus remains extrachromosomal (episomal). Interestingly, not all integration events provide a growth advantage to basal cervical epithelial cells or lead to increased levels of the virus oncogenes E6 and E7, when compared with episome-containing basal cells. The factors that provide a competitive advantage to some integrants, but not others, are complex and include virus and host contributions. Gene expression from integrated and episomal HRHPV is regulated through host epigenetic mechanisms affecting the virus long control region (LCR), which appear to be of functional importance. New approaches to treating HRHPV-associated mucosal neoplasia include knockout of integrated HRHPV DNA, depletion of virus transcripts and inhibition of virus early gene transcription through targeting or use of epigenetic modifiers. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  10. Effects of Chinese Liquors on Cardiovascular Disease Risk Factors in Healthy Young Humans

    Directory of Open Access Journals (Sweden)

    Ju-Sheng Zheng

    2012-01-01

    Full Text Available Objectives. To elucidate whether consumption of two Chinese liquors, tea-flavor liquor (TFL and traditional Chinese liquor (TCL have protective effects on cardiovascular disease (CVD risk factors in healthy human subjects. Methods. Forty-five healthy subjects (23 men, 22 women, aged 23–28, were recruited and randomized into two groups: TFL and TCL, and consumed 30 mL/day (45% (v/v alcohol of either liquor for 28 days. Results. Serum high-density lipoprotein cholesterol/low-density lipoprotein cholesterol (HDL-C/LDL-C and apolipoprotein A1 were significantly increased, and total cholesterol (TC and TC/HDL-C were significantly decreased after the intervention in both groups (P<0.05. Serum uric acid (P=0.004 for TFL, P=0.001 for TCL, glucose (P<0.001 for TFL, P<0.001 for TCL and endothelial adhesion molecules (P<0.05 were significantly decreased after the intervention. ADP-induced whole blood platelet aggregation was also significantly decreased after the intervention in both TFL and TCL groups (P<0.05. Conclusions. TFL and TCL consumption had protective effects on CVD risk factors in young humans. However, the results were valid only for 28 days, and that the possibility of adverse effect (liver, kidney of chronic alcohol consumption should be considered.

  11. Transgenic mice expressing human glucocerebrosidase variants: utility for the study of Gaucher disease.

    Science.gov (United States)

    Sanders, Angela; Hemmelgarn, Harmony; Melrose, Heather L; Hein, Leanne; Fuller, Maria; Clarke, Lorne A

    2013-08-01

    Gaucher disease is an autosomal recessively inherited storage disorder caused by deficiency of the lysosomal hydrolase, acid β-glucosidase. The disease manifestations seen in Gaucher patients are highly heterogeneous as is the responsiveness to therapy. The elucidation of the precise factors responsible for this heterogeneity has been challenging as the development of clinically relevant animal models of Gaucher disease has been problematic. Although numerous murine models for Gaucher disease have been described each has limitations in their specific utility. We describe here, transgenic murine models of Gaucher disease that will be particularly useful for the study of pharmacological chaperones. We have produced stable transgenic mouse strains that individually express wild type, N370S and L444P containing human acid β-glucosidase and show that each of these transgenic lines rescues the lethal phenotype characteristic of acid β-glucosidase null mice. Both the N370S and L444P transgenic models show early and progressive elevations of tissue sphingolipids with L444P mice developing progressive splenic Gaucher cell infiltration. We demonstrate the potential utility of these new transgenic models for the study of Gaucher disease pathogenesis. In addition, since these mice produce only human enzyme, they are particularly relevant for the study of pharmacological chaperones that are specifically targeted to human acid β-glucosidase and the common mutations underlying Gaucher disease. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Dog as a model in studies on human hereditary diseases and their gene therapy.

    Science.gov (United States)

    Switonski, Marek

    2014-03-01

    During the last 15 years spectacular progress has been achieved in knowledge on the dog genome organization and the molecular background of hereditary diseases in this species. A majority of canine genetic diseases have their counterparts in humans and thus dogs are considered as a very important large animal model in human biomedicine. Among canine monogenic diseases with known causative gene mutations there are two large groups classified as retinal dystrophies and lysosomal storage diseases. Specific types of these diseases are usually diagnosed in a single or several breeds. A well known disorder, restricted to a single breed, is congenital stationary night blindness described in Briards. This disease is a counterpart of Leber amaurosis in children. On the other hand, one of the most common monogenic human diseases (Duchenne muscular dystrophy), has its canine counterparts in several breeds (e.g., the Golden retriever, Beagle and German short-haired pointer). For some of the canine diseases gene therapy strategy was successfully applied, e.g., for congenital stationary night blindness, rod-cone dystrophy and muccopolysaccharydoses type I, IIIB and VII. Since phenotypic variability between the breeds is exceptionally high, the dog is an interesting model to study the molecular background of congenital malformations (e.g., dwarfism and osteoporosis imperfecta). Also disorders of sexual development (DSD), especially testicular or ovotesticular DSD (78,XX; SRY-negative), which is widely distributed across dozens of breeds, are of particular interest. Studies on the genetic background of canine cancers, a major health problem in this species, are also quite advanced. On the other hand, genetic studies on canine counterparts of major human complex diseases (e.g., obesity, the metabolic syndrome and diabetes mellitus) are still in their infancy. Copyright © 2014 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish

  13. The comparative analysis of results of surgical treatment of myasthenia in the remote periods of disease

    Directory of Open Access Journals (Sweden)

    L. Zaslavsky

    2016-01-01

    Full Text Available Based on long-term follow-up to perform comparative analysis of long-term results of surgical treatment of myasthenia. A retrospective analysis of long-term results of surgical treatment of 146 patients with myasthenia has been carried out. We used the modified Keynes classification to estimate the severity of myasthenia and to summarize the data relating to therapy volume and treatment results. In dependence on the type of thymus lesion patients were divided into two groups. Thymus hyperplasia was verified at — 106 (72.6 % patients, tumor lesion of the thymus gland (thymoma — at 40 (27.4 % ones. The results were estimated in the following periods after thymectomy: 1—2 years, 3—4 years, 5—6 years, 7 — 9 years, 10—14 years, and over 15 years. Short- and longterm results of surgical treatment of myasthenia for the patients without tumor lesions of the thymus gland were significantly better. Positive effects of surgical treatment of myasthenia in patients with hyperplasia are observed after 1 year of surgery (p = 0.0023, and the best results are observed after 5 — 6 year of the disease, then after 7 — 9 year one notes some deterioration of state (p = 0.026. In the myasthenia patients with thymoma one notes the similar trends in dynamics of state, but in general, the results are significantly (p = 0.042 badly than in the group of the patients with hyperplasia. Starting from the first year after operation treatment the patients with myasthenia with thymus hyperplasia have statistically significant (p = 0.048 decrease of average doses of glucocorticoids, and anticholinesterase drugs. The statistically best treatment results were noted for the patients operated at the first year of the disease. Positive result of surgical treatment of myasthenia is noted both in the short- and long-term period and at thymomas. In the group of patients with thymoma one has noted significantly badly results in comparison with group of hyperplasia. It is

  14. [Functional results of Hirschsprung's disease patients after Duhamel and De la Torre procedures].

    Science.gov (United States)

    Fernández Ibieta, M; Sánchez Morote, J M; Martínez Castaño, I; Reyes Ríos, P; Cabrejos Perotti, K; Rojas Ticona, J; Ruiz Pruneda, R; Aranda García, M J; Roqués Serradilla, J L; Trujillo Ascanio, A; Hernández Bermejo, J P; Ruiz Jiménez, J I

    2013-10-01

    Long term results of different surgical techniques in Hirschsprung's Disease (HD) are contradictory. There are still no long term large or multicentric reports about functional results of De la Torre technique. We have studied the mid term functional results of the patients operated on Duhamel (D) and De la Torre (dlT) pull-through procedures. We collected data from medical records and telephone interviews of the HD patients operated in our unit in the last 16 years. 38 patients were found. Ages ranged from 1.5 to 21 years. Mean age was 7.7 years. Median follow up was 5.9 years. 33 (86.8%) had rectosigmoid disease and 5 (13.2%) had long segment disease. D procedure was performed in 17 (44.7%), Soave in 1 (2.6%), Duhamel-Lester-Martin in 4 (10.5%) and dlT pull-through in 16(42%). In the last visit record, 12 (31.6%), had constipation, and fecal leaks were noted in 11 (33.3%) of the 33 patients > or = 4 years old.. 10 patients (29.4% of the > or = 4 years old group) referred encopresis along the follow-up. Patients from the D group referred higher rates of constipation than those in the dlT group (53.3% vs 20% p=0.048). dlT patients referred more frequency of leaks (46,1% vs 13,3%, p=0,05) Children with very short resections (Encopresis was similar in all groups. Both techniques show similar functional results in the mid term, although children in the D group were more prone to constipation and those in the dlT group presented more fecal leaks. All patients with EH need long follow-ups.

  15. Human microbiomes and their roles in dysbiosis, common diseases, and novel therapeutic approaches.

    Science.gov (United States)

    Belizário, José E; Napolitano, Mauro

    2015-01-01

    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.

  16. 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.

  17. Ethical issues in Alzheimer's disease research involving human subjects.

    Science.gov (United States)

    Davis, Dena S

    2017-12-01

    As we aggressively pursue research to cure and prevent Alzheimer's disease, we encounter important ethical challenges. None of these challenges, if handled thoughtfully, would pose insurmountable barriers to research. But if they are ignored, they could slow the research process, alienate potential study subjects and do damage to research recruits and others. These challenges are (1) the necessity of very large cohorts of research subjects, recruited for lengthy studies, probably ending only in the subjects' death; (2) the creation of cohorts of 'study ready' volunteers, many of whom will be competent to consent at the beginning of the process, but move into cognitive impairment later; (3) reliance on adaptive trial design, creating challenges for informed consent, equipoise and justice; (4) the use of biomarkers and predictive tests that describe risk rather than certainty, and that can threaten participants' welfare if the information is obtained by insurance companies or long-term care providers; (5) the use of study partners that creates unique risks of harm to the relationship of subject and study partner. We need greater attention, at all levels, to these complex ethical issues. Work on these issues should be included in research plans, from the federal to the local, and should be supported through NIH in the same way that it supported work on the ethical, legal and social implications of genetic research. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  18. Human exposure to bisphenol A by biomonitoring: Methods, results and assessment of environmental exposures

    International Nuclear Information System (INIS)

    Dekant, Wolfgang; Voelkel, Wolfgang

    2008-01-01

    Human exposure to bisphenol A is controversially discussed. This review critically assesses methods for biomonitoring of bisphenol A exposures and reported concentrations of bisphenol A in blood and urine of non-occupationally ('environmentally') exposed humans. From the many methods published to assess bisphenol A concentrations in biological media, mass spectrometry-based methods are considered most appropriate due to high sensitivity, selectivity and precision. In human blood, based on the known toxicokinetics of bisphenol A in humans, the expected very low concentrations of bisphenol A due to rapid biotransformation and the very rapid excretion result in severe limitations in the use of reported blood levels of bisphenol A for exposure assessment. Due to the rapid and complete excretion of orally administered bisphenol A, urine samples are considered as the appropriate body fluid for bisphenol A exposure assessment. In urine samples from several cohorts, bisphenol A (as glucuronide) was present in average concentrations in the range of 1-3 μg/L suggesting that daily human exposure to bisphenol A is below 6 μg per person (< 0.1 μg/kg bw/day) for the majority of the population

  19. Biodiversity loss, emerging infectious diseases and impact on human and crops

    International Nuclear Information System (INIS)

    Shinwari, Z.K.; Gilani, S.A.; Khan, A.L.

    2012-01-01

    We are losing biodiversity through several factors ranging from global warming, climatic change, unsustainable use of natural resources, human settlements, demand for food, medicine etc. Consequently, the biodiversity losses are causing emergence of infectious diseases (EIDs) which are making them more virulent than the past. Both biodiversity loss and emergence of diseases significantly impact the human derived benefits in-terms of economy and food. Ecological stability, productivity and food-web interactions are indirectly correlated with biodiversity and any change in these will cause losses in biodiversity that would certainly influence the human derived benefits and crops. The current article reviews the biodiversity losses and emerging infectious diseases at various levels reported by recent literature which will help in current status of EIDs and future recommendations. (author)

  20. Analysis of the genetic basis of disease in the context of worldwide human relationships and migration.

    Directory of Open Access Journals (Sweden)

    Erik Corona

    2013-05-01

    Full Text Available Genetic diversity across different human populations can enhance understanding of the genetic basis of disease. We calculated the genetic risk of 102 diseases in 1,043 unrelated individuals across 51 populations of the Human Genome Diversity Panel. We found that genetic risk for type 2 diabetes and pancreatic cancer decreased as humans migrated toward East Asia. In addition, biliary liver cirrhosis, alopecia areata, bladder cancer, inflammatory bowel disease, membranous nephropathy, systemic lupus erythematosus, systemic sclerosis, ulcerative colitis, and vitiligo have undergone genetic risk differentiation. This analysis represents a large-scale attempt to characterize genetic risk differentiation in the context of migration. We anticipate that our findings will enable detailed analysis pertaining to the driving forces behind genetic risk differentiation.

  1. Perturbation of the Human Microbiome as a Contributor to Inflammatory Bowel Disease

    Directory of Open Access Journals (Sweden)

    Bayan Missaghi

    2014-06-01

    Full Text Available The human microbiome consist of the composite genome of native flora that have evolved with humanity over millennia and which contains 150-fold more genes than the human genome. A “healthy” microbiome plays an important role in the maintenance of health and prevention of illness, inclusive of autoimmune disease such as inflammatory bowel disease (IBD. IBD is a prevalent spectrum of disorders, most notably defined by Crohn’s disease (CD and ulcerative colitis (UC, which are associated with considerable suffering, morbidity, and cost. This review presents an outline of the loss of a normal microbiome as an etiology of immune dysregulation and IBD pathogenesis initiation. We, furthermore, summarize the knowledge on the role of a healthy microbiome in terms of its diversity and important functional elements and, lastly, conclude with some of the therapeutic interventions and modalities that are now being explored as potential applications of microbiome-host interactions.

  2. DISEASE MODIFYING THERAPY AND OUTCOME OF RHEUMATOID ARTHRITIS: RETROSPECTIVE ASSESSMENT OF LONG-TERM RESULTS

    Directory of Open Access Journals (Sweden)

    D. E. Karateyev

    2000-01-01

    Full Text Available Aim of study: To investigate the relation between patterns of basic treatment and the outcome of disease in patients with rheumatoid arthritis (RA. Material and methods: We studied retrospectively two groups of patients with RA (1987 ACR criteria: 1 main group - died (72 patients, mean duration of disease from the onset to death 12.8±0.9 years; 2 control group - alive to 1999 with duration of disease at least 15 years (90 patients, mean follow-up period 19.4±0.47 years. Results: Some patterns of basic treatment were observed: 1 "passive ” strategy - only hydroxychloroquine or sulphasalazine during many years; 2 "inteirupted " treatment - early treatment gold or cytotoxics, but when improvement occurred, therapy with DMARD was interrupted for 1-2 years or more, after that re-started etc.; 3 “emergency” strategy’ - 7-10years of "passive" treatment, after that se\\>ere destruction and/or amyloidosis appeared, and cytotoxics started; 4 typical "pyramid " strategy; 5 "active " strategy - early start of treatment with active DMARD (melotrexate, gold with consecutive change of DMARDs without interruption of basic treatment (very close to "sawtooth ” strategy. The most of died patients were treated with "passive ” and "interrupted" strategies, but the most of patients in control group were treated with "pyramid” and "active" strategies. Conclusion: active strategy of basic treatment has a positive influence on the survival ofpatients with R.A.

  3. Infection of immunodeficient horses with Sarcocystis neurona does not result in neurologic disease.

    Science.gov (United States)

    Sellon, Debra C; Knowles, Donald P; Greiner, Ellis C; Long, Maureen T; Hines, Melissa T; Hochstatter, Tressa; Tibary, Ahmed; Dame, John B

    2004-11-01

    Equine protozoal myeloencephalitis is a progressive neurologic disease of horses most commonly caused by infection with the apicomplexan parasite Sarcocystis neurona. Factors affecting neuroinvasion and neurovirulence have not been determined. We investigated the pathogenesis of infection with S. neurona in horses with severe combined immune deficiency (SCID). Two immunocompetent (IC) Arabian horses and two Arabian horses with SCID were infected orally with 5 x 10(5) sporocysts of S. neurona. Four IC horses and one SCID horse were infected intravenously (i.v.) with 5 x 10(8) merozoites of the WSU-1 isolate of S. neurona. Despite prolonged parasitemia and persistent infection of visceral tissues (skeletal muscle, cardiac muscle, lung, liver, and spleen) as demonstrated by PCR and culture, SCID horses did not develop neurologic signs after oral or i.v. infection. S. neurona was undetectable in the neuronal tissues of SCID horses by either PCR, immunohistochemistry, or culture. In contrast, although parasitemia was undetectable in orally infected IC horses and of only short duration in i.v. infected IC horses, four of six IC horses developed neurologic signs. S. neurona was detectable by PCR and/or culture of neural tissue but not visceral tissue of IC horses with neurologic disease. Infected SCID horses are unable to clear S. neurona from visceral tissues, but the infection does not result in neurologic signs; in contrast, IC horses rapidly control parasitemia and infection of visceral tissues but frequently experience neuroinvasion and exhibit clinical signs of neurologic disease.

  4. The results of the radioiodine-therapy of benign thyroid diseases respecting the applied radiation dose

    International Nuclear Information System (INIS)

    Maier, C.

    1994-09-01

    452 patients with benign thyroid diseases had been explored after 6 weeks, 6 months, 1 year, 5 years and 10 years after undergone radioiodine treatment retrospectively with regard to the applied radiation dose. A relevant relation between the radiation dose and the rate of hypothyroidism could only be proved as a tendency. Treating hyperthyroidism with radioiodine, the rates of hypothyroidism after therapy were not caused by significantly higher radiation doses. Therefore suggestions to change the used radiation-doses basically cannot be made. The applied doses of radiation are sufficient to achieve a rather satisfactory effect in healing hyperthyroidism. Cases of malignancy after radioiodine therapy could not be found in this population. The effective half-life determination before therapy can be neglected, because there was found a significant difference between the pre-therapeutically estimated half-life and the post-therapeutically measured effective half-life of radioiodine. Instead, fixed values of effective half-life should be used for each group of benign thyroid diseases. The radiation therapy still seems to be an efficient treatment to cure benign thyroid diseases with rare side effects. It also can be applied to patients below the age of 40. Generally it is an alternative to drug-therapy or surgery, always considering the individual relation between gain and risk. In this respect good results can be obtained and a relapse of hyperthyroidism is hardly to expect. (author)

  5. Human Prolactin Point Mutations and Their Projected Effect on Vasoinhibin Generation and Vasoinhibin-Related Diseases

    Directory of Open Access Journals (Sweden)

    Jakob Triebel

    2017-11-01

    Full Text Available BackgroundA dysregulation of the generation of vasoinhibin hormones by proteolytic cleavage of prolactin (PRL has been brought into context with diabetic retinopathy, retinopathy of prematurity, preeclampsia, pregnancy-induced hypertension, and peripartum cardiomyopathy. Factors governing vasoinhibin generation are incompletely characterized, and the composition of vasoinhibin isoforms in human tissues or compartments, such as the circulation, is unknown. The aim of this study was to determine the possible contribution of PRL point mutations to the generation of vasoinhibins as well as to project their role in vasoinhibin-related diseases.MethodsProlactin sequences, point mutations, and substrate specificity information about the PRL cleaving enzymes cathepsin D, matrix metalloproteinases 8 and 13, and bone-morphogenetic protein 1 were retrieved from public databases. The consequences of point mutations in regard to their possible effect on vasoinhibin levels were projected on the basis of a score indicating the suitability of a particular sequence for enzymatic cleavage that result in vasoinhibin generation. The relative abundance and type of vasoinhibin isoforms were estimated by comparing the relative cleavage efficiency of vasoinhibin-generating enzymes.ResultsSix point mutations leading to amino acid substitutions in vasoinhibin-generating cleavage sites were found and projected to either facilitate or inhibit vasoinhibin generation. Four mutations affecting vasoinhibin generation in cancer tissues were found. The most likely composition of the relative abundance of vasoinhibin isoforms is projected to be 15 > 17.2 > 16.8 > 17.7 > 18 kDa vasoinhibin.ConclusionProlactin point mutations are likely to influence vasoinhibin levels by affecting the proteolysis efficiency of vasoinhibin-generating enzymes and should be monitored in patients with vasoinhibin-related diseases. Attempts to characterize vasoinhibin-related diseases

  6. Thermodynamic perspectives on genetic instructions, the laws of biology, diseased states and human population control

    Science.gov (United States)

    Saier, M. H.

    2014-01-01

    This article examines in a broad perspective entropy and some examples of its relationship to evolution, genetic instructions and how we view diseases. Many knowledge gaps abound, hence our understanding is still fragmented and incomplete. Living organisms are programmed by functional genetic instructions (FGI), through cellular communication pathways, to grow and reproduce by maintaining a variety of hemistable, ordered structures (low entropy). Living organisms are far from equilibrium with their surrounding environmental systems, which tends towards increasing disorder (increasing entropy). Organisms must free themselves from high entropy (high disorder) to maintain their cellular structures for a period of time sufficient enough to allow reproduction and the resultant offspring to reach reproductive ages. This time interval varies for different species. Bacteria, for example need no sexual parents; dividing cells are nearly identical to the previous generation of cells, and can begin a new cell cycle without delay under appropriate conditions. By contrast, human infants require years of care before they can reproduce. Living organisms maintain order in spite of their changing surrounding environment, that decreases order according to the second law of thermodynamics. These events actually work together since living organisms create ordered biological structures by increasing local entropy. From a disease perspective, viruses and other disease agents interrupt the normal functioning of cells. The pressure for survival may result in mechanisms that allow organisms to resist attacks by viruses, other pathogens, destructive chemicals and physical agents such as radiation. However, when the attack is successful, the organism can be damaged until the cell, tissue, organ or entire organism is no longer functional and entropy increases. PMID:21262480

  7. Circular RNAs: Biogenesis, Function and Role in Human Diseases

    Directory of Open Access Journals (Sweden)

    John Greene

    2017-06-01

    potential disease biomarkers and therapeutic targets in cancer.

  8. Future perspective of induced pluripotent stem cells for diagnosis, drug screening and treatment of human diseases.

    Science.gov (United States)

    Lian, Qizhou; Chow, Yenyen; Esteban, Miguel Angel; Pei, Duanqing; Tse, Hung-Fat

    2010-07-01

    Recent advances in stem cell biology have transformed the understanding of cell physiology and developmental biology such that it can now play a more prominent role in the clinical application of stem cell and regenerative medicine. Success in the generation of human induced pluripotent stem cells (iPS) as well as related emerging technology on the iPS platform provide great promise in the development of regenerative medicine. Human iPS cells show almost identical properties to human embryonic stem cells (ESC) in pluripotency, but avoid many of their limitations of use. In addition, investigations into reprogramming of somatic cells to pluripotent stem cells facilitate a deeper understanding of human stem cell biology. The iPS cell technology has offered a unique platform for studying the pathogenesis of human disease, pharmacological and toxicological testing, and cell-based therapy. Nevertheless, significant challenges remain to be overcome before the promise of human iPS cell technology can be realised.

  9. New perspectives on evolutionary medicine: the relevance of microevolution for human health and disease.

    Science.gov (United States)

    Rühli, Frank Jakobus; Henneberg, Maciej

    2013-04-29

    Evolutionary medicine (EM) is a growing field focusing on the evolutionary basis of human diseases and their changes through time. To date, the majority of EM studies have used pure theories of hominin macroevolution to explain the present-day state of human health. Here, we propose a different approach by addressing more empirical and health-oriented research concerning past, current and future microevolutionary changes of human structure, functions and pathologies. Studying generation-to-generation changes of human morphology that occurred in historical times, and still occur in present-day populations under the forces of evolution, helps to explain medical conditions and warns clinicians that their current practices may influence future humans. Also, analyzing historic tissue specimens such as mummies is crucial in order to address the molecular evolution of pathogens, of the human genome, and their coadaptations.

  10. UK Iatrogenic Creutzfeldt-Jakob disease: investigating human prion transmission across genotypic barriers using human tissue-based and molecular approaches.

    Science.gov (United States)

    Ritchie, Diane L; Barria, Marcelo A; Peden, Alexander H; Yull, Helen M; Kirkpatrick, James; Adlard, Peter; Ironside, James W; Head, Mark W

    2017-04-01

    Creutzfeldt-Jakob disease (CJD) is the prototypic human prion disease that occurs most commonly in sporadic and genetic forms, but it is also transmissible and can be acquired through medical procedures, resulting in iatrogenic CJD (iCJD). The largest numbers of iCJD cases that have occurred worldwide have resulted from contaminated cadaveric pituitary-derived human growth hormone (hGH) and its use to treat primary and secondary growth hormone deficiency. We report a comprehensive, tissue-based and molecular genetic analysis of the largest series of UK hGH-iCJD cases reported to date, including in vitro kinetic molecular modelling of genotypic factors influencing prion transmission