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Sample records for human disease caused

  1. 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

  2. [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).

  3. ANIMAL PATHOGENS THAT MAY CAUSE HUMAN DISEASE THAT ORIGINATE FROM FARM OPERATIONS

    Science.gov (United States)

    The recent increase in concentrated animal feeding operations in the United States has caused renewed concern regarding the infectious diseases that may be passed from farm animals to humans via the environment. It is also known that more than 20 recent epidemics among humans cou...

  4. 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.

  5. Human Hemorrhagic Fever Causing Arenaviruses: Molecular Mechanisms Contributing to Virus Virulence and Disease Pathogenesis

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    Junjie Shao

    2015-05-01

    Full Text Available Arenaviruses include multiple human pathogens ranging from the low-risk lymphocytic choriomeningitis virus (LCMV to highly virulent hemorrhagic fever (HF causing viruses such as Lassa (LASV, Junin (JUNV, Machupo (MACV, Lujo (LUJV, Sabia (SABV, Guanarito (GTOV, and Chapare (CHPV, for which there are limited preventative and therapeutic measures. Why some arenaviruses can cause virulent human infections while others cannot, even though they are isolated from the same rodent hosts, is an enigma. Recent studies have revealed several potential pathogenic mechanisms of arenaviruses, including factors that increase viral replication capacity and suppress host innate immunity, which leads to high viremia and generalized immune suppression as the hallmarks of severe and lethal arenaviral HF diseases. This review summarizes current knowledge of the roles of each of the four viral proteins and some known cellular factors in the pathogenesis of arenaviral HF as well as of some human primary cell-culture and animal models that lend themselves to studying arenavirus-induced HF disease pathogenesis. Knowledge gained from these studies can be applied towards the development of novel therapeutics and vaccines against these deadly human pathogens.

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

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    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.

  7. What Causes Heart Disease?

    Science.gov (United States)

    ... page from the NHLBI on Twitter. What Causes Heart Disease? Research suggests that coronary heart disease (CHD) begins with damage to the lining and ... causing coronary microvascular disease (MVD). Coronary MVD is heart disease that affects the heart's tiny arteries. The cause ...

  8. Environmental sources of rapid growing nontuberculous mycobacteria causing disease in humans.

    NARCIS (Netherlands)

    Ingen, J. van; Boeree, M.J.; Dekhuijzen, P.N.R.; Soolingen, D. van

    2009-01-01

    Nontuberculous mycobacteria are environmental, opportunistic pathogens whose role in human disease is increasingly recognized, especially regarding the rapid growing mycobacteria (RGM). RGM are recovered from various environmental sources, both natural and man-made. In water systems, RGM can survive

  9. Identification of the porcine homologous of human disease causing trinucleotide repeat sequences

    DEFF Research Database (Denmark)

    Madsen, Lone Bruhn; Thomsen, Bo; Sølvsten, Christina Ane Elisabeth

    2007-01-01

    expansion in the repeat number of intragenic trinucleotide repeats (TNRs) is associated with a variety of inherited human neurodegenerative diseases. To study the compositionof TNRs in a mammalian species representing an evolutionary intermediate between humans and arodents, we describe in this p...

  10. Perforinopathy: a spectrum of human immune disease caused by defective perforin delivery or function.

    Science.gov (United States)

    Voskoboinik, Ilia; Trapani, Joseph A

    2013-12-12

    Congenital perforin deficiency is considered a rare cause of human immunopathology and immune dysregulation, and classically presents as a fatal illness early in infancy. However, we propose that a group of related disorders in which killer lymphocytes deliver only partially active perforin or a reduced quantum of wild-type perforin to the immune synapse should be considered part of an extended syndrome with overlapping but more variable clinical features. Apart from the many rare mutations scattered over the coding sequences, up to 10% of Caucasians carry the severely hypomorphic PRF1 allele C272 > T (leading to A91V mutation) and the overall prevalence of the homozygous state for A91V is around 1 in 600 individuals. We therefore postulate that the partial loss of perforin function and its clinical consequences may be more common then currently suspected. An acute clinical presentation is infrequent in A91V heterozygous individuals, but we postulate that the partial loss of perforin function may potentially be manifested in childhood or early adulthood as "idiopathic" inflammatory disease, or through increased cancer susceptibility - either hematological malignancy or multiple, independent primary cancers. We suggest the new term "perforinopathy" to signify the common functional endpoints of all the known consequences of perforin deficiency and failure to deliver fully functional perforin.

  11. Perforinopathy: a spectrum of human immune disease caused by defective perforin delivery or function

    Directory of Open Access Journals (Sweden)

    Joseph A. Trapani

    2013-12-01

    Full Text Available Congenital perforin deficiency is considered a rare cause of human immunopathology and immune dysregulation, and classically presents as a fatal illness early in infancy. However, we propose that a group of related disorders in which killer lymphocytes deliver only partially active perforin or a reduced quantum of wild-type perforin to the immune synapse should be considered part of an extended syndrome with overlapping but more variable clinical features. Apart from the many rare mutations scattered over the coding sequences, up to 10% of Caucasians carry the severely hypomorphic PRF1 allele C272>T (leading to A91V mutation and the overall prevalence of the homozygous state for A91V is around 1 in 600 individuals. We therefore postulate that the partial loss of perforin function and its clinical consequences may be more common then currently suspected. An acute clinical presentation is infrequent in A91V heterozygous individuals, but we postulate that the partial loss of perforin function may potentially be manifested in childhood or early adulthood as ‘idiopathic’ inflammatory disease, or through increased cancer susceptibility – either hematological malignancy or multiple, independent primary cancers. We suggest the new term ‘perforinopathy’ to signify the common functional endpoints of all the known consequences of perforin-deficiency and failure to deliver fully functional perforin.

  12. Paternal age effect mutations and selfish spermatogonial selection: causes and consequences for human disease.

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    Goriely, Anne; Wilkie, Andrew O M

    2012-02-10

    Advanced paternal age has been associated with an increased risk for spontaneous congenital disorders and common complex diseases (such as some cancers, schizophrenia, and autism), but the mechanisms that mediate this effect have been poorly understood. A small group of disorders, including Apert syndrome (caused by FGFR2 mutations), achondroplasia, and thanatophoric dysplasia (FGFR3), and Costello syndrome (HRAS), which we collectively term "paternal age effect" (PAE) disorders, provides a good model to study the biological and molecular basis of this phenomenon. Recent evidence from direct quantification of PAE mutations in sperm and testes suggests that the common factor in the paternal age effect lies in the dysregulation of spermatogonial cell behavior, an effect mediated molecularly through the growth factor receptor-RAS signal transduction pathway. The data show that PAE mutations, although arising rarely, are positively selected and expand clonally in normal testes through a process akin to oncogenesis. This clonal expansion, which is likely to take place in the testes of all men, leads to the relative enrichment of mutant sperm over time-explaining the observed paternal age effect associated with these disorders-and in rare cases to the formation of testicular tumors. As regulation of RAS and other mediators of cellular proliferation and survival is important in many different biological contexts, for example during tumorigenesis, organ homeostasis and neurogenesis, the consequences of selfish mutations that hijack this process within the testis are likely to extend far beyond congenital skeletal disorders to include complex diseases, such as neurocognitive disorders and cancer predisposition.

  13. Human papillomavirus in cervical cancer and oropharyngeal cancer: One cause, two diseases.

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    Berman, Tara A; Schiller, John T

    2017-06-15

    Human papillomavirus (HPV) causes greater than 5% of cancers worldwide, including all cervical cancers and an alarmingly increasing proportion of oropharyngeal cancers (OPCs). Despite markedly reduced cervical cancer incidence in industrialized nations with organized screening programs, cervical cancer remains the second most common cause of death from cancer in women worldwide, as developing countries lack resources for universal, high-quality screening. In the United States, HPV-related OPC is only 1 of 5 cancers with a rising incidence since 1975 and now has taken over the cervix as the most common site of HPV-related cancer. Similar trends follow throughout North America and Europe. The need for early detection and prevention is paramount. Despite the common etiologic role of HPV in the development of cervical cancer and HPV-associated OPC, great disparity exists between incidence, screening modalities (or lack thereof), treatment, and prevention in these 2 very distinct cohorts. These differences in cervical cancer and HPV-associated OPC and their impact are discussed here. Cancer 2017;123:2219-2229. © 2017 American Cancer Society. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  14. Capturing all disease-causing mutations for clinical and research use: toward an effortless system for the Human Variome Project.

    Science.gov (United States)

    Cotton, Richard G H; Al Aqeel, Aida I; Al-Mulla, Fahd; Carrera, Paola; Claustres, Mireille; Ekong, Rosemary; Hyland, Valentine J; Macrae, Finlay A; Marafie, Makia J; Paalman, Mark H; Patrinos, George P; Qi, Ming; Ramesar, Rajkumar S; Scott, Rodney J; Sijmons, Rolf H; Sobrido, María-Jesús; Vihinen, Mauno

    2009-12-01

    The collection of genetic variants that cause inherited disease (causative mutation) has occurred for decades albeit in an ad hoc way, for research and clinical purposes. More recently, the access to collections of mutations causing specific diseases has become essential for appropriate genetic health care. Because information has accumulated, it has become apparent that there are many gaps in our ability to correctly annotate all the changes that are being identified at ever increasing rates. The Human Variome Project (www.humanvariomeproject.org) was initiated to facilitate integrated and systematic collection and access to this data. This manuscript discusses how collection of such data may be facilitated through new software and strategies in the clinical genetics and diagnostic laboratory communities.

  15. Proteflazid® and local immunity in diseases caused by human papillomavirus, herpesvirus and mixed urogenital infections.

    Science.gov (United States)

    Kaminsky, Vjacheslav; Chernyshov, Viktor; Grynevych, Oleksandr; Benyuk, Vasil; Kornatskaya, Alla; Shalko, Miroslava; Usevich, Igor; Revenko, Oleg; Shepetko, Maxim; Solomakha, Ludmila

    2017-03-21

    Reporting of clinical trials results for Proteflazid® in the drug formulation suppositories and vaginal swabs soaked in the solution of the drug to the local immunity of the female reproductive tract. The aim of study was to examine the state of local immunity in the reproductive tract of women with sexually transmitted diseases caused by human papillomavirus, herpes viruses (Type 1, 2) and mixed infection (herpes viruses + chlamydia). The trials involved 216 women with viral sexually transmitted diseases: Cervical Dysplasia associated with papillomavirus infection (HPV) (Group 1); Herpes genitalis type 1 (HSV- 1) and type 2 (HSV-1) (Group 2); mixed infection - HSV-1, HSV-2 and chlamydia (Group 3). Treatment results have confirmed that Proteflazid® contributes to sustainable performance improvement of basic factors of local immunity - sIgA, lysozyme and complement component C3 in the cervical mucus for all three groups of women. Proteflazid® enhances level of local immunity markers (sIgA, lysozyme, C3 complement component) and improves their ratios. Also it intensifies anticontagious activity of mucosal protection and female reproductive system as whole, during treatment diseases caused by human papillomavirus, herpesvirus and mixed urogenital infections (herpesvirus and chlamydia).

  16. West Nile virus lineage 2 as a cause of zoonotic neurological disease in humans and horses in southern Africa.

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    Venter, Marietjie; Swanepoel, Robert

    2010-10-01

    West Nile virus (WNV) is widely distributed in South Africa, but since a few cases of neurological disease have been reported from this region, endemic lineage 2 strains were postulated to be of low virulence. Several cases of nonfatal encephalitis in humans as well as fatal cases in a foal, dog, and ostrich chicks have, however, been associated with lineage 2 WNV in South Africa. The pathogenesis of lineage 2 WNV strains was investigated using mouse neuroinvasive experiments, gene expression experiments, and genome sequence comparisons which indicated that lineage 2 strains that are highly pathogenic exist. To determine whether cases of WNV were being missed in South Africa, horses with fever and neurological disease were investigated. Several cases of WNV were identified, all associated with severe neurological disease, 85% of which had to be euthanized or died. All cases positive by RT-PCR were shown to belong to lineage 2 WNV by DNA sequencing and phylogenetic analysis. Two cases of occupational infection were investigated, including a case of zoonotic transmission to a veterinarian who performed an autopsy on one of the horses as well as a laboratory infection after a needle stick injury with a neuroinvasive lineage 2 strain. Both resulted in neurological disease. Cytokine expression was investigated in the second case to assess the immunopathogenesis of WNV. Collectively, these studies suggest that lineage 2 WNV may be significantly under estimated as a cause of neurological disease in South Africa.

  17. Emergence in China of human disease due to avian influenza A(H10N8)--cause for concern?

    Science.gov (United States)

    To, Kelvin K W; Tsang, Alan K L; Chan, Jasper F W; Cheng, Vincent C C; Chen, Honglin; Yuen, Kwok-Yung

    2014-03-01

    In December 2013, China reported the first human case of avian influenza A(H10N8). A 73-year-old female with chronic diseases who had visited a live poultry market succumbed with community-acquired pneumonia. While human infections with avian influenza viruses are usually associated with subtypes prevalent in poultries, A(H10N8) isolates were mostly found in migratory birds and only recently in poultries. Although not possible to predict whether this single intrusion by A(H10N8) is an accident or the start of another epidemic like the preceding A(H7N9) and A(H5N1), several features suggest that A(H10N8) is a potential threat to humans. Recombinant H10 could attach to human respiratory epithelium, and A(H10N4) virus could cause severe infections in minks and chickens. A(H10N8) viruses contain genetic markers for mammalian adaptation and virulence in the haemagglutinin (A135T, S138A[H3 numbering]), M1(N30D, T215A), NS1(P42S) and PB2(E627K) protein. Studies on this human A(H10N8) isolate will reveal its adaptability to humans. Clinicians should alert the laboratory to test for A(H5,6,7,9,10) viruses in patients with epidemiological exposure in endemic geographical areas especially when human influenza A(H1,3) and B are negative. Vigilant virological and serological surveillance for A(H10N8) in human, poultry and wild bird is important for following the trajectory of this emerging influenza virus.

  18. Trypanosomatid parasites causing neglected diseases.

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    Nussbaum, K; Honek, J; Cadmus, C M C v C; Efferth, T

    2010-01-01

    Parasitic diseases such as Kala azar (visceral leishmaniasis), Chagas disease human (American trypanosomiasis) and African sleeping sickness (African trypanosomiasis) are affecting more than 27 million people worldwide. They are categorized amongst the most important neglected diseases causing approximately 150,000 deaths annually. As no vaccination is available, treatment is solely dependent on chemotherapeutic drugs. This review provides a comprehensive insight into the treatment of Kala azar, Chagas disease and African sleeping sickness. In addition to established drugs, novel small molecule- based therapeutic approaches are discussed. Drugs currently used for the treatment of Kala azar include pentavalent antimonials, Amphotericin B, Miltefosine, and Paromomycin. Liposomal formulations such as AmBisome provide promising alternatives. Furthermore, antiproliferative compounds might open new avenues in Kala azar treatment. Regarding Chagas disease, chemotherapy is based on two drugs, Nifurtimox and Benznidazole. However, sequencing of T. cruzi genome in the year 2005 raises a hope for new drug targets. Proteases, sterols and sialic acids are potential promising drug targets. Suramin, Pentamidine, Melarsporol and Eflornithine are well-established drugs to treat African sleeping sickness. New treatment options include combination therapy of Eflornithine and Nifurtimox, a Chagas disease therapeutic.. However, all approved chemotherapeutic compounds for trypanosomatid diseases suffer from high toxicity. Further, increasing resistance limits their efficacy and compliance.

  19. Crystal Structure of Human Dihydrolipoamide Dehydrogenase: NAD[superscript +]/NADH Binding and the Structural Basis of Disease-causing Mutations

    Energy Technology Data Exchange (ETDEWEB)

    Brautigam, Chad A.; Chuang, Jacinta L.; Tomchick, Diana R.; Machius, Mischa; Chuang, David T. (U. of Texas-SMED)

    2010-07-13

    Human dihydrolipoamide dehydrogenase (hE3) is an enzymatic component common to the mitochondrial {alpha}-ketoacid dehydrogenase and glycine decarboxylase complexes. Mutations to this homodimeric flavoprotein cause the often-fatal human disease known as E3 deficiency. To catalyze the oxidation of dihydrolipoamide, hE3 uses two molecules: noncovalently bound FAD and a transiently bound substrate, NAD{sup +}. To address the catalytic mechanism of hE3 and the structural basis for E3 deficiency, the crystal structures of hE3 in the presence of NAD{sup +} or NADH have been determined at resolutions of 2.5 {angstrom} and 2.1 {angstrom}, respectively. Although the overall fold of the enzyme is similar to that of yeast E3, these two structures differ at two loops that protrude from the proteins and at their FAD-binding sites. The structure of oxidized hE3 with NAD{sup +} bound demonstrates that the nicotinamide moiety is not proximal to the FAD. When NADH is present, however, the nicotinamide base stacks directly on the isoalloxazine ring system of the FAD. This is the first time that this mechanistically requisite conformation of NAD{sup +} or NADH has been observed in E3 from any species. Because E3 structures were previously available only from unicellular organisms, speculations regarding the molecular mechanisms of E3 deficiency were based on homology models. The current hE3 structures show directly that the disease-causing mutations occur at three locations in the human enzyme: the dimer interface, the active site, and the FAD and NAD{sup +}-binding sites. The mechanisms by which these mutations impede the function of hE3 are discussed.

  20. Capturing all disease-causing mutations for clinical and research use : Toward an effortless system for the Human Variome Project

    NARCIS (Netherlands)

    Cotton, Richard G. H.; Al Aqeel, Aida I.; Al-Mulla, Fahd; Carrera, Paola; Claustres, Mireille; Ekong, Rosemary; Hyland, Valentine J.; Macrae, Finlay A.; Marafie, Makia J.; Paalman, Mark H.; Patrinos, George P.; Qi, Ming; Ramesar, Rajkumar S.; Scott, Rodney J.; Sijmons, Rolf H.; Sobrido, Maria-Jesus; Vihinen, Mauno

    2009-01-01

    The collection of genetic variants that cause inherited disease (causative mutation) has occurred for decades albeit in an ad hoc way, for research and clinical purposes. More recently, the access to collections of mutations causing specific diseases has become essential for appropriate genetic heal

  1. Clustering self-organizing maps (SOM) method for human papillomavirus (HPV) DNA as the main cause of cervical cancer disease

    Science.gov (United States)

    Bustamam, A.; Aldila, D.; Fatimah, Arimbi, M. D.

    2017-07-01

    One of the most widely used clustering method, since it has advantage on its robustness, is Self-Organizing Maps (SOM) method. This paper discusses the application of SOM method on Human Papillomavirus (HPV) DNA which is the main cause of cervical cancer disease, the most dangerous cancer in developing countries. We use 18 types of HPV DNA-based on the newest complete genome. By using open-source-based program R, clustering process can separate 18 types of HPV into two different clusters. There are two types of HPV in the first cluster while 16 others in the second cluster. The analyzing result of 18 types HPV based on the malignancy of the virus (the difficultness to cure). Two of HPV types the first cluster can be classified as tame HPV, while 16 others in the second cluster are classified as vicious HPV.

  2. Canine disorder mirrors human disease: exonic deletion in HES7 causes autosomal recessive spondylocostal dysostosis in miniature Schnauzer dogs.

    Directory of Open Access Journals (Sweden)

    Cali E Willet

    Full Text Available Spondylocostal dysostosis is a congenital disorder of the axial skeleton documented in human families from diverse racial backgrounds. The condition is characterised by truncal shortening, extensive hemivertebrae and rib anomalies including malalignment, fusion and reduction in number. Mutations in the Notch signalling pathway genes DLL3, MESP2, LFNG, HES7 and TBX6 have been associated with this defect. In this study, spondylocostal dysostosis in an outbred family of miniature schnauzer dogs is described. Computed tomography demonstrated that the condition mirrors the skeletal defects observed in human cases, but unlike most human cases, the affected dogs were stillborn or died shortly after birth. Through gene mapping and whole genome sequencing, we identified a single-base deletion in the coding region of HES7. The frameshift mutation causes loss of functional domains essential for the oscillatory transcriptional autorepression of HES7 during somitogenesis. A restriction fragment length polymorphism test was applied within the immediate family and supported a highly penetrant autosomal recessive mode of inheritance. The mutation was not observed in wider testing of 117 randomly sampled adult miniature schnauzer and six adult standard schnauzer dogs; providing a significance of association of Praw = 4.759e-36 (genome-wide significant. Despite this apparently low frequency in the Australian population, the allele may be globally distributed based on its presence in two unrelated sires from geographically distant locations. While isolated hemivertebrae have been observed in a small number of other dog breeds, this is the first clinical and genetic diagnosis of spontaneously occurring spondylocostal dysostosis in a non-human mammal and offers an excellent model in which to study this devastating human disorder. The genetic test can be utilized by dog breeders to select away from the disease and avoid unnecessary neonatal losses.

  3. Richard Bradley: a unified, living agent theory of the cause of infectious diseases of plants, animals, and humans in the first decades of the 18th century.

    Science.gov (United States)

    Santer, Melvin

    2009-01-01

    During the years 1714 to 1721, Richard Bradley, who was later to become the first Professor of Botany at Cambridge University, proposed a unified, unique, living agent theory of the cause of infectious diseases of plants and animals and the plague of humans. Bradley's agents included microscopic organisms, revealed by the studies of Robert Hooke and Antony van Leeuwenhoek. His theory derived from his experimental studies of plants and their diseases and from microscopic observation of animalcules in different naturally occurring and artificial environments. He concluded that there was a microscopic world of "insects" that lived and reproduced under the appropriate conditions, and that infectious diseases of plants were caused by such "insects." Since there are structural and functional similarities between plants and animals, Bradley concluded that microscopic organisms caused human and animal infectious diseases as well. However, his living agent cause of infectious diseases was not accepted by the contemporary scientific society.

  4. The carrying pigeons of the cell: exosomes and their role in infectious diseases caused by human pathogens.

    Science.gov (United States)

    Fleming, Adam; Sampey, Gavin; Chung, Myung-Chul; Bailey, Charles; van Hoek, Monique L; Kashanchi, Fatah; Hakami, Ramin M

    2014-07-01

    Exosomes have recently been classified as the newest family members of 'bioactive vesicles' that function to promote intercellular communication. Long ignored and thought to be only a mechanism by which cellular waste is removed, exosomes have garnered a huge amount of interest in recent years as their critical functions in maintaining homeostasis through intercellular communication and also in different types of diseases have been demonstrated. Many groundbreaking studies of exosome functions have been performed in the cancer field and the infectious disease areas of study, revealing the importance and also the fascinating complexity of exosomal packaging, targeting, and functions. Selective packaging of exosomes in response to the type of infection, exosomal modulation of the immune response and host signaling pathways, exosomal regulation of pathogen spread, and effects of exosomes on the degree of pathogenesis have all been well documented. In this review, we provide a synthesis of the current understanding of the role of exosomes during infections caused by human pathogens and discuss the implications of these findings for a better understanding of pathogenic mechanisms and future therapeutic and diagnostic applications.

  5. What Causes Heart Valve Disease?

    Science.gov (United States)

    ... a heart attack or injury to the heart. Rheumatic Fever Untreated strep throat or other infections with strep bacteria that progress to rheumatic fever can cause heart valve disease. When the body ...

  6. The Microbiome: The Trillions of Microorganisms That Maintain Health and Cause Disease in Humans and Companion Animals.

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    Rodrigues Hoffmann, A; Proctor, L M; Surette, M G; Suchodolski, J S

    2016-01-01

    The microbiome is the complex collection of microorganisms, their genes, and their metabolites, colonizing the human and animal mucosal surfaces, digestive tract, and skin. It is now well known that the microbiome interacts with its host, assisting in digestion and detoxification, supporting immunity, protecting against pathogens, and maintaining health. Studies published to date have demonstrated that healthy individuals are often colonized with different microbiomes than those with disease involving various organ systems. This review covers a brief history of the development of the microbiome field, the main objectives of the Human Microbiome Project, and the most common microbiomes inhabiting the human respiratory tract, companion animal digestive tract, and skin in humans and companion animals. The main changes in the microbiomes in patients with pulmonary, gastrointestinal, and cutaneous lesions are described.

  7. Structural and Biochemical Consequences of Disease-Causing Mutations in the Ankyrin Repeat Domain of the Human TRPV4 Channel

    Energy Technology Data Exchange (ETDEWEB)

    Inada, Hitoshi; Procko, Erik; Sotomayor, Marcos; Gaudet, Rachelle (Harvard-Med); (Harvard)

    2012-10-23

    The TRPV4 calcium-permeable cation channel plays important physiological roles in osmosensation, mechanosensation, cell barrier formation, and bone homeostasis. Recent studies reported that mutations in TRPV4, including some in its ankyrin repeat domain (ARD), are associated with human inherited diseases, including neuropathies and skeletal dysplasias, probably because of the increased constitutive activity of the channel. TRPV4 activity is regulated by the binding of calmodulin and small molecules such as ATP to the ARD at its cytoplasmic N-terminus. We determined structures of ATP-free and -bound forms of human TRPV4-ARD and compared them with available TRPV-ARD structures. The third inter-repeat loop region (Finger 3 loop) is flexible and may act as a switch to regulate channel activity. Comparisons of TRPV-ARD structures also suggest an evolutionary link between ARD structure and ATP binding ability. Thermal stability analyses and molecular dynamics simulations suggest that ATP increases stability in TRPV-ARDs that can bind ATP. Biochemical analyses of a large panel of TRPV4-ARD mutations associated with human inherited diseases showed that some impaired thermal stability while others weakened ATP binding ability, suggesting molecular mechanisms for the diseases.

  8. Disease Outbreaks Caused by Water.

    Science.gov (United States)

    Craun, Gunther F.

    1978-01-01

    Presents a literature review of the disease outbreaks caused by drinking polluted water, covering publications of 1976-77. Some of the waterborn outbreaks included are: (1) cholera; (2) gastroenteritis; (3) giardiasis; and (4) typhoid fever and salmonellosis. A list of 66 references is also presented. (HM)

  9. Human Caused Fire and Acres

    Data.gov (United States)

    Bureau of Land Management, Department of the Interior — Number of wildland fires and acres burned as a result of human causes, from 2001 through 2008 (updated annually). Displayed by the eleven Geographic Areas used by...

  10. Nongenetic causes of Parkinson's disease.

    Science.gov (United States)

    Chade, A R; Kasten, M; Tanner, C M

    2006-01-01

    Study of the nongenetic causes of Parkinson's disease (PD) was encouraged by discovery of a cluster of parkinsonism produced by neurotoxic pyridine 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the 1980s. Since that time, epidemiologic investigations have suggested risk factors, though their results do not establish causality. Pesticide exposure has been associated with increased risk in many studies. Other proposed risks include rural residence and certain occupations. Cigarette smoking, use of coffee/caffeine, and non-steroidal antiinflammatory drugs (NSAIDs) all appear to lower risk of PD, while dietary lipid and milk consumption, high caloric intake, and head trauma may increase risk. The cause of PD is likely multifactorial. Underlying genetic susceptibility and combinations of risk and protective factors likely all contribute. The combined research effort by epidemiologists, geneticists, and basic scientists will be needed to clarify the cause(s) of PD.

  11. Cardiovascular disease in human immunodeficiency virus-infection as a cause of hospitalization: a case-series in a General Hospital in Peru.

    Science.gov (United States)

    Valenzuela-Rodríguez, Germán; Mezones-Holguín, Edward; Mendo-Urbina, Fernando; Rodríguez-Morales, Alfonso J

    2015-01-01

    Cardiovascular disease in the context of human immunodeficiency virus infection has become a major clinical concern in recent years. In the current report we assess hospitalizations due to cardiovascular disease in human immunodeficiency virus patients in a Social Security reference hospital in Peru. A retrospective study was carried out between January 1996 and December 2012 in a General Hospital in Lima, Peru. We included 26 patients hospitalized due to cardiovascular disease. Mean age was 46.3 years (SD 12.5), predominantly male (57.7%). Ten patients (38.4%) were in Acquired Immunodeficiency Syndrome stages. Seventeen (65.4%) received high-active-antiretroviral therapy. Eleven (42.3%) had cardiac involvement and 15 (57.7%) had non-cardiac vascular involvement. The most frequent causes of cardiac involvement were pericardial effusion and myocardial infarction. On the other hand, deep vein thrombosis and stroke were the most frequent for non-cardiac vascular involvement. Cardiovascular disease is an important cause of hospitalization in Peruvian human immunodeficiency virus patients, with differences between immunosuppression stages. Further studies analyzing associated factors are warranted. Copyright © 2015 Elsevier Editora Ltda. All rights reserved.

  12. Periodontal (Gum) Disease: Causes, Symptoms, and Treatments

    Science.gov (United States)

    ... for providing oral care. NIDCR > OralHealth > Topics > Gum (Periodontal) Diseases > Periodontal (Gum) Disease: Causes, Symptoms, and Treatments Periodontal ( ... U.S. currently have some form of the disease. Periodontal diseases range from simple gum inflammation to serious disease ...

  13. Pediatric genetic diseases causing glaucoma

    Science.gov (United States)

    Ichhpujani, Parul; Singh, Rohan B.

    2014-01-01

    Glaucomatous optic neuropathy may be considered as an endpoint of multiple systemic factors. Genetic conditions commonly causing glaucoma in children and adolescents include Axenfeld-Reiger syndrome, aniridia, Marfan syndrome, Weill-Marchessani syndrome, Sturge-Weber syndrome, Rubinstein-Taybi syndrome, nevus of Ota, congenital rubella and neurofibromatosis type 1. In the recent years, with the advancements in genetic research our understanding of the fundamental causes of glaucoma associated with inherited disorders has improved. In addition to intraocular pressure reduction, it is important for the clinician to be familiar with the multiple systemic associations with glaucoma, to re-evaluate treatment frequently, and to target the underlying disease process, if present. PMID:27625878

  14. Long-Range Structural Effects of a Charcot-Marie-Tooth Disease-Causing Mutation in Human Glycyl-TRNA Synthetase

    Energy Technology Data Exchange (ETDEWEB)

    Xie, W.; Nangle, L.A.; Zhang, W.; Schimmel, P.; Yang, X.-L.

    2009-06-04

    Functional expansion of specific tRNA synthetases in higher organisms is well documented. These additional functions may explain why dominant mutations in glycyl-tRNA synthetase (GlyRS) and tyrosyl-tRNA synthetase cause Charcot-Marie-Tooth (CMT) disease, the most common heritable disease of the peripheral nervous system. At least 10 disease-causing mutant alleles of GlyRS have been annotated. These mutations scatter broadly across the primary sequence and have no apparent unifying connection. Here we report the structure of wild type and a CMT-causing mutant (G526R) of homodimeric human GlyRS. The mutation is at the site for synthesis of glycyl-adenylate, but the rest of the two structures are closely similar. Significantly, the mutant form diffracts to a higher resolution and has a greater dimer interface. The extra dimer interactions are located {approx}30 {angstrom} away from the G526R mutation. Direct experiments confirm the tighter dimer interaction of the G526R protein. The results suggest the possible importance of subtle, long-range structural effects of CMT-causing mutations at the dimer interface. From analysis of a third crystal, an appended motif, found in higher eukaryote GlyRSs, seems not to have a role in these long-range effects.

  15. Allovahlkampfia spelaea Causing Keratitis in Humans

    Science.gov (United States)

    Tolba, Mohammed Essa Marghany; Huseein, Enas Abdelhameed Mahmoud; Farrag, Haiam Mohamed Mahmoud; Mohamed, Hanan El Deek; Kobayashi, Seiki; Suzuki, Jun; Ali, Tarek Ahmed Mohamed; Sugano, Sumio

    2016-01-01

    Background Free-living amoebae are present worldwide. They can survive in different environment causing human diseases in some instances. Acanthamoeba sp. is known for causing sight-threatening keratitis in humans. Free-living amoeba keratitis is more common in developing countries. Amoebae of family Vahlkampfiidae are rarely reported to cause such affections. A new genus, Allovahlkampfia spelaea was recently identified from caves with no data about pathogenicity in humans. We tried to identify the causative free-living amoeba in a case of keratitis in an Egyptian patient using morphological and molecular techniques. Methods Pathogenic amoebae were culture using monoxenic culture system. Identification through morphological features and 18S ribosomal RNA subunit DNA amplification and sequencing was done. Pathogenicity to laboratory rabbits and ability to produce keratitis were assessed experimentally. Results Allovahlkampfia spelaea was identified as a cause of human keratitis. Whole sequence of 18S ribosomal subunit DNA was sequenced and assembled. The Egyptian strain was closely related to SK1 strain isolated in Slovenia. The ability to induce keratitis was confirmed using animal model. Conclusions This the first time to report Allovahlkampfia spelaea as a human pathogen. Combining both molecular and morphological identification is critical to correctly diagnose amoebae causing keratitis in humans. Use of different pairs of primers and sequencing amplified DNA is needed to prevent misdiagnosis. PMID:27415799

  16. Allovahlkampfia spelaea Causing Keratitis in Humans.

    Directory of Open Access Journals (Sweden)

    Mohammed Essa Marghany Tolba

    2016-07-01

    Full Text Available Free-living amoebae are present worldwide. They can survive in different environment causing human diseases in some instances. Acanthamoeba sp. is known for causing sight-threatening keratitis in humans. Free-living amoeba keratitis is more common in developing countries. Amoebae of family Vahlkampfiidae are rarely reported to cause such affections. A new genus, Allovahlkampfia spelaea was recently identified from caves with no data about pathogenicity in humans. We tried to identify the causative free-living amoeba in a case of keratitis in an Egyptian patient using morphological and molecular techniques.Pathogenic amoebae were culture using monoxenic culture system. Identification through morphological features and 18S ribosomal RNA subunit DNA amplification and sequencing was done. Pathogenicity to laboratory rabbits and ability to produce keratitis were assessed experimentally.Allovahlkampfia spelaea was identified as a cause of human keratitis. Whole sequence of 18S ribosomal subunit DNA was sequenced and assembled. The Egyptian strain was closely related to SK1 strain isolated in Slovenia. The ability to induce keratitis was confirmed using animal model.This the first time to report Allovahlkampfia spelaea as a human pathogen. Combining both molecular and morphological identification is critical to correctly diagnose amoebae causing keratitis in humans. Use of different pairs of primers and sequencing amplified DNA is needed to prevent misdiagnosis.

  17. Necrotizing Fasciitis Resulting from Human Bites: A Report of Two Cases of Disease Caused by Group A Streptococci

    Directory of Open Access Journals (Sweden)

    Christopher A Sikora

    2005-01-01

    Full Text Available Necrotizing fasciitis is a serious and potentially life-threatening condition. Although bite wounds are common, they are not frequently reported as a cause of necrotizing fasciitis. In the present article, two cases of bite-associated necrotizing fasciitis caused by group A streptococcus are reported. Previously published cases are also reviewed.

  18. Experimental chronic hepatitis B infection of neonatal tree shrews (Tupaia belangeri chinensis: A model to study molecular causes for susceptibility and disease progression to chronic hepatitis in humans

    Directory of Open Access Journals (Sweden)

    Wang Qi

    2012-08-01

    Full Text Available Abstract Background Hepatitis B virus (HBV infection continues to be an escalating global health problem. Feasible and effective animal models for HBV infection are the prerequisite for developing novel therapies for this disease. The tree shrew (Tupaia is a small animal species evolutionary closely related to humans, and thus is permissive to certain human viral pathogens. Whether tree shrews could be chronically infected with HBV in vivo has been controversial for decades. Most published research has been reported on adult tree shrews, and only small numbers of HBV infected newborn tree shrews had been observed over short time periods. We investigated susceptibility of newborn tree shrews to experimental HBV infection as well as viral clearance over a protracted time period. Results Forty-six newborn tree shrews were inoculated with the sera from HBV-infected patients or tree shrews. Serum and liver samples of the inoculated animals were periodically collected and analyzed using fluorescence quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, Southern blot, and immunohistochemistry. Six tree shrews were confirmed and four were suspected as chronically HBV-infected for more than 48 (up to 228 weeks after inoculation, including three that had been inoculated with serum from a confirmed HBV-infected tree shrew. Conclusions Outbred neonatal tree shrews can be long-term chronically infected with HBV at a frequency comparable to humans. The model resembles human disease where also a smaller proportion of infected individuals develop chronic HBV related disease. This model might enable genetic and immunologic investigations which would allow determination of underlying molecular causes favoring susceptibility for chronic HBV infection and disease establishment vs. viral clearance.

  19. Leucine-rich α2-glycoprotein is a novel biomarker of neurodegenerative disease in human cerebrospinal fluid and causes neurodegeneration in mouse cerebral cortex.

    Directory of Open Access Journals (Sweden)

    Masakazu Miyajima

    Full Text Available Leucine-rich α2-glycoprotein (LRG is a protein induced by inflammation. It contains a leucine-rich repeat (LRR structure and easily binds with other molecules. However, the function of LRG in the brain during aging and neurodegenerative diseases has not been investigated. Here, we measured human LRG (hLRG concentration in the cerebrospinal fluid (CSF and observed hLRG expression in post-mortem human cerebral cortex. We then generated transgenic (Tg mice that over-expressed mouse LRG (mLRG in the brain to examine the effects of mLRG accumulation. Finally, we examined protein-protein interactions using a protein microarray method to screen proteins with a high affinity for hLRG. The CSF concentration of hLRG increases with age and is significantly higher in patients with Parkinson's disease with dementia (PDD and progressive supranuclear palsy (PSP than in healthy elderly people, idiopathic normal pressure hydrocephalus (iNPH patients, and individuals with Alzheimer's disease (AD. Tg mice exhibited neuronal degeneration and neuronal decline. Accumulation of LRG in the brains of PDD and PSP patients is not a primary etiological factor, but it is thought to be one of the causes of neurodegeneration. It is anticipated that hLRG CSF levels will be a useful biomarker for the early diagnosis of PDD and PSP.

  20. Piscine mycobacteriosis: a literature review covering the agent and the disease it causes in fish and humans.

    Science.gov (United States)

    Decostere, A; Hermans, K; Haesebrouck, F

    2004-04-19

    Mycobacterium marinum, M. fortuitum and M. chelonae are the etiological agents of fish mycobacteriosis. Fish mycobacteriosis is a disseminated infection reported in more than 150 fish species and is usually accompanied by emaciation and death over a period of months to years. Granulomas are formed both externally and scattered throughout the internal organs. Treatment is in most cases unsatisfactory and the overall recommendation is to destroy the diseased stock, particularly since these pathogens are capable of affecting man as well as fish. Especially fish handlers and aquarium hobbyists are infected and the disease is mostly confined to the superficial, cooler body tissues, most often the extremities. Dissemination is apparently rare but has been reported.

  1. An outbreak of acute respiratory disease caused by a virus associated RNA II gene mutation strain of human adenovirus 7 in China, 2015

    Science.gov (United States)

    Liang, Beibei; Wu, Fuli; Li, Hao; Liu, Hongbo; Sheng, Chunyu; Ma, Qiuxia; Yang, Chaojie; Xie, Jing; Li, Peng; Jia, Leili; Wang, Ligui; Du, Xinying; Qiu, Shaofu; Song, Hongbin

    2017-01-01

    Human adenovirus 7 (HAdV-7) strains are a major cause of acute respiratory disease (ARD) among adults and children, associated with fatal pneumonia. An ARD outbreak caused by HAdV-7 that involved 739 college students was reported in this article. To better understand the underlying cause of this large-scale epidemic, virus strains were isolated from infected patients and sequence variations of the whole genome sequence were detected. Evolutionary trees and alignment results indicated that the major capsid protein genes hexon and fibre were strongly conserved among serotype 7 strains in China at that time. Instead, the HAdV-7 strains presented three thymine deletions in the virus associated RNA (VA RNA) II terminal region. We also found that the mutation might lead to increased mRNA expression of an adjacent gene, L1 52/55K, and thus promoted faster growth. These findings suggest that sequence variation of VA RNA II gene was a potential cause of such a severe HAdV-7 infection and this gene should be a new-emerging factor to be monitored for better understanding of HAdV-7 infection. PMID:28225804

  2. What Causes Coronary Microvascular Disease?

    Science.gov (United States)

    ... inside the arteries. Risk factors for atherosclerosis include: Diabetes . It is a disease in which the body’s blood sugar level is too high because the body doesn’t make enough insulin or doesn’t use its insulin properly. Family history of early heart disease . Your risk of atherosclerosis ...

  3. Addison's Disease: Symptoms and Causes

    Science.gov (United States)

    ... Low blood sugar (hypoglycemia) Nausea, diarrhea or vomiting Abdominal pain Muscle or joint pains Irritability Depression Body hair loss ... in both men and women. They cause sexual development in men, and influence muscle mass, libido and ...

  4. Two-photon excited endogenous fluorescence for label-free in vivo imaging ingestion of disease-causing bacteria by human leukocytes

    Science.gov (United States)

    Zeng, Yan; Yan, Bo; Sun, Qiqi; Teh, Seng Khoon; Zhang, Wei; Wen, Zilong; Qu, Jianan Y.

    2013-02-01

    Real time and in vivo monitoring leukocyte behavior provides unique information to understand the physiological and pathological process of infection. In this study, we demonstrate that two-photon excited reduced nicotinamide adenine dinucleotide (NADH) fluorescence provides imaging contrast to distinguish granulocyte and agranulocyte. By using spectral and time-resolved NADH fluorescence, we study the immune response of human neutrophils against bacterial infection (Escherichia coli). The two-photon excited NADH fluorescence images clearly review the morphological changes from resting neutrophils (round shape) to activated neutrophils (ruffle shape) during phagocytosis. The free-tobound NADH ratio of neutrophils decreases after ingesting disease-causing pathogen: Escherichia coli. This finding may provide a new optical tool to investigate inflammatory processes by using NADH fluorescence in vivo.

  5. 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.

  6. Re-emergent human adenovirus genome type 7d caused an acute respiratory disease outbreak in Southern China after a twenty-one year absence.

    Science.gov (United States)

    Zhao, Suhui; Wan, Chengsong; Ke, Changwen; Seto, Jason; Dehghan, Shoaleh; Zou, Lirong; Zhou, Jie; Cheng, Zetao; Jing, Shuping; Zeng, Zhiwei; Zhang, Jing; Wan, Xuan; Wu, Xianbo; Zhao, Wei; Zhu, Li; Seto, Donald; Zhang, Qiwei

    2014-12-08

    Human adenoviruses (HAdVs) are highly contagious pathogens causing acute respiratory disease (ARD), among other illnesses. Of the ARD genotypes, HAdV-7 presents with more severe morbidity and higher mortality than the others. We report the isolation and identification of a genome type HAdV-7d (DG01_2011) from a recent outbreak in Southern China. Genome sequencing, phylogenetic analysis, and restriction endonuclease analysis (REA) comparisons with past pathogens indicate HAdV-7d has re-emerged in Southern China after an absence of twenty-one years. Recombination analysis reveals this genome differs from the 1950s-era prototype and vaccine strains by a lateral gene transfer, substituting the coding region for the L1 52/55 kDa DNA packaging protein from HAdV-16. DG01_2011 descends from both a strain circulating in Southwestern China (2010) and a strain from Shaanxi causing a fatality and outbreak (Northwestern China; 2009). Due to the higher morbidity and mortality rates associated with HAdV-7, the surveillance, identification, and characterization of these strains in population-dense China by REA and/or whole genome sequencing are strongly indicated. With these accurate identifications of specific HAdV types and an epidemiological database of regional HAdV pathogens, along with the HAdV genome stability noted across time and space, the development, availability, and deployment of appropriate vaccines are needed.

  7. Did transmission of Helicobacter pylori from humans cause a disease outbreak in a colony of Stripe-faced Dunnarts (Sminthopsis macroura)?

    Science.gov (United States)

    2011-01-01

    Since the discovery that Helicobacter pylori causes a range of pathologies in the stomachs of infected humans, it has become apparent that Helicobacters are found in a diverse range of animal species where they are frequently associated with disease. In 2003 and 2004, there were two outbreaks of increased mortality associated with gastric bleeding and weight-loss in a captive colony of the Australian marsupial, the Stripe-faced Dunnart (Sminthopsis macroura). The presence of gastric pathology led to an investigation of potential Helicobacter pathogenesis in these animals. Histological examination revealed the presence of gastritis, and PCR analysis confirmed the presence of Helicobacter infection in the stomachs of these marsupials. Surprisingly, sequencing of 16S rRNA from these bacteria identified the species as H. pylori and PCR confirmed the strain to be positive for the important pathogenesis factor, cagA. We therefore describe, for the first time, an apparent reverse zoonotic infection of Stripe-faced Dunnarts with H. pylori. Already prone to pathological effects of stress (as experienced during breeding season), concomitant H. pylori infection appears to be a possible essential but not sufficient co-factor in prototypic gastric bleeding and weight loss in these marsupials. The Stripe-faced Dunnart could represent a new model for investigating Helicobacter-driven gastric pathology. Infections from their human handlers, specifically of H. pylori, may be a potential risk to captive colonies of marsupials. PMID:21314909

  8. Did transmission of Helicobacter pylori from humans cause a disease outbreak in a colony of Stripe-faced Dunnarts (Sminthopsis macroura?

    Directory of Open Access Journals (Sweden)

    Every Alison L

    2011-02-01

    Full Text Available Abstract Since the discovery that Helicobacter pylori causes a range of pathologies in the stomachs of infected humans, it has become apparent that Helicobacters are found in a diverse range of animal species where they are frequently associated with disease. In 2003 and 2004, there were two outbreaks of increased mortality associated with gastric bleeding and weight-loss in a captive colony of the Australian marsupial, the Stripe-faced Dunnart (Sminthopsis macroura. The presence of gastric pathology led to an investigation of potential Helicobacter pathogenesis in these animals. Histological examination revealed the presence of gastritis, and PCR analysis confirmed the presence of Helicobacter infection in the stomachs of these marsupials. Surprisingly, sequencing of 16S rRNA from these bacteria identified the species as H. pylori and PCR confirmed the strain to be positive for the important pathogenesis factor, cagA. We therefore describe, for the first time, an apparent reverse zoonotic infection of Stripe-faced Dunnarts with H. pylori. Already prone to pathological effects of stress (as experienced during breeding season, concomitant H. pylori infection appears to be a possible essential but not sufficient co-factor in prototypic gastric bleeding and weight loss in these marsupials. The Stripe-faced Dunnart could represent a new model for investigating Helicobacter-driven gastric pathology. Infections from their human handlers, specifically of H. pylori, may be a potential risk to captive colonies of marsupials.

  9. Pathologic and phenotypic alterations in a mouse expressing a connexin47 missense mutation that causes Pelizaeus-Merzbacher-like disease in humans.

    Directory of Open Access Journals (Sweden)

    Oliver Tress

    2011-07-01

    Full Text Available Gap junction channels are intercellular conduits that allow diffusional exchange of ions, second messengers, and metabolites. Human oligodendrocytes express the gap junction protein connexin47 (Cx47, which is encoded by the GJC2 gene. The autosomal recessive mutation hCx47M283T causes Pelizaeus-Merzbacher-like disease 1 (PMLD1, a progressive leukodystrophy characterized by hypomyelination, retarded motor development, nystagmus, and spasticity. We introduced the human missense mutation into the orthologous position of the mouse Gjc2 gene and inserted the mCx47M282T coding sequence into the mouse genome via homologous recombination in embryonic stem cells. Three-week-old homozygous Cx47M282T mice displayed impaired rotarod performance but unchanged open-field behavior. 10-15-day-old homozygous Cx47M282T and Cx47 null mice revealed a more than 80% reduction in the number of cells participating in glial networks after biocytin injections into oligodendrocytes in sections of corpus callosum. Homozygous expression of mCx47M282T resulted in reduced MBP expression and astrogliosis in the cerebellum of ten-day-old mice which could also be detected in Cx47 null mice of the same age. Three-month-old homozygous Cx47M282T mice exhibited neither altered open-field behavior nor impaired rotarod performance anymore. Adult mCx47M282T expressing mice did not show substantial myelin alterations, but homozygous Cx47M282T mice, additionally deprived of connexin32, which is also expressed in oligodendrocytes, died within six weeks after birth and displayed severe myelin defects accompanied by astrogliosis and activated microglia. These results strongly suggest that PMLD1 is caused by the loss of Cx47 channel function that results in impaired panglial coupling in white matter tissue.

  10. 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...

  11. Mycobacterium paratuberculosis as a cause of Crohn's disease.

    Science.gov (United States)

    McNees, Adrienne L; Markesich, Diane; Zayyani, Najah R; Graham, David Y

    2015-01-01

    Crohn's disease is a chronic inflammatory bowel disease of unknown cause, affecting approximately 1.4 million North American people. Due to the similarities between Crohn's disease and Johne's disease, a chronic enteritis in ruminant animals caused by Mycobacterium avium paratuberculosis (MAP) infection, MAP has long been considered to be a potential cause of Crohn's disease. MAP is an obligate intracellular pathogen that cannot replicate outside of animal hosts. MAP is widespread in dairy cattle and because of environmental contamination and resistance to pasteurization and chlorination, humans are frequently exposed through contamination of food and water. MAP can be cultured from the peripheral mononuclear cells from 50-100% of patients with Crohn's disease, and less frequently from healthy individuals. Association does not prove causation. We discuss the current data regarding MAP as a potential cause of Crohn's disease and outline what data will be required to firmly prove or disprove the hypothesis.

  12. Chromatin remodeling and human disease.

    Science.gov (United States)

    Huang, Cheng; Sloan, Emily A; Boerkoel, Cornelius F

    2003-06-01

    In the past few years, there has been a nascent convergence of scientific understanding of inherited human diseases with epigenetics. Identified epigenetic processes involved in human disease include covalent DNA modifications, covalent histone modifications, and histone relocation. Each of these processes influences chromatin structure and thereby regulates gene expression and DNA methylation, replication, recombination, and repair. The importance of these processes for nearly all aspects of normal growth and development is illustrated by the array of multi-system disorders and neoplasias caused by their dysregulation.

  13. Interstitial lung disease probably caused by imipramine.

    Science.gov (United States)

    Deshpande, Prasanna R; Ravi, Ranjani; Gouda, Sinddalingana; Stanley, Weena; Hande, Manjunath H

    2014-01-01

    Drugs are rarely associated with causing interstitial lung disease (ILD). We report a case of a 75-year-old woman who developed ILD after exposure to imipramine. To our knowledge, this is one of the rare cases of ILD probably caused due to imipramine. There is need to report such rare adverse effects related to ILD and drugs for better management of ILD.

  14. An unusual cause of pancytopenia: Whipple's disease

    Directory of Open Access Journals (Sweden)

    Nay T. Tun

    2014-04-01

    Full Text Available Whipple's disease is a systemic infectious disease caused by the bacteria Tropheryma whipplei. The most common clinical manifestations of Whipple's disease are weight loss (92%, hypoalbuminemia and steatorrhea (91%, respectively, diarrhea (72%, arthralgia (67%, and abdominal pain (55%. Neurological signs and symptoms from dementia to oculomasticatory myorhythmia or oculofacioskeletal myorhythmia (pathognomonic of Whipple's disease, lymphadenopathy, and fatigue can also be present. Pancytopenia is a rare and less recognized clinical feature in Whipple's disease patients. We are describing a case where a middle-aged Caucasian male diagnosed with Whipple's disease was found to have pancytopenia. Etiology of pancytopenia is postulated to be due to the invasion of bone marrow by T. whipplei. It is important to recognize that bone marrow involvement by the Whipple bacillus is not uncommon. In the presence of lymphadenopathy and pancytopenia, clinicians should think of Whipple's disease as a differential diagnosis apart from lymphoma or other non-specific granulomatous reticuloendothelial disorders.

  15. Retroviruses and human disease.

    OpenAIRE

    1987-01-01

    Over the past 25 years animal retroviruses have been favoured subjects of research by virologists, oncologists, and molecular biologists. Retroviruses have given us reverse transcriptase, oncogenes, and cloning vectors that may one day be exploited for human gene therapy. They have also given us leukaemia and the acquired immune deficiency syndrome (AIDS). Kawasaki disease and tropical spastic paraparesis are thought to be associated with retrovirus infection, and other diseases such as de Qu...

  16. Disease Caused by Chemical and Physical Agents

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    2011286 Relationship between the methylation and mutation of p53 gene and endemic arsenism caused by coal-burning. ZHANG Aihua(張愛華),et al.Dept Toxicol,Guiyang Med Coll,Guiyang 550004.Abstract:Objective To explore the influence of arsenic pollution caused by coal-burning on methylation(promoter and exon 5) and mutation(exon 5) of human p53 gene,and to analyze the

  17. Occupational respiratory disease caused by acrylates.

    Science.gov (United States)

    Savonius, B; Keskinen, H; Tuppurainen, M; Kanerva, L

    1993-05-01

    Acrylates are compounds used in a variety of industrial fields and their use is increasing. They have many features which make them superior to formerly used chemicals, regarding both their industrial use and their possible health effects. Contact sensitization is, however, one of their well known adverse health effects but they may also cause respiratory symptoms. We report on 18 cases of respiratory disease, mainly asthma, caused by different acrylates, 10 cases caused by cyanoacrylates, four by methacrylates and two cases by other acrylates.

  18. Chilli anthracnose disease caused by Colletotrichum species

    Institute of Scientific and Technical Information of China (English)

    Po Po THAN; Haryudian PRIHASTUTI; Sitthisack PHOULIVONG; Paul W.J. TAYLOR; Kevin D. HYDE

    2008-01-01

    Anthracnose disease is one of the major economic constraints to chilli production worldwide, especially in tropical and subtropical regions. Accurate taxonomic information is necessary for effective disease control management. In the Colletotrichum patho-system, different Colletotrichum species can be associated with anthracnose of the same host. Little information is known concerning the interactions of the species associated with the chilli anthracnose although several Colletotrichum species have been reported as causal agents of chilli anthracnose disease worldwide. The ambiguous taxonomic status of Colletotrichum species has resulted in inaccurate identification which may cause practical problems in plant breeding and disease management. Although the management and control of anthracnose disease are still being extensively researched, commercial eultivars of Capsicum annuum that are resistant to the pathogens that cause chilli anthracnose have not yet been developed. This paper reviews the causal agents of chilli anthracnose, the disease cycle, conventional methods in identification of the pathogen and molecular approaches that have been used for the identification of Colletotrichum species. Pathogenetic variation and population structure of the causal agents of chilli anthracnose along with the current taxonomic status of Colletotrichum species are discussed. Future developments leading to the disease management strategies are suggested.

  19. Chilli anthracnose disease caused by Colletotrichum species.

    Science.gov (United States)

    Than, Po Po; Prihastuti, Haryudian; Phoulivong, Sitthisack; Taylor, Paul W J; Hyde, Kevin D

    2008-10-01

    Anthracnose disease is one of the major economic constraints to chilli production worldwide, especially in tropical and subtropical regions. Accurate taxonomic information is necessary for effective disease control management. In the Colletotrichum patho-system, different Colletotrichum species can be associated with anthracnose of the same host. Little information is known concerning the interactions of the species associated with the chilli anthracnose although several Colletotrichum species have been reported as causal agents of chilli anthracnose disease worldwide. The ambiguous taxonomic status of Colletotrichum species has resulted in inaccurate identification which may cause practical problems in plant breeding and disease management. Although the management and control of anthracnose disease are still being extensively researched, commercial cultivars of Capsicum annuum that are resistant to the pathogens that cause chilli anthracnose have not yet been developed. This paper reviews the causal agents of chilli anthracnose, the disease cycle, conventional methods in identification of the pathogen and molecular approaches that have been used for the identification of Colletotrichum species. Pathogenetic variation and population structure of the causal agents of chilli anthracnose along with the current taxonomic status of Colletotrichum species are discussed. Future developments leading to the disease management strategies are suggested.

  20. Invasive Disease Caused by Nontypeable Haemophilus Influenzae

    Centers for Disease Control (CDC) Podcasts

    2015-11-12

    Dr. Elizabeth Briere discusses Nontypeable Haemophilus influenzae which causes a variety of infections in children and adults.  Created: 11/12/2015 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 11/17/2015.

  1. Symptoms and Causes of Peptic Ulcer Disease

    Science.gov (United States)

    ... pylori are spiral-shaped bacteria that can cause peptic ulcer disease by damaging the mucous coating that protects the lining of the stomach and duodenum. Once H. pylori have damaged the mucous coating, powerful stomach acid can get through to the sensitive lining. Together, ...

  2. Genes Causing Male Infertility in Humans

    Institute of Scientific and Technical Information of China (English)

    Lawrence C. Layman

    2002-01-01

    There are an accumulating number of identified gene mutations that cause infertility in humans. Most of the known gene mutations impair normal puberty and subsequently cause infertility by either hypothalamic /pituitary deficiency of important tropic factors to the gonad or by gonadal genes.

  3. An unusual cause of granulomatous disease

    Directory of Open Access Journals (Sweden)

    Higgins Bernard

    2007-03-01

    Full Text Available Abstract Background Chronic granulomatous disease (CGD is an inherited disorder of phagocytic cells caused by an inability to generate active microbicidal oxygen species required kill certain types of fungi and bacteria. This leads to recurrent life-threatening bacterial and fungal infections with tissue granuloma formation. Case presentation We describe a case of X-linked Chronic granulomatous disease (CGD diagnosed in an 18-year-old male. He initially presented with granulomatous disease mimicking sarcoidosis and was treated with corticosteroids. He subsequently developed Burkholderia cepacia complex pneumonia and further investigation confirmed a diagnosis of CGD. Conclusion Milder phenotypes of CGD are now being recognised. CGD should be considered in patients of any age with granulomatous diseases, especially if there is a history of recurrent or atypical infection.

  4. Could astrocytes be the primary target of an offending agent causing the primary degenerative diseases of the human central nervous system? A hypothesis.

    Science.gov (United States)

    Sica, Roberto E

    2015-05-01

    Most of the named primary degenerative diseases of the human central nervous system have been attributed to a direct, primary damage of some particular population of neurons. Within the spectrum of these illnesses there are disorders like amyotrophic lateral sclerosis, fronto-temporal dementia, Alzheimer's dementia, Parkinson's disease, Huntington's dementia and cerebellar ataxias affecting exclusively the human species. In the last years it has been shown that non-neural cells, mainly astrocytes, have a crucial role in the starting and development of these diseases. We suggest that the causative agent of these illnesses gets home first within the astrocytes, rather than the neurons, making them sick by modifying the structure of some proteins; from these cells the abnormal process would start a trip to other astrocytes having the same genetic, metabolic, structural and functional profiles that the originally affected astrocytes have, going through the gap junctions which connect that particular population devoted to a particular set of neurons. This appears to be a likely hypothesis because the astrocytes related to a defined population of neurons have their own, private properties and characteristics needed to support one particular set of neurons performing a defined function, making them a different and unique population, a fact which would limit the spreading of the disease to those astrocytes, sparing other astrocyte populations which do not share those characteristics. If this were the mechanism underlying these illnesses, the neurons, which their health depends on those astrocytes, would be deprived of their patronage and would start all the changes that characterizes a programmed cell death, and the clinical manifestations of a defined pathology would consequently appear. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Uncommon causes of occupational interstitial lung diseases.

    Science.gov (United States)

    Gong, H

    1996-09-01

    Uncommon causes of occupational interstitial lung disease, or pneumoconiosis, are being increasingly recognized and diagnosed. The fibrogenic potential of numerous types of respirable inorganic particles remains poorly understood but is significantly determined by lung deposition and clearance, the agent's size and solubility, host susceptibility, and other factors. Microanalytic techniques have improved the identification of uncommon or unusual biopersistent particles or elements in fibrotic lung tissue. Recent findings in workers exposed to manmade vitreous fibers, silicon carbide, talc, titanium, cerium, and polyvinyl chloride provide new clinical insights into not only their specific fibrogenic capabilities but also in the broader appreciation that many cases of unexplained interstitial lung disease may be caused by occupational exposures to one or more uncommon airborne substances.

  6. Invasive Disease Caused by Nontypeable Haemophilus influenzae

    Science.gov (United States)

    de Jonge, Marien I.

    2015-01-01

    The incidence of severe Haemophilus influenza infections, such as sepsis and meningitis, has declined substantially since the introduction of the H. influenzae serotype b vaccine. However, the H. influenzae type b vaccine fails to protect against nontypeable H. influenzae strains, which have become increasingly frequent causes of invasive disease, especially among children and the elderly. We summarize recent literature supporting the emergence of invasive nontypeable H. influenzae and describe mechanisms that may explain its increasing prevalence over the past 2 decades. PMID:26407156

  7. Immunogenetics and the cause of autoimmune disease.

    Science.gov (United States)

    Baxter, A G

    1997-01-01

    Autoimmune disease results from the action of environmental factors on a predisposed genotype. In this review, the role of genetic susceptibility in the aetiology of autoimmune disease is examined. As the genetics of autoimmune diabetes has been studied more intensively than that of other autoimmune diseases, supporting evidence is drawn principally from that example. Autoimmune diseases are not inherited as entities but as constitutions which confer an increased probability of developing disease. It is proposed that there are two components to autoimmune disease susceptibility. One confers susceptibility to autoimmunity per se, while the other determines tissue specificity. In this review, the concept of liability is introduced as a tool used in quantitative genetics and is applied to the analysis of autoimmune diabetes by considering a threshold model. In this example, empirically derived incidence figures are used to calculate heritability which is a relative measure of the influence of genetics and environmental factors. The validity of applying the concept of liability to diabetes is confirmed by examining the values of heritability calculated from empirical data obtained from different kindred relationships, and by confirming that the assumptions on which liability is based are supported by recent gene mapping data. Finally, the physiological significance of liability is considered and its significance to the cause of autoimmunity discussed.

  8. 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.

  9. Spectrum of Disease Caused by Rhodococcus equi in Human Immunodeficiency Virus Infection: Report of a Case and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Sandra K Willsie-Ediger

    1990-01-01

    Full Text Available Since the first report of Rhodococcus equi infection in an acquired immune deficiency syndrome patient in 1986, seven additional cases have been described. A patient is described in whom the diagnosis was delayed due to misidentification of the organism as an atypical mycobacterial species. The literature regarding R equi infection in persons infected with the human immunodeficiency virus is reviewed. The most common presentation is one of a chronic, indolent pulmonary infiltrative disease (78%. Fever (78%, cough (67%, and hemoptysis (44% are frequently present. Coexistent opportunistic illnesses are common (67%. In the laboratory identification of this organism, it is important to communicate the clinical setting to the microbiologist and to recognize the potential for the organism to be overlooked as normal flora or a contaminant, or misidentified as an organism with similar phenotypic characteristics (Nocardia species or a rapidly growing mycobacterium. Based on experience in foals, therapy with erythromycin and rifampin is suggested.

  10. Global emergence of Alphaviruses that cause arthritis in humans

    Directory of Open Access Journals (Sweden)

    Olivia Wesula Lwande

    2015-12-01

    Full Text Available Arthropod-borne viruses (arboviruses may cause severe emerging and re-emerging infectious diseases, which pose a significant threat to human and animal health in the world today. These infectious diseases range from mild febrile illnesses, arthritis, and encephalitis to haemorrhagic fevers. It is postulated that certain environmental factors, vector competence, and host susceptibility have a major impact on the ecology of arboviral diseases. Presently, there is a great interest in the emergence of Alphaviruses because these viruses, including Chikungunya virus, O'nyong'nyong virus, Sindbis virus, Ross River virus, and Mayaro virus, have caused outbreaks in Africa, Asia, Australia, Europe, and America. Some of these viruses are more common in the tropics, whereas others are also found in temperate regions, but the actual factors driving Alphavirus emergence and re-emergence remain unresolved. Furthermore, little is known about the transmission dynamics, pathophysiology, genetic diversity, and evolution of circulating viral strains. In addition, the clinical presentation of Alphaviruses may be similar to other diseases such as dengue, malaria, and typhoid, hence leading to misdiagnosis. However, the typical presence of arthritis may distinguish between Alphaviruses and other differential diagnoses. The absence of validated diagnostic kits for Alphaviruses makes even routine surveillance less feasible. For that purpose, this review describes the occurrence, genetic diversity, clinical characteristics, and the mechanisms involving Alphaviruses causing arthritis in humans. This information may serve as a basis for better awareness and detection of Alphavirus-caused diseases during outbreaks and in establishing appropriate prevention and control measures.

  11. Global emergence of Alphaviruses that cause arthritis in humans.

    Science.gov (United States)

    Lwande, Olivia Wesula; Obanda, Vincent; Bucht, Göran; Mosomtai, Gladys; Otieno, Viola; Ahlm, Clas; Evander, Magnus

    2015-01-01

    Arthropod-borne viruses (arboviruses) may cause severe emerging and re-emerging infectious diseases, which pose a significant threat to human and animal health in the world today. These infectious diseases range from mild febrile illnesses, arthritis, and encephalitis to haemorrhagic fevers. It is postulated that certain environmental factors, vector competence, and host susceptibility have a major impact on the ecology of arboviral diseases. Presently, there is a great interest in the emergence of Alphaviruses because these viruses, including Chikungunya virus, O'nyong'nyong virus, Sindbis virus, Ross River virus, and Mayaro virus, have caused outbreaks in Africa, Asia, Australia, Europe, and America. Some of these viruses are more common in the tropics, whereas others are also found in temperate regions, but the actual factors driving Alphavirus emergence and re-emergence remain unresolved. Furthermore, little is known about the transmission dynamics, pathophysiology, genetic diversity, and evolution of circulating viral strains. In addition, the clinical presentation of Alphaviruses may be similar to other diseases such as dengue, malaria, and typhoid, hence leading to misdiagnosis. However, the typical presence of arthritis may distinguish between Alphaviruses and other differential diagnoses. The absence of validated diagnostic kits for Alphaviruses makes even routine surveillance less feasible. For that purpose, this review describes the occurrence, genetic diversity, clinical characteristics, and the mechanisms involving Alphaviruses causing arthritis in humans. This information may serve as a basis for better awareness and detection of Alphavirus-caused diseases during outbreaks and in establishing appropriate prevention and control measures.

  12. 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.

  13. Alloxan-Induced Diabetes Causes Morphological and Ultrastructural Changes in Rat Liver that Resemble the Natural History of Chronic Fatty Liver Disease in Humans

    Directory of Open Access Journals (Sweden)

    Amanda Natália Lucchesi

    2015-01-01

    Full Text Available Purpose. This study evaluated the long-term effects of alloxan-induced diabetes in rat liver. Methods. Thirty nondiabetic control rats (NC and 30 untreated diabetic (UD rats were divided into three subgroups sacrificed after 6, 14, or 26 weeks. Clinical and laboratory parameters were assessed. Fresh liver weight and its relationship with body weight were obtained, and liver tissue was analyzed. Results. UD rats showed sustained hyperglycemia, high glycosylated hemoglobin, and low plasma insulin. High serum levels of AST and ALT were observed in UD rats after 2 weeks, but only ALT remained elevated throughout the experiment. Fresh liver weight was equal between NC and UD rats, but the fresh liver weight/body weight ratio was significantly higher in UD rats after 14 and 26 weeks. UD rats showed liver morphological changes characterized by hepatic sinusoidal enlargement and micro- and macrovesicular hepatocyte fatty degeneration with progressive liver structure loss, steatohepatitis, and periportal fibrosis. Ultrastructural changes of hepatocytes, such as a decrease in the number of intracytoplasmic organelles and degeneration of mitochondria, rough endoplasmic reticulum, and nuclei, were also observed. Conclusion. Alloxan-induced diabetes triggered liver morphological and ultrastructural changes that closely resembled human disease, ranging from steatosis to steatohepatitis and liver fibrosis.

  14. Genetic Mapping in Human Disease

    OpenAIRE

    Altshuler, David; Daly, Mark J; Lander, Eric S.

    2008-01-01

    Genetic mapping provides a powerful approach to identify genes and biological processes underlying any trait influenced by inheritance, including human diseases. We discuss the intellectual foundations of genetic mapping of Mendelian and complex traits in humans, examine lessons emerging from linkage analysis of Mendelian diseases and genome-wide association studies of common diseases, and discuss questions and challenges that lie ahead.

  15. Clouds caused by human activities: the anthropoclouds

    Science.gov (United States)

    Mazon, Jordi; Costa, Marcel; Pino, David; Lorente, Jeroni

    2013-04-01

    The classification of clouds is based on the pioneering classification carried out by Howard (1804). In this classification, and also in the successive editions of the International Classification of Clouds published by the World Meteorological Organization (WMO, 1975, 1987) 10 basic cloud genera are included and described. In all cases, the cause that leads to the formation of clouds remains as a secondary issue. It is assumed that all of them are exclusively produced by natural mechanisms without any human intervention. However, aerosol and water vapour emissions produced by human activity may increase cloud formation having an increasing importance in the atmospheric energy budget and consequently in the earth's climate. Effectively, since the end of the Nineteenth century, human activity has been injecting large amounts of water vapour into the atmosphere, cloud condensation nuclei and hot air mainly generated in the combustion processes that under certain spatial and temporal conditions can enhance cloud formation. These anthropogenic aerosols are linked to the climate and the water cycle (Kaufman et al, 2002). The aim of this communication is to point out the anthropic origin of some clouds in the cloud classification. Several cases of the 7 basic genera cloud caused by human activities will be shown to discuss the importance of differentiating the origin of clouds in weather observations. This differentiation would improve the understanding the contribution of these clouds to climate change. To differentiate the clouds formed by human activity, we propose to use the prefix anthropo- before the scientific name (and a- before the abbreviation) in some of the 10 basic clouds defined by the International Classification of Clouds, those which could have an anthropic origin, and thus begin new data of cloud observations that could help future research to improve the effect of human activity in the troposphere.

  16. DNA replication stress: causes, resolution and disease.

    Science.gov (United States)

    Mazouzi, Abdelghani; Velimezi, Georgia; Loizou, Joanna I

    2014-11-15

    DNA replication is a fundamental process of the cell that ensures accurate duplication of the genetic information and subsequent transfer to daughter cells. Various pertubations, originating from endogenous or exogenous sources, can interfere with proper progression and completion of the replication process, thus threatening genome integrity. Coordinated regulation of replication and the DNA damage response is therefore fundamental to counteract these challenges and ensure accurate synthesis of the genetic material under conditions of replication stress. In this review, we summarize the main sources of replication stress and the DNA damage signaling pathways that are activated in order to preserve genome integrity during DNA replication. We also discuss the association of replication stress and DNA damage in human disease and future perspectives in the field. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  17. Male Infertility and Its Causes in Human

    Directory of Open Access Journals (Sweden)

    Toshinobu Miyamoto

    2012-01-01

    Full Text Available Infertility is one of the most serious social problems facing advanced nations. In general, approximate half of all cases of infertility are caused by factors related to the male partner. To date, various treatments have been developed for male infertility and are steadily producing results. However, there is no effective treatment for patients with nonobstructive azoospermia, in which there is an absence of mature sperm in the testes. Although evidence suggests that many patients with male infertility have a genetic predisposition to the condition, the cause has not been elucidated in the vast majority of cases. This paper discusses the environmental factors considered likely to be involved in male infertility and the genes that have been clearly shown to be involved in male infertility in humans, including our recent findings.

  18. [Gastrointestinal human myiasis caused by Eristalis tenax].

    Science.gov (United States)

    Kun, M; Kreiter, A; Semenas, L

    1998-08-01

    The myiasis observed in Bariloche are characterized and the probable conditions under which the infestations took place established. The larvae obtained from faeces of 2 patients were identified as Eristalis tenax (Diptera: Syrphidae) according to Hartley (1961) and Organización Panamericana de la Salud keys (1962). These 2 cases of human gastrointestinal myiasis were the first to be registered in Bariloche (Patagonia, Argentina) and their characteristics were similar to those described for this species in other parts of the world. The lack of specific control measures in the domestic water supply system was the most probable cause of the infestation. This event extends the distribution of E. tenax and human gastrointestinal myiasis in South America to 41 degrees 03' S.

  19. A rare cause of acute flaccid paralysis: Human coronaviruses

    Directory of Open Access Journals (Sweden)

    Cokyaman Turgay

    2015-01-01

    Full Text Available Acute flaccid paralysis (AFP is a life-threatening clinical entity characterized by weakness in the whole body muscles often accompanied by respiratory and bulbar paralysis. The most common cause is Gullian-Barre syndrome, but infections, spinal cord diseases, neuromuscular diseases such as myasthenia gravis, drugs and toxins, periodic hypokalemic paralysis, electrolyte disturbances, and botulism should be considered as in the differential diagnosis. Human coronaviruses (HCoVs cause common cold, upper and lower respiratory tract disease, but in the literature presentation with the lower respiratory tract infection and AFP has not been reported previously. In this study, pediatric case admitted with lower respiratory tract infection and AFP, who detected for HCoV 229E and OC43 co-infection by the real-time polymerase chain reaction, has been reported for the first time.

  20. Gaucher disease causing sudden cardiac death

    Directory of Open Access Journals (Sweden)

    Yehia Saleh

    2016-09-01

    Full Text Available A 17-year-old male patient with Gaucher disease was presented to our institution complaining of rapid irregular palpitations. Echocardiography showed the presence of critical aortic stenosis due to Gaucher disease.

  1. [Aluminum, hypothetic cause of Alzheimer disease].

    Science.gov (United States)

    Pailler, F M; Bequet, D; Corbé, H; Giudicelli, C P

    1995-03-11

    A great deal of research has focused on aluminium as a putative causative factor in Alzheimer's disease. We measured by atomic absorption spectrophotometry aluminium levels in blood, urine and cerebrospinal fluid from 15 patients with Alzheimer's disease, compared with 20 control individuals. There were no statistically significant differences between the two groups. This suggests that aluminium is not a causative factor for Alzheimer's disease.

  2. [Primary human demodicosis. A disease sui generis].

    Science.gov (United States)

    Hsu, C-K; Zink, A; Wei, K-J; Dzika, E; Plewig, G; Chen, W

    2015-03-01

    Human Demodex mites (Demodex folliculorum and Demodex brevis) are unique in that they are an obligate human ectoparasite that can inhabit the pilosebaceous unit lifelong without causing obvious host immune response in most cases. The mode of symbiosis between humans and human Demodex mites is unclear, while the pathogenicity of human Demodex mites in many inflammatory skin diseases is now better understood. Primary human demodicosis is a skin disease sui generis not associated with local or systemic immunosuppression. Diagnosis is often underestimated and differentiation from folliculitis, papulopustular rosacea and perioral dermatitis is not always straightforward. Dependent on the morphology and degree of inflammation, the clinical manifestations can be classified into spinulate, papulopustular, nodulocystic, crustic and fulminant demodicosis. Therapy success can be achieved only with acaricides/arachidicides. The effective doses, optimal regimen and antimicrobial resistance remain to be determined.

  3. [Pulmonary hypertension caused by left heart disease].

    Science.gov (United States)

    Erer, Betül; Eren, Mehmet

    2010-09-01

    Increased resistance to pulmonary venous drainage is the main mechanism in pulmonary hypertension (PH) developing due to left heart disease. This condition may occur as a result of various diseases affecting left ventricle, left atrium, mitral or aortic valves. Pulmonary hypertension is the common and well-recognized complication of left ventricular systolic dysfunction and pulmonary arterial hypertension accompanying chronic heart failure is related to increased mortality. Treatment should be tailored according to the underlying disease.

  4. Animal Diseases Caused by Orbiviruses, Algeria

    Science.gov (United States)

    Madani, Hafsa; Casal, Jordi; Alba, Anna; Allepuz, Alberto; Cêtre-Sossah, Catherine; Hafsi, Leila; Kount-Chareb, Houria; Bouayed-Chaouach, Nadera; Saadaoui, Hassiba

    2011-01-01

    Antibodies against bluetongue virus were detected in cattle, sheep, goats, and camels in Algeria in 2008. Antibodies against epizootic hemorrhagic disease virus were detected in cattle, but antibodies against African horse sickness virus were not detected in horses and mules. Epizootic hemorrhagic disease in northern Africa poses a major risk for the European Union. PMID:22172371

  5. Diseases caused by mutations in ORAI1 and STIM1

    Science.gov (United States)

    Lacruz, Rodrigo S.; Feske, Stefan

    2015-01-01

    Ca2+ release-activated Ca2+ (CRAC) channels mediate a specific form of Ca2+ influx called store-operated Ca2+ entry (SOCE) that contributes to the function of many cell types. CRAC channels are formed by ORAI1 proteins located in the plasma membrane, which form its ion-conducting pore. ORAI1 channels are activated by stromal interaction molecule (STIM) 1 and STIM2 located in the endoplasmic reticulum. Loss- and gain-of-function gene mutations in ORAI1 and STIM1 in human patients cause distinct disease syndromes. CRAC channelopathy is caused by loss-of-function mutations in ORAI1 and STIM1 that abolish CRAC channel function and SOCE; it is characterized by severe combined immunodeficiency (SCID)-like disease, autoimmunity, muscular hypotonia, and ectodermal dysplasia, with defects in dental enamel. The latter defect emphasizes an important role of CRAC channels in tooth development. By contrast, autosomal dominant gain-of-function mutations in these genes result in constitutive CRAC channel activation, SOCE, and increased intracellular Ca2+ levels that are associated with an overlapping spectrum of diseases, including non-syndromic tubular aggregate myopathy (TAM) and York platelet and Stormorken syndromes, two syndromes defined, besides myopathy, by thrombocytopenia, thrombopathy, and bleeding diathesis. The fact that myopathy results from loss- and gain-of-function mutations in ORAI1 and STIM1 highlights the importance of CRAC channels for Ca2+ homeostasis in skeletal muscle function. The cellular dysfunction and clinical disease spectrum observed in mutant patients provide important information about the molecular regulation of ORAI1 and STIM1 proteins and the role of CRAC channels in human physiology. PMID:26469693

  6. Viral diseases and human evolution

    OpenAIRE

    2000-01-01

    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 l...

  7. [3] Diseases Caused By Bacterial Pathogens In Inland Water

    OpenAIRE

    若林, 久嗣; 吉田, 照豊; 野村, 哲一; 中井, 敏博; 高野, 倫一

    2016-01-01

    Bacterial diseases cause huge damages in fish farms worldwide, and numerous bacterial pathogens from inland and saline waters have been identified and studied for their characterization, diagnosis, prevention and control. In this chapter, eight important fish diseases viz. 1) streptococcosis (inland water), 2) furunculosis, 3) bacterial gill disease, 4) columnaris disease, 5) bacterial cold-water disease, 6) red spot disease, 7) edwardsiellosis (Edwardsiella ictaluri), and 8) motile aeromonad...

  8. Cis-regulatory mutations in human disease.

    Science.gov (United States)

    Epstein, Douglas J

    2009-07-01

    Cis-acting regulatory sequences are required for the proper temporal and spatial control of gene expression. Variation in gene expression is highly heritable and a significant determinant of human disease susceptibility. The diversity of human genetic diseases attributed, in whole or in part, to mutations in non-coding regulatory sequences is on the rise. Improvements in genome-wide methods of associating genetic variation with human disease and predicting DNA with cis-regulatory potential are two of the major reasons for these recent advances. This review will highlight select examples from the literature that have successfully integrated genetic and genomic approaches to uncover the molecular basis by which cis-regulatory mutations alter gene expression and contribute to human disease. The fine mapping of disease-causing variants has led to the discovery of novel cis-acting regulatory elements that, in some instances, are located as far away as 1.5 Mb from the target gene. In other cases, the prior knowledge of the regulatory landscape surrounding the gene of interest aided in the selection of enhancers for mutation screening. The success of these studies should provide a framework for following up on the large number of genome-wide association studies that have identified common variants in non-coding regions of the genome that associate with increased risk of human diseases including, diabetes, autism, Crohn's, colorectal cancer, and asthma, to name a few.

  9. 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.

  10. DISEASE CAUSED BY CHEMICAL AND PHYSICAL AGENTS

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    2003161 Study on mechanism of carcinogenic effect and genetic damage of arsenism caused by burning coal. ZHANG Aihua(张爱华), et al. Dept Prev Med, Guiyang Med Coll, Guiyang 550004. Guiyang 550009. Chin J Endemiol 2003; 22( 1): 12-15.

  11. Unusual causes of intrahepatic cholestatic liver disease

    Institute of Scientific and Technical Information of China (English)

    Elias E Mazokopakis; John A Papadakis; Diamantis P Kofteridis

    2007-01-01

    We report five cases with unusual causes of intrahepatic cholestasis,including consumption of Teucrium polium (family Lamiaceae) in the form of tea,Stauffer's syndrome,treatment with tamoxifen citrate for breast cancer,infection with Coxiella Burnetii (acute Q fever),and infection with Brucella melitensis (acute brucellosis).

  12. Lipophilic chemical exposure as a cause of cardiovascular disease

    OpenAIRE

    Zeliger, Harold I.

    2013-01-01

    Environmental chemical exposure has been linked to numerous diseases in humans. These diseases include cancers; neurological and neurodegenerative diseases; metabolic disorders including type 2 diabetes, metabolic syndrome and obesity; reproductive and developmental disorders; and endocrine disorders. Many studies have associated the link between exposures to environmental chemicals and cardiovascular disease (CVD). These chemicals include persistent organic pollutants (POPs); the plastic exu...

  13. [Stressors as the cause of gerontopsychiatric diseases].

    Science.gov (United States)

    Oesterreich, K

    1984-01-01

    It is permitted to apply concepts of stress theory to clinical geropsychiatry. Biographical factors, health, illness, organic and psychosocial factors of immediate and indirect kind are very important on development and course of geropsychiatric disease. Special significance has the influence of aging. Quantity and quality of stressors must be judged as non-specificial causal factors. Treatment depends on ascertained factors. The interpretation is explained on examples of depression, dementia, and institutionalism syndrome.

  14. Diseases Caused by Chemical and Physical Agents

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    2005150 Fluorosis on expression of nocotinic acety-choline acetylcholine receptors in protein and gene levels in human SH-SY5Y neuroblastoma cells. GUAN Zhi-zhong(官志忠)?, et al. Key Lab Molec Biol, Guiyang Med Coll, Guizhou 550004. Chin J Prev Med, 2005;39(1):26-29. Objective: To investigate the influence of fluorosis on nicotinic acetylcholine receptors (nAChRs) in protein and gene levels in SH-SY5Y cells and the mecha-

  15. DNA characterization of the spirochete that causes Lyme disease.

    Science.gov (United States)

    Schmid, G P; Steigerwalt, A G; Johnson, S E; Barbour, A G; Steere, A C; Robinson, I M; Brenner, D J

    1984-01-01

    Lyme disease, a tick-borne disease long recognized in Europe but only recently recognized in the United States, was shown in 1982-1983 to be caused by a spirochete, the Lyme disease spirochete. Whether one or more species of the spirochete exists is unknown, as is its taxonomic status. To answer these questions, we determined (i) the DNA base (guanidine-plus-cytosine) content for five strains; (ii) the DNA relatedness of 10 strains from Europe or the United States (isolated from ticks, humans, and a mouse) by DNA hybridization (hydroxyapatite assay at 50 and 65 degrees C); and (iii) the DNA relatedness to other pathogenic spirochetes. The guanine-plus-cytosine content of the Lyme disease spirochete strains was 27.5 to 29.0 mol%, most similar to those of Borrelia hermsii (30.6 mol%) and Treponema hyodysenteriae (25.6 mol%) among the other spirochetes tested. DNA hybridization studies with 32P-labeled DNA from Lyme disease spirochete strain TLO-005, a human blood isolate, revealed divergence (unpaired bases) within related nucleotide sequences of only 0.0 to 1.0% for all nine Lyme disease spirochete strains tested for relatedness to TLO-005. Relatedness values of seven strains to TLO-005 were 58 to 98% (mean, 71%) in 50 degrees C reactions and 50 to 93% (mean, 69%) in 65 degrees C reactions. Two other strains, from which very low yields of DNA were obtained, showed less relatedness (36 to 50 degrees C, 38 to 47% at 65 degrees C). These were nonetheless considered to belong to the same species because of the low amount of divergence in the sequences related to TLO-005 and the absence of decreased relatedness in reactions done at 65 degrees Celsius compared with those done at 50 degrees Celsius. DNA from strain TLO-005 showed relatedness of 1% to DNAs of two leptospires and 16% relatedness to DNA from T. hyodysenteriae. B. hermsii DNA was 30 to 40% related to three Lyme disease spirochete strains in 50 degrees Celsius reactions. Divergence in these reactions was 16

  16. [Human factors caused the third plague epidemic in Harbin].

    Science.gov (United States)

    Jin, Dong-Ying; Li, Zhi-Ping

    2011-03-01

    The third plague epidemic in Harbin broke out in 1946 and ended in 1954. Different from the first two plague epidemics (imported), the third prevalence was both imported and idiopathic infectious disease which was caused by human factors. Japanese troops set forbidden zones to build a biological weapon center, which destroyed the natural environment and offered a good growth condition for Citellus Undulatus. In 1945, on the eve of surrender, the Japanese blew up the Unit 731 germ factory located in a bungalow district, which caused diffusion of infected plague fleas. Mice of the district were infected and a man-made plague focus was created. During the prevalence of the third plague, prevention departments at all levels took a series of actions and with people's efforts, the plague was effectively controlled.

  17. Lack of exercise is a major cause of chronic diseases

    OpenAIRE

    Booth, Frank W.; Roberts, Christian K.; Laye, Matthew J.

    2012-01-01

    Chronic diseases are major killers in the modern era. Physical inactivity is a primary cause of most chronic diseases. The initial third of the article considers: activity and prevention definitions; historical evidence showing physical inactivity is detrimental to health and normal organ functional capacities; cause vs. treatment; physical activity and inactivity mechanisms differ; gene-environment interaction [including aerobic training adaptations, personalized medicine, and...

  18. Tenosynovitis caused by texting: an emerging disease.

    Science.gov (United States)

    Ashurst, John V; Turco, Domenic A; Lieb, Brian E

    2010-05-01

    De Quervain tenosynovitis is characterized by pain that overlies the radial aspect of the wrist and that is aggravated by ulnar deviation of the hand. The most common cause of de Quervain tenosynovitis is overuse of the thumb musculature. The authors report a case of bilateral de Quervain tenosynovitis observed in a woman aged 48 years at a rural outpatient primary care office. The condition was induced by the patient's excessive use of the text messaging feature on her cellular telephone. Treatment, including naproxen, cock-up wrist splints, and limitation of texting, resulted in complete recovery of the patient. The authors urge physicians to be aware of the potential association between a patient's tenosynovitis symptoms and excessive texting.

  19. Linking Microbiota to Human Diseases

    DEFF Research Database (Denmark)

    Wu, Hao; Tremaroli, Valentina; Bäckhed, F

    2015-01-01

    diabetes (T2D), and irritable bowel syndrome, and some animal experiments have suggested causality. However, few studies have validated causality in humans and the underlying mechanisms remain largely to be elucidated. We discuss how systems biology approaches combined with new experimental technologies......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...... may disentangle some of the mechanistic details in the complex interactions of diet, microbiota, and host metabolism and may provide testable hypotheses for advancing our current understanding of human-microbiota interaction....

  20. Disease causing mutations of calcium channels.

    Science.gov (United States)

    Lorenzon, Nancy M; Beam, Kurt G

    2008-01-01

    Calcium ions play an important role in the electrical excitability of nerve and muscle, as well as serving as a critical second messenger for diverse cellular functions. As a result, mutations of genes encoding calcium channels may have subtle affects on channel function yet strongly perturb cellular behavior. This review discusses the effects of calcium channel mutations on channel function, the pathological consequences for cellular physiology, and possible links between altered channel function and disease. Many cellular functions are directly or indirectly regulated by the free cytosolic calcium concentration. Thus, calcium levels must be very tightly regulated in time and space. Intracellular calcium ions are essential second messengers and play a role in many functions including, action potential generation, neurotransmitter and hormone release, muscle contraction, neurite outgrowth, synaptogenesis, calcium-dependent gene expression, synaptic plasticity and cell death. Calcium ions that control cell activity can be supplied to the cell cytosol from two major sources: the extracellular space or intracellular stores. Voltage-gated and ligand-gated channels are the primary way in which Ca(2+) ions enter from the extracellular space. The sarcoplasm reticulum (SR) in muscle and the endoplasmic reticulum in non-muscle cells are the main intracellular Ca(2+) stores: the ryanodine receptor (RyR) and inositol-triphosphate receptor channels are the major contributors of calcium release from internal stores.

  1. [Human hantavirus diseases - still neglected zoonoses?].

    Science.gov (United States)

    Vrbovská, V; Chalupa, P; Straková, P; Hubálek, Z; Rudolf, I

    2015-10-01

    Hantavirus disease is the most common rodent-borne viral infection in the Czech Republic, with a mean annual incidence of 0.02 cases per 100 000 population and specific antibodies detected in 1% of the human population. Four hantaviruses (Puumala, Dobrava-Belgrade, Tula, and Seewis) circulate in this country, of which Puumala virus (responsible for a mild form of hemorrhagic fever with renal syndrome called nephropathia epidemica) and Dobrava-Belgrade virus (causing haemorrhagic fever with renal syndrome) have been proven to cause human disease. The aim of this study is to provide a comprehensive review of the hantaviruses occurring in the Czech Republic, based on the literature published during the past three decades, including their geographical distribution and clinical symptoms. The recent detection of Tula virus in an immunocompromised person as well as reports of Seoul virus infections in Europe highlight the possible emergence of neglected hantavirus infections in the foreseeable future.

  2. Rheumatologic diseases as the cause of fever of unknown origin

    NARCIS (Netherlands)

    Mulders-Manders, C.M.; Simon, A.; Bleeker-Rovers, C.P.

    2016-01-01

    In 30% of patients with fever or inflammation of unknown origin (FUO/IUO), the cause is eventually found to be a rheumatologic disease such as autoimmune or granulomatous disease or vasculitis. Most of these patients suffer from an uncommon presentation of a common disease, instead of an uncommon

  3. Human parasitic meningitis caused by Angiostrongylus cantonensis infection in Taiwan.

    Science.gov (United States)

    Tsai, Hung-Chin; Chen, Yao-Shen; Yen, Chuan-Min

    2013-06-01

    The major cause of eosinophilic meningitis in Taiwan is Angiostrongylus cantonensis. Humans are infected by ingesting terrestrial and freshwater snails and slugs. In 1998 and 1999, two outbreaks of eosinophilic meningitis caused by A. cantonensis infection were reported among 17 adult male immigrant Thai laborers who had eaten raw golden apple snails (Pomacea canaliculata). Another outbreak associated with consuming a health drink consisting of raw vegetable juice was reported in 2001. These adult cases differed from reports in the 1970s and 1980s, in which most of the cases were in children. With improvements in public health and education of foreign laborers, there have since been only sporadic cases in Taiwan. Review of clinical research indicates inconsistent association of Magnetic Resonance Imaging (MRI) results with clinical features of eosinophilic meningitis. MRI features were nonspecific but there was an association between the presence of high brain MRI signal intensities and severity of peripheral and cerebrospinal fluid (CSF) eosinophilia. Inflammatory markers have been identified in the CSF of patients with eosinophilic meningitis caused by A. cantonensis infection, and vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and the matrix metalloproteinase system may be associated with blood-brain barrier disruption. Eosinophilic meningitis caused by A. cantonensis infection is not a reportable disease in Taiwan. It is important that a public advisory and education program be developed to reduce future accidental infection.

  4. Incidence rate of external genital lesions (EGL) caused by human papillomavirus infection in Czech population

    OpenAIRE

    Petráš, Marek

    2016-01-01

    Incidence of external genital lesions (EGL) caused by human papillomaviruses in the Czech population Marek Petráš Abstract Genital warts (condyloma acuminate) caused up to 90% cases by two human papillomaviruses of type 6 and 11 are not life-threatening diseases but can cause not only clinical symptoms (burning, itching, bleeding, and pain) but also psychosocial stress, embarrassment, and anxiety making for impaired quality of life. The aim of this cross-sectional study was to determine the p...

  5. [Anaphylaxis caused by human seminal fluid].

    Science.gov (United States)

    Rubira, N; Roger, A; Nogueiras, C; Server, T; Guspi, R; Cadahia, A

    1995-01-01

    Anaphylaxis to human seminal fluid (HSF) is rare. We present an atopic woman with postcoital cutaneous and respiratory symptoms. Prick by prick to HSF was positive. CAP to FSH was also positive (4 KU/l). The clinical findings, differential diagnosis and different treatments are discussed.

  6. Unsolved issues related to human mitochondrial diseases.

    Science.gov (United States)

    Lombès, Anne; Auré, Karine; Bellanné-Chantelot, Christine; Gilleron, Mylène; Jardel, Claude

    2014-05-01

    Human mitochondrial diseases, defined as the diseases due to a mitochondrial oxidative phosphorylation defect, represent a large group of very diverse diseases with respect to phenotype and genetic causes. They present with many unsolved issues, the comprehensive analysis of which is beyond the scope of this review. We here essentially focus on the mechanisms underlying the diversity of targeted tissues, which is an important component of the large panel of these diseases phenotypic expression. The reproducibility of genotype/phenotype expression, the presence of modifying factors, and the potential causes for the restricted pattern of tissular expression are reviewed. Special emphasis is made on heteroplasmy, a specific feature of mitochondrial diseases, defined as the coexistence within the cell of mutant and wild type mitochondrial DNA molecules. Its existence permits unequal segregation during mitoses of the mitochondrial DNA populations and consequently heterogeneous tissue distribution of the mutation load. The observed tissue distributions of recurrent human mitochondrial DNA deleterious mutations are diverse but reproducible for a given mutation demonstrating that the segregation is not a random process. Its extent and mechanisms remain essentially unknown despite recent advances obtained in animal models.

  7. Human laryngitis caused by Clinostomum complanatum.

    Science.gov (United States)

    Hara, Hirotaka; Miyauchi, Yuji; Tahara, Shinsaku; Yamashita, Hiroshi

    2014-02-01

    A 64-year-old Japanese man visited our outpatient department complaining of an irritable sensation in the throat, occurring two days after eating raw freshwater fish (carp sashimi) at a Japanese-style inn. During laryngeal endoscopy, a slow-moving worm (fluke) was found attached to the surface of the right aryepiglottic fold. After inhalation of 4% lidocaine, the fluke was removed using endoscopic forceps. Patient's throat symptoms immediately improved. The worm was microscopically identified as Clinostomum complanatum. C. complanatum is a digenetic trematode that usually infects fish-eating water birds. Clinostomum infections in humans are rare, and only 21 cases have been described in Japan and Korea. C. complanatum infection is known to occur after eating raw freshwater fish, which is a secondary intermediate host. In humans, the metacercariae are released into the stomach and migrate through the esophagus before lodging in the throat. Primary therapy involves endoscopic removal of the worm.

  8. Celiac disease: A missed cause of metabolic bone disease

    Directory of Open Access Journals (Sweden)

    Ashu Rastogi

    2012-01-01

    Full Text Available Introduction: Celiac disease (CD is a highly prevalent autoimmune disease. The symptoms of CD are varied and atypical, with many patients having no gastrointestinal symptoms. Metabolic bone disease (MBD is a less recognized manifestation of CD associated with spectrum of musculoskeletal signs and symptoms, viz. bone pains, proximal muscle weakness, osteopenia, osteoporosis, and fracture. We here report five patients who presented with severe MBD as the only manifestation of CD. Materials and Methods: Records of 825 patients of CD diagnosed during 2002-2010 were retrospectively analyzed for clinical features, risk factors, signs, biochemical, and radiological parameters. Results: We were able to identify five patients (0.6% of CD who had monosymptomatic presentation with musculoskeletal symptoms and signs in the form of bone pains, proximal myopathy, and fragility fractures without any gastrointestinal manifestation. All the five patients had severe MBD in the form of osteopenia, osteoporosis, and fragility fractures. Four of the five patients had additional risk factors such as antiepileptic drugs, chronic alcohol consumption, malnutrition, and associated vitamin D deficiency which might have contributed to the severity of MBD. Conclusion: Severe metabolic disease as the only presentation of CD is rare. Patients show significant improvement in clinical, biochemical, and radiological parameters with gluten-free diet, calcium, and vitamin D supplementation. CD should be looked for routinely in patients presenting with unexplained MBD.

  9. Chagas disease and human migration

    Directory of Open Access Journals (Sweden)

    Felipe Guhl

    2000-08-01

    Full Text Available Human Chagas disease is a purely accidental occurrence. As humans came into contact with the natural foci of infection might then have become infected as a single addition to the already extensive host range of Trypanosoma cruzi that includes other primates. Thus began a process of adaptation and domiciliation to human habitations through which the vectors had direct access to abundant food as well as protection from climatic changes and predators. Our work deals with the extraction and specific amplification by polymerase chain reaction of T. cruzi DNA obtained from mummified human tissues and the positive diagnosis of Chagas disease in a series of 4,000-year-old Pre-Hispanic human mummies from the northern coast of Chile. The area has been inhabited at least for 7,000 years, first by hunters, fishers and gatherers, and then gradually by more permanent settlements. The studied specimens belonged to the Chinchorro culture, a people inhabiting the area now occupied by the modern city of Arica. These were essentially fishers with a complex religious ideology, which accounts for the preservation of their dead in the way of mummified bodies, further enhanced by the extremely dry conditions of the desert. Chinchorro mummies are, perhaps, the oldest preserved bodies known to date.

  10. Malakoplakia of the esophagus caused by human papillomavirus infection

    Institute of Scientific and Technical Information of China (English)

    Ya-Li Yang; Yu-Cheng Xie; Xiao-Ling Li; Jing Guo; Tao Sun; Jing Tang

    2012-01-01

    Malakoplakia is a rare granulomatous disease probably caused by infection and characterized histologically by Michaelis-Gutmann bodies.We report a more rarely seen case esophageal malakoplakia in a 54-year-old woman.She presented with coughing while eating and drinking.Gastroscopy showed yellow nodules in the esophagus,and endoscopic ultrasonography showed a space-occupying lesion in the substratum of the esophageal mucosa.All findings highly resembled esophageal cancer.Histopathological examination finally indentified this space-occupying lesion as malakoplakia and not cancer.Immunohistochemistry showed that she had human papillomavirus (HPV) infection in the esophagus,which indicates that infection was responsible for the malakoplakia.This is believed to be the first case of malakoplakia in the esophagus,and more importantly,we established that HPV infection was the initiator of esophageal malakoplakia.

  11. [Human prion diseases in the Czech Republic].

    Science.gov (United States)

    Rohan, Z; Rusina, R; Marešová, M; Matěj, R

    2015-09-01

    Human prion diseases are a group of very rare diseases with a unique pathogenesis and, due to an inauspicious prognosis and unavailability of therapy, with fatal consequences. The etiopathogenetic background is the presence of pathologically misfolded prion protein, highly resistant to denaturation, the aggregation and presence of which in the brain tissue causes irreversible neuronal damage. The most frequent prion disease in humans is Creutzfeldt-Jakob disease (CJD) which occurs in sporadic, hereditary/familial, or acquired/infectious/iatrogenic forms. A new form of CJD, variant CJD, is considered to be linked to dietary exposure to beef products from cattle infected with bovine spongiform encephalopathy (BSE) and to infection via blood transfusion. The clinical picture of these diseases is characterized by a rapidly progressing dementia, cerebellar and extrapyramidal symptoms, and rather specific MRI, EEG, and CSF findings. Clinically, the diagnosis is described as possible or probable prion disease and needs to be confirmed by neuropathological or immunological investigation of the brain tissue. Epidemiological data from the Czech Republic spanning the last decade are presented.

  12. Distribution and harmfulness of leech-caused human disease in the mainland of China%中国大陆人体水蛭病的地区分布与危害

    Institute of Scientific and Technical Information of China (English)

    郑德福; 陈漪澜; 肖宁; 高丽霞; 李定越; 李佳圆; 田洪春; 陈闯; 陈建平; 廖玮

    2009-01-01

    目的 总结中国大陆近50年水蛭病在人群中的地区分布与危害、水蛭在人体的寄生部位及多种不同的治疗方法. 方法 收集、分析国内50年来不同地区的水蛭病资料,对所获资料进行归类分析. 结果 共收集到1 003例病例资料,分析结果显示中国大陆水蛭病分布在15个省、自治区;患者年龄为1.5岁至73岁不等;以农民、幼女、学生为主,其次为伐木工、采集工;发病季节以夏季为主,秋季次之;患者病程为1~365 d以上不等;虫体寄生部位以鼻腔、阴道、咽喉部较为常见,眼部、上颌窦、肠腔、膀胱、外阴、胃、皮下极为罕见;患者临床表现为失血、贫血、恐惧、紧张、头昏、头痛、腹痛、腹泻、恶心、呕吐、鼻塞、呼吸受阻、血痰、咯血等,部份患者失血量在200~300 ml之间,重者达600 ml. 结论 水蛭病主要发生于国内某些地区,特别是西南的广西、贵州、四川、云南及中南的湖北,沿海的福建、广东等省(自治区)边远山区的农村,对人体的危害尤其对成年劳动者与幼女的危害较大.%Objective To summarize and analyze the distribution and harmfulness of leech-cansed dis-ease among populations, parasitized locations of leeches in human body and different treatment measures against this disease in mainland of China in the last 50 years. Methods To collect the information from varieties of medical books, journals, bulletins, monograph and journals for parasitological subjects, as well as leech-caused disease data reported from different regions. Results Information of 1 003 cases were collected and the data revealed that leech-caused diseases were found in 15 provinces or autonomous regions yet, and the patients' a-ges ranged from 1.5 to 73. Most of these victims were farmers, little girls and students, and next were lumber-men. The high incident season of the disease was summer followed by autumn. Disease course lasted from 1 day to 365

  13. [Alzheimer's disease and human memory].

    Science.gov (United States)

    Eustache, F; Giffard, B; Rauchs, G; Chételat, G; Piolino, P; Desgranges, B

    2006-10-01

    Memory disorders observed in Alzheimer's disease gave rise, from the eighties, to a detailed analysis into the framework of cognitive neuropsychology which aimed at describing the deficits of very specific processes. Beyond their clinical interest, these studies contributed to the modelisation of human memory thanks to the characterization of different memory systems and their relationships. The first part of this paper gives an overview of the memory deficits in Alzheimer's disease and insists on particular cognitive phenomena. Hence, several examples are developed in the domains of semantic memory (such as hyperpriming and hypopriming effects) and autobiographical memory. Recent results highlight the existence of severe autobiographical amnesia observed in all neurodegenerative diseases, though with contrasting profiles: Ribot's gradient in Alzheimer's disease (showing that remote memories are better preserved than recent ones), reverse gradient in semantic dementia and no clear gradient in the frontal variant of frontotemporal dementia. The second part of this article presents advances in cognitive neuroscience searching to disclose the cerebral substrates of these cognitive deficits in Alzheimer's disease. The studies using functional imaging techniques are the most informative regarding this problematic. While showing the dysfunctions of an extended network, they emphasize the selectivity of cerebral damages that are at the root of very specific cognitive dysfunctions, coming close in that way to the conceptions of cognitive neuropsychology. These neuroimaging studies unravel the existence of compensatory mechanisms, which until recently were clearly missing in the literature on neurodegenerative diseases. These different researches lead to a wide conception of human memory, not just limited to simple instrumental processes (encoding, storage, retrieval), but necessarily covering models of identity and continuity of the subject, which interact in a dynamic way

  14. 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.

  15. Human lagochilascariasis-A rare helminthic disease.

    Directory of Open Access Journals (Sweden)

    Dulcinea Maria Barbosa Campos

    2017-06-01

    Full Text Available Lagochilascariasis is a parasitic disease caused by a helminth of the order Ascaroidea, genus Lagochilascaris that comprises 6 species, among which only Lagochilascaris minor Leiper, 1909, is implicated in the human form of the disease. It is remarkable that the majority of cases of human lagochilascariasis in the Americas have been reported in Brazil. The natural definitive hosts of this parasite seem to be wild felines and canines. Lagochilascariasis is mostly a chronic human disease that can persist for several years, in which the parasite burrows into the subcutaneous tissues of the neck, paranasal sinuses, and mastoid. L. minor exhibits remarkable ability to migrate through the tissues of its hosts, destroying even bone tissue. Fatal cases have been described in which the parasite was found in the lungs or central nervous system. Treatment is often palliative, with recurrence of lesions. This paper summarizes the main features of the disease and its etiologic agent, including prevalence, life cycle, clinical course, and treatment.

  16. Complete Genome Sequences of Four Different Bordetella sp. Isolates Causing Human Respiratory Infections

    Science.gov (United States)

    Peng, Yanhui; Loparev, Vladimir; Batra, Dhwani; Bowden, Katherine E.; Cassiday, Pamela K.; Davis, Jamie K.; Johnson, Taccara; Juieng, Phalasy; Miner, Christine E.; Rowe, Lori; Sheth, Mili; Tondella, M. Lucia; Williams, Margaret M.

    2016-01-01

    Species of the genus Bordetella associate with various animal hosts, frequently causing respiratory disease. Bordetella pertussis is the primary agent of whooping cough and other Bordetella species can cause similar cough illness. Here, we report four complete genome sequences from isolates of different Bordetella species recovered from human respiratory infections.

  17. Mitochondria: impaired mitochondrial translation in human disease.

    Science.gov (United States)

    Boczonadi, Veronika; Horvath, Rita

    2014-03-01

    Defects of the mitochondrial protein synthesis cause a subgroup of mitochondrial diseases, which are usually associated with decreased activities of multiple respiratory chain (RC) enzymes. The clinical presentations of these disorders are often disabling, progressive or fatal, affecting the brain, liver, skeletal muscle, heart and other organs. Currently there are no effective cures for these disorders and treatment is at best symptomatic. The diagnosis in patients with multiple respiratory chain complex defects is particularly difficult because of the massive number of nuclear genes potentially involved in intra-mitochondrial protein synthesis. Many of these genes are not yet linked to human disease. Whole exome sequencing rapidly changed the diagnosis of these patients by identifying the primary defect in DNA, and preventing the need for invasive and complex biochemical testing. Better understanding of the mitochondrial protein synthesis apparatus will help us to explore disease mechanisms and will provide clues for developing novel therapies.

  18. 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.

  19. Highly pathogenic Alzheimer's disease presenilin 1 P117R mutation causes a specific increase in p53 and p21 protein levels and cell cycle dysregulation in human lymphocytes.

    Science.gov (United States)

    Bialopiotrowicz, Emilia; Szybinska, Aleksandra; Kuzniewska, Bozena; Buizza, Laura; Uberti, Daniela; Kuznicki, Jacek; Wojda, Urszula

    2012-01-01

    Cell cycle (CC) reentry in neurons precedes the formation of amyloid-β (Aβ) plaques in Alzheimer's disease (AD). CC alterations were also detected in lymphocytes from sporadic AD patients. In the present study, we investigated the influence of nine presenilin 1 (PS1) mutations (P117R, M139V, L153V, H163R, S170F, F177L, I213F, L226F, E318G) on CC and Aβ production in immortalized B-lymphocytes from familial AD (FAD) patients and in stably transfected human embryonic kidney cells. In both cell types, only the P117R mutation increased levels of key G1/S phase regulatory proteins, p53, and its effector p21, causing G1 phase prolongation with simultaneous S phase shortening, and lowering basal apoptosis. The CC changes were rescued by inhibition of p53, but not of γ-secretase. Moreover, the investigated PS1 mutants showed differences in the increased levels of secreted Aβ40 and Aβ42 and in Aβ42/Aβ40 ratios, but these differences did not correlate with CC patterns. Altogether, we found that both CC regulation and Aβ production differentiate PS1 mutations, and that CC PS1 activity is mediated by p53/p21 signaling but not by γ-secretase activity. The identified CC dysregulation linked with increased p53 and p21 protein levels distinguishes the highly pathogenic PS1 P117R mutation and may contribute to the specific severity of the clinical progression of FAD associated with the mutation in the PS1 117 site. These findings suggest that impairment in lymphocyte CC might play a pathogenic function in AD and are relevant to the development of new diagnostic approaches and personalized therapeutic strategies.

  20. Heartworm disease in animals and humans.

    Science.gov (United States)

    McCall, John W; Genchi, Claudio; Kramer, Laura H; Guerrero, Jorge; Venco, Luigi

    2008-01-01

    Heartworm disease due to Dirofilaria immitis continues to cause severe disease and even death in dogs and other animals in many parts of the world, even though safe, highly effective and convenient preventatives have been available for the past two decades. Moreover, the parasite and vector mosquitoes continue to spread into areas where they have not been reported previously. Heartworm societies have been established in the USA and Japan and the First European Dirofilaria Days (FEDD) Conference was held in Zagreb, Croatia, in February of 2007. These organizations promote awareness, encourage research and provide updated guidelines for the diagnosis, treatment and prevention of heartworm disease. The chapter begins with a review of the biology and life cycle of the parasite. It continues with the prevalence and distribution of the disease in domestic and wild animals, with emphasis on more recent data on the spreading of the disease and the use of molecular biology techniques in vector studies. The section on pathogenesis and immunology also includes a discussion of the current knowledge of the potential role of the Wolbachia endosymbiont in inflammatory and immune responses to D. immitis infection, diagnostic use of specific immune responses to the bacteria, immunomodulatory activity and antibiotic treatment of infected animals. Canine, feline and ferret heartworm disease are updated with regard to the clinical presentation, diagnosis, prevention, therapy and management of the disease, with special emphasis on the recently described Heartworm Associated Respiratory Disease (HARD) Syndrome in cats. The section devoted to heartworm infection in humans also includes notes on other epizootic filariae, particularly D. repens in humans in Europe. The chapter concludes with a discussion on emerging strategies in heartworm treatment and control, highlighting the potential role of tetracycline antibiotics in adulticidal therapy.

  1. Human Microbiota and Ophthalmic Disease.

    Science.gov (United States)

    Lu, Louise J; Liu, Ji

    2016-09-01

    The human ocular surface, consisting of the cornea and conjunctiva, is colonized by an expansive, diverse microbial community. Molecular-based methods, such as 16S rRNA sequencing, has allowed for more comprehensive and precise identification of the species composition of the ocular surface microbiota compared to traditional culture-based methods. Evidence suggests that the normal microbiota plays a protective immunological role in preventing the proliferation of pathogenic species and thus, alterations in the homeostatic microbiome may be linked to ophthalmic pathologies. Further investigation of the ocular surface microbiome, as well as the microbiome of other areas of the body such as the oral mucosa and gut, and their role in the pathophysiology of diseases is a significant, emerging field of research, and may someday enable the development of novel probiotic approaches for the treatment and prevention of ophthalmic diseases.

  2. Human Cytomegalovirus and Autoimmune Disease

    Directory of Open Access Journals (Sweden)

    Anne Halenius

    2014-01-01

    Full Text Available Human cytomegalovirus (HCMV represents a prototypic pathogenic member of the β-subgroup of the herpesvirus family. A range of HCMV features like its lytic replication in multiple tissues, the lifelong persistence through periods of latency and intermitting reactivation, the extraordinary large proteome, and extensive manipulation of adaptive and innate immunity make HCMV a high profile candidate for involvement in autoimmune disorders. We surveyed the available literature for reports on HCMV association with onset or exacerbation of autoimmune disease. A causative linkage between HCMV and systemic lupus erythematosus (SLE, systemic sclerosis (SSc, diabetes mellitus type 1, and rheumatoid arthritis (RA is suggested by the literature. However, a clear association of HCMV seroprevalence and disease could not be established, leaving the question open whether HCMV could play a coresponsible role for onset of disease. For convincing conclusions population-based prospective studies must be performed in the future. Specific immunopathogenic mechanisms by which HCMV could contribute to the course of autoimmune disease have been suggested, for example, molecular mimicry by UL94 in SSc and UL83/pp65 in SLE patients, as well as aggravation of joint inflammation by induction and expansion of CD4+/CD28− T-cells in RA patients. Further studies are needed to validate these findings and to lay the grounds for targeted therapeutic intervention.

  3. Aluminium and human breast diseases.

    Science.gov (United States)

    Darbre, P D; Pugazhendhi, D; Mannello, F

    2011-11-01

    The human breast is exposed to aluminium from many sources including diet and personal care products, but dermal application of aluminium-based antiperspirant salts provides a local long-term source of exposure. Recent measurements have shown that aluminium is present in both tissue and fat of the human breast but at levels which vary both between breasts and between tissue samples from the same breast. We have recently found increased levels of aluminium in noninvasively collected nipple aspirate fluids taken from breast cancer patients (mean 268 ± 28 μg/l) compared with control healthy subjects (mean 131 ± 10 μg/l) providing evidence of raised aluminium levels in the breast microenvironment when cancer is present. The measurement of higher levels of aluminium in type I human breast cyst fluids (median 150 μg/l) compared with human serum (median 6 μg/l) or human milk (median 25 μg/l) warrants further investigation into any possible role of aluminium in development of this benign breast disease. Emerging evidence for aluminium in several breast structures now requires biomarkers of aluminium action in order to ascertain whether the presence of aluminium has any biological impact. To this end, we report raised levels of proteins that modulate iron homeostasis (ferritin, transferrin) in parallel with raised aluminium in nipple aspirate fluids in vivo, and we report overexpression of mRNA for several S100 calcium binding proteins following long-term exposure of MCF-7 human breast cancer cells in vitro to aluminium chlorhydrate.

  4. Coffee intake, cardiovascular disease and all-cause mortality

    DEFF Research Database (Denmark)

    Nordestgaard, Ask Tybjærg; Nordestgaard, Børge Grønne

    2016-01-01

    BACKGROUND: Coffee has been associated with modestly lower risk of cardiovascular disease and all-cause mortality in meta-analyses; however, it is unclear whether these are causal associations. We tested first whether coffee intake is associated with cardiovascular disease and all-cause mortality...... observationally; second, whether genetic variations previously associated with caffeine intake are associated with coffee intake; and third, whether the genetic variations are associated with cardiovascular disease and all-cause mortality. METHODS: First, we used multivariable adjusted Cox proportional hazard...... regression models evaluated with restricted cubic splines to examine observational associations in 95 366 White Danes. Second, we estimated mean coffee intake according to five genetic variations near the AHR (rs4410790; rs6968865) and CYP1A1/2 genes (rs2470893; rs2472297; rs2472299). Third, we used sex...

  5. Cause-specific mortality among spouses of Parkinson disease patients

    DEFF Research Database (Denmark)

    Nielsen, Malene; Hansen, Johnni; Ritz, Beate

    2014-01-01

    BACKGROUND: Caring for a chronically ill spouse is stressful, but the health effects of caregiving are not fully understood. We studied the effect on mortality of being married to a person with Parkinson disease. METHODS: All patients in Denmark with a first-time hospitalization for Parkinson...... disease between 1986 and 2009 were identified, and each case was matched to five population controls. We further identified all spouses of those with Parkinson disease (n = 8,515) and also the spouses of controls (n = 43,432). All spouses were followed in nationwide registries until 2011. RESULTS: Among...... men, being married to a Parkinson disease patient was associated with a slightly higher risk of all-cause mortality (hazard ratio = 1.06 [95% confidence interval = 1.00-1.11]). Mortality was particularly high for death due to external causes (1.42 [1.09-1.84]) including suicide (1.89 [1...

  6. Novel clones of Streptococcus pneumoniae causing invasive disease in Malaysia.

    Directory of Open Access Journals (Sweden)

    Johanna M Jefferies

    Full Text Available Although Streptococcus pneumoniae is a leading cause of childhood disease in South East Asia, little has previously been reported regarding the epidemiology of invasive pneumococcal disease in Malaysia and very few studies have explored pneumococcal epidemiology using multilocus sequence typing (MLST. Here we describe serotype, multilocus sequence type (ST, and penicillin susceptibility of thirty pneumococcal invasive disease isolates received by the University of Malaya Medical Centre between February 2000 and January 2007 and relate this to the serotypes included in current pneumococcal conjugate vaccines. A high level of diversity was observed; fourteen serotypes and 26 sequence types (ST, (11 of which were not previously described were detected from 30 isolates. Penicillin non-susceptible pneumococci accounted for 33% of isolates. The extent of molecular heterogeneity within carried and disease-causing Malaysian pneumococci remains unknown. Larger surveillance and epidemiological studies are now required in this region to provide robust evidence on which to base future vaccine policy.

  7. Causes of Mortality and Diseases in Farmed Deer in Switzerland

    Directory of Open Access Journals (Sweden)

    Veronika Sieber

    2010-01-01

    Full Text Available To investigate diseases and causes of mortality in Swiss farmed deer, deer found dead or shot due to diseased condition between March 2003 and December 2004 were requested for a complete postmortem examination. One hundred and sixty-two animals were submitted. Perinatal mortality, necrobacillosis in 3 week to 6 month old deer, and endoparasitosis in 6 month to 2 year old deer were identified as the most important causes of loss, followed by ruminal acidosis, which was diagnosed in 22% of deer older than 1 year. Congenital malformations were observed in 15% of deer less than 6 months old. Reportable infectious diseases known as major problems in deer farming in other countries were rare (yersiniosis, malignant catarrhal fever or not observed (tuberculosis, chronic wasting disease. Overall, the results indicate that the Swiss deer population does not present major health problems of concern for domestic animals.

  8. Dental erosion caused by gastroesophageal reflux disease: a case report

    OpenAIRE

    Cengiz,Seda; Cengiz, M ?nan?; Sara?, Y ?inasi

    2009-01-01

    Introduction Chronic regurgitation of gastric acids in patients with gastroesophageal reflux disease may cause dental erosion, which can lead in combination with attrition or bruxism to extensive loss of coronal tooth tissue. Case presentation This clinical report describes treatment of severe tooth wear of a gastroesophageal reflux disease patient who is 54-year-old Turkish male patient. After his medical treatment, severe tooth wear, bruxism and decreased vertical dimensions were determined...

  9. Lipophilic chemical exposure as a cause of cardiovascular disease.

    Science.gov (United States)

    Zeliger, Harold I

    2013-06-01

    Environmental chemical exposure has been linked to numerous diseases in humans. These diseases include cancers; neurological and neurodegenerative diseases; metabolic disorders including type 2 diabetes, metabolic syndrome and obesity; reproductive and developmental disorders; and endocrine disorders. Many studies have associated the link between exposures to environmental chemicals and cardiovascular disease (CVD). These chemicals include persistent organic pollutants (POPs); the plastic exudates bisphenol A and phthalates; low molecular weight hydrocarbons (LMWHCs); and poly nuclear aromatic hydrocarbons (PAHs). Here it is reported that though the chemicals reported on differ widely in chemical properties and known points of attack in humans, a common link exists between them. All are lipophilic species that are found in serum. Environmentally induced CVD is related to total lipophilic chemical load in the blood. Lipophiles serve to promote the absorption of otherwise not absorbed toxic hydrophilic species that promote CVD.

  10. Spontaneous expulsive suprachoroidal hemorrhage caused by decompensated liver disease

    Directory of Open Access Journals (Sweden)

    Krishnagopal Srikanth

    2013-01-01

    Full Text Available Expulsive suprachoroidal hemorrhage can be surgical or spontaneous. Spontaneous expulsive suprachoroidal hemorrhage (SESCH is a rare entity. Most of the reported cases of SESCH were caused by a combination of corneal pathology and glaucoma. We are reporting a rare presentation of SESCH with no pre-existing glaucoma or corneal pathology and caused by massive intra- and peri-ocular hemorrhage due to decompensated liver disease.

  11. CRISPR/Cas9 facilitates investigation of neural circuit disease using human iPSCs: mechanism of epilepsy caused by an SCN1A loss-of-function mutation

    OpenAIRE

    2016-01-01

    Mutations in SCN1A, the gene encoding the α subunit of Nav1.1 channel, can cause epilepsies with wide ranges of clinical phenotypes, which are associated with the contrasting effects of channel loss-of-function or gain-of-function. In this project, CRISPR/Cas9- and TALEN-mediated genome-editing techniques were applied to induced pluripotent stem cell (iPSC)-based-disease model to explore the mechanism of epilepsy caused by SCN1A loss-of-function mutation. By fluorescently labeling GABAergic s...

  12. Lack of exercise is a major cause of chronic diseases

    Science.gov (United States)

    Booth, Frank W.; Roberts, Christian K.; Laye, Matthew J.

    2014-01-01

    Chronic diseases are major killers in the modern era. Physical inactivity is a primary cause of most chronic diseases. The initial third of the article considers: activity and prevention definitions; historical evidence showing physical inactivity is detrimental to health and normal organ functional capacities; cause vs. treatment; physical activity and inactivity mechanisms differ; gene-environment interaction [including aerobic training adaptations, personalized medicine, and co-twin physical activity]; and specificity of adaptations to type of training. Next, physical activity/exercise is examined as primary prevention against 35 chronic conditions [Accelerated biological aging/premature death, low cardiorespiratory fitness (VO2max), sarcopenia, metabolic syndrome, obesity, insulin resistance, prediabetes, type 2 diabetes, non-alcoholic fatty liver disease, coronary heart disease, peripheral artery disease, hypertension, stroke, congestive heart failure, endothelial dysfunction, arterial dyslipidemia, hemostasis, deep vein thrombosis, cognitive dysfunction, depression and anxiety, osteoporosis, osteoarthritis, balance, bone fracture/falls, rheumatoid arthritis, colon cancer, breast cancer, endometrial cancer, gestational diabetes, preeclampsia, polycystic ovary syndrome, erectile dysfunction, pain, diverticulitis, constipation, and gallbladder diseases]. The article ends with consideration of deterioration of risk factors in longer-term sedentary groups; clinical consequences of inactive childhood/adolescence; and public policy. In summary, the body rapidly maladapts to insufficient physical activity, and if continued, results in substantial decreases in both total and quality years of life. Taken together, conclusive evidence exists that physical inactivity is one important cause of most chronic diseases. In addition, physical activity primarily prevents, or delays, chronic diseases, implying that chronic disease need not be an inevitable outcome during life

  13. Circadian clock disruption in neurodegenerative diseases: Cause and effect?

    Directory of Open Access Journals (Sweden)

    Erik Steven Musiek

    2015-02-01

    Full Text Available Disturbance of the circadian system, manifested as disrupted daily rhythms of physiologic parameters such as sleep, activity, and hormone secretion, has long been observed as a symptom of several neurodegenerative diseases, including Alzheimer Disease. Circadian abnormalities have generally been considered consequences of the neurodegeneration. Recent evidence suggests, however, that circadian disruption might actually contribute to the neurodegenerative process, and thus might be a modifiable cause of neural injury. Herein we will review the evidence implicating circadian rhythms disturbances and clock gene dysfunction in neurodegeneration, with an emphasis on future research directions and potential therapeutic implications for neurodegenerative diseases.

  14. Chilli anthracnose disease caused by Colletotrichum species§

    Science.gov (United States)

    Than, Po Po; Prihastuti, Haryudian; Phoulivong, Sitthisack; Taylor, Paul W.J.; Hyde, Kevin D.

    2008-01-01

    Anthracnose disease is one of the major economic constraints to chilli production worldwide, especially in tropical and subtropical regions. Accurate taxonomic information is necessary for effective disease control management. In the Colletotrichum patho-system, different Colletotrichum species can be associated with anthracnose of the same host. Little information is known concerning the interactions of the species associated with the chilli anthracnose although several Colletotrichum species have been reported as causal agents of chilli anthracnose disease worldwide. The ambiguous taxonomic status of Colletotrichum species has resulted in inaccurate identification which may cause practical problems in plant breeding and disease management. Although the management and control of anthracnose disease are still being extensively researched, commercial cultivars of Capsicum annuum that are resistant to the pathogens that cause chilli anthracnose have not yet been developed. This paper reviews the causal agents of chilli anthracnose, the disease cycle, conventional methods in identification of the pathogen and molecular approaches that have been used for the identification of Colletotrichum species. Pathogenetic variation and population structure of the causal agents of chilli anthracnose along with the current taxonomic status of Colletotrichum species are discussed. Future developments leading to the disease management strategies are suggested. PMID:18837103

  15. 一起由引进养殖黑山羊导致人感染羊痘病暴发的调查%An outbreak of human orf disease caused by introduced black goats

    Institute of Scientific and Technical Information of China (English)

    高飞; 袁珩; 凌华; 龙江; 朱保平; 马会来; 李勤

    2011-01-01

    Objective To identify risk factors for a human orf disease outbreak in a village in Chongqing city. Methods Standardized case-definition was set and a case-finding program was conducted among all the residents of the village. All the patients were interviewed using a standardized questionnaire and collected fluids in the skin rash for laboratory testing. A retrospective cohort investigation was conducted among all the village residents who introduced the black goats to analyze the risk of orf infection, in relation to the mode and frequency of contacts to the infected goats. Results We found 18 cases (including 16 suspected cases and 2 confirmed cases) among the members of 10 families that introduced the black goats. Village residents who had ever used their legs to grip the goats were nearly five times as likely to develop orf disease as those who did not (RR=4.98, 95%CI: 1.34-75.27). Village residents who had ever washed and wiped the goats were three times as likely to develop orf disease as those who had not (RR = 3.09,95%CI: 0.98-45.38). The frequency of contacts with the infected goats was associated with the risk of developing orf disease in a dose-response fashion (x2 test for trends: P= 0.006).Frequently wearing long trousers when dealing with the goats appeared as a protective factor (RR=0.30,95%CI: 0.15-0.78). Conclusion This outbreak was caused by the introduced black goats which carried and infected by the orf virus. Direct physical contact with infected goats but without wearing protective clothing were risk factors for the development of human orf disease.%目的 查明重庆市某村人群中暴发羊痘病的危险因素。方法采用统一的病例定义,在全村村民中搜索病例,病例采用统一调查问卷进行访谈,并采集疱疹液进行实验室检验。对全村引进养殖黑山羊的农户开展回顾性队列研究,分析与病羊接触方式、接触频度及接触时防护情况等与发病

  16. Colletotrichum species causing anthracnose disease of chili in China

    NARCIS (Netherlands)

    Diao, Y.-Z.; Zhang, C.; Liu, F.; Wang, W.-Z.; Liu, L.; Cai, L.; Liu, X.-L.

    2017-01-01

    Anthracnose caused by Colletotrichum species is a serious disease of more than 30 plant genera. Several Colletotrichum species have been reported to infect chili in different countries. Although China is the largest chiliproducing country, little is known about the species that have been infecting c

  17. Colletotrichum species causing anthracnose disease of chili in China

    NARCIS (Netherlands)

    Diao, Y.-Z.; Zhang, C.; Liu, F.; Wang, W.-Z.; Liu, L.; Cai, L.; Liu, X.-L.

    2017-01-01

    Anthracnose caused by Colletotrichum species is a serious disease of more than 30 plant genera. Several Colletotrichum species have been reported to infect chili in different countries. Although China is the largest chiliproducing country, little is known about the species that have been infecting

  18. A sodium-channel mutation causes isolated cardiac conduction disease

    NARCIS (Netherlands)

    Tan, HL; Bink-Boelkens, MTE; Bezzina, CR; Viswanathan, PC; Beaufort-Krol, GCM; van Tintelen, PJ; van den Berg, MP; Wilde, AAM; Balser, [No Value

    2001-01-01

    Cardiac conduction disorders slow the heart rhythm and cause disability in millions of people worldwide. Inherited mutations in SCN5A, the gene encoding the human cardiac sodium (Na+) channel, have been associated with rapid heart rhythms that occur suddenly and are life-threatening(1-3); however, a

  19. Features of 5'-splice-site efficiency derived from disease-causing mutations and comparative genomics

    DEFF Research Database (Denmark)

    Roca, Xavier; Olson, Andrew J; Rao, Atmakuri R

    2007-01-01

    Many human diseases, including Fanconi anemia, hemophilia B, neurofibromatosis, and phenylketonuria, can be caused by 5'-splice-site (5'ss) mutations that are not predicted to disrupt splicing, according to position weight matrices. By using comparative genomics, we identify pairwise dependencies...

  20. Congenital Heart Disease: Causes, Diagnosis, Symptoms, and Treatments.

    Science.gov (United States)

    Sun, RongRong; Liu, Min; Lu, Lei; Zheng, Yi; Zhang, Peiying

    2015-07-01

    The congenital heart disease includes abnormalities in heart structure that occur before birth. Such defects occur in the fetus while it is developing in the uterus during pregnancy. About 500,000 adults have congenital heart disease in USA (WebMD, Congenital heart defects medications, www.WebMD.com/heart-disease/tc/congenital-heart-defects-medications , 2014). 1 in every 100 children has defects in their heart due to genetic or chromosomal abnormalities, such as Down syndrome. The excessive alcohol consumption during pregnancy and use of medications, maternal viral infection, such as Rubella virus, measles (German), in the first trimester of pregnancy, all these are risk factors for congenital heart disease in children, and the risk increases if parent or sibling has a congenital heart defect. These are heart valves defects, atrial and ventricular septa defects, stenosis, the heart muscle abnormalities, and a hole inside wall of the heart which causes defect in blood circulation, heart failure, and eventual death. There are no particular symptoms of congenital heart disease, but shortness of breath and limited ability to do exercise, fatigue, abnormal sound of heart as heart murmur, which is diagnosed by a physician while listening to the heart beats. The echocardiogram or transesophageal echocardiogram, electrocardiogram, chest X-ray, cardiac catheterization, and MRI methods are used to detect congenital heart disease. Several medications are given depending on the severity of this disease, and catheter method and surgery are required for serious cases to repair heart valves or heart transplantation as in endocarditis. For genetic study, first DNA is extracted from blood followed by DNA sequence analysis and any defect in nucleotide sequence of DNA is determined. For congenital heart disease, genes in chromosome 1 show some defects in nucleotide sequence. In this review the causes, diagnosis, symptoms, and treatments of congenital heart disease are described.

  1. 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

  2. HIV and the spectrum of human disease.

    Science.gov (United States)

    Lucas, Sebastian; Nelson, Ann Marie

    2015-01-01

    Infection with the human immunodeficiency virus (HIV) causes systemic T cell destruction and reduced cell-mediated immunity that leads to a wide range of opportunistic infections and cancers. Second, it directly damages many tissues - gut, brain, lung - through mononuclear cell infection and activation. Third, through immune activation and effects on endothelia, it can cause more subtle systemic organ damage, such as chronic cardiovascular, hepatic, pulmonary and central nervous system disease. Antiretroviral treatment has enabled HIV-infected persons to live with chronic infection, although with some side-effects and mortality, including reactions due to the immune reconstitution inflammatory syndrome (IRIS). As cohorts of infected people get older, age-related diseases will combine with chronic HIV infection to produce disabilities whose scale is not yet understood. HIV is detectable in tissues by immunohistochemistry when infection loads are high, such as at first presentation. Pathologists should proactively consider HIV disease in routine diagnostic work, so as to identify more HIV-infected patients and enable their optimal management.

  3. Rheumatologic diseases as the cause of fever of unknown origin.

    Science.gov (United States)

    Mulders-Manders, C M; Simon, A; Bleeker-Rovers, C P

    2016-10-01

    In 30% of patients with fever or inflammation of unknown origin (FUO/IUO), the cause is eventually found to be a rheumatologic disease such as autoimmune or granulomatous disease or vasculitis. Most of these patients suffer from an uncommon presentation of a common disease, instead of an uncommon disease. We demonstrate the diagnostic challenge with several cases. The workup of FUO is based on the identification of potential diagnostic clues (PDCs). In the absence of PDCs, a standardized diagnostic protocol should be followed, including early FDG-PET/CT. Other imaging techniques or invasive diagnostic techniques should be reserved for those in whom PDCs are present. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Cause-specific mortality among spouses of Parkinson disease patients.

    Science.gov (United States)

    Nielsen, Malene; Hansen, Johnni; Ritz, Beate; Nordahl, Helene; Schernhammer, Eva; Wermuth, Lene; Rod, Naja Hulvej

    2014-03-01

    Caring for a chronically ill spouse is stressful, but the health effects of caregiving are not fully understood. We studied the effect on mortality of being married to a person with Parkinson disease. All patients in Denmark with a first-time hospitalization for Parkinson disease between 1986 and 2009 were identified, and each case was matched to five population controls. We further identified all spouses of those with Parkinson disease (n = 8,515) and also the spouses of controls (n = 43,432). All spouses were followed in nationwide registries until 2011. Among men, being married to a Parkinson disease patient was associated with a slightly higher risk of all-cause mortality (hazard ratio = 1.06 [95% confidence interval = 1.00-1.11]). Mortality was particularly high for death due to external causes (1.42 [1.09-1.84]) including suicide (1.89 [1.05-3.42]) and death from undefined symptoms/abnormal findings (1.25 [1.07-1.47]). Censoring at the time of death of the patient attenuated the findings for all-cause mortality in husbands (1.02 [0.95-1.09]), indicating that part of the association is with bereavement. Still, living with a person with Parkinson disease 5 years after first Parkinson hospitalization was associated with higher risk of all-cause mortality for both husbands (1.15 [1.07-1.23]) and wives (1.11 [1.04-1.17]). Caring for a spouse with a serious chronic illness is associated with a slight but consistent elevation in mortality risk.

  5. The Inflammatory Heart Diseases: Causes, Symptoms, and Treatments.

    Science.gov (United States)

    Lu, Lei; Sun, RongRong; Liu, Min; Zheng, Yi; Zhang, Peiying

    2015-07-01

    The inflammation of the heart muscles, such as myocarditis, the membrane sac which surrounds the heart called as pericarditis, and the inner lining of the heart or the myocardium, heart muscle as endocarditis are known as the inflammatory heart diseases. Inflammation of heart is caused by known infectious agents, viruses, bacteria, fungi or parasites, and by toxic materials from the environment, water, food, air, toxic gases, smoke, and pollution, or by an unknown origin. Myocarditis is induced by infection of heart muscle by virus like sarcoidosis and immune diseases. The symptoms include chest pain, angina, pain in heart muscle, and shortness of breath, edema, swelling of feet or ankles, and fatigue. The ECG, X-ray, and MRI can diagnose the disease; blood test and rise in enzymes levels provide abnormality in heart function. The treatment includes use of antibiotics for inflammation of heart muscle and medications. The ultrasound imaging indicates further damage to the heart muscle. In severe cases of infection heart failure can occur so long-term medications are necessary to control inflammation. The various biomarkers are reported for the inflammatory heart diseases. The causes, symptoms and treatments of inflammatory heart diseases are described.

  6. Helicobacter pylori and autoimmune disease: Cause or bystander

    Science.gov (United States)

    Smyk, Daniel S; Koutsoumpas, Andreas L; Mytilinaiou, Maria G; Rigopoulou, Eirini I; Sakkas, Lazaros I; Bogdanos, Dimitrios P

    2014-01-01

    Helicobacter pylori (H. pylori) is the main cause of chronic gastritis and a major risk factor for gastric cancer. This pathogen has also been considered a potential trigger of gastric autoimmunity, and in particular of autoimmune gastritis. However, a considerable number of reports have attempted to link H. pylori infection with the development of extra-gastrointestinal autoimmune disorders, affecting organs not immediately relevant to the stomach. This review discusses the current evidence in support or against the role of H. pylori as a potential trigger of autoimmune rheumatic and skin diseases, as well as organ specific autoimmune diseases. We discuss epidemiological, serological, immunological and experimental evidence associating this pathogen with autoimmune diseases. Although over one hundred autoimmune diseases have been investigated in relation to H. pylori, we discuss a select number of papers with a larger literature base, and include Sjögrens syndrome, rheumatoid arthritis, systemic lupus erythematosus, vasculitides, autoimmune skin conditions, idiopathic thrombocytopenic purpura, autoimmune thyroid disease, multiple sclerosis, neuromyelitis optica and autoimmune liver diseases. Specific mention is given to those studies reporting an association of anti-H. pylori antibodies with the presence of autoimmune disease-specific clinical parameters, as well as those failing to find such associations. We also provide helpful hints for future research. PMID:24574735

  7. Recent efforts to model human diseases in vivo in Drosophila.

    Science.gov (United States)

    Pfleger, Cathie M; Reiter, Lawrence T

    2008-01-01

    Upon completion of sequencing the Drosophila genome, it was estimated that 61% of human disease-associated genes had sequence homologs in flies, and in some diseases such as cancer, the number was as high as 68%. We now know that as many as 75% of the genes associated with genetic disease have counterparts in Drosophila. Using better tools for mutation detection, association studies and whole genome analysis the number of human genes associated with genetic disease is steadily increasing. These detection efforts are outpacing the ability to assign function and understand the underlying cause of the disease at the molecular level. Drosophila models can therefore advance human disease research in a number of ways by: establishing the normal role of these gene products during development, elucidating the mechanism underlying disease pathology, and even identifying candidate therapeutic agents for the treatment of human disease. At the 49(th) Annual Drosophila Research Conference in San Diego this year, a number of labs presented their exciting findings on Drosophila models of human disease in both platform presentations and poster sessions. Here we can only briefly review some of these developments, and we apologize that we do not have the time or space to review all of the findings presented which use Drosophila to understand human disease etiology.

  8. [Bacterial infection as a cause of infertility in humans].

    Science.gov (United States)

    Sleha, Radek; Boštíková, Vanda; Salavec, Miloslav; Mosio, Petra; Kusáková, Eva; Kukla, Rudolf; Mazurová, Jaroslava; Spliňo, Miroslav

    2013-04-01

    Microorganisms which are present in the human urogenital tract may be involved in the development of inflammatory changes negatively affecting the genitals in both men and women. Pathological conditions due to inflammatory alterations may result in complete loss of fertility. Infections of the urogenital tract are responsible for 15% of all cases of infertility in couples. Negative impact on the human reproduction is mainly caused by direct damage to the genital tract mucosa by metabolic products of microorganisms or by induction of pro-inflammatory responses of the body. Another mechanism is indirect impact of microorganisms on the genital function. Moreover, the effect of bacteria on spermatogenesis and semen quality is important in men. Infections mainly caused by Chlamydia trachomatis or Neisseria gonorrhoeae represent the greatest risk in terms of permanent consequences for human reproduction. As for other sexually transmitted disorders, such as infections caused by Gardnerella vaginalis, urogenital mycoplasmas or ureaplasmas, the link between infection and infertility has been intensively researched.

  9. Human brain disease recreated in mice

    Energy Technology Data Exchange (ETDEWEB)

    Marx, J.

    1990-12-14

    In the early 1980s, neurologist Stanley Prusiner suggested that scrapie, an apparently infectious degenerative brain disease of sheep, could be transmitted by prions, infectious particles made just of protein - and containing no nucleic acids. But prion research has come a long way since then. In 1985, the cloning of the gene encoding the prion protein proved that it does in fact exist. And the gene turned out to be widely expressed in the brains of higher organisms, a result suggesting that the prion protein has a normal brain function that can somehow be subverted, leading to brain degeneration. Then studies done during the past 2 years suggested that specific mutations in the prion gene might cause two similar human brain diseases, Gerstmann-Straeussler-Scheinker syndrome (GSS) and Creutzfelt-Jakob disease. Now, Prusiner's group at the University of California, San Francisco, has used genetic engineering techniques to recreate GSS by transplanting the mutated prion gene into mice. Not only will the animal model help neurobiologists answer the many remaining questions about prions and how they work, but it may also shed some light on other neurodegenerative diseases as well.

  10. Causes of chronic kidney disease in Egyptian children

    Directory of Open Access Journals (Sweden)

    Hesham Safouh

    2015-01-01

    Full Text Available There are very few published reports on the causes of chronic kidney disease (CKD in Egyptian children. We reviewed the records of 1018 (males 56.7%, age ranged from 1 to 19 years Egyptian patients suffering from CKD and followed-up at the pediatric nephrology units (outpatient clinics and dialysis units of 11 universities over a period of two years. The mean of the estimated glomerular filtration rate was 12.5 mL/min/1.73 m 2 . Children with CKD stage I and stage II comprised 4.4% of the studied group, while those with stage III, IV and V comprised 19.7%, 18.3% and 57.6%, respectively. The most common single cause of CKD was obstructive uropathy (21.7%, followed by primary glomerulonephritis (15.3%, reflux/urinary tract infection (14.6%, aplasia/hypoplasia (9.8% and familial/metabolic diseases (6.8%; unknown causes accounted for 20.6% of the cases. Of the 587 patients who had reached end-stage renal disease, 93.5% was treated with hemodialysis and only 6.5% were treated with peritoneal dialysis.

  11. Viral Agents Causing Brown Cap Mushroom Disease of Agaricus bisporus.

    Science.gov (United States)

    Eastwood, Daniel; Green, Julian; Grogan, Helen; Burton, Kerry

    2015-10-01

    The symptoms of viral infections of fungi range from cryptic to severe, but there is little knowledge of the factors involved in this transition of fungal/viral interactions. Brown cap mushroom disease of the cultivated Agaricus bisporus is economically important and represents a model system to describe this transition. Differentially expressed transcript fragments between mushrooms showing the symptoms of brown cap mushroom disease and control white noninfected mushrooms have been identified and sequenced. Ten of these RNA fragments have been found to be upregulated over 1,000-fold between diseased and nondiseased tissue but are absent from the Agaricus bisporus genome sequence and hybridize to double-stranded RNAs extracted from diseased tissue. We hypothesize that these transcript fragments are viral and represent components of the disease-causing agent, a bipartite virus with similarities to the family Partitiviridae. The virus fragments were found at two distinct levels within infected mushrooms, at raised levels in infected, nonsymptomatic, white mushrooms and at much greater levels (3,500 to 87,000 times greater) in infected mushrooms exhibiting brown coloration. In addition, differential screening revealed 9 upregulated and 32 downregulated host Agaricus bisporus transcripts. Chromametric analysis was able to distinguish color differences between noninfected white mushrooms and white infected mushrooms at an early stage of mushroom growth. This method may be the basis for an "on-farm" disease detection assay.

  12. Cat-scratch disease causing status epilepticus in children.

    Science.gov (United States)

    Easley, R B; Cooperstock, M S; Tobias, J D

    1999-01-01

    Status epilepticus from cat-scratch encephalopathy is often recalcitrant to usual therapies, causing treatment to focus on critical care management of the patient that may require aggressive interventions, such as continuous pentobarbital administration. We describe two children whose initial clinical presentation of cat-scratch disease was status epilepticus with normal cerebrospinal fluid studies. A history of cat exposure (specifically, kitten and/or fleas), regional lymphadenopathy, and a papule or inoculation site should be sought, but are not essential for diagnosis. The presumptive diagnosis of cat-scratch disease can be made by serology alone even in the absence of classic diagnostic criteria. Our two cases and other reports in the literature show a favorable prognosis in most cases, despite the occurrence of status epilepticus. The diagnosis of cat-scratch disease should be strongly considered in all children with unexplained status epilepticus or encephalopathy and serologic testing for Bartonella henselae should be done.

  13. Vascular pathology: Cause or effect in Alzheimer disease?

    Science.gov (United States)

    Rius-Pérez, S; Tormos, A M; Pérez, S; Taléns-Visconti, R

    2015-09-15

    Alzheimer disease (AD) is the main cortical neurodegenerative disease. The incidence of this disease increases with age, causing significant medical, social and economic problems, especially in countries with ageing populations. This review aims to highlight existing evidence of how vascular dysfunction may contribute to cognitive impairment in AD, as well as the therapeutic possibilities that might arise from this evidence. The vascular hypothesis emerged as an alternative to the amyloid cascade hypothesis as an explanation for the pathophysiology of AD. This hypothesis locates blood vessels as the origin for a variety of pathogenic pathways that lead to neuronal damage and dementia. Destruction of the organisation of the blood brain barrier, decreased cerebral blood flow, and the establishment of an inflammatory context would thus be responsible for any subsequent neuronal damage since these factors promote aggregation of β-amyloid peptide in the brain. The link between neurodegeneration and vascular dysfunction pathways has provided new drug targets and therapeutic approaches that will add to the treatments for AD. It is difficult to determine whether the vascular component in AD is the cause or the effect of the disease, but there is no doubt that vascular pathology has an important relationship with AD. Vascular dysfunction is likely to act synergistically with neurodegenerative changes in a cycle that exacerbates the cognitive impairment found in AD. Copyright © 2015 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  14. Genetically Modified Pig Models for Human Diseases

    Institute of Scientific and Technical Information of China (English)

    Nana Fan; Liangxue Lai

    2013-01-01

    Genetically modified animal models are important for understanding the pathogenesis of human disease and developing therapeutic strategies.Although genetically modified mice have been widely used to model human diseases,some of these mouse models do not replicate important disease symptoms or pathology.Pigs are more similar to humans than mice in anatomy,physiology,and genome.Thus,pigs are considered to be better animal models to mimic some human diseases.This review describes genetically modified pigs that have been used to model various diseases including neurological,cardiovascular,and diabetic disorders.We also discuss the development in gene modification technology that can facilitate the generation of transgenic pig models for human diseases.

  15. Identification of a Disease on Cocoa Caused by Fusariumin Sulawesi

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    Ade Rosmana

    2013-12-01

    Full Text Available A disease presumed to be caused by Fusarium was observed in cocoa open fields with few or without shade trees. Within the population of cocoa trees in the field, some trees had died, some had yellowing leaves and dieback, and the others were apparently healthy. In order to demonstrate Fusarium species as the causal pathogen and to obtain information concerning the incidence of the disease, its distribution and its impact on sustainability of cocoa, isolation of the pathogen, inoculation of cocoa seedlings with isolates and a survey of disease has been conducted. Fusarium was isolated from roots and branches, and inoculated onto cocoa seedlings (one month old via soil. Symptoms appeared within 3-4 weeks after infection. These symptoms consisted of yellowing of leaves beginning from the bottom until the leaves falldown, and browning internal of vascular tissue. Darkened vascular traces in the petiole characteristic of vascularstreak dieback infection were absent. The occurrence of Fusarium in the field was characterized by the absence of obvious signs of fungal infestation on root of infected trees, yellowing of leaves on twigs, dieback, and tree mortality in severe infestations. Disease incidence could reach 77% and in this situation it was difficult for trees recover from heavy infections or to be regenerated in the farm. The study proves that Fusarium is a pathogen causing dieback and the disease is called as Fusarium vascular dieback (FVD. Its development is apparently enhanced by dry conditions in the field. Key words: Fusarium sp., vascular disease, dieback, FVD, Theobroma cacao L.

  16. HTT-lowering reverses Huntington's disease immune dysfunction caused by NFκB pathway dysregulation.

    Science.gov (United States)

    Träger, Ulrike; Andre, Ralph; Lahiri, Nayana; Magnusson-Lind, Anna; Weiss, Andreas; Grueninger, Stephan; McKinnon, Chris; Sirinathsinghji, Eva; Kahlon, Shira; Pfister, Edith L; Moser, Roger; Hummerich, Holger; Antoniou, Michael; Bates, Gillian P; Luthi-Carter, Ruth; Lowdell, Mark W; Björkqvist, Maria; Ostroff, Gary R; Aronin, Neil; Tabrizi, Sarah J

    2014-03-01

    Huntington's disease is an inherited neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. The peripheral innate immune system contributes to Huntington's disease pathogenesis and has been targeted successfully to modulate disease progression, but mechanistic understanding relating this to mutant huntingtin expression in immune cells has been lacking. Here we demonstrate that human Huntington's disease myeloid cells produce excessive inflammatory cytokines as a result of the cell-intrinsic effects of mutant huntingtin expression. A direct effect of mutant huntingtin on the NFκB pathway, whereby it interacts with IKKγ, leads to increased degradation of IκB and subsequent nuclear translocation of RelA. Transcriptional alterations in intracellular immune signalling pathways are also observed. Using a novel method of small interfering RNA delivery to lower huntingtin expression, we show reversal of disease-associated alterations in cellular function-the first time this has been demonstrated in primary human cells. Glucan-encapsulated small interfering RNA particles were used to lower huntingtin levels in human Huntington's disease monocytes/macrophages, resulting in a reversal of huntingtin-induced elevated cytokine production and transcriptional changes. These findings improve our understanding of the role of innate immunity in neurodegeneration, introduce glucan-encapsulated small interfering RNA particles as tool for studying cellular pathogenesis ex vivo in human cells and raise the prospect of immune cell-directed HTT-lowering as a therapeutic in Huntington's disease.

  17. Statistical aspects and risks of human-caused earthquakes

    Science.gov (United States)

    Klose, C. D.

    2013-12-01

    The seismological community invests ample human capital and financial resources to research and predict risks associated with earthquakes. Industries such as the insurance and re-insurance sector are equally interested in using probabilistic risk models developed by the scientific community to transfer risks. These models are used to predict expected losses due to naturally occurring earthquakes. But what about the risks associated with human-caused earthquakes? Such risk models are largely absent from both industry and academic discourse. In countries around the world, informed citizens are becoming increasingly aware and concerned that this economic bias is not sustainable for long-term economic growth, environmental and human security. Ultimately, citizens look to their government officials to hold industry accountable. In the Netherlands, for example, the hydrocarbon industry is held accountable for causing earthquakes near Groningen. In Switzerland, geothermal power plants were shut down or suspended because they caused earthquakes in canton Basel and St. Gallen. The public and the private non-extractive industry needs access to information about earthquake risks in connection with sub/urban geoengineeing activities, including natural gas production through fracking, geothermal energy production, carbon sequestration, mining and water irrigation. This presentation illuminates statistical aspects of human-caused earthquakes with respect to different geologic environments. Statistical findings are based on the first catalog of human-caused earthquakes (in Klose 2013). Findings are discussed which include the odds to die during a medium-size earthquake that is set off by geomechanical pollution. Any kind of geoengineering activity causes this type of pollution and increases the likelihood of triggering nearby faults to rupture.

  18. THE HUMAN RISKS CAUSED BY DEINDUSTRIALI-SATION. CASE STUDY: CERNA RIVER BASIN (HUNEDOARA COUNTY

    Directory of Open Access Journals (Sweden)

    G. C. SOFIA

    2015-03-01

    Full Text Available Human Risks caused by deindustrialization. Case Study: Cerna River Basin (Hunedoara County. Industrial restructuring during economic transition has affected the population, causing loss of jobs, reduced income, increased poverty and emphasizing social inequalities and marginalization phenomenon. These have led to population decline, massive emigration, difficulties in finding a job as well as an increased incidence of certain diseases, negatively influencing socio-economic development of the area.

  19. Metatranscriptomics of the human oral microbiome during health and disease.

    Science.gov (United States)

    Jorth, Peter; Turner, Keith H; Gumus, Pinar; Nizam, Nejat; Buduneli, Nurcan; Whiteley, Marvin

    2014-04-01

    The human microbiome plays important roles in health, but when disrupted, these same indigenous microbes can cause disease. The composition of the microbiome changes during the transition from health to disease; however, these changes are often not conserved among patients. Since microbiome-associated diseases like periodontitis cause similar patient symptoms despite interpatient variability in microbial community composition, we hypothesized that human-associated microbial communities undergo conserved changes in metabolism during disease. Here, we used patient-matched healthy and diseased samples to compare gene expression of 160,000 genes in healthy and diseased periodontal communities. We show that health- and disease-associated communities exhibit defined differences in metabolism that are conserved between patients. In contrast, the metabolic gene expression of individual species was highly variable between patients. These results demonstrate that despite high interpatient variability in microbial composition, disease-associated communities display conserved metabolic profiles that are generally accomplished by a patient-specific cohort of microbes. IMPORTANCE The human microbiome project has shown that shifts in our microbiota are associated with many diseases, including obesity, Crohn's disease, diabetes, and periodontitis. While changes in microbial populations are apparent during these diseases, the species associated with each disease can vary from patient to patient. Taking into account this interpatient variability, we hypothesized that specific microbiota-associated diseases would be marked by conserved microbial community behaviors. Here, we use gene expression analyses of patient-matched healthy and diseased human periodontal plaque to show that microbial communities have highly conserved metabolic gene expression profiles, whereas individual species within the community do not. Furthermore, disease-associated communities exhibit conserved changes

  20. Chromosomal inversions between human and chimpanzee lineages caused by retrotransposons.

    Directory of Open Access Journals (Sweden)

    Jungnam Lee

    Full Text Available The long interspersed element-1 (LINE-1 or L1 and Alu elements are the most abundant mobile elements comprising 21% and 11% of the human genome, respectively. Since the divergence of human and chimpanzee lineages, these elements have vigorously created chromosomal rearrangements causing genomic difference between humans and chimpanzees by either increasing or decreasing the size of genome. Here, we report an exotic mechanism, retrotransposon recombination-mediated inversion (RRMI, that usually does not alter the amount of genomic material present. Through the comparison of the human and chimpanzee draft genome sequences, we identified 252 inversions whose respective inversion junctions can clearly be characterized. Our results suggest that L1 and Alu elements cause chromosomal inversions by either forming a secondary structure or providing a fragile site for double-strand breaks. The detailed analysis of the inversion breakpoints showed that L1 and Alu elements are responsible for at least 44% of the 252 inversion loci between human and chimpanzee lineages, including 49 RRMI loci. Among them, three RRMI loci inverted exonic regions in known genes, which implicates this mechanism in generating the genomic and phenotypic differences between human and chimpanzee lineages. This study is the first comprehensive analysis of mobile element bases inversion breakpoints between human and chimpanzee lineages, and highlights their role in primate genome evolution.

  1. Traffic jam: a compendium of human diseases that affect intracellular transport processes.

    Science.gov (United States)

    Aridor, M; Hannan, L A

    2000-11-01

    As sequencing of the human genome nears completion, the genes that cause many human diseases are being identified and functionally described. This has revealed that many human diseases are due to defects of intracellular trafficking. This 'Toolbox' catalogs and briefly describes these diseases.

  2. Wolbachia endosymbionts and human disease control.

    Science.gov (United States)

    Slatko, Barton E; Luck, Ashley N; Dobson, Stephen L; Foster, Jeremy M

    2014-07-01

    Most human filarial nematode parasites and arthropods are hosts for a bacterial endosymbiont, Wolbachia. In filaria, Wolbachia are required for normal development, fertility and survival, whereas in arthropods, they are largely parasitic and can influence development and reproduction, but are generally not required for host survival. Due to their obligate nature in filarial parasites, Wolbachia have been a target for drug discovery initiatives using several approaches including diversity and focused library screening and genomic sequence analysis. In vitro and in vivo anti-Wolbachia antibiotic treatments have been shown to have adulticidal activity, a long sought goal of filarial parasite drug discovery. In mosquitoes, it has been shown that the presence of Wolbachia can inhibit the transmission of certain viruses, such as Dengue, Chikungunya, Yellow Fever, West Nile, as well as the infectivity of the malaria-causing protozoan, Plasmodium and filarial nematodes. Furthermore, Wolbachia can cause a form of conditional sterility that can be used to suppress populations of mosquitoes and additional medically important insects. Thus Wolbachia, a pandemic endosymbiont offers great potential for elimination of a wide-variety of devastating human diseases.

  3. Focal epithelial hyperplasia caused by human papillomavirus 13.

    Science.gov (United States)

    Saunders, Natasha R; Scolnik, Dennis; Rebbapragada, Anuradha; Koelink, Eric; Craw, Lindsey; Roth, Sherryn; Aronson, Leya; Perusini, Stephen; Silverman, Michael S

    2010-06-01

    Focal epithelial hyperplasia is a benign, papulo-nodular disease of the oral cavity. It is rare, affecting primarily Native American populations during childhood. It is closely associated with human papillomavirus 13 and 32. This report describes the diagnosis of 2 cases of focal epithelial hyperplasia in children from southern Guyana. The diagnosis was made using clinical criteria, polymerase chain reaction, and DNA sequencing.

  4. Human Lymphadenopathy Caused by Ratborne Bartonella, Tbilisi, Georgia.

    Science.gov (United States)

    Kandelaki, George; Malania, Lile; Bai, Ying; Chakvetadze, Neli; Katsitadze, Guram; Imnadze, Paata; Nelson, Christina; Harrus, Shimon; Kosoy, Michael

    2016-03-01

    Lymphadenopathy and fever that developed in a woman in Tbilisi, Georgia, most likely were caused by a ratborne Bartonella strain related B. tribocorum and B. elizabethae. The finding suggests that this Bartonella strain could be spread by infected rats and represents a potential human risk.

  5. Uncovering disease-disease relationships through the incomplete human interactome

    Science.gov (United States)

    Menche, Jörg; Sharma, Amitabh; Kitsak, Maksim; Ghiassian, Susan; Vidal, Marc; Loscalzo, Joseph; Barabási, Albert-László

    2015-01-01

    According to the disease module hypothesis the cellular components associated with a disease segregate in the same neighborhood of the human interactome, the map of biologically relevant molecular interactions. Yet, given the incompleteness of the interactome and the limited knowledge of disease-associated genes, it is not obvious if the available data has sufficient coverage to map out modules associated with each disease. Here we derive mathematical conditions for the identifiability of disease modules and show that the network-based location of each disease module determines its pathobiological relationship to other diseases. For example, diseases with overlapping network modules show significant co-expression patterns, symptom similarity, and comorbidity, while diseases residing in separated network neighborhoods are clinically distinct. These tools represent an interactome-based platform to predict molecular commonalities between clinically related diseases, even if they do not share disease genes. PMID:25700523

  6. Loss of function mutation in LOX causes thoracic aortic aneurysm and dissection in humans.

    Science.gov (United States)

    Lee, Vivian S; Halabi, Carmen M; Hoffman, Erin P; Carmichael, Nikkola; Leshchiner, Ignaty; Lian, Christine G; Bierhals, Andrew J; Vuzman, Dana; Mecham, Robert P; Frank, Natasha Y; Stitziel, Nathan O

    2016-08-01

    Thoracic aortic aneurysms and dissections (TAAD) represent a substantial cause of morbidity and mortality worldwide. Many individuals presenting with an inherited form of TAAD do not have causal mutations in the set of genes known to underlie disease. Using whole-genome sequencing in two first cousins with TAAD, we identified a missense mutation in the lysyl oxidase (LOX) gene (c.893T > G encoding p.Met298Arg) that cosegregated with disease in the family. Using clustered regularly interspaced short palindromic repeats (CRISPR)/clustered regularly interspaced short palindromic repeats-associated protein-9 nuclease (Cas9) genome engineering tools, we introduced the human mutation into the homologous position in the mouse genome, creating mice that were heterozygous and homozygous for the human allele. Mutant mice that were heterozygous for the human allele displayed disorganized ultrastructural properties of the aortic wall characterized by fragmented elastic lamellae, whereas mice homozygous for the human allele died shortly after parturition from ascending aortic aneurysm and spontaneous hemorrhage. These data suggest that a missense mutation in LOX is associated with aortic disease in humans, likely through insufficient cross-linking of elastin and collagen in the aortic wall. Mutation carriers may be predisposed to vascular diseases because of weakened vessel walls under stress conditions. LOX sequencing for clinical TAAD may identify additional mutation carriers in the future. Additional studies using our mouse model of LOX-associated TAAD have the potential to clarify the mechanism of disease and identify novel therapeutics specific to this genetic cause.

  7. Pelvic Hydatid Disease: CT and MRI Findings Causing Sciatica

    Energy Technology Data Exchange (ETDEWEB)

    Sanal, Hatice Tuba; Kocaoglu, Murat; Bulakbasi, Nail; Yildirim, Duzgun [Gulhane Military Medical School, Department of Radiology, 06018, Ankara (Turkmenistan)

    2007-12-15

    Pelvic masses, especially hydatid disease, rarely present with sciatica. We present the computed tomography (CT) and the magnetic resonance imaging (MRI) findings of a 49-year-old female patient with presacral hydatid disease, who was evaluated for her sciatica. We also want to emphasize the importance of assessing the pelvis of patients with symptoms and clinical findings that are inconsistent and that cannot be satisfactorily explained by the spinal imaging findings. isc herniation in the lumbar spine is a well-known etiology of back pains and sciatica, but whenever disc herniation of the lumbar spine is excluded by the employed imaging modalities, then the pelvis should be examined for other possible etiologies of nerve compression. We describe here a patient, who was complaining of sciatica, with no abnormal findings in her lumbar spinal magnetic resonance imaging (MRI). The cause of her sciatica was found to be associated with a pelvic hydatid cyst compressing the lumbosacral nerve plexus. In conclusion, if no pathology is evident for the lumbar discal structures, in connection with the cause of sciatica and lumbar back pains, then the pelvis should also be examined for the possible etiologies of compression of the lumbosacral nerve plexus. Whenever a multiseptated cyst is come across in a patient of an endemic origin with a positive history for hydatid disease like surgery, indicating recurrence, hydatid cyst is the most likely diagnosis.

  8. Ultrasonographic Findings of Extratesticular Diseases Causing Acute Scrotal Disorders

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Jae Joon; Lee, Tack; Chang, So Yong; Kim, Myeong Jin; Yoo, Hyung Sik; Lee, Jong Tae [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1996-12-15

    To evaluate the kinds of extratesticular diseases causing acute scrotal disorders by emergent sonography of the scrotum. Scrotal sonography in sixty-five patients, with age ranging from 5months to 82 years (mean : 27.3 years), with acute scrotal pain and swelling, was prospectively carried out by either a 10 or 7.5 MHz transducer. We evaluated the size and echogenicity of the epididymis, the presence of extratesticular solid mass or cyst, testicular involvement by extratesticular diseases, calcification, hydrocele and scrotal wall thickening. The most common cause of acute scrotal disorders was acute epididymitis (n= 50), followed by acute epididymo-orchitis (n = 4), mumps epididymo-orchitis (n = 2), enlarged epididymis secondary to testicular torsion (n = 2), infected hydrocele (n = 2), epididymal cyst (n = 2), rupture of varicocele (n = 1), angioneurotic edema (n = 1), and sperm granuloma (n = 1). Hydrocele was seen in 20 cases, and epididymal calcification was noted in 6 cases. Emergent scrotal sonography was useful for correct diagnosis and proper treatment in patients with acute scrotal disorders, especially in the differentiation of the acute epididymitis from other intrascrotal diseases

  9. 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.

  10. Does biodiversity protect humans against infectious disease?

    Science.gov (United States)

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

    2014-04-01

    Control of human infectious disease has been promoted as a valuable ecosystem service arising from the conservation of biodiversity. There are two commonly discussed mechanisms by which biodiversity loss could increase rates of infectious disease in a landscape. First, loss of competitors or predators could facilitate an increase in the abundance of competent reservoir hosts. Second, biodiversity loss could disproportionately affect non-competent, or less competent reservoir hosts, which would otherwise interfere with pathogen transmission to human populations by, for example, wasting the bites of infected vectors. A negative association between biodiversity and disease risk, sometimes called the "dilution effect hypothesis," has been supported for a few disease agents, suggests an exciting win-win outcome for the environment and society, and has become a pervasive topic in the disease ecology literature. Case studies have been assembled to argue that the dilution effect is general across disease agents. Less touted are examples in which elevated biodiversity does not affect or increases infectious disease risk for pathogens of public health concern. In order to assess the likely generality of the dilution effect, we review the association between biodiversity and public health across a broad variety of human disease agents. Overall, we hypothesize that conditions for the dilution effect are unlikely to be met for most important diseases of humans. Biodiversity probably has little net effect on most human infectious diseases but, when it does have an effect, observation and basic logic suggest that biodiversity will be more likely to increase than to decrease infectious disease risk.

  11. Pulmonary disease in patients with human immunodeficiency virus infection

    DEFF Research Database (Denmark)

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

    1989-01-01

    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...... 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...

  12. Seeking environmental causes of neurodegenerative disease and envisioning primary prevention.

    Science.gov (United States)

    Spencer, Peter S; Palmer, Valerie S; Kisby, Glen E

    2016-09-01

    Pathological changes of the aging brain are expressed in a range of neurodegenerative disorders that will impact increasing numbers of people across the globe. Research on the causes of these disorders has focused heavily on genetics, and strategies for prevention envision drug-induced slowing or arresting disease advance before its clinical appearance. We discuss a strategic shift that seeks to identify the environmental causes or contributions to neurodegeneration, and the vision of primary disease prevention by removing or controlling exposure to culpable agents. The plausibility of this approach is illustrated by the prototypical neurodegenerative disease amyotrophic lateral sclerosis and parkinsonism-dementia complex (ALS-PDC). This often-familial long-latency disease, once thought to be an inherited genetic disorder but now known to have a predominant or exclusive environmental origin, is in the process of disappearing from the three heavily affected populations, namely Chamorros of Guam and Rota, Japanese residents of Kii Peninsula, Honshu, and Auyu and Jaqai linguistic groups on the island of New Guinea in West Papua, Indonesia. Exposure via traditional food and/or medicine (the only common exposure in all three geographic isolates) to one or more neurotoxins in seed of cycad plants is the most plausible if yet unproven etiology. Neurotoxin dosage and/or subject age at exposure might explain the stratified epidemic of neurodegenerative disease on Guam in which high-incidence ALS peaked and declined before that of PD, only to be replaced today by a dementing disorder comparable to Alzheimer's disease. Exposure to the Guam environment is also linked to the delayed development of ALS among a subset of Chamorro and non-Chamorro Gulf War/Era veterans, a summary of which is reported here for the first time. Lessons learned from this study and from 65 years of research on ALS-PDC include the exceptional value of initial, field-based informal investigation of

  13. Parasitic diseases in humans transmitted by vectors.

    Science.gov (United States)

    Cholewiński, Marcin; Derda, Monika; Hadaś, Edward

    2015-01-01

    Despite the considerable progress of medicine, parasitic diseases still pose a great threat to human health and life. Among parasitic diseases, those transmitted by vectors, mainly arthropods, play a particular role. These diseases occur most frequently in the poorest countries and affect a vast part of the human population. They include malaria, babesiosis, trypanosomiasis, leishmaniasis and filariasis. This study presents those vector-transmitted diseases that are responsible for the greatest incidence and mortality of people on a global scale. Attention is focused primarily on diseases transmitted by mosquitoes, flies, Hemiptera and ticks.

  14. [DIABETIC NEPHROPATHY AS A CAUSE OF CHRONIC KIDNEY DISEASE].

    Science.gov (United States)

    Kos, Ivan; Prkačin, Ingrid

    2014-12-01

    Diabetic nephropathy is the leading cause of end-stage chronic kidney disease in most developed countries. Hyperglycemia, hypertension and genetic predisposition are the main risk factors for the development of diabetic nephropathy. Elevated serum lipids, smoking habits, and the amount and origin of dietary protein also seem to play a role as risk factors. Clinical picture includes a progressive increase in albuminuria, decline in glomerular filtration, hypertension, and a high risk of cardiovascular morbidity and mortality. Screening for albuminuria should be performed yearly, starting 5 years after diagnosis in type 1 diabetes or earlier in the presence of adolescence or poor metabolic control. In patients with type 2 diabetes, screening should be performed at diagnosis and yearly thereafter. Patients with albuminuria should undergo evaluation regarding the presence of associated comorbidities, especially retinopathy and macrovascular disease. Achieving the best metabolic control (HbA1c diabetes.

  15. Remnant cholesterol as a cause of ischemic heart disease

    DEFF Research Database (Denmark)

    Varbo, Anette; Benn, Marianne; Nordestgaard, Børge G

    2014-01-01

    This review focuses on remnant cholesterol as a causal risk factor for ischemic heart disease (IHD), on its definition, measurement, atherogenicity, and levels in high risk patient groups; in addition, present and future pharmacological approaches to lowering remnant cholesterol levels...... are considered. Observational studies show association between elevated levels of remnant cholesterol and increased risk of cardiovascular disease, even when remnant cholesterol levels are defined, measured, or calculated in different ways. In-vitro and animal studies also support the contention that elevated...... levels of remnant cholesterol may cause atherosclerosis same way as elevated levels of low-density lipoprotein (LDL) cholesterol, by cholesterol accumulation in the arterial wall. Genetic studies of variants associated with elevated remnant cholesterol levels show that an increment of 1mmol/L (39mg...

  16. Subcutaneous phaeohyphomycosis caused by Exophiala jeanselmei in collagen disease patient.

    Science.gov (United States)

    Nomura, Masayo; Maeda, Manabu; Seishima, Mariko

    2010-12-01

    Phaeohyphomycosis is a rare fungal infection that is more commonly associated with compromised patients. We present herein an 81-year-old man with collagen disease and chronic interstitial pneumonia who developed subcutaneous phaeohyphomycosis caused by Exophiala jeanselmei. The main pathogen of phaeohyphomycosis had been considered to be E. jeanselmei complex. This has recently been divided into several species by using a molecular technique. The main pathogen of phaeohyphomycosis is Exophiala xenobiotica, and E. jeanselmei is rather a rare pathogen of this disease. Although p.o. itraconazole and terbinafine administration was not effective for this patient, these antifungal agents were used for preventing systemic dissemination in this immunocompromised host.

  17. A Novel Virus Causes Scale Drop Disease in Lates calcarifer.

    Directory of Open Access Journals (Sweden)

    Ad de Groof

    2015-08-01

    Full Text Available From 1992 onwards, outbreaks of a previously unknown illness have been reported in Asian seabass (Lates calcarifer kept in maricultures in Southeast Asia. The most striking symptom of this emerging disease is the loss of scales. It was referred to as scale drop syndrome, but the etiology remained enigmatic. By using a next-generation virus discovery technique, VIDISCA-454, sequences of an unknown virus were detected in serum of diseased fish. The near complete genome sequence of the virus was determined, which shows a unique genome organization, and low levels of identity to known members of the Iridoviridae. Based on homology of a series of putatively encoded proteins, the virus is a novel member of the Megalocytivirus genus of the Iridoviridae family. The virus was isolated and propagated in cell culture, where it caused a cytopathogenic effect in infected Asian seabass kidney and brain cells. Electron microscopy revealed icosahedral virions of about 140 nm, characteristic for the Iridoviridae. In vitro cultured virus induced scale drop syndrome in Asian seabass in vivo and the virus could be reisolated from these infected fish. These findings show that the virus is the causative agent for the scale drop syndrome, as each of Koch's postulates is fulfilled. We have named the virus Scale Drop Disease Virus. Vaccines prepared from BEI- and formalin inactivated virus, as well as from E. coli produced major capsid protein provide efficacious protection against scale drop disease.

  18. Huntington's disease as caused by 34 CAG repeats.

    Science.gov (United States)

    Andrich, Jürgen; Arning, Larissa; Wieczorek, Stefan; Kraus, Peter H; Gold, Ralf; Saft, Carsten

    2008-04-30

    Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder caused by an abnormal expansion of a polymorphic stretch of CAG repeats in the coding 5' part of the HD gene on chromosome 4p. Expansions of CAG blocks beyond 35 repeats are associated with the clinical presentation of HD. There is an intermediate range of rare alleles between 27 and 35 CAG repeats with a higher risk for further expansion in subsequent generations. Here, we report a 75-year-old male with clinical features of HD and 34 CAG repeat units.

  19. The automated system for prevention of industrial-caused diseases

    Science.gov (United States)

    Varnavsky, A. N.

    2017-01-01

    The paper presents the automated system intended to prevent industrial-caused diseases of workers, the basis of which is represented by algorithms of preventing several negative functional conditions (stress, monotony). The emergence of such state shall be determined based on an analysis of bioelectric signals, in particular, skin-galvanic reactions. Proceeding from the dynamics of the functional state, the automated system offers to perform an optimized set of measures to restore the health of the worker. Implementation of an automated system is presented in Visual Programming system LabVIEW.

  20. The superior vena cava syndrome caused by malignant disease

    Energy Technology Data Exchange (ETDEWEB)

    Eren, Suat [Department of Radiology, Faculty of Medicine, Atatuerk University, 25240 Erzurum (Turkey)]. E-mail: suateren@atauni.edu.tr; Karaman, Adem [Department of Radiology, Faculty of Medicine, Atatuerk University, 25240 Erzurum (Turkey); Okur, Adnan [Department of Radiology, Faculty of Medicine, Atatuerk University, 25240 Erzurum (Turkey)

    2006-07-15

    Objective: The superior vena cava (SVC) obstruction by malignant diseases is either by direct invasion and compression or by tumour thrombus of the SVC. Whatever is its cause, obstruction of the SVC causes elevated pressure in the veins draining into the SVC and increased or reversed blood flow through collateral vessels. Severity of the syndrome depends on the collateral vascular system development. Therefore, imaging of the collateral veins with variable location and connection is important in determining the extension and management of the disease. Our aims are to describe collateral vessels of the superior vena cava syndrome (SVCS) related with the malignant diseases and to assess the ability of multi-detector row CT with multiplanar and 3D volume rendering techniques in determining and describing collateral circulations. Materials and methods: We present CT angiography findings of seven patients with small cell carcinoma of the lung (n = 2), squamous cell carcinoma of the lung (n = 3), Hodgkin disease of the thorax (n = 1), and squamous cell carcinoma of the oesophagus (n = 1). The patients received contrast-enhanced CT scans of the chest and abdomen on a multi-detector row CT during breath holding at suspended inspiration. Results: CT images revealed the cause and level of the SVC obstruction in all patients with axial and multiplanar reconstructed images. The SVC showed total obstruction in five patients and partial obstruction in two patients. The most common experienced collateral vessels were azygos vein (6), intercostal veins (6), mediastinal veins (6), paravertebral veins (5), hemiazygos vein (5), thoracoepigastric vein (5), internal mammary vein (5), thoracoacromioclavicular venous plexus (5), and anterior chest wall veins (5). While one case showed the portal-systemic shunt, V. cordis media and sinus coronarius with phrenic veins were enlarged in two cases, and the left adrenal vein was enlarged in a patient. In one case, the azygos vein with reversed

  1. Lipoprotein (a) as a cause of cardiovascular disease

    DEFF Research Database (Denmark)

    Nordestgaard, Børge G; Langsted, Anne

    2016-01-01

    Human epidemiologic and genetic evidence using the Mendelian randomization approach in large-scale studies now strongly supports that elevated lipoprotein (a) [Lp(a)] is a causal risk factor for cardiovascular disease, that is, for myocardial infarction, atherosclerotic stenosis, and aortic valve......-2 in Lp(a) could be through wound healing during childbirth, infections, and injury, a role that, in addition, could lead to more blood clots promoting stenosis of arteries and the aortic valve, and myocardial infarction. Randomized placebo-controlled trials of Lp(a) reduction in individuals...

  2. On Latest Developments in China's Human Rights Cause

    Institute of Scientific and Technical Information of China (English)

    LONG CHENG; TAN MINZHEN

    2011-01-01

    @@ China's human rights cause has undergone a new phase of development under the reform and opening-up policy that became official in the late 1970s.The changes include a shift from protection of human rights by law to Constitutional protection, an expansion of protection in scope not only for social rights but also for the right to freedoms, an extension from domestic protection to international protection, an increase in the intensity of protection, and a practice for protecting not only protection of the collective but also protection of the individual.

  3. Some Pathogenic Bacteria of Livestock Origin as a Cause of Foodborne Diseases

    Directory of Open Access Journals (Sweden)

    Anni Kusumaningsih

    2010-09-01

    Full Text Available Food are essentialy required for cell metabolism in human physiologyc. Food should be free from biological, chemical, and physical contamination and also hazardous substances. All of them are able to disrupt physiological homeostatis resulting disorder or diseases. Diseases resulted by those contaminant are called food borne disease. One of the important contaminants is biological contaminant especially pathogenic bacterias. Some pathogenic bacteria such as Salmonella spp., Escherichia coli, Bacillus anthracis, Clostridium spp., Listeria monocytogenes, Campylobacter spp., Vibrio cholerae, Enterobacter sakazakii, Shigella, are able to cause symptomatic diseases. Overall, the general symptoms of the diseases due to pathogenic bacterial infection are gastric pain, nausea, vomit, headache, loss of appetite, fever, and also dehydration.

  4. Exposure to lipophilic chemicals as a cause of neurological impairments, neurodevelopmental disorders and neurodegenerative diseases.

    Science.gov (United States)

    Zeliger, Harold I

    2013-09-01

    Many studies have associated environmental exposure to chemicals with neurological impairments (NIs) including neuropathies, cognitive, motor and sensory impairments; neurodevelopmental disorders (NDDs) including autism and attention deficit hyperactivity disorder (ADHD); neurodegenerative diseases (NDGs) including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis (ALS). The environmental chemicals shown to induce all these diseases include persistent organic pollutants (POPs), the plastic exudates bisphenol A and phthalates, low molecular weight hydrocarbons (LMWHCs) and polynuclear aromatic hydrocarbons (PAHs). It is reported here that though these chemicals differ widely in their chemical properties, reactivities and known points of attack in humans, a common link does exist between them. All are lipophilic species found in serum and they promote the sequential absorption of otherwise non-absorbed toxic hydrophilic species causing these diseases.

  5. Adult Scheuermann’s disease as cause of mechanic dorsalgia

    Directory of Open Access Journals (Sweden)

    F.P. Cantatore

    2011-09-01

    Full Text Available Scheuermann’s disease (SD or vertebral osteochondrosis is the most frequent cause of non postural kyphosis and one of more frequent cause of adolescent’s dorsalgia. The criteria for the diagnosis are: more than 5° of wedging of at least three adjacent vertebrae at the apex of the kyphosis; a toracic kyphosis of more than 45° of Cobb’s degree; Schmorl’s nodes and endplates irregularities. In addition to classic SD, there are radiological alterations that remain asintomatic for a long time to reveal in adult age: in that case it speaks of adult Scheuermann’s disease (ASD. We considered the diagnosis of patients came from April 2006 to April 2007 on Day Hospital in our Clinic. ASD was diagnosed, besides, in 10 of these patients. 7 patients had previous diagnosis such as: dorsal Spondiloarthrosis (4 subjects; Osteoporosis with vertebral fractures (3 subjects. All these diagnosis was not confirmed by us. In case of chronic dorsalgia of adult, ASD is rarely considered as differential diagnosis. Besides, the vertebral dorsalgia, even in absence of red flags as fever, astenia, ipersedimetry, functional loss and aching spinal processes to tapping, could hide a serious scene that lead us to be careful in the differential diagnosis, because of similar radiological pictures of the MSA to other pathology as spondylodiscitis, primitive or metastasic spinal tumors, and brittleness vertebral fractures

  6. Challenges to communicate risks of human-caused earthquakes

    Science.gov (United States)

    Klose, C. D.

    2014-12-01

    The awareness of natural hazards has been up-trending in recent years. In particular, this is true for earthquakes, which increase in frequency and magnitude in regions that normally do not experience seismic activity. In fact, one of the major concerns for many communities and businesses is that humans today seem to cause earthquakes due to large-scale shale gas production, dewatering and flooding of mines and deep geothermal power production. Accordingly, without opposing any of these technologies it should be a priority of earth scientists who are researching natural hazards to communicate earthquake risks. This presentation discusses the challenges that earth scientists are facing to properly communicate earthquake risks, in light of the fact that human-caused earthquakes are an environmental change affecting only some communities and businesses. Communication channels may range from research papers, books and class room lectures to outreach events and programs, popular media events or even social media networks.

  7. Comparative Genomic Analysis of Human Fungal Pathogens Causing Paracoccidioidomycosis

    OpenAIRE

    Desjardins, Christopher A; Champion, Mia D.; Holder, Jason W.; Muszewska, Anna; Goldberg, Jonathan; Bailao, Alexandre M.; Brigido, Marcelo de Macedo; Silva Ferreira, Marcia Eliana da; Garcia, Ana Maria; Grynberg, Marcin; Gujja, Sharvari; Heiman, David I.; Henn, Matthew R.; Kodira, Chinnappa D.; Leon-Narvaez, Henry

    2011-01-01

    Paracoccidioides is a fungal pathogen and the cause of paracoccidioidomycosis, a health-threatening human systemic mycosis endemic to Latin America. Infection by Paracoccidioides, a dimorphic fungus in the order Onygenales, is coupled with a thermally regulated transition from a soil-dwelling filamentous form to a yeast-like pathogenic form. To better understand the genetic basis of growth and pathogenicity in Paracoccidioides, we sequenced the genomes of two strains of Paracoccidioides brasi...

  8. [Proventricular dilatation disease and Avian Bornavirus as a possible cause].

    Science.gov (United States)

    Lierz, M; Herden, C; Herzog, S; Piepenbring, A

    2010-01-01

    Proventricular Dilatation Disease (PDD) is a very important letal disease in parrots. It affects several psittacine species and is a high risk factor for the health of breeding collections, but is rarely observed in other avian families. To date, the etiology of the disease remained unclear, though a virus infection was always assumed. Recently, a novel virus (Avian Bornavirus [ABV]) was discovered in parrots suffering from PDD so that ABV is now considered as the most likely cause. Despite the fact that clinically healthy birds may be infected with ABV, several studies demonstrate a correlation between ABV-infection and clinically present PDD. Apart from direct virus detection, serological methods allow the demonstration of an infection. Currently, Avian Bornavirus is the leading candidate as the aetiologic agent of PDD. Breeding collections and birds planned to be introduced into collections should therefore be investigated by molecular biological and serological methods for the presence of an ABV-infection. The diagnostic value of the demonstration of an ABV-infection for the diagnosis of a clinically present PDD has to be investigated further.

  9. Human-caused Indo-Pacific warm pool expansion.

    Science.gov (United States)

    Weller, Evan; Min, Seung-Ki; Cai, Wenju; Zwiers, Francis W; Kim, Yeon-Hee; Lee, Donghyun

    2016-07-01

    The Indo-Pacific warm pool (IPWP) has warmed and grown substantially during the past century. The IPWP is Earth's largest region of warm sea surface temperatures (SSTs), has the highest rainfall, and is fundamental to global atmospheric circulation and hydrological cycle. The region has also experienced the world's highest rates of sea-level rise in recent decades, indicating large increases in ocean heat content and leading to substantial impacts on small island states in the region. Previous studies have considered mechanisms for the basin-scale ocean warming, but not the causes of the observed IPWP expansion, where expansion in the Indian Ocean has far exceeded that in the Pacific Ocean. We identify human and natural contributions to the observed IPWP changes since the 1950s by comparing observations with climate model simulations using an optimal fingerprinting technique. Greenhouse gas forcing is found to be the dominant cause of the observed increases in IPWP intensity and size, whereas natural fluctuations associated with the Pacific Decadal Oscillation have played a smaller yet significant role. Further, we show that the shape and impact of human-induced IPWP growth could be asymmetric between the Indian and Pacific basins, the causes of which remain uncertain. Human-induced changes in the IPWP have important implications for understanding and projecting related changes in monsoonal rainfall, and frequency or intensity of tropical storms, which have profound socioeconomic consequences.

  10. Molecular basis of telomere dysfunction in human genetic diseases.

    Science.gov (United States)

    Sarek, Grzegorz; Marzec, Paulina; Margalef, Pol; Boulton, Simon J

    2015-11-01

    Mutations in genes encoding proteins required for telomere structure, replication, repair and length maintenance are associated with several debilitating human genetic disorders. These complex telomere biology disorders (TBDs) give rise to critically short telomeres that affect the homeostasis of multiple organs. Furthermore, genome instability is often a hallmark of telomere syndromes, which are associated with increased cancer risk. Here, we summarize the molecular causes and cellular consequences of disease-causing mutations associated with telomere dysfunction.

  11. The Leeuwenhoek Lecture 2001. Animal origins of human infectious disease.

    Science.gov (United States)

    Weiss, R A

    2001-06-29

    Since time immemorial animals have been a major source of human infectious disease. Certain infections like rabies are recognized as zoonoses caused in each case by direct animal-to-human transmission. Others like measles became independently sustained with the human population so that the causative virus has diverged from its animal progenitor. Recent examples of direct zoonoses are variant Creutzfeldt-Jakob disease arising from bovine spongiform encephalopathy, and the H5N1 avian influenza outbreak in Hong Kong. Epidemics of recent animal origin are the 1918-1919 influenza pandemic, and acquired immune deficiency syndrome caused by human immunodeficiency virus (HIV). Some retroviruses jump into and out of the chromosomal DNA of the host germline, so that they oscillate between being inherited Mendelian traits or infectious agents in different species. Will new procedures like animal-to-human transplants unleash further infections? Do microbes become more virulent upon cross-species transfer? Are animal microbes a threat as biological weapons? Will the vast reservoir of immunodeficient hosts due to the HIV pandemic provide conditions permissive for sporadic zoonoses to take off as human-to-human transmissible diseases? Do human infections now pose a threat to endangered primates? These questions are addressed in this lecture.

  12. Disability Weights Measurement for 228 Causes of Disease in the Korean Burden of Disease Study 2012.

    Science.gov (United States)

    Ock, Minsu; Lee, Jin Yong; Oh, In Hwan; Park, Hyesook; Yoon, Seok Jun; Jo, Min Woo

    2016-11-01

    Disability weight for each disease plays a key role in combining years lived with disability and years of life lost in disability adjusted life year. For the Korean Burden of Disease 2012 study, we have conducted a re-estimation of disability weights for causes of disease by adapting the methodology of a recent Global Burden of Disease study. Our study was conducted through a self-administered web-based survey using a paired comparison (PC) as the main valuation method. A total of 496 physicians and medical college students who were attending in third or fourth grade of a regular course conducted the survey. We applied a probit regression on the PC data and computed the predicted probabilities of each cause of disease from the coefficient estimates of the probit regression. We used 'being dead (1)' and 'full health (0)' as anchor points to rescale the predicted probability of each cause of disease on a scale of 0 to 1. By this method, disability weights for a total of 228 causes of disease were estimated. There was a fairly high correlation between the disability weights of overlapping causes of disease from this study and a previous South Korean study despite the differences in valuation methods and time periods. In conclusion, we have shown that disability weights can be estimated based on a PC by including 'full health' and 'being dead' as anchor points without resorting to a person trade-off. Through developments in the methodology of disability weights estimation from this study, disability weights can be easily estimated and continuously revised.

  13. Stem cell differentiation and human liver disease

    Institute of Scientific and Technical Information of China (English)

    Wen-Li Zhou; Claire N Medine; Liang Zhu; David C Hay

    2012-01-01

    Human stem cells are scalable cell populations capable of cellular differentiation.This makes them a very attractive in vitro cellular resource and in theory provides unlimited amounts of primary cells.Such an approach has the potential to improve our understanding of human biology and treating disease.In the future it may be possible to deploy novel stem cell-based approaches to treat human liver diseases.In recent years,efficient hepatic differentiation from human stem cells has been achieved by several research groups including our own.In this review we provide an overview of the field and discuss the future potential and limitations of stem cell technology.

  14. CRISPR/Cas9 facilitates investigation of neural circuit disease using human iPSCs: mechanism of epilepsy caused by an SCN1A loss-of-function mutation

    Science.gov (United States)

    Liu, J; Gao, C; Chen, W; Ma, W; Li, X; Shi, Y; Zhang, H; Zhang, L; Long, Y; Xu, H; Guo, X; Deng, S; Yan, X; Yu, D; Pan, G; Chen, Y; Lai, L; Liao, W; Li, Z

    2016-01-01

    Mutations in SCN1A, the gene encoding the α subunit of Nav1.1 channel, can cause epilepsies with wide ranges of clinical phenotypes, which are associated with the contrasting effects of channel loss-of-function or gain-of-function. In this project, CRISPR/Cas9- and TALEN-mediated genome-editing techniques were applied to induced pluripotent stem cell (iPSC)-based-disease model to explore the mechanism of epilepsy caused by SCN1A loss-of-function mutation. By fluorescently labeling GABAergic subtype in iPSC-derived neurons using CRISPR/Cas9, we for the first time performed electrophysiological studies on SCN1A-expressing neural subtype and monitored the postsynaptic activity of both inhibitory and excitatory types. We found that the mutation c.A5768G, which led to no current of Nav1.1 in exogenously transfected system, influenced the properties of not only Nav current amount, but also Nav activation in Nav1.1-expressing GABAergic neurons. The two alterations in Nav further reduced the amplitudes and enhanced the thresholds of action potential in patient-derived GABAergic neurons, and led to weakened spontaneous inhibitory postsynaptic currents (sIPSCs) in the patient-derived neuronal network. Although the spontaneous excitatory postsynaptic currents (sEPSCs) did not change significantly, when the frequencies of both sIPSCs and sEPSCs were further analyzed, we found the whole postsynaptic activity transferred from the inhibition-dominated state to excitation in patient-derived neuronal networks, suggesting that changes in sIPSCs alone were sufficient to significantly reverse the excitatory level of spontaneous postsynaptic activity. In summary, our findings fill the gap of our knowledge regarding the relationship between SCN1A mutation effect recorded on exogenously transfected cells and on Nav1.1-expressing neurons, and reveal the physiological basis underlying epileptogenesis caused by SCN1A loss-of-function mutation. PMID:26731440

  15. Evidence for α-synuclein prions causing multiple system atrophy in humans with parkinsonism.

    Science.gov (United States)

    Prusiner, Stanley B; Woerman, Amanda L; Mordes, Daniel A; Watts, Joel C; Rampersaud, Ryan; Berry, David B; Patel, Smita; Oehler, Abby; Lowe, Jennifer K; Kravitz, Stephanie N; Geschwind, Daniel H; Glidden, David V; Halliday, Glenda M; Middleton, Lefkos T; Gentleman, Steve M; Grinberg, Lea T; Giles, Kurt

    2015-09-22

    Prions are proteins that adopt alternative conformations that become self-propagating; the PrP(Sc) prion causes the rare human disorder Creutzfeldt-Jakob disease (CJD). We report here that multiple system atrophy (MSA) is caused by a different human prion composed of the α-synuclein protein. MSA is a slowly evolving disorder characterized by progressive loss of autonomic nervous system function and often signs of parkinsonism; the neuropathological hallmark of MSA is glial cytoplasmic inclusions consisting of filaments of α-synuclein. To determine whether human α-synuclein forms prions, we examined 14 human brain homogenates for transmission to cultured human embryonic kidney (HEK) cells expressing full-length, mutant human α-synuclein fused to yellow fluorescent protein (α-syn140*A53T-YFP) and TgM83(+/-) mice expressing α-synuclein (A53T). The TgM83(+/-) mice that were hemizygous for the mutant transgene did not develop spontaneous illness; in contrast, the TgM83(+/+) mice that were homozygous developed neurological dysfunction. Brain extracts from 14 MSA cases all transmitted neurodegeneration to TgM83(+/-) mice after incubation periods of ∼120 d, which was accompanied by deposition of α-synuclein within neuronal cell bodies and axons. All of the MSA extracts also induced aggregation of α-syn*A53T-YFP in cultured cells, whereas none of six Parkinson's disease (PD) extracts or a control sample did so. Our findings argue that MSA is caused by a unique strain of α-synuclein prions, which is different from the putative prions causing PD and from those causing spontaneous neurodegeneration in TgM83(+/+) mice. Remarkably, α-synuclein is the first new human prion to be identified, to our knowledge, since the discovery a half century ago that CJD was transmissible.

  16. Impacts of Gut Bacteria on Human Health and Diseases

    Directory of Open Access Journals (Sweden)

    Yu-Jie Zhang

    2015-04-01

    Full Text Available 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.

  17. 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 ... A correlation between epigenetic DNA modifications and human life span ... Most studies demonstrated that aging is associated with a relaxation in ...

  18. Lipoprotein X Causes Renal Disease in LCAT Deficiency.

    Science.gov (United States)

    Ossoli, Alice; Neufeld, Edward B; Thacker, Seth G; Vaisman, Boris; Pryor, Milton; Freeman, Lita A; Brantner, Christine A; Baranova, Irina; Francone, Nicolás O; Demosky, Stephen J; Vitali, Cecilia; Locatelli, Monica; Abbate, Mauro; Zoja, Carlamaria; Franceschini, Guido; Calabresi, Laura; Remaley, Alan T

    2016-01-01

    Human familial lecithin:cholesterol acyltransferase (LCAT) deficiency (FLD) is characterized by low HDL, accumulation of an abnormal cholesterol-rich multilamellar particle called lipoprotein-X (LpX) in plasma, and renal disease. The aim of our study was to determine if LpX is nephrotoxic and to gain insight into the pathogenesis of FLD renal disease. We administered a synthetic LpX, nearly identical to endogenous LpX in its physical, chemical and biologic characteristics, to wild-type and Lcat-/- mice. Our in vitro and in vivo studies demonstrated an apoA-I and LCAT-dependent pathway for LpX conversion to HDL-like particles, which likely mediates normal plasma clearance of LpX. Plasma clearance of exogenous LpX was markedly delayed in Lcat-/- mice, which have low HDL, but only minimal amounts of endogenous LpX and do not spontaneously develop renal disease. Chronically administered exogenous LpX deposited in all renal glomerular cellular and matrical compartments of Lcat-/- mice, and induced proteinuria and nephrotoxic gene changes, as well as all of the hallmarks of FLD renal disease as assessed by histological, TEM, and SEM analyses. Extensive in vivo EM studies revealed LpX uptake by macropinocytosis into mouse glomerular endothelial cells, podocytes, and mesangial cells and delivery to lysosomes where it was degraded. Endocytosed LpX appeared to be degraded by both human podocyte and mesangial cell lysosomal PLA2 and induced podocyte secretion of pro-inflammatory IL-6 in vitro and renal Cxl10 expression in Lcat-/- mice. In conclusion, LpX is a nephrotoxic particle that in the absence of Lcat induces all of the histological and functional hallmarks of FLD and hence may serve as a biomarker for monitoring recombinant LCAT therapy. In addition, our studies suggest that LpX-induced loss of endothelial barrier function and release of cytokines by renal glomerular cells likely plays a role in the initiation and progression of FLD nephrosis.

  19. Pain in chronic kidney disease: prevalence, cause and management.

    Science.gov (United States)

    Kafkia, Theodora; Chamney, Melissa; Drinkwater, Anna; Pegoraro, Marisa; Sedgewick, John

    2011-06-01

    Pain is an unpleasant sensory and emotional experience and is the most common symptom experienced by renal patients. It can be caused by primary co-morbid diseases, renal replacement therapies, medication or treatment side effects, and its intensity varies from moderate to severe. Pain management in renal patients is difficult, since the distance between pain relief and toxicity is very small. This paper will provide an algorithm for pain management proposed using paracetamol, nonsteroid anti-inflamatory drugs (NSAIDs), mild and stronger opioids as well as complementary techniques. Quality of Life (QoL) and overall enhancement of the patient experience through better pain management are also discussed. To improve pain management it is essential that nurses recognise that they have direct responsibilities related to pain assessment and tailoring of opioid analgesics and better and more detailed education.

  20. 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......Protein misfolding is a common event in living cells. In young and healthy cells, the misfolded protein load is disposed of by protein quality control (PQC) systems. In aging cells and in cells from certain individuals with genetic diseases, the load may overwhelm the PQC capacity, resulting...... in accumulation of misfolded proteins. Dependent on the properties of the protein and the efficiency of the PQC systems, the accumulated protein may be degraded or assembled into toxic oligomers and aggregates. To illustrate this concept, we discuss a number of very different protein misfolding diseases including...

  1. Contemporary Approaches for Identifying Rare Bone Disease Causing Genes

    Institute of Scientific and Technical Information of China (English)

    Charles R.Farber; Thomas L.Clemens

    2013-01-01

    Recent improvements in the speed and accuracy of DNA sequencing, together with increasingly sophisti-cated mathematical approaches for annotating gene networks, have revolutionized the field of human genetics and made these once time consuming approaches assessable to most investigators. In the field of bone research, a particularly active area of gene discovery has occurred in patients with rare bone disorders such as osteogenesis imperfecta (OI) that are caused by mutations in single genes. In this perspective, we highlight some of these technological advances and describe how they have been used to identify the genetic determinants underlying two previously unexplained cases of OI. The widespread availability of advanced methods for DNA sequencing and bioinformatics analysis can be expected to greatly facilitate identification of novel gene networks that normally function to control bone formation and maintenance.

  2. Hypoxemia in patients with COPD: cause, effects, and disease progression.

    LENUS (Irish Health Repository)

    Kent, Brian D

    2012-02-01

    Chronic obstructive pulmonary disease (COPD) is a leading cause of death and disability internationally. Alveolar hypoxia and consequent hypoxemia increase in prevalence as disease severity increases. Ventilation\\/perfusion mismatch resulting from progressive airflow limitation and emphysema is the key driver of this hypoxia, which may be exacerbated by sleep and exercise. Uncorrected chronic hypoxemia is associated with the development of adverse sequelae of COPD, including pulmonary hypertension, secondary polycythemia, systemic inflammation, and skeletal muscle dysfunction. A combination of these factors leads to diminished quality of life, reduced exercise tolerance, increased risk of cardiovascular morbidity, and greater risk of death. Concomitant sleep-disordered breathing may place a small but significant subset of COPD patients at increased risk of these complications. Long-term oxygen therapy has been shown to improve pulmonary hemodynamics, reduce erythrocytosis, and improve survival in selected patients with severe hypoxemic respiratory failure. However, the optimal treatment for patients with exertional oxyhemoglobin desaturation, isolated nocturnal hypoxemia, or mild-to-moderate resting daytime hypoxemia remains uncertain.

  3. Hypoxemia in patients with COPD: cause, effects, and disease progression

    Directory of Open Access Journals (Sweden)

    Brian D Kent

    2011-03-01

    Full Text Available Brian D Kent1,2, Patrick D Mitchell1, Walter T McNicholas1,21Pulmonary and Sleep Disorders Unit, St. Vincent’s University Hospital, Dublin; 2Conway Institute of Biomolecular and Biomedical Research, University College Dublin, IrelandAbstract: Chronic obstructive pulmonary disease (COPD is a leading cause of death and disability internationally. Alveolar hypoxia and consequent hypoxemia increase in prevalence as disease severity increases. Ventilation/perfusion mismatch resulting from progressive airflow limitation and emphysema is the key driver of this hypoxia, which may be exacerbated by sleep and exercise. Uncorrected chronic hypoxemia is associated with the development of adverse sequelae of COPD, including pulmonary hypertension, secondary polycythemia, systemic inflammation, and skeletal muscle dysfunction. A combination of these factors leads to diminished quality of life, reduced exercise tolerance, increased risk of cardiovascular morbidity, and greater risk of death. Concomitant sleep-disordered breathing may place a small but significant subset of COPD patients at increased risk of these complications. Long-term oxygen therapy has been shown to improve pulmonary hemodynamics, reduce erythrocytosis, and improve survival in selected patients with severe hypoxemic respiratory failure. However, the optimal treatment for patients with exertional oxyhemoglobin desaturation, isolated nocturnal hypoxemia, or mild-to-moderate resting daytime hypoxemia remains uncertain.Keywords: COPD, hypoxia, sleep, inflammation, pulmonary hypertension

  4. 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.

  5. Human Echinococcosis: A Neglected Disease

    Directory of Open Access Journals (Sweden)

    António Menezes da Silva

    2010-01-01

    Full Text Available Echinococcosis is among the most neglected parasitic diseases. Development of new drugs and other treatment modalities receives very little attention, if any. In most developed countries, Cystic Echinococcosis (CE is an imported disease of very low incidence and prevalence and is found almost exclusively in migrants from endemic regions. In endemic regions, predominantly settings with limited resources, patient numbers are high. Whole communities do not have access to appropriate treatment. The choice of treatment modalities is limited because of poor infrastructure and shortage of equipment and drugs. In this context, CE meets the criteria for a neglected disease. Furthermore, the terminology related to the designations around the parasite, its evolution and some therapeutic procedures is not uniform and sometimes inappropriate terms and wrong designations are used based on incorrect concepts. Although all of us know the different aspects of the disease it is pertinent to remember some important points and, above all, to clarify some aspects concerning the hydatid cyst's nomenclature in order to understand better the therapeutic options in the liver locations, particularly the different surgical approaches.

  6. Patho-epigenetics of Infectious Diseases Caused by Intracellular Bacteria.

    Science.gov (United States)

    Niller, Hans Helmut; Minarovits, Janos

    2016-01-01

    In multicellular eukaryotes including plants, animals and humans, epigenetic reprogramming may play a role in the pathogenesis of a wide variety of diseases. Recent studies revealed that in addition to viruses, pathogenic bacteria are also capable to dysregulate the epigenetic machinery of their target cells. In this chapter we focus on epigenetic alterations induced by bacteria infecting humans. Most of them are obligate or facultative intracellular bacteria that produce either bacterial toxins and surface proteins targeting the host cell membrane, or synthesise effector proteins entering the host cell nucleus. These bacterial products typically elicit histone modifications, i.e. alter the "histone code". Bacterial pathogens are capable to induce alterations of host cell DNA methylation patterns, too. Such changes in the host cell epigenotype and gene expression pattern may hinder the antibacterial immune response and create favourable conditions for bacterial colonization, growth, or spread. Epigenetic dysregulation mediated by bacterial products may also facilitate the production of inflammatory cytokines and other inflammatory mediators affecting the epigenotype of their target cells. Such indirect epigenetic changes as well as direct interference with the epigenetic machinery of the host cells may contribute to the initiation and progression of malignant tumors associated with distinct bacterial infections.

  7. 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.

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

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    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.

  9. Human Dermatitis Caused by Ophionyssus natricis, a Snake Mite.

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    Emad Amanatfard

    2014-12-01

    Full Text Available Ophionyssus natricis is a purely blood sucking parasite of snakes and of worldwide distribution. Infected snakes often exhibit lethargy, pruritus, crusting dermatitis, and behavioral changes. Ophionyssus natricis can also attack humans, causing popular vesiculo-bullous eruption of the skin. A 29 years old man working in zoo, Sari, Mazandaran, Iran, presented itchy papullar eruption of the skin. He had noticed small insects fixed on his skin and large numbers of these same insects on a python and its cage in the zoo. Regarding totheir morphological characteristics they were diagnosed as O. natricis (Geravis, 1844, a snake mite. It is the first report of O. natricis from Iran.

  10. Haploinsufficiency of TAB2 causes congenital heart defects in humans

    DEFF Research Database (Denmark)

    Thienpont, Bernard; Zhang, Litu; Postma, Alex V;

    2010-01-01

    Congenital heart defects (CHDs) are the most common major developmental anomalies and the most frequent cause for perinatal mortality, but their etiology remains often obscure. We identified a locus for CHDs on 6q24-q25. Genotype-phenotype correlations in 12 patients carrying a chromosomal deletion...... in cardiac development was further supported by its conserved expression in the developing human and zebrafish heart. Moreover, a critical, dosage-sensitive role during development was demonstrated by the cardiac defects observed upon titrated knockdown of tab2 expression in zebrafish embryos...

  11. Extent, Causes, and Consequences of Small RNA Expression Variation in Human Adipose Tissue

    OpenAIRE

    Leopold Parts; Hedman, Åsa K.; Sarah Keildson; Knights, Andrew J.; Cei Abreu-Goodger; Martijn van de Bunt; José Afonso Guerra-Assunção; Nenad Bartonicek; Stijn van Dongen; Reedik Mägi; James Nisbet; Amy Barrett; Mattias Rantalainen; Nica, Alexandra C.; Quail, Michael A

    2012-01-01

    Small RNAs are functional molecules that modulate mRNA transcripts and have been implicated in the aetiology of several common diseases. However, little is known about the extent of their variability within the human population. Here, we characterise the extent, causes, and effects of naturally occurring variation in expression and sequence of small RNAs from adipose tissue in relation to genotype, gene expression, and metabolic traits in the MuTHER reference cohort. We profiled the expressio...

  12. Does anxiety cause freezing of gait in Parkinson's disease?

    Directory of Open Access Journals (Sweden)

    Kaylena A Ehgoetz Martens

    Full Text Available Individuals with Parkinson's disease (PD commonly experience freezing of gait under time constraints, in narrow spaces, and in the dark. One commonality between these different situations is that they may all provoke anxiety, yet anxiety has never been directly examined as a cause of FOG. In this study, virtual reality was used to induce anxiety and evaluate whether it directly causes FOG. Fourteen patients with PD and freezing of gait (Freezers and 17 PD without freezing of gait (Non-Freezers were instructed to walk in two virtual environments: (i across a plank that was located on the ground (LOW, (ii across a plank above a deep pit (HIGH. Multiple synchronized motion capture cameras updated participants' movement through the virtual environment in real-time, while their gait was recorded. Anxiety levels were evaluated after each trial using self-assessment manikins. Freezers performed the experiment on two separate occasions (in their ON and OFF state. Freezers reported higher levels of anxiety compared to Non-Freezers (p < 0.001 and all patients reported greater levels of anxiety when walking across the HIGH plank compared to the LOW (p < 0.001. Freezers experienced significantly more freezing of gait episodes (p = 0.013 and spent a significantly greater percentage of each trial frozen (p = 0.005 when crossing the HIGH plank. This finding was even more pronounced when comparing Freezers in their OFF state. Freezers also had greater step length variability in the HIGH compared to the LOW condition, while the step length variability in Non-Freezers did not change. In conclusion, this was the first study to directly compare freezing of gait in anxious and non-anxious situations. These results present strong evidence that anxiety is an important mechanism underlying freezing of gait and supports the notion that the limbic system may have a profound contribution to freezing in PD.

  13. Has solar variability caused climate change that affected human culture?

    Science.gov (United States)

    Feynman, Joan

    If solar variability affects human culture it most likely does so by changing the climate in which the culture operates. Variations in the solar radiative input to the Earth's atmosphere have often been suggested as a cause of such climate change on time scales from decades to tens of millennia. In the last 20 years there has been enormous progress in our knowledge of the many fields of research that impinge on this problem; the history of the solar output, the effect of solar variability on the Earth's mean climate and its regional patterns, the history of the Earth's climate and the history of mankind and human culture. This new knowledge encourages revisiting the question asked in the title of this talk. Several important historical events have been reliably related to climate change including the Little Ice Age in northern Europe and the collapse of the Classical Mayan civilization in the 9th century AD. In the first section of this paper we discus these historical events and review the evidence that they were caused by changes in the solar output. Perhaps the most important event in the history of mankind was the development of agricultural societies. This began to occur almost 12,000 years ago when the climate changed from the Pleistocene to the modern climate of the Holocene. In the second section of the paper we will discuss the suggestion ( Feynman and Ruzmaikin, 2007) that climate variability was the reason agriculture developed when it did and not before.

  14. Agrarian diet and diseases of affluence – Do evolutionary novel dietary lectins cause leptin resistance?

    Directory of Open Access Journals (Sweden)

    Jönsson Tommy

    2005-12-01

    Full Text Available Abstract Background The global pattern of varying prevalence of diseases of affluence, such as obesity, cardiovascular disease and diabetes, suggests that some environmental factor specific to agrarian societies could initiate these diseases. Presentation of the hypothesis We propose that a cereal-based diet could be such an environmental factor. Through previous studies in archaeology and molecular evolution we conclude that humans and the human leptin system are not specifically adapted to a cereal-based diet, and that leptin resistance associated with diseases of affluence could be a sign of insufficient adaptation to such a diet. We further propose lectins as a cereal constituent with sufficient properties to cause leptin resistance, either through effects on metabolism central to the proper functions of the leptin system, and/or directly through binding to human leptin or human leptin receptor, thereby affecting the function. Testing the hypothesis Dietary interventions should compare effects of agrarian and non-agrarian diets on incidence of diseases of affluence, related risk factors and leptin resistance. A non-significant (p = 0.10 increase of cardiovascular mortality was noted in patients advised to eat more whole-grain cereals. Our lab conducted a study on 24 domestic pigs in which a cereal-free hunter-gatherer diet promoted significantly higher insulin sensitivity, lower diastolic blood pressure and lower C-reactive protein as compared to a cereal-based swine feed. Testing should also evaluate the effects of grass lectins on the leptin system in vivo by diet interventions, and in vitro in various leptin and leptin receptor models. Our group currently conducts such studies. Implications of the hypothesis If an agrarian diet initiates diseases of affluence it should be possible to identify the responsible constituents and modify or remove them so as to make an agrarian diet healthier.

  15. Rhombencephalitis Caused by Listeria monocytogenes in Humans and Ruminants: A Zoonosis on the Rise?

    Science.gov (United States)

    Oevermann, Anna; Zurbriggen, Andreas; Vandevelde, Marc

    2010-01-01

    Listeriosis is an emerging zoonotic infection of humans and ruminants worldwide caused by Listeria monocytogenes (LM). In both host species, CNS disease accounts for the high mortality associated with listeriosis and includes rhombencephalitis, whose neuropathology is strikingly similar in humans and ruminants. This review discusses the current knowledge about listeric encephalitis, and involved host and bacterial factors. There is an urgent need to study the molecular mechanisms of neuropathogenesis, which are poorly understood. Such studies will provide a basis for the development of new therapeutic strategies that aim to prevent LM from invading the brain and spread within the CNS. PMID:20204066

  16. Rhombencephalitis Caused by Listeria monocytogenes in Humans and Ruminants: A Zoonosis on the Rise?

    Directory of Open Access Journals (Sweden)

    Anna Oevermann

    2010-01-01

    Full Text Available Listeriosis is an emerging zoonotic infection of humans and ruminants worldwide caused by Listeria monocytogenes (LM. In both host species, CNS disease accounts for the high mortality associated with listeriosis and includes rhombencephalitis, whose neuropathology is strikingly similar in humans and ruminants. This review discusses the current knowledge about listeric encephalitis, and involved host and bacterial factors. There is an urgent need to study the molecular mechanisms of neuropathogenesis, which are poorly understood. Such studies will provide a basis for the development of new therapeutic strategies that aim to prevent LM from invading the brain and spread within the CNS.

  17. The ordered assembly of tau is the gain-of-toxic function that causes human tauopathies.

    Science.gov (United States)

    Goedert, Michel

    2016-10-01

    A pathological pathway leading from soluble to insoluble and filamentous tau underlies human tauopathies. This ordered assembly causes disease and is the gain-of-toxic function. It involves the transition from an intrinsically disordered monomer to a highly structured filament. Based on recent findings, one can divide the ordered assembly into propagation of pathology and neurodegeneration. Short tau fibrils constitute the major species of seed-competent tau in the brains of mice transgenic for human P301S tau. The molecular species of aggregated tau that are essential for neurodegeneration remain to be identified. Copyright © 2016. Published by Elsevier Inc.

  18. The complement system in human cardiometabolic disease.

    Science.gov (United States)

    Hertle, E; Stehouwer, C D A; van Greevenbroek, M M J

    2014-10-01

    The complement system has been implicated in obesity, fatty liver, diabetes and cardiovascular disease (CVD). Complement factors are produced in adipose tissue and appear to be involved in adipose tissue metabolism and local inflammation. Thereby complement links adipose tissue inflammation to systemic metabolic derangements, such as low-grade inflammation, insulin resistance and dyslipidaemia. Furthermore, complement has been implicated in pathophysiological mechanisms of diet- and alcohol induced liver damage, hyperglycaemia, endothelial dysfunction, atherosclerosis and fibrinolysis. In this review, we summarize current evidence on the role of the complement system in several processes of human cardiometabolic disease. C3 is the central component in complement activation, and has most widely been studied in humans. C3 concentrations are associated with insulin resistance, liver dysfunction, risk of the metabolic syndrome, type 2 diabetes and CVD. C3 can be activated by the classical, the lectin and the alternative pathway of complement activation; and downstream activation of C3 activates the terminal pathway. Complement may also be activated via extrinsic proteases of the coagulation, fibrinolysis and the kinin systems. Studies on the different complement activation pathways in human cardiometabolic disease are limited, but available evidence suggests that they may have distinct roles in processes underlying cardiometabolic disease. The lectin pathway appeared beneficial in some studies on type 2 diabetes and CVD, while factors of the classical and the alternative pathway were related to unfavourable cardiometabolic traits. The terminal complement pathway was also implicated in insulin resistance and liver disease, and appears to have a prominent role in acute and advanced CVD. The available human data suggest a complex and potentially causal role for the complement system in human cardiometabolic disease. Further, preferably longitudinal studies are needed to

  19. Attention! Cardiac tamponade may be caused by underlying Castleman's disease.

    Science.gov (United States)

    Atay, Hilmi; Kelkitli, Engin; Okuyucu, Muhammed; Yildiz, Levent; Turgut, Mehmet

    2015-05-01

    Castleman's disease is a rarely observed lymphoproliferative disease. In the literature, various signs and symptoms of the disease have been reported; one of these is secondary cardiac tamponade. We describe the case of a 41-year-old man who developed cardiac tamponade during examination, and who was later diagnosed with Castleman's disease, based on his lymph node biopsies.

  20. Mycoplasma genitalium: An Emerging Cause of Pelvic Inflammatory Disease

    Directory of Open Access Journals (Sweden)

    Catherine L. Haggerty

    2011-01-01

    Full Text Available Mycoplasma genitalium is a sexually transmitted pathogen that is increasingly identified among women with pelvic inflammatory disease (PID. Although Chlamydia trachomatis and Neisseria gonorrhoeae frequently cause PID, up to 70% of cases have an unidentified etiology. This paper summarizes evidence linking M. genitalium to PID and its long-term reproductive sequelae. Several PCR studies have demonstrated that M. genitalium is associated with PID, independent of gonococcal and chlamydial infection. Most have been cross-sectional, although one prospective investigation suggested that M. genitalium was associated with over a thirteenfold risk of endometritis. Further, a nested case-control posttermination study demonstrated a sixfold increased risk of PID among M. genitalium positive patients. Whether or not M. genitalium upper genital tract infection results in long-term reproductive morbidity is unclear, although tubal factor infertility patients have been found to have elevated M. genitalium antibodies. Several lines of evidence suggest that M. genitalium is likely resistant to many frequently used PID treatment regimens. Correspondingly, M. genitalium has been associated with treatment failure following cefoxitin and doxycycline treatment for clinically suspected PID. Collectively, strong evidence suggests that M. genitalium is associated with PID. Further study of M. genitalium upper genital tract infection diagnosis, treatment and long-term sequelae is warranted.

  1. Oral manifestations caused by the linear IgA disease.

    Science.gov (United States)

    Eguia del Valle, Asier; Aguirre Urízar, José Manuel; Martínez Sahuquillo, Angel

    2004-01-01

    The Linear IgA deposit related disease or Linear IgA disease (LAD) is a chronic, uncommon and autoimmunological mucocutaneous disease, characterised by linear IgA deposits along the basement membrane zone. In mainly cases, moreover cutaneous lesions, there are oral mucosal and other mucosal lesions. There are also, some cases published of Linear IgA disease limited to oral mucosa. The known of this disease is important for the establishment of a correct differential diagnosis in cases of blistering mucocutaneous diseases. In this paper, we analyze the most important features of this disease, attending specially to the oral manifestations.

  2. A derangement of the brain wound healing process may cause some cases of Alzheimer's disease.

    Science.gov (United States)

    Lehrer, Steven; Rheinstein, Peter H

    2016-08-01

    A derangement of brain wound healing may cause some cases of Alzheimer's disease. Wound healing, a highly complex process, has four stages: hemostasis, inflammation, repair, and remodeling. Hemostasis and the initial phases of inflammation in brain tissue are typical of all vascularized tissue, such as skin. However, distinct differences arise in brain tissue during the later stages of inflammation, repair, and remodeling, and closely parallel the changes of Alzheimer's disease. Our hypothesis -- Alzheimer's disease is brain wound healing gone awry at least in some cases -- could be tested by measuring progression with biomarkers for the four stages of wound healing in humans or appropriate animal models. Autopsy studies might be done. Chronic traumatic encephalopathy might also result from the brain wound healing process.

  3. Crystal structure of glycogen debranching enzyme and insights into its catalysis and disease-causing mutations.

    Science.gov (United States)

    Zhai, Liting; Feng, Lingling; Xia, Lin; Yin, Huiyong; Xiang, Song

    2016-04-18

    Glycogen is a branched glucose polymer and serves as an important energy store. Its debranching is a critical step in its mobilization. In animals and fungi, the 170 kDa glycogen debranching enzyme (GDE) catalyses this reaction. GDE deficiencies in humans are associated with severe diseases collectively termed glycogen storage disease type III (GSDIII). We report crystal structures of GDE and its complex with oligosaccharides, and structure-guided mutagenesis and biochemical studies to assess the structural observations. These studies reveal that distinct domains in GDE catalyse sequential reactions in glycogen debranching, the mechanism of their catalysis and highly specific substrate recognition. The unique tertiary structure of GDE provides additional contacts to glycogen besides its active sites, and our biochemical experiments indicate that they mediate its recruitment to glycogen and regulate its activity. Combining the understanding of the GDE catalysis and functional characterizations of its disease-causing mutations provides molecular insights into GSDIII.

  4. Inflammatory pseudotumor in the liver and right omentum caused by pelvic inflammatory disease: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Byun, Hyuk Jun; Kim, Seong Hoon [Dept. of Radiology, Daegu Fatima Hospital, Daegu (Korea, Republic of)

    2015-08-15

    Inflammatory pseudotumor can develop in any part of the human body. It is one of the most important tumor-mimicking lesions that require differential diagnosis. There are various causes of inflammatory pseudotumor, one of which is infection and its resultant inflammation. Pelvic inflammatory disease (PID) often causes perihepatitis, which is called Fitz-Hugh-Curtis syndrome. In Fitz-Hugh-Curtis syndrome, bacteria spread along the right paracolic gutter, causing inflammation of the right upper quadrant peritoneal surfaces and the right lobe of the liver. We experienced a case of PID with accompanying inflammatory pseudotumor in the liver and the right omentum. This case identically correlates with the known intraperitoneal spreading pathway involved in Fitz-Hugh-Curtis syndrome, and hence, we present this case report.

  5. Pancreatitis in hand-foot-and-mouth disease caused by enterovirus 71.

    Science.gov (United States)

    Zhang, Yu-Feng; Deng, Hui-Ling; Fu, Jia; Zhang, Yu; Wei, Jian-Qiang

    2016-02-14

    Some viruses, including certain members of the enterovirus genus, have been reported to cause pancreatitis, especially Coxsackie virus. However, no case of human enterovirus 71 (EV71) associated with pancreatitis has been reported so far. We here report a case of EV71-induced hand-foot-and-mouth disease (HFMD) presenting with pancreatitis in a 2-year-old girl. This is the first report of a patient with acute pancreatitis in HFMD caused by EV71. We treated the patient conservatively with nasogastric suction, intravenous fluid and antivirals. The patient's symptoms improved after 8 d, and recovered without complications. We conclude that EV71 can cause acute pancreatitis in HFMD, which should be considered in differential diagnosis, especially in cases of idiopathic pancreatitis.

  6. COPA mutations impair ER-Golgi transport causing hereditary autoimmune-mediated lung disease and arthritis

    Science.gov (United States)

    Watkin, Levi B.; Jessen, Birthe; Wiszniewski, Wojciech; Vece, Timothy; Jan, Max; Sha, Youbao; Thamsen, Maike; Santos-Cortez, Regie L. P.; Lee, Kwanghyuk; Gambin, Tomasz; Forbes, Lisa; Law, Christopher S.; Stray-Petersen, Asbjørg; Cheng, Mickie H.; Mace, Emily M.; Anderson, Mark S.; Liu, Dongfang; Tang, Ling Fung; Nicholas, Sarah K.; Nahmod, Karen; Makedonas, George; Canter, Debra; Kwok, Pui-Yan; Hicks, John; Jones, Kirk D.; Penney, Samantha; Jhangiani, Shalini N.; Rosenblum, Michael D.; Dell, Sharon D.; Waterfield, Michael R.; Papa, Feroz R.; Muzny, Donna M.; Zaitlen, Noah; Leal, Suzanne M.; Gonzaga-Jauregui, Claudia; Boerwinkle, Eric; Eissa, N. Tony; Gibbs, Richard A.; Lupski, James R.; Orange, Jordan S.; Shum, Anthony K.

    2015-01-01

    Advances in genomics have allowed unbiased genetic studies of human disease with unexpected insights into the molecular mechanisms of cellular immunity and autoimmunity1. We performed whole exome sequencing (WES) and targeted sequencing in patients with an apparent Mendelian syndrome of autoimmune disease characterized by high-titer autoantibodies, inflammatory arthritis and interstitial lung disease (ILD). In five families, we identified four unique deleterious variants in the Coatomer subunit alpha (COPA) gene all located within the same functional domain. We hypothesized that mutant COPA leads to a defect in intracellular transport mediated by coat protein complex I (COPI)2–4. We show that COPA variants impair binding of proteins targeted for retrograde Golgi to ER transport and demonstrate that expression of mutant COPA leads to ER stress and the upregulation of Th17 priming cytokines. Consistent with this pattern of cytokine expression, patients demonstrated a significant skewing of CD4+ T cells toward a T helper 17 (Th17) phenotype, an effector T cell population implicated in autoimmunity5,6. Our findings uncover an unexpected molecular link between a vesicular transport protein and a syndrome of autoimmunity manifested by lung and joint disease. These findings provide a unique opportunity to understand how alterations in cellular homeostasis caused by a defect in the intracellular trafficking pathway leads to the generation of human autoimmune disease. PMID:25894502

  7. 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.

  8. Estimation of cumulative cadmium intake causing Itai-itai disease.

    Science.gov (United States)

    Inaba, Takeya; Kobayashi, Etsuko; Suwazono, Yasushi; Uetani, Mirei; Oishi, Mitsuhiro; Nakagawa, Hideaki; Nogawa, Koji

    2005-11-15

    This study was undertaken to estimate the amount of cadmium (Cd) exposure needed for the development of Itai-itai disease. The investigated subjects comprised 82 Itai-itai disease patients and 11 persons requiring observation who were admitted in 1977 and 1978 for medical testing. With the period when the Itai-itai disease patients started to perceive leg/back pain defined as the 'mild disease onset', and the period when they experienced the most severe manifestations such as ambulatory disturbance and bone fractures defined as 'severe disease onset'. Relative cumulative person number distribution according to life time cadmium intake (LCD) at mild disease onset, severe disease onset, and time of death was depicted as an sigmoid curve and the establishment of probit regression lines was demonstrated between them. LCD at the time when mild disease onset and severe disease onset were recognized in half of the Itai-itai disease patients was 3.1 and 3.8 g, respectively. Furthermore, LCD at the time when mild disease onset and severe disease onset were recognized in 5% of the Itai-itai disease patients was calculated to be 2.6 and 3.3 g, respectively. The present results clarify that Itai-itai disease, the most severe stage of chronic Cd poisoning, occurs at levels of Cd consumption amounting to approximately three-fold of those currently seen in Japan.

  9. Engineering large animal models of human disease.

    Science.gov (United States)

    Whitelaw, C Bruce A; Sheets, Timothy P; Lillico, Simon G; Telugu, Bhanu P

    2016-01-01

    The recent development of gene editing tools and methodology for use in livestock enables the production of new animal disease models. These tools facilitate site-specific mutation of the genome, allowing animals carrying known human disease mutations to be produced. In this review, we describe the various gene editing tools and how they can be used for a range of large animal models of diseases. This genomic technology is in its infancy but the expectation is that through the use of gene editing tools we will see a dramatic increase in animal model resources available for both the study of human disease and the translation of this knowledge into the clinic. Comparative pathology will be central to the productive use of these animal models and the successful translation of new therapeutic strategies.

  10. Human Causes of Aeolian Desertification in Northern China

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Aeolian desertification has rapidly developed in the past 50 years in Northern China,covered an area of 0.386 million km2 by 2000,affected nearly 170 million population,and caused the direct and indirect economic loss of about $6.75(U.S.dollar) billion per year.Here we present several lines of evidence to demonstrate that human activities guided by policy shifts have been a major force to drive aeolian desertification via changes in land-use patterns and intensity.It is suggested that the desertification can be curbed or even reversed by adopting prevention and control measures with ecologically sound land-use practices in China.

  11. Chemotherapy Side Effects: A Cause of Heart Disease?

    Science.gov (United States)

    ... Can chemotherapy side effects increase the risk of heart disease? Answers from Timothy J. Moynihan, M.D. Chemotherapy side effects may increase the risk of heart disease, including weakening of the heart muscle (cardiomyopathy) and ...

  12. Chrpsomva bezziana, The Cause of Myiasis on animal And Human : Problem and Control

    Directory of Open Access Journals (Sweden)

    April H Wardhana

    2006-09-01

    Full Text Available Myiasis is an infestation of larvae (Diptera into the live host tissue of warm-blooded animals including humans . This disease is often found in tropical countries, particularly in the community with low socio-economic level. From many flies causing myiasis, Chrysomya bezziana is medically the most important agent due to its obligate parasite property and causing economies losses . Some myiasis cases on humans and animals in Indonesia are caused by C. bezziana larvae infestation or mixed infestation with Sarcophaga sp . Sulawesi, East Sumba, Lombok, Sumbawa, Papua and Java islands were reported as myiasis endemic areas . Myiasis cases on animals occurred after parturition (vulval myiasis then is followed by umbilical myiasis on their calf or traumatic wounds, while myiasis on humans are caused by untreated fresh wounds or chronic wounds such as leprosy, diabetes, etc . Besides, nature holes like nose, eyes, ears or mouth are also reported as entry port for those larvae . Clinical signs of myiasis are various and non-specific depends on location of infested part of body, i.e . fever, inflammation, pruritus, headache, vertigo, swelling and hipereosinophilia . There would be serious conditions with secondary infection by bacteria . Myiasis treatment on animals is simpler than humans . Surgical operation is often carried out on infested human part of bodies . Insecticides were used to treat animal myiasis but had raised resistant . Myiasis treatment on humans may be done locally or systemically . Antibiotic broad spectrum or which is suitable with culture and resistance status of bacteria were given for systemic treatment . Chloroform and turpentine with ratio 1 : 4 were used for local treatment . Some of essential oils have also been tested in laboratory as an alternative medicine for both humans and animals myiasis .

  13. Changes in adult neurogenesis in neurodegenerative diseases: Cause or consequence?

    NARCIS (Netherlands)

    Thompson, A.; Boekhoorn, K.; van Dam, A.-M.; Lucassen, P.J.

    2008-01-01

    This review addresses the role of adult hippocampal neurogenesis and stem cells in some of the most common neurodegenerative disorders and their related animal models. We discuss recent literature in relation to Alzheimer's disease and dementia, Parkinson's disease, Huntington's disease, amyotrophic

  14. Changes in adult neurogenesis in neurodegenerative diseases: Cause or consequence?

    NARCIS (Netherlands)

    Thompson, A.; Boekhoorn, K.; van Dam, A.-M.; Lucassen, P.J.

    2008-01-01

    This review addresses the role of adult hippocampal neurogenesis and stem cells in some of the most common neurodegenerative disorders and their related animal models. We discuss recent literature in relation to Alzheimer's disease and dementia, Parkinson's disease, Huntington's disease, amyotrophic

  15. Diagnosis of human heritable diseases--laboratory approaches and outcomes.

    Science.gov (United States)

    Dowton, S B; Slaugh, R A

    1995-05-01

    Detection of mutant human genes is rapidly becoming an integral part of clinical practice. Human disease may arise by genetic deletion, insertion, fusion, point mutation, or amplification of unstable sequences. Such changes in structure may occur in germ cells or somatically. Rapid advances in understanding the complex nuclear and mitochondrial genomes necessitates deployment of a variety of methods to identify aberrant genes. These techniques include polymerase chain reaction, Southern transfer, and allele-specific hybridization studies, as well as methods to unmask mismatches between mutant and normal sequences. Development of protein truncation tests has added a vehicle for assessing larger DNA segments for mutations that cause premature translational termination. Linkage analysis remains an important tool where direct assay of disease-causing mutations is not possible. Considerations of confidentiality, informed consent, and insurability are important whenever genetic testing is used. These issues will assume increasing importance as presymptomatic testing for heritable predispositions emerges for common conditions.

  16. DNA microarray analysis of Salmonella serotype Typhimurium strains causing different symptoms of disease

    Directory of Open Access Journals (Sweden)

    Helms Morten

    2010-03-01

    Full Text Available Abstract Background Salmonella enterica subsp. enterica is one of the leading food-borne pathogens in the USA and European countries. Outcome of human Salmonella serotype Typhimurium infections ranges from mild self-limiting diarrhoea to severe diarrhoea that requires hospitalization. Increased knowledge of the mechanisms that are responsible for causing infection and especially the severity of infection is of high interest. Results Strains were selected from patients with mild infections (n = 9 and patients with severe infections (n = 9 and clinical data allowed us to correct for known underlying diseases. Additionally, outbreak isolates (n = 3 were selected. Strains were analyzed on a DNA-DNA microarray for presence or absence of 281 genes covering marker groups of genes related to pathogenicity, phages, antimicrobial resistance, fimbriae, mobility, serotype and metabolism. Strains showed highly similar profiles when comparing virulence associated genes, but differences between strains were detected in the prophage marker group. The Salmonella virulence plasmid was present in 72% of the strains, but presence or absence of the virulence plasmid did not correspond to disease symptoms. A dendrogram clustered strains into four groups. Clustering confirmed DT104 as being a clonal phagetype. Clustering of the remaining strains was mainly correlated to presence or absence of the virulence plasmid and mobile elements such as transposons. Each of the four clusters in the tree represented an almost equal amount of strains causing severe or mild symptoms of infection. Conclusions We investigated clinical significance of known virulence factors of Salmonella serotype Typhimurium strains causing different disease symptoms, and conclude that the few detected differences in Salmonella serotype Typhimurium do not affect outcome of human disease.

  17. Globotriaosylsphingosine accumulation and not alpha-galactosidase-A deficiency causes endothelial dysfunction in Fabry disease.

    Directory of Open Access Journals (Sweden)

    Mehdi Namdar

    Full Text Available BACKGROUND: Fabry disease (FD is caused by a deficiency of the lysosomal enzyme alpha-galactosidase A (GLA resulting in the accumulation of globotriaosylsphingosine (Gb3 in a variety of tissues. While GLA deficiency was always considered as the fulcrum of the disease, recent attention shifted towards studying the mechanisms through which Gb3 accumulation in vascular cells leads to endothelial dysfunction and eventually multiorgan failure. In addition to the well-described macrovascular disease, FD is also characterized by abnormalities of microvascular function, which have been demonstrated by measurements of myocardial blood flow and coronary flow reserve. To date, the relative importance of Gb3 accumulation versus GLA deficiency in causing endothelial dysfunction is not fully understood; furthermore, its differential effects on cardiac micro- and macrovascular endothelial cells are not known. METHODS AND RESULTS: In order to assess the effects of Gb3 accumulation versus GLA deficiency, human macro- and microvascular cardiac endothelial cells (ECs were incubated with Gb3 or silenced by siRNA to GLA. Gb3 loading caused deregulation of several key endothelial pathways such as eNOS, iNOS, COX-1 and COX-2, while GLA silencing showed no effects. Cardiac microvascular ECs showed a greater susceptibility to Gb3 loading as compared to macrovascular ECs. CONCLUSIONS: Deregulation of key endothelial pathways as observed in FD vasculopathy is likely caused by intracellular Gb3 accumulation rather than deficiency of GLA. Human microvascular ECs, as opposed to macrovascular ECs, seem to be affected earlier and more severely by Gb3 accumulation and this notion may prove fundamental for future progresses in early diagnosis and management of FD patients.

  18. Disease modeling and drug screening for neurological diseases using human induced pluripotent stem cells

    Institute of Scientific and Technical Information of China (English)

    Xiao-hong XU; Zhong ZHONG

    2013-01-01

    With the general decline of pharmaceutical research productivity,there are concerns that many components of the drug discovery process need to be redesigned and optimized.For example,the human immortalized cell lines or animal primary cells commonly used in traditional drug screening may not faithfully recapitulate the pathological mechanisms of human diseases,leading to biases in assays,targets,or compounds that do not effectively address disease mechanisms.Recent advances in stem cell research,especially in the development of induced pluripotent stem cell (iPSC) technology,provide a new paradigm for drug screening by permitting the use of human cells with the same genetic makeup as the patients without the typical quantity constraints associated with patient primary cells.In this article,we will review the progress made to date on cellular disease models using human stem cells,with a focus on patient-specific iPSCs for neurological diseases.We will discuss the key challenges and the factors that associated with the success of using stem cell models for drug discovery through examples from monogenic diseases,diseases with various known genetic components,and complex diseases caused by a combination of genetic,environmental and other factors.

  19. Disease modeling and drug screening for neurological diseases using human induced pluripotent stem cells.

    Science.gov (United States)

    Xu, Xiao-hong; Zhong, Zhong

    2013-06-01

    With the general decline of pharmaceutical research productivity, there are concerns that many components of the drug discovery process need to be redesigned and optimized. For example, the human immortalized cell lines or animal primary cells commonly used in traditional drug screening may not faithfully recapitulate the pathological mechanisms of human diseases, leading to biases in assays, targets, or compounds that do not effectively address disease mechanisms. Recent advances in stem cell research, especially in the development of induced pluripotent stem cell (iPSC) technology, provide a new paradigm for drug screening by permitting the use of human cells with the same genetic makeup as the patients without the typical quantity constraints associated with patient primary cells. In this article, we will review the progress made to date on cellular disease models using human stem cells, with a focus on patient-specific iPSCs for neurological diseases. We will discuss the key challenges and the factors that associated with the success of using stem cell models for drug discovery through examples from monogenic diseases, diseases with various known genetic components, and complex diseases caused by a combination of genetic, environmental and other factors.

  20. Does infectious disease cause global variation in the frequency of intrastate armed conflict and civil war?

    Science.gov (United States)

    Letendre, Kenneth; Fincher, Corey L; Thornhill, Randy

    2010-08-01

    Geographic and cross-national variation in the frequency of intrastate armed conflict and civil war is a subject of great interest. Previous theory on this variation has focused on the influence on human behaviour of climate, resource competition, national wealth, and cultural characteristics. We present the parasite-stress model of intrastate conflict, which unites previous work on the correlates of intrastate conflict by linking frequency of the outbreak of such conflict, including civil war, to the intensity of infectious disease across countries of the world. High intensity of infectious disease leads to the emergence of xenophobic and ethnocentric cultural norms. These cultures suffer greater poverty and deprivation due to the morbidity and mortality caused by disease, and as a result of decreased investment in public health and welfare. Resource competition among xenophobic and ethnocentric groups within a nation leads to increased frequency of civil war. We present support for the parasite-stress model with regression analyses. We find support for a direct effect of infectious disease on intrastate armed conflict, and support for an indirect effect of infectious disease on the incidence of civil war via its negative effect on national wealth. We consider the entanglements of feedback of conflict into further reduced wealth and increased incidence of disease, and discuss implications for international warfare and global patterns of wealth and imperialism.

  1. Beyond membrane channelopathies: alternative mechanisms underlying complex human disease

    Institute of Scientific and Technical Information of China (English)

    Konstantinos Dean BOUDOULAS; Peter J MOHLER

    2011-01-01

    Over the past fifteen years, our understanding of the molecular mechanisms underlying human disease has flourished in large part due to the discovery of gene mutations linked with membrane ion channels and transporters. In fact, ion channel defects ("channelopathies" - the focus of this review series) have been associated with a spectrum of serious human disease phenotypes including cystic fibrosis, cardiac arrhythmia, diabetes, skeletal muscle defects, and neurological disorders. However, we now know that human disease, particularly excitable cell disease, may be caused by defects in non-ion channel polypeptides including in cellular components residing well beneath the plasma membrane. For example, over the past few years, a new class of potentially fatal cardiac arrhythmias has been linked with cytoplasmic proteins that include sub-membrane adapters such as ankyrin-B (ANK2),ankyrin-G (ANK3), and alpha-1 syntrophin, membrane coat proteins including caveolin-3 (CAV3), signaling platforms including yotiao (AKAPg), and cardiac enzymes (GPD1L). The focus of this review is to detail the exciting role of lamins, yet another class of gene products that have provided elegant new insight into human disease.

  2. Accumulation of SOD1 mutants in postnatal motoneurons does not cause motoneuron pathology or motoneuron disease.

    Science.gov (United States)

    Lino, Maria Maddalena; Schneider, Corinna; Caroni, Pico

    2002-06-15

    Transgenic mice expressing high levels of familial amyotrophic lateral sclerosis (FALS)-associated mutant superoxide dismutase 1 (SOD1) under the control of a human SOD1 minigene (hMg) accumulate mutant protein ubiquitously and develop motoneuron disease. However, restricted expression of SOD1 mutants in neurons apparently does not cause motor impairments in mice. Here, we investigated the possible pathogenic roles of mutant SOD1 accumulation in motoneurons. First, we used a Thy1 expression cassette to drive high constitutive expression of transgene in postnatal mouse neurons, including upper and lower motoneurons. Second, we expressed human (h) SOD1(G93A) and hSOD1(G85R) as transgenes (i.e., two SOD1 mutants with aggressive pathogenic properties in inducing FALS). Third, in addition to clinical signs of disease, we monitored early signs of disease onset and pathogenesis, including muscle innervation, astrogliosis in the spinal cord, and accumulation of ubiquitinated deposits in motoneurons and astrocytes. We report that high-level expression and accumulation of the mutant proteins in neurons failed to produce any detectable sign of pathology or disease in these transgenic mice. Crossing hMg-SOD1(G93A) mice (Gurney et al., 1994) with Thy1-SOD1(G93A) mice produced double-transgenic mice with spinal cord SOD1(G93A) levels that were approximately twofold higher than in the hMg-SOD1(G93A) single transgenics but did not affect the onset or progression of pathology or motoneuron disease. The accumulation of mutant SOD1 in postnatal motoneurons is thus not sufficient and probably also not critical to induce or accelerate motoneuron disease in FALS mice. The pathogenic process in FALS may involve non-neuronal cells, and selective vulnerability of motoneurons to this process may lead to motoneuron pathology and disease.

  3. Refsum disease is caused by mutations in the phytanoyl-CoA hydroxylase gene.

    Science.gov (United States)

    Jansen, G A; Ofman, R; Ferdinandusse, S; Ijlst, L; Muijsers, A O; Skjeldal, O H; Stokke, O; Jakobs, C; Besley, G T; Wraith, J E; Wanders, R J

    1997-10-01

    Refsum disease is an autosomal-recessively inherited disorder characterized clinically by a tetrad of abnormalities: retinitis pigmentosa, peripheral neuropathy, cerebellar ataxia and elevated protein levels in the cerebrospinal fluid (CSF) without an increase in the number of cells in the CSF. All patients exhibit accumulation of an unusual branched-chain fatty acid, phytanic acid (3,7,11,15-tetramethylhexadecanoic acid), in blood and tissues. Biochemically, the disease is caused by the deficiency of phytanoyl-CoA hydroxylase (PhyH), a peroxisomal protein catalyzing the first step in the alpha-oxidation of phytanic acid. We have purified PhyH from rat-liver peroxisomes and determined the N-terminal amino-acid sequence, as well as an additional internal amino-acid sequence obtained after Lys-C digestion of the purified protein. A search of the EST database with these partial amino-acid sequences led to the identification of the full-length human cDNA sequence encoding PhyH: the open reading frame encodes a 41.2-kD protein of 338 amino acids, which contains a cleavable peroxisomal targeting signal type 2 (PTS2). Sequence analysis of PHYH fibroblast cDNA from five patients with Refsum disease revealed distinct mutations, including a one-nucleotide deletion, a 111-nucleotide deletion and a point mutation. This analysis confirms our finding that Refsum disease is caused by a deficiency of PhyH.

  4. EYS Mutations Causing Autosomal Recessive Retinitis Pigmentosa: Changes of Retinal Structure and Function with Disease Progression

    Directory of Open Access Journals (Sweden)

    David B. McGuigan

    2017-07-01

    Full Text Available Mutations in the EYS (eyes shut homolog gene are a common cause of autosomal recessive (ar retinitis pigmentosa (RP. Without a mammalian model of human EYS disease, there is limited understanding of details of disease expression and rates of progression of the retinal degeneration. We studied clinically and with chromatic static perimetry, spectral-domain optical coherence tomography (OCT, and en face autofluoresence imaging, a cohort of 15 patients (ages 12–51 at first visit, some of whom had longitudinal data of function and structure. Rod sensitivity was able to be measured by chromatic perimetry in most patients at their earliest visits and some patients retained patchy rod function into the fifth decade of life. As expected from RP, cone sensitivity persisted after rod function was no longer measurable. The photoreceptor nuclear layer of the central retina was abnormal except at the fovea in most patients at first visit. Perifoveal disease measured over a period of years indicated that photoreceptor structural loss was followed by dysmorphology of the inner retina and loss of retinal pigment epithelial integrity. Although there could be variability in severity, preliminary analyses of the rates of vision loss suggested that EYS is a more rapidly progressive disease than other ciliopathies causing arRP, such as USH2A and MAK.

  5. Enhancing the prioritization of disease-causing genes through tissue specific protein interaction networks.

    Directory of Open Access Journals (Sweden)

    Oded Magger

    Full Text Available The prioritization of candidate disease-causing genes is a fundamental challenge in the post-genomic era. Current state of the art methods exploit a protein-protein interaction (PPI network for this task. They are based on the observation that genes causing phenotypically-similar diseases tend to lie close to one another in a PPI network. However, to date, these methods have used a static picture of human PPIs, while diseases impact specific tissues in which the PPI networks may be dramatically different. Here, for the first time, we perform a large-scale assessment of the contribution of tissue-specific information to gene prioritization. By integrating tissue-specific gene expression data with PPI information, we construct tissue-specific PPI networks for 60 tissues and investigate their prioritization power. We find that tissue-specific PPI networks considerably improve the prioritization results compared to those obtained using a generic PPI network. Furthermore, they allow predicting novel disease-tissue associations, pointing to sub-clinical tissue effects that may escape early detection.

  6. A Disease-Causing Variant in PCNA Disrupts a Promiscuous Protein Binding Site.

    Science.gov (United States)

    Duffy, Caroline M; Hilbert, Brendan J; Kelch, Brian A

    2016-03-27

    The eukaryotic DNA polymerase sliding clamp, proliferating cell nuclear antigen or PCNA, is a ring-shaped protein complex that surrounds DNA to act as a sliding platform for increasing processivity of cellular replicases and for coordinating various cellular pathways with DNA replication. A single point mutation, Ser228Ile, in the human PCNA gene was recently identified to cause a disease whose symptoms resemble those of DNA damage and repair disorders. The mutation lies near the binding site for most PCNA-interacting proteins. However, the structural consequences of the S228I mutation are unknown. Here, we describe the structure of the disease-causing variant, which reveals a large conformational change that dramatically transforms the binding pocket for PCNA client proteins. We show that the mutation markedly alters the binding energetics for some client proteins, while another, p21(CIP1), is only mildly affected. Structures of the disease variant bound to peptides derived from two PCNA partner proteins reveal that the binding pocket can adjust conformation to accommodate some ligands, indicating that the binding site is dynamic and pliable. Our work has implications for the plasticity of the binding site in PCNA and reveals how a disease mutation selectively alters interactions to a promiscuous binding site that is critical for DNA metabolism.

  7. Modeling human muscle disease in zebrafish

    OpenAIRE

    Guyon, Jeffrey R.; Steffen, Leta S; Howell, Melanie H.; Pusack, Timothy J; Lawrence, Chris; Kunkel, Louis M

    2007-01-01

    Modeling human muscle disease in zebrafish correspondence: Corresponding author. Children's Hospital Boston, Enders Bldg, Rm 570, 300 Longwood Ave Boston, MA 02115. Tel.: +1 617 355 7576. (Kunkel, Louis M.) (Kunkel, Louis M.) Program in Genomics and Howard Hughes Medical Institute at Children's Hospital Boston - Boston--> , MA 02115--> - UNITED STATES (Guyon, Jeffrey R.) Program in Genomics a...

  8. A nonsense mutation in the acid α-glucosidase gene causes Pompe disease in Finnish and Swedish Lapphunds.

    Science.gov (United States)

    Seppälä, Eija H; Reuser, Arnold J J; Lohi, Hannes

    2013-01-01

    Pompe disease is a recessively inherited and often fatal disorder caused by the deficiency of acid α-glucosidase, an enzyme encoded by the GAA gene and needed to break down glycogen in lysosomes. This glycogen storage disease type II has been reported also in Swedish Lapphund dogs. Here we describe the genetic defect in canine Pompe disease and show that three related breeds from Scandinavia carry the same mutation. The affected dogs are homozygous for the GAA c.2237G>A mutation leading to a premature stop codon at amino acid position 746. The corresponding mutation has previously been reported in humans and causes infantile Pompe disease in combination with a second fully deleterious mutation. The affected dogs from both the Finnish as well as the Swedish breed mimic infantile-onset Pompe disease genetically, but also clinico-pathologically. Therefore this canine model provides a valuable tool for preclinical studies aimed at the development of gene therapy in Pompe disease.

  9. Castleman Disease: An Unexpected Cause of a Solitary Pleural Mass

    Directory of Open Access Journals (Sweden)

    Fiachra Moloney

    2013-01-01

    Full Text Available Castleman disease (CD is a rare benign lymphoproliferative disorder, the etiology of which is unclear. Clinically it may manifest as localized disease (unicentric or disseminated disease (multicentric. CD occurs in the thorax in 70% of cases, abdomen and pelvis in 15%, and in the neck in 10–15% of cases. We present a case of a pleural mass located posteriorly in a paraspinal location, which was discovered incidentally in a 50-year-old man and was subsequently resected followed by an unexpected diagnosis of Castleman disease on histological examination. In this report, we review the clinical and histological findings in a rare presentation of Castleman disease and discuss the findings in this case as part of an overall review of the typical radiological findings seen in Castleman disease.

  10. Rheumatoid arthritis is an autoimmune disease caused by periodontal pathogens

    OpenAIRE

    2013-01-01

    Mesut OgrendikDivision of Physical Therapy and Rheumatology, Nazilli State Hospital, Nazilli, TurkeyAbstract: A statistically significant association between periodontal disease (PD) and systemic diseases has been identified. Rheumatoid arthritis (RA), which is a chronic inflammatory joint disease, exhibits similar characteristics and pathogenesis to PD. The association between RA and PD has been investigated, and numerous publications on this subject exist. Approximately 20 bacterial species...

  11. Historical perspectives on music as a cause of disease.

    Science.gov (United States)

    Kennaway, James

    2015-01-01

    The relationship between music and medicine is generally understood in the benign context of music therapy, but, as this chapter shows, there is a long parallel history of medical theories that suggest that music can cause real physical and mental illness. During the seventeenth and eighteenth centuries, the idea of music as an expression of universal harmony was challenged by a more mechanistic model of nervous stimulation. By the 1790s, there was a substantial discourse on the dangers of musical overstimulation to health in medicine, literature, and etiquette books. During the nineteenth century, the sense of music as a pathogenic stimulant gained in influence. It was often linked to fears about sexuality, female gynecological health, and theories of hypnosis and degeneration. In the twentieth century, the debate on the medical perils of the wrong kinds of music became overtly politicized in Germany and the Soviet Union. Likewise, the opponents of jazz, particularly in the United States, often turned to medicine to fend off its supposed social, moral, and physical consequences. The Cold War saw an extensive discourse on the idea of musical "brainwashing," that rumbled on into the 1990s. Today, regular media panics about pathological music are mirrored by alarming evidence of the deliberate use of music to harm listeners in the context of the so-called War on Terror. Can music make you ill? Music therapy is a common if perhaps rather neglected part of medicine, but its diametric opposite, the notion that music might lead to real mental and physical illness, may seem improbable. In fact, over the last two hundred years, there have been many times when as much was written about the medical dangers of music as about its potential benefits. Since the eighteenth century, fears about music's effects on the nerves and the mind have created a remarkably extensive discourse on pathological music based on a view of both music and the causation of disease as matters of

  12. [Infectious diseases caused by carbapenemase-producing Enterobacteriaceae--a particular challenge for antibacterial therapy].

    Science.gov (United States)

    Stock, Ingo

    2014-05-01

    Enterobacteriaceae species such as Escherichia coli and Klebsiella pneumoniae are among the most common human pathogens. They are responsible for a wide range of community-acquired and nosocomial diseases. Many of the illnesses caused by these bacteria could be treated with beta-lactams for several decades. The increasing use of carbapenems for the treatment of diseases caused by Enterobacteriaceae expressing extended spectrum beta-lactamases, however, lead to the selection and spread of carbapenemase-producing pathogens. Such bacteria are not only resistant to virtually all beta-lactams, but also to numerous other antibiotics such as quinolones, co-trimoxazole, nitrofurantoin, tetracyclines and most aminoglycosides. During the last years, carbapenemase-producing Enterobacteriaceae have spread into almost all regions of the world. Klebsiella pneumoniae carbapenemases (KPC, belonging to Ambler class A), OXA-48 enzymes and their derivatives (belonging to Ambler class D) as well as some metallo-beta-lactamases (Ambler class B) such as NDM, VIM and IMP are the most important carbapenemases produced by Enterobacteriaceae strains. In Germany, the metallo-carbapenemase GIM-1, which has never been proven in bacteria outside Germany, is also of clinical significance. There is no established antibacterial therapy for these difficult-to-treat diseases. For the treatment of severe diseases caused by carbapenemase-producing bacteria, fosfomycin, gentamicin and tigecycline, polymyxins such as polymyxin B or colistin as well as carbapenems, are frequently applied. Combination antibiotic treatment may be more effective than monotherapy for severe ill patients with serious diseases. The most promising new treatment options arise with the development of avibactam. This non-beta-lactam beta-lactamase inhibitor shows good activity against (nearly) all class A and class C beta-lactamases (including strains expressing class A carbapenemases and/or derepressed AmpC enzymes) as well as

  13. Living with intestinal failure caused by Crohn disease: not letting the disease conquer life.

    Science.gov (United States)

    Carlsson, Eva; Persson, Eva

    2015-01-01

    This article reports the findings of what it means to live with intestinal failure caused by Crohn disease and how it influences daily life. Ten patients, 7 with an ostomy and 7 on home parenteral nutrition followed up at an outpatient clinic for patients with intestinal failure, were interviewed using a qualitative, phenomenological-hermeneutic method. The analysis of the transcribed data is described thematically and resulted in 3 main themes; (a) struggling to not be controlled by the disease, (b) walking on a thin thread, and (c) being seen as a person, not just as a patient. These themes led to the comprehensive understanding that living with intestinal failure was interpreted as the criticality of maintaining control over one's life and body while maintaining autonomy and not letting the disease conquer life. Life entails a constant struggle with much planning to live as normally as possible and get the most out of life. It was of great importance to be seen as a person and not just as a disease, affirm that life as it is has meaning, there is a state of suffering related to the disease, there are existential issues, and suffering is related to care.

  14. Zoonotic tuberculosis in human beings caused by Mycobacterium bovis-a call for action.

    Science.gov (United States)

    Olea-Popelka, Francisco; Muwonge, Adrian; Perera, Alejandro; Dean, Anna S; Mumford, Elizabeth; Erlacher-Vindel, Elisabeth; Forcella, Simona; Silk, Benjamin J; Ditiu, Lucica; El Idrissi, Ahmed; Raviglione, Mario; Cosivi, Ottorino; LoBue, Philip; Fujiwara, Paula I

    2017-01-01

    Mycobacterium tuberculosis is recognised as the primary cause of human tuberculosis worldwide. However, substantial evidence suggests that the burden of Mycobacterium bovis, the cause of bovine tuberculosis, might be underestimated in human beings as the cause of zoonotic tuberculosis. In 2013, results from a systematic review and meta-analysis of global zoonotic tuberculosis showed that the same challenges and concerns expressed 15 years ago remain valid. These challenges faced by people with zoonotic tuberculosis might not be proportional to the scientific attention and resources allocated in recent years to other diseases. The burden of zoonotic tuberculosis in people needs important reassessment, especially in areas where bovine tuberculosis is endemic and where people live in conditions that favour direct contact with infected animals or animal products. As countries move towards detecting the 3 million tuberculosis cases estimated to be missed annually, and in view of WHO's end TB strategy endorsed by the health authorities of WHO Member States in 2014 to achieve a world free of tuberculosis by 2035, we call on all tuberculosis stakeholders to act to accurately diagnose and treat tuberculosis caused by M bovis in human beings. Copyright © 2017 World Health Organization. Published by Elsevier Ltd/Inc/BV. All rights reserved. Published by Elsevier Ltd.. All rights reserved.

  15. Identifying photoreceptors in blind eyes caused by RPE65 mutations: Prerequisite for human gene therapy success.

    Science.gov (United States)

    Jacobson, Samuel G; Aleman, Tomas S; Cideciyan, Artur V; Sumaroka, Alexander; Schwartz, Sharon B; Windsor, Elizabeth A M; Traboulsi, Elias I; Heon, Elise; Pittler, Steven J; Milam, Ann H; Maguire, Albert M; Palczewski, Krzysztof; Stone, Edwin M; Bennett, Jean

    2005-04-26

    Mutations in RPE65, a gene essential to normal operation of the visual (retinoid) cycle, cause the childhood blindness known as Leber congenital amaurosis (LCA). Retinal gene therapy restores vision to blind canine and murine models of LCA. Gene therapy in blind humans with LCA from RPE65 mutations may also have potential for success but only if the retinal photoreceptor layer is intact, as in the early-disease stage-treated animals. Here, we use high-resolution in vivo microscopy to quantify photoreceptor layer thickness in the human disease to define the relationship of retinal structure to vision and determine the potential for gene therapy success. The normally cone photoreceptor-rich central retina and rod-rich regions were studied. Despite severely reduced cone vision, many RPE65-mutant retinas had near-normal central microstructure. Absent rod vision was associated with a detectable but thinned photoreceptor layer. We asked whether abnormally thinned RPE65-mutant retina with photoreceptor loss would respond to treatment. Gene therapy in Rpe65(-/-) mice at advanced-disease stages, a more faithful mimic of the humans we studied, showed success but only in animals with better-preserved photoreceptor structure. The results indicate that identifying and then targeting retinal locations with retained photoreceptors will be a prerequisite for successful gene therapy in humans with RPE65 mutations and in other retinal degenerative disorders now moving from proof-of-concept studies toward clinical trials.

  16. Causes and consequences of increased sympathetic activity in renal disease

    NARCIS (Netherlands)

    Joles, JA; Koomans, HA

    2004-01-01

    Much evidence indicates increased sympathetic nervous activity (SNA) in renal disease. Renal ischemia is probably a primary event leading to increased SNA. Increased SNA often occurs in association with hypertension. However, the deleterious effect of increased SNA on the diseased kidney is not only

  17. Can Epiphytes reduce disease symptoms caused by Phytophthora ramorum

    Science.gov (United States)

    Leaf infection of ornamental species by Phytophthora ramorum has a significant impact on the spread of this disease. Fungicides have had limited effects on controlling this disease. With increasing concerns that repeated fungicide applications will exasperate the potential for fungicide resistance...

  18. Recent genetic discoveries implicating ion channels in human cardiovascular diseases.

    Science.gov (United States)

    George, Alfred L

    2014-04-01

    The term 'channelopathy' refers to human genetic disorders caused by mutations in genes encoding ion channels or their interacting proteins. Recent advances in this field have been enabled by next-generation DNA sequencing strategies such as whole exome sequencing with several intriguing and unexpected discoveries. This review highlights important discoveries implicating ion channels or ion channel modulators in cardiovascular disorders including cardiac arrhythmia susceptibility, cardiac conduction phenotypes, pulmonary and systemic hypertension. These recent discoveries further emphasize the importance of ion channels in the pathophysiology of human disease and as important druggable targets.

  19. Adult human metapneumonovirus (hMPV) pneumonia mimicking Legionnaire's disease.

    Science.gov (United States)

    Cunha, Burke A; Irshad, Nadia; Connolly, James J

    2016-01-01

    In adults hospitalized with viral pneumonias the main differential diagnostic consideration is influenza pneumonia. The respiratory viruses causing viral influenza like illnesses (ILIs), e.g., RSV may closely resemble influenza. Rarely, extrapulmonary findings of some ILIs may resemble Legionnaire's disease (LD), e.g., adenovirus, human parainfluenza virus (HPIV-3). We present a most unusual case of human metapneumonovirus pneumonia (hMPV) with some characteristic extrapulmonary findings characteristic of LD, e.g., relative bradycardia, as well as mildly elevated serum transaminases and hyphosphatemia. We believe this is the first reported case of hMPV pneumonia in a hospitalized adult that had some features of LD.

  20. Receptor-mediated endocytosis of α-galactosidase A in human podocytes in Fabry disease

    DEFF Research Database (Denmark)

    Prabakaran, Thaneas; Nielsen, Rikke; Larsen, Jakob Vejby;

    2011-01-01

    Injury to the glomerular podocyte is a key mechanism in human glomerular disease and podocyte repair is an important therapeutic target. In Fabry disease, podocyte injury is caused by the intracellular accumulation of globotriaosylceramide. This study identifies in the human podocyte three endocy...

  1. Receptor-Mediated Endocytosis of α-Galactosidase A in Human Podocytes in Fabry Disease

    DEFF Research Database (Denmark)

    Prabakaran, Thaneas; Nielsen, Rikke; Larsen, Jakob Vejby;

    2011-01-01

    Injury to the glomerular podocyte is a key mechanism in human glomerular disease and podocyte repair is an important therapeutic target. In Fabry disease, podocyte injury is caused by the intracellular accumulation of globotriaosylceramide. This study identifies in the human podocyte three endocy...

  2. 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

  3. 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.|info:eu-repo/dai/nl/072306122; 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

  4. An Unusual Cause of Postaural Swelling: Kimura’s Disease

    Directory of Open Access Journals (Sweden)

    Purodha Prasad

    2017-07-01

    Full Text Available Introduction: Kimura’s disease (KD is an allergic inflammatory disorder of unknown etiology endemic in Orientals. Kimura’s disease was first mentioned by Kimm and Szeto in China in 1937. Kimura’s disease is commonly encountered in Asia and is mostly reported in Japan, China, Singapore and Honkong. However, only a few cases have been reported in the Indian subcontinent. Case Report: A case of Kimura’s disease in a young male managed by surgery is reported in addition to a literature review. Conclusion: Diagnosis is made on the basis of histopathological analysis, clinical presentation, and laboratory investigations. Long term follow-up is required as Kimura’s disease is prone for recurrence.

  5. [Relationship of bilirubin to diseases caused by increased oxidative stress].

    Science.gov (United States)

    Vítek, L

    2013-07-01

    Oxidative stress contributes importantly to pathogenesis of numerous civilization diseases, including cardiovascular diseases, cancer, as well as autoimmune and neurodegenerative conditions. Bilirubin is the major product of the heme catabolic pathway in the intravascular compartment. For long time, bilirubin was considered to be only a waste product, however, recent data from the last 2 decades have proved its important antioxidant properties, which contributes to defense against increased oxidative stress. Numerous experimental as well as clinical studies have demonstrated association between low bilirubin concentrations and cardiovascular diseases, diabetes, certain cancers, autoimunne diseases, such as lupus erythematodes, or rheumatoid arthritis or neurological psychiatric disorders, such as schizofrenia. On the other hand, subjects with mildly elevated blood bilirubin levels, typical for Gilbert syndrome, have decreased risk of these diseases.

  6. Human Parechovirus 3: The Most Common Viral Cause of Meningoencephalitis in Young Infants.

    Science.gov (United States)

    Renaud, Christian; Harrison, Christopher J

    2015-09-01

    Human parechoviruses (HPeVs) were initially classified as echoviruses. HPeVs occur worldwide, comprising up to 17 genotypes. HPeV1 and HPeV3 are most common. Clinical disease varies somewhat among genotypes. HPeV1 causes mostly gastrointestinal infections. HPeV3's prominence is due to its causing sepsis syndromes and central nervous system (CNS) infections in young infants. Currently, HPeV3 is the most common single cause of aseptic meningitis/meningoencephalitis in infants less than 90 days old in North America, usually with biannual summer-fall seasonality. HPeV3 CNS infections usually lack cerebrospinal fluid pleocytosis. Mortality and sequelae are uncommon, usually accompanying initially severe or neurologically complicated acute illnesses. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Does elevated C-reactive protein cause human atherothrombosis? Novel insights from genetics, intervention trials, and elsewhere

    DEFF Research Database (Denmark)

    Nordestgaard, Børge

    2009-01-01

    PURPOSE OF REVIEW: To evaluate evidence from human epidemiology, mechanistic studies, animal studies, human genetics, and human intervention trials to address whether elevated C-reactive protein (CRP) causes human atherothrombotic cardiovascular disease. RECENT FINDINGS: Human epidemiology...... demonstrates that elevated CRP levels are associated with increased risk of atherothrombosis. Mechanistic and animal studies provide evidence both for and against a causal relationship of CRP with atherothrombosis. Human genetics demonstrate that genetic variation in the CRP gene is associated with lifelong...... increased CRP levels, but not with increased risk of atherothrombosis. A human intervention trial in healthy people with low LDL cholesterol and elevated CRP demonstrated that aggressive statin treatment caused reductions of 50% in LDL cholesterol, 37% in CRP, 50% in atherothrombotic cardiovascular events...

  8. Cryptococcus gattii: An Emerging Cause of Fungal Disease in North America

    Directory of Open Access Journals (Sweden)

    Ashwin Dixit

    2009-01-01

    Full Text Available During the latter half of the twentieth century, fungal pathogens such as Cryptococcus neoformans were increasingly recognized as a significant threat to the health of immune compromised populations throughout the world. Until recently, the closely related species C. gattii was considered to be a low-level endemic pathogen that was confined to tropical regions such as Australia. Since 1999, C. gattii has emerged in the Pacific Northwest region of North America and has been responsible for a large disease epidemic among generally healthy individuals. The changing epidemiology of C. gattii infection is likely to be a consequence of alterations in fungal ecology and biology and illustrates its potential to cause serious human disease. This review summarizes selected biological and clinical aspects of C. gattii that are particularly relevant to the recent North American outbreak and compares these to the Australian and South American experience.

  9. [Frequent causes of diarrhea: celiac disease and lactose intolerance].

    Science.gov (United States)

    Jankowiak, Carsten; Ludwig, Diether

    2008-06-15

    Celiac disease and lactose intolerance are both relatively frequent diseases with symptoms occurring after ingestion of certain food components. In celiac disease wheat gluten and related proteins of other cereals induce an inflammatory disease of the small intestine in predisposed individuals, leading to gastrointestinal and extraintestinal symptoms. Moreover, there is an association with many other diseases and besides classic symptoms (diarrhea, weight loss, malabsorption) atypical courses with less or lacking gastrointestinal symptoms exist. The prevalence is about 1 : 100 (Europe, USA) and higher than supposed earlier. Diagnostic criteria include serologic tests (tissue transglutaminase antibody, endomysial antibody) and characteristic small bowel histology (lymphocytic infiltration, villous atrophy). Therapy is a strict and lifelong gluten-free diet. Rarely, refractory disease or lack of compliance are associated with increased risk of malignancy and worse prognosis. Lactose intolerance is attributed to low intestinal lactase levels, due to reduced genetic expression or mucosal injury and consequent intolerance to dairy products. The frequency is varying in different ethnic groups, occurring in 10-15% of Northern European people. Intensity of clinical symptoms (diarrhea, abdominal pain, bloating) depends on the amount of ingested lactose and individual activity of intestinal lactase. The capacity of lactose malabsorption can be measured using the noninvasive lactose breath hydrogen test. The treatment is based on a reduced dietary lactose intake or in case of secondary form treatment of the underlying disease.

  10. Review: Environmental mycobacteria as a cause of human infection

    Directory of Open Access Journals (Sweden)

    Samuel Halstrom

    2015-01-01

    Full Text Available Pulmonary infections with nontuberculous mycobacteria (NTM are recognized as a problem in immunodeficient individuals and are increasingly common in older people with no known immune defects. NTM are found in soil and water, but factors influencing transmission from the environment to humans are mostly unknown. Studies of the epidemiology of NTM disease have matched some clinical isolates of NTM with isolates from the patient's local environment. Definitive matching requires strain level differentiation based on molecular analyses, including partial sequencing, PCR-restriction fragment length polymorphism (RFLP analysis, random amplified polymorphic DNA (RAPD PCR, repetitive element (rep- PCR and pulsed field gel electrophoresis (PFGE of large restriction fragments. These approaches have identified hospital and residential showers and faucets, hot-tubs and garden soil as sources of transmissible pathogenic NTM. However, gaps exist in the literature, with many clinical isolates remaining unidentified within environments that have been tested, and few studies investigating NTM transmission in developing countries. To understand the environmental reservoirs and transmission routes of pathogenic NTM, different environments, countries and climates must be investigated.

  11. Polymorphism of the human vitronectin gene causes vitronectin blood type.

    Science.gov (United States)

    Kubota, K; Hayashi, M; Oishi, N; Sakaki, Y

    1990-03-30

    Human blood plasma/sera are classified into three distinct vitronectin types based on the relative amount of the 75 kDa polypeptide to its cleavage product of 65 kDa. We asked whether the vitronectin blood types correlated with the polymorphism of the vitronectin gene. A portion of the vitronectin gene was amplified by using polymerase chain reaction and digested with a restriction enzyme PmaC I which may distinguish the base sequence causing the polymorphic change at the amino acid position 381. Amplified DNAs of the blood type I (75 kDa-rich), II (75/65 kDa-even), and III (65 kDa-rich) were shown to be resistant, moderately sensitive and completely sensitive to PmaC I, respectively. These results suggest that Thr at position 381 is essential for the cleavage of the vitronectin 75 kDa polypeptide and that three possible combinations of two codominant alleles of vitronectin determine three vitronectin blood types.

  12. CONTROL OF ANIMAL DISEASES CAUSED BY BACTERIA: PRINCIPLES AND APPROACHES

    Directory of Open Access Journals (Sweden)

    K. Ahmad

    2005-10-01

    Full Text Available To continue to exist, a bacterial pathogen must reproduce and be disseminated among its hosts. Thus, an important aspect of bacterial disease control is a consideration of how reproduction and dissemination of the organism occur. One must identify components of bacterial dissemination that are primarily responsible for a particular disease. Control measures should be directed toward that part of the cycle which is most susceptible to control the weakest links in the chain of disease process. Reducing or eliminating the source or reservoir of infection, breaking the connection between the source of the infection and susceptible animals and reducing the number of susceptible animals by raising the general level of herd immunity with immunization are three main kinds of control measures against bacterial diseases.

  13. "Moya-moya' disease caused by cranial trauma.

    Science.gov (United States)

    Fernandez-Alvarez, E; Pineda, M; Royo, C; Manzanares, R

    1979-01-01

    A case of "moya-moya" disease of a 12-year-old boy is reported. The clinical history started at 3 years 2 months after cranial trauma. The patient developed mental retardation, hemiparesis and seizures.

  14. GAUCHER´S DISEASE: A RARE CAUSE OF FANCONI SYNDROME?

    Directory of Open Access Journals (Sweden)

    Musso CG

    2007-01-01

    Full Text Available Gaucher´s disease consists of a genetic autosomic recesive alteration that leads to a reduction in the acid glucosil-ceramide beta-glucosidase enzyme. This enzyme brakes the glucosilceramide, a substance from which many esphingo and glucolipids are synthesized. Even though the renal compromise is not frequent in Gaucher disease, proteinuria (in nephrotic range or not and glomerulonephritis have been described in this illness.Fanconi syndrome is charaterized by a dysfunction in the proximal tubular reabsorption. Among the etiologies of Fanconi syndrome there are many metabolic diseases, but no association has been described yet in the literature between Fanconi syndrome and Gaucher disease. We present the following case report where this association was observed.

  15. diseases and causes of death among the popes 1. introduction

    African Journals Online (AJOL)

    present as is to be expected in an older population group, and acute terminal febrile illnesses ... disease, gallstones, cancer, dysentery, the plague, lung infection, gangrene of a leg, ..... Information on the patients' medical histories is limited.

  16. Rheumatoid arthritis is an autoimmune disease caused by periodontal pathogens

    Directory of Open Access Journals (Sweden)

    Ogrendik M

    2013-05-01

    Full Text Available Mesut OgrendikDivision of Physical Therapy and Rheumatology, Nazilli State Hospital, Nazilli, TurkeyAbstract: A statistically significant association between periodontal disease (PD and systemic diseases has been identified. Rheumatoid arthritis (RA, which is a chronic inflammatory joint disease, exhibits similar characteristics and pathogenesis to PD. The association between RA and PD has been investigated, and numerous publications on this subject exist. Approximately 20 bacterial species have been identified as periodontal pathogens, and these organisms are linked to various types of PD. The most analyzed species of periodontopathic bacteria are Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia, and Aggregatibacter actinomycetemcomitans. Antibodies and DNA from these oral pathogens have been isolated from the sera and synovial fluids of RA patients. This rapid communication describes the role of periodontal pathogens in the etiopathogenesis of RA.Keywords: etiopathogenesis, chronic arthritis, periodontitis, Porphyromonas gingivalis, systemic disease, animal models, antibiotics

  17. 4.DISEASE CAUSED BY CHEMICAL AND PHYSICAL AGENTS

    Institute of Scientific and Technical Information of China (English)

    1992-01-01

    920225 The report of organophosphoruspesticides causing delayed dysneuria in 143cases.ZHANG Cilu (张慈禄),et al.JiaojiangHosp.Chin J Neurol & Psychiat 1991;24(6):336-338.This article reports delayed dysneuria in 143

  18. Kimura′s disease: An uncommon cause of lymphadenopathy

    Directory of Open Access Journals (Sweden)

    Kumar Veerendra

    2010-01-01

    Full Text Available Lymph node enlargement of neck and axilla is one of the common presenting complaints in pediatrics. We are presenting here a very rare cause of axillary lymphadenopathy detected in a toddler.

  19. Chilli anthracnose disease caused by Colletotrichum species§

    OpenAIRE

    Than, Po Po; Prihastuti, Haryudian; Phoulivong, Sitthisack; Paul W.J. TAYLOR; Hyde, Kevin D.

    2008-01-01

    Anthracnose disease is one of the major economic constraints to chilli production worldwide, especially in tropical and subtropical regions. Accurate taxonomic information is necessary for effective disease control management. In the Colletotrichum patho-system, different Colletotrichum species can be associated with anthracnose of the same host. Little information is known concerning the interactions of the species associated with the chilli anthracnose although several Colletotrichum specie...

  20. Advances in chromatin remodeling and human disease.

    Science.gov (United States)

    Cho, Kyoung Sang; Elizondo, Leah I; Boerkoel, Cornelius F

    2004-06-01

    Epigenetic factors alter phenotype without changing genotype. A primary molecular mechanism underlying epigenetics is the alteration of chromatin structure by covalent DNA modifications, covalent histone modifications, and nucleosome reorganization. Remodeling of chromatin structure regulates DNA methylation, replication, recombination, and repair as well as gene expression. As these functions would predict, dysfunction of the proteins that remodel chromatin causes an array of multi-system disorders and neoplasias. Insights from these diseases suggest that during embryonic and fetal life, environmental distortions of chromatin remodeling encode a 'molecular memory' that predispose the individual to diseases in adulthood.

  1. SERCA2 Haploinsufficiency in a Mouse Model of Darier Disease Causes a Selective Predisposition to Heart Failure.

    Science.gov (United States)

    Prasad, Vikram; Lorenz, John N; Lasko, Valerie M; Nieman, Michelle L; Huang, Wei; Wang, Yigang; Wieczorek, David W; Shull, Gary E

    2015-01-01

    Null mutations in one copy of ATP2A2, the gene encoding sarco/endoplasmic reticulum Ca(2+)-ATPase isoform 2 (SERCA2), cause Darier disease in humans, a skin condition involving keratinocytes. Cardiac function appears to be unimpaired in Darier disease patients, with no evidence that SERCA2 haploinsufficiency itself causes heart disease. However, SERCA2 deficiency is widely considered a contributing factor in heart failure. We therefore analyzed Atp2a2 heterozygous mice to determine whether SERCA2 haploinsufficiency can exacerbate specific heart disease conditions. Despite reduced SERCA2a levels in heart, Atp2a2 heterozygous mice resembled humans in exhibiting normal cardiac physiology. When subjected to hypothyroidism or crossed with a transgenic model of reduced myofibrillar Ca(2+)-sensitivity, SERCA2 deficiency caused no enhancement of the disease state. However, when combined with a transgenic model of increased myofibrillar Ca(2+)-sensitivity, SERCA2 haploinsufficiency caused rapid onset of hypertrophy, decompensation, and death. These effects were associated with reduced expression of the antiapoptotic Hax1, increased levels of the proapoptotic genes Chop and Casp12, and evidence of perturbations in energy metabolism. These data reveal myofibrillar Ca(2+)-sensitivity to be an important determinant of the cardiac effects of SERCA2 haploinsufficiency and raise the possibility that Darier disease patients are more susceptible to heart failure under certain conditions.

  2. Elevated Remnant Cholesterol Causes Both Low-Grade Inflammation and Ischemic Heart Disease, Whereas Elevated Low-Density Lipoprotein Cholesterol Causes Ischemic Heart Disease Without Inflammation

    DEFF Research Database (Denmark)

    Varbo, Anette; Tybjærg-Hansen, Anne; Nordestgaard, Børge G

    2013-01-01

    Elevated nonfasting remnant cholesterol and low-density lipoprotein (LDL) cholesterol are causally associated with ischemic heart disease (IHD), but whether elevated nonfasting remnant cholesterol and LDL cholesterol both cause low-grade inflammation is currently unknown....

  3. The role of formins in human disease.

    Science.gov (United States)

    DeWard, Aaron D; Eisenmann, Kathryn M; Matheson, Stephen F; Alberts, Arthur S

    2010-02-01

    Formins are a conserved family of proteins that play key roles in cytoskeletal remodeling. They nucleate and processively elongate non-branched actin filaments and also modulate microtubule dynamics. Despite their significant contributions to cell biology and development, few studies have directly implicated formins in disease pathogenesis. This review highlights the roles of formins in cell division, migration, immunity, and microvesicle formation in the context of human disease. In addition, we discuss the importance of controlling formin activity and protein expression to maintain cell homeostasis.

  4. Human papillomavirus-associated diseases and cancers

    Institute of Scientific and Technical Information of China (English)

    Lan Yang; Jianbo Zhu Co-first author; Xiaoyue Song; Yan Qi; Xiaobin Cui; Feng Li 

    2015-01-01

    Human papilomaviruses (HPVs) have been detected in cervical cancer cels and skin papiloma cels, which have a variety of types, including low-risk and high-risk types. HPV genome replication requires the host cel’s DNA synthesis machinery, and HPVs encode proteins that maintain diferentiated epithelial cels in a replication-competent state. HPV types are tissue-specific and generaly produce diferent types of le-sions, either benign or malignant. This review examines diferent HPV types and their associated diseases and presents therapeutic options for the treatment of HPV-positive diseases.

  5. Gordon Wilson Lecture: Infectious Disease Causes of Cancer: Opportunities for Prevention and Treatment.

    Science.gov (United States)

    Howley, Peter M

    2015-01-01

    The role of infectious agents in cancer is generally underappreciated. However, approximately 20% of human cancers are caused by infectious agents and as such they rank second only to tobacco as a potentially preventable cause in humans. Specific viruses, parasites, and bacteria have been linked to specific human cancers. The infectious etiology for these specific cancers provides opportunities for prevention and treatment.

  6. Mapping gene associations in human mitochondria using clinical disease phenotypes.

    Directory of Open Access Journals (Sweden)

    Curt Scharfe

    2009-04-01

    Full Text Available Nuclear genes encode most mitochondrial proteins, and their mutations cause diverse and debilitating clinical disorders. To date, 1,200 of these mitochondrial genes have been recorded, while no standardized catalog exists of the associated clinical phenotypes. Such a catalog would be useful to develop methods to analyze human phenotypic data, to determine genotype-phenotype relations among many genes and diseases, and to support the clinical diagnosis of mitochondrial disorders. Here we establish a clinical phenotype catalog of 174 mitochondrial disease genes and study associations of diseases and genes. Phenotypic features such as clinical signs and symptoms were manually annotated from full-text medical articles and classified based on the hierarchical MeSH ontology. This classification of phenotypic features of each gene allowed for the comparison of diseases between different genes. In turn, we were then able to measure the phenotypic associations of disease genes for which we calculated a quantitative value that is based on their shared phenotypic features. The results showed that genes sharing more similar phenotypes have a stronger tendency for functional interactions, proving the usefulness of phenotype similarity values in disease gene network analysis. We then constructed a functional network of mitochondrial genes and discovered a higher connectivity for non-disease than for disease genes, and a tendency of disease genes to interact with each other. Utilizing these differences, we propose 168 candidate genes that resemble the characteristic interaction patterns of mitochondrial disease genes. Through their network associations, the candidates are further prioritized for the study of specific disorders such as optic neuropathies and Parkinson disease. Most mitochondrial disease phenotypes involve several clinical categories including neurologic, metabolic, and gastrointestinal disorders, which might indicate the effects of gene defects

  7. Antibacterial activity of leaves extracts of Trifolium alexandrinum Linn. against pathogenic bacteria causing tropical diseases

    Institute of Scientific and Technical Information of China (English)

    Abdul Viqar Khan; Qamar Uddin Ahmed; Indu Shukla; Athar Ali Khan

    2012-01-01

    Objective: To investigate antibacterial potential of Trifolium alexandrinum (T. alexandrinum) Linn. against seven gram positive and eleven gram negative hospital isolated human pathogenic bacterial strains responsible for many tropical diseases. Methods: Non-polar and polar extracts of the leaves of T. alexandrinum i.e., hexane, dichloromethane (DCM), ethyl acetate (EtOAc), methanol (MeOH) and aqueous (AQ) extracts at five different concentrations (1, 2, 5, 10 and 15 mg/mL) were prepared to evaluate their antibacterial value. NCCL standards were strictly followed to perform antimicrobial disc susceptibility test using disc diffusion method. Results: Polar extracts demonstrated significant antibacterial activity against tested pathogens. EtOAc and MeOH extracts showed maximum antibacterial activity with higher inhibition zone and were found effective against seventeen of the tested pathogens. While AQ plant extract inhibited the growth of sixteen of the test strains. EtOAc and MeOH plant extracts inhibited the growth of all seven gram positive and ten of the gram negative bacterial strains. Conclusions: The present study strongly confirms the effectiveness of crude leaves extracts against tested human pathogenic bacterial strains causing several tropical diseases. Since Egyptian clover is used as a fodder plant, it could be helpful in controlling various infectious diseases associated with cattle as well.

  8. Clustering of Parkinson disease: shared cause or coincidence?

    Science.gov (United States)

    Kumar, Ajit; Calne, Susan M; Schulzer, Michael; Mak, Edwin; Wszolek, Zbigniew; Van Netten, Chris; Tsui, Joseph K C; Stoessl, A Jon; Calne, Donald B

    2004-07-01

    The spatial and temporal pattern of excessive disease occurrence, termed clustering, may provide clues about the underlying etiology. To report the occurrence of 3 clusters of Parkinson disease (PD) in Canada. We determined the population groups containing the clusters, geographical limits, and duration of exposure to the specific environments. We tested whether there was an excessive presence of Parkinson disease by calculating the probability of the observed cases occurring under the null hypothesis that the disease developed independently and at random in cluster subjects. Results of genetic testing for mutations in the alpha-synuclein, parkin, tau genes, and spinocerebellar ataxia genes (SCA2 and SCA3) were negative. The probabilities of random occurrence (P values) in the 3 clusters were P = 7.9 x 10 (-7)for cluster 1, P = 2.6 x 10 (-7)for cluster 2, and P = 1.5 x 10 (-7)for cluster 3. Our findings indicate an important role for environmental causation in Parkinson disease. A possible role exists for environmental factors such as viral infection and toxins in the light of current evidence.

  9. Positive Selection during the Evolution of the Blood Coagulation Factors in the Context of Their Disease-Causing Mutations

    Science.gov (United States)

    Rallapalli, Pavithra M.; Orengo, Christine A.; Studer, Romain A.; Perkins, Stephen J.

    2014-01-01

    Blood coagulation occurs through a cascade of enzymes and cofactors that produces a fibrin clot, while otherwise maintaining hemostasis. The 11 human coagulation factors (FG, FII–FXIII) have been identified across all vertebrates, suggesting that they emerged with the first vertebrates around 500 Ma. Human FVIII, FIX, and FXI are associated with thousands of disease-causing mutations. Here, we evaluated the strength of selective pressures on the 14 genes coding for the 11 factors during vertebrate evolution, and compared these with human mutations in FVIII, FIX, and FXI. Positive selection was identified for fibrinogen (FG), FIII, FVIII, FIX, and FX in the mammalian Primates and Laurasiatheria and the Sauropsida (reptiles and birds). This showed that the coagulation system in vertebrates was under strong selective pressures, perhaps to adapt against blood-invading pathogens. The comparison of these results with disease-causing mutations reported in FVIII, FIX, and FXI showed that the number of disease-causing mutations, and the probability of positive selection were inversely related to each other. It was concluded that when a site was under positive selection, it was less likely to be associated with disease-causing mutations. In contrast, sites under negative selection were more likely to be associated with disease-causing mutations and be destabilizing. A residue-by-residue comparison of the FVIII, FIX, and FXI sequence alignments confirmed this. This improved understanding of evolutionary changes in FVIII, FIX, and FXI provided greater insight into disease-causing mutations, and better assessments of the codon sites that may be mutated in applications of gene therapy. PMID:25158795

  10. Human infections caused by free-living amoebae

    Directory of Open Access Journals (Sweden)

    Katarzyna Król-Turmińska

    2017-05-01

    Amoebic diseases are difficult to diagnose which leads to delayed treatment, and result in a high mortality rate. Considering those issues, there is an urgent need to draw more attention to this type of diseases.

  11. Gastrointestinal diseases of Napoleon in Saint Helena: causes of death.

    Science.gov (United States)

    Di Costanzo, Jacques

    2002-01-01

    The fact that Napoleon Ist died from gastric cancer seems to be well established. Arguments for the hypothesis of chronic arsenic poisoning have recently been developed in the literature. This study, focused on the gastrointestinal diseases of Napoleon in Saint Helena, is based on a confrontation between the clinical semiological anamnesis and the anatomical data in the autopsy report by F. Antommarchi. Napoleon presented several gastrointestinal diseases: gall-bladder lithiasis complicated with angiocholitis, chronic colitis and certainly a gastric cancer. Death was consecutive to perforation of the gastric lesion leading to haemorrhagic vomitis and multiorgan failure. The description of the gastric lesions during autopsy is consistent with the diagnosis of cancer. The course of the clinical events is closely correlated with the anatomic lesions. There is strong evidence that Napoleon died from an acute complication of his gastric disease.

  12. Rheumatoid arthritis is an autoimmune disease caused by periodontal pathogens.

    Science.gov (United States)

    Ogrendik, Mesut

    2013-01-01

    A statistically significant association between periodontal disease (PD) and systemic diseases has been identified. Rheumatoid arthritis (RA), which is a chronic inflammatory joint disease, exhibits similar characteristics and pathogenesis to PD. The association between RA and PD has been investigated, and numerous publications on this subject exist. Approximately 20 bacterial species have been identified as periodontal pathogens, and these organisms are linked to various types of PD. The most analyzed species of periodontopathic bacteria are Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia, and Aggregatibacter actinomycetemcomitans. Antibodies and DNA from these oral pathogens have been isolated from the sera and synovial fluids of RA patients. This rapid communication describes the role of periodontal pathogens in the etiopathogenesis of RA.

  13. An unusual cause of cervical lymphadenopathy: Kikuchi-Fujimoto disease

    Directory of Open Access Journals (Sweden)

    Mehmet Uluğ

    2012-03-01

    Full Text Available Kikuchi-Fujimoto disease (KFD, also known as histiocytic necrotizing lymphadenitis, is an uncommon clinical and pathologicalself-limited feature of benign prognosis that may mimic many other diseases diagnosed chiefly in youngadults. The etiology of the disease is unknown although several investigators postulate viral, parasitic and autoimmuneetiologies. The most common symptoms are cervical lymphadenopathy and fever. Diagnosis is usually rendered withexcisional biopsy of lymph nodes and through histopathological findings. Non-steroidal anti-inflammatory drugs areused for the treatment. In this report, two cases of KFD without any associated infectious and/or non-infectious conditionswere presented. J Microbiol Infect Dis 2012; 2(1: 21-25

  14. An unusual cause of optic neuritis:rickettsiosis disease

    Institute of Scientific and Technical Information of China (English)

    Loukil; Hanen; Snoussi; Mouna; Frikha; Faten; Ben; Salah; Raida; Jallouli; Moez; Cherif; Yosra; EI; Aoud; Sahar; Marzouk; Sameh; Bahloul; Zouhir

    2014-01-01

    Optic neuritis(ON) may be associated to a range of autoimmune or infectious diseases.We report herein a case of ON induced by Rickettsia conorii.A 53-year-old woman presented with a recent decrease in visual acuity and headache.ON was diagnosed on the basis of ophthalmologic examination and flash visual evoked potentials.Etiological investigation made in our department eliminated first autoimmune disorders(vasculitis and connective tissue diseases).Rickettsial optic neuritis was confirmed by detection of specific antibodies in serum and the negativity of other serologic tests.An association between corticosteroids and cyclines was prescribed with improvement of visual acuity.

  15. An unusual cause of optic neuritis:rickettsiosis disease

    Institute of Scientific and Technical Information of China (English)

    Loukil Hanen; Snoussi Mouna; Frikha Faten; Ben Salah Raida; Jallouli Moez; ChérifYosra; ElAoud Sahar; Marzouk Sameh; Bahloul Zouhir

    2014-01-01

    Optic neuritis (ON) may be associated to a range of autoimmune or infectious diseases. We report herein a case of ON induced by Rickettsia conorii. A 53-year-old woman presented with a recent decrease in visual acuity and headache. ON was diagnosed on the basis of ophthalmologic examination and flash visual evoked potentials. Etiological investigation made in our department eliminated first autoimmune disorders (vasculitis and connective tissue diseases). Rickettsial optic neuritis was confirmed by detection of specific antibodies in serum and the negativity of other serologic tests. An association between corticosteroids and cyclines was prescribed with improvement of visual acuity.

  16. Evidence that human papillomavirus causes inverted papilloma is sparse.

    Science.gov (United States)

    Justice, Jeb M; Davis, Kern M; Saenz, Daniel A; Lanza, Donald C

    2014-12-01

    Controversy exists regarding the pathogenesis of inverted papilloma as it relates to the involvement of human papillomavirus (HPV). The purpose of this report is to describe the prevalence of HPV in nondysplastic, "early inverted papilloma" and to summarize HPV detection rates in the general population and in other HPV related neoplasia. This case series report characterizes consecutive inverted papilloma patients from January 2005 to August 2012 with regard to smoking history, dysplasia, and HPV detection rates. Presence or absence of low/high risk HPV was determined by standardized in situ hybridization DNA probes. Medline literature review was performed to determine the prevalence of HPV in inverted papilloma without moderate or severe dysplasia. Thirty-six consecutive patients were identified with an average age of 63.6 (range, 40-84) years; gender: 23 men, 13 women. More than half (55%) were active or former smokers (14% active and 41% former). High/low risk HPV was present in 1 in 36 (2.7%) patients and 1 in 36 (2.7%) had mild dysplasia. In the literature review: (1) HPV was detected in 16.4% of inverted papilloma without dysplasia; (2) oral cavity HPV detection was 4.2% to 11.4% in the normal population; and (3) HPV was normally detected in 85% to 95% of HPV-related neoplasia. Given histological features of inverted papilloma and comparatively low detection rates of HPV in inverted papilloma without dysplasia (2.7%), as well as the summary of the world literature, HPV is not related to the initial pathogenesis of inverted papilloma or inverted papilloma's tendency to persist or recur. It is postulated that since inverted papilloma is more an inflammatory polyp, it is susceptible to secondary HPV infection because of its metaplasia. Tobacco and other causes of respiratory epithelium remodeling are more plausible explanations for the initial tissue transformation to inverted papilloma. © 2014 ARS-AAOA, LLC.

  17. Comparative Genomic Analysis of Human Fungal Pathogens Causing Paracoccidioidomycosis

    Science.gov (United States)

    Desjardins, Christopher A.; Champion, Mia D.; Holder, Jason W.; Muszewska, Anna; Goldberg, Jonathan; Bailão, Alexandre M.; Brigido, Marcelo Macedo; Ferreira, Márcia Eliana da Silva; Garcia, Ana Maria; Grynberg, Marcin; Gujja, Sharvari; Heiman, David I.; Henn, Matthew R.; Kodira, Chinnappa D.; León-Narváez, Henry; Longo, Larissa V. G.; Ma, Li-Jun; Malavazi, Iran; Matsuo, Alisson L.; Morais, Flavia V.; Pereira, Maristela; Rodríguez-Brito, Sabrina; Sakthikumar, Sharadha; Salem-Izacc, Silvia M.; Sykes, Sean M.; Teixeira, Marcus Melo; Vallejo, Milene C.; Walter, Maria Emília Machado Telles; Yandava, Chandri; Young, Sarah; Zeng, Qiandong; Zucker, Jeremy; Felipe, Maria Sueli; Goldman, Gustavo H.; Haas, Brian J.; McEwen, Juan G.; Nino-Vega, Gustavo; Puccia, Rosana; San-Blas, Gioconda; Soares, Celia Maria de Almeida; Birren, Bruce W.; Cuomo, Christina A.

    2011-01-01

    Paracoccidioides is a fungal pathogen and the cause of paracoccidioidomycosis, a health-threatening human systemic mycosis endemic to Latin America. Infection by Paracoccidioides, a dimorphic fungus in the order Onygenales, is coupled with a thermally regulated transition from a soil-dwelling filamentous form to a yeast-like pathogenic form. To better understand the genetic basis of growth and pathogenicity in Paracoccidioides, we sequenced the genomes of two strains of Paracoccidioides brasiliensis (Pb03 and Pb18) and one strain of Paracoccidioides lutzii (Pb01). These genomes range in size from 29.1 Mb to 32.9 Mb and encode 7,610 to 8,130 genes. To enable genetic studies, we mapped 94% of the P. brasiliensis Pb18 assembly onto five chromosomes. We characterized gene family content across Onygenales and related fungi, and within Paracoccidioides we found expansions of the fungal-specific kinase family FunK1. Additionally, the Onygenales have lost many genes involved in carbohydrate metabolism and fewer genes involved in protein metabolism, resulting in a higher ratio of proteases to carbohydrate active enzymes in the Onygenales than their relatives. To determine if gene content correlated with growth on different substrates, we screened the non-pathogenic onygenale Uncinocarpus reesii, which has orthologs for 91% of Paracoccidioides metabolic genes, for growth on 190 carbon sources. U. reesii showed growth on a limited range of carbohydrates, primarily basic plant sugars and cell wall components; this suggests that Onygenales, including dimorphic fungi, can degrade cellulosic plant material in the soil. In addition, U. reesii grew on gelatin and a wide range of dipeptides and amino acids, indicating a preference for proteinaceous growth substrates over carbohydrates, which may enable these fungi to also degrade animal biomass. These capabilities for degrading plant and animal substrates suggest a duality in lifestyle that could enable pathogenic species of

  18. Comparative genomic analysis of human fungal pathogens causing paracoccidioidomycosis.

    Directory of Open Access Journals (Sweden)

    Christopher A Desjardins

    2011-10-01

    Full Text Available Paracoccidioides is a fungal pathogen and the cause of paracoccidioidomycosis, a health-threatening human systemic mycosis endemic to Latin America. Infection by Paracoccidioides, a dimorphic fungus in the order Onygenales, is coupled with a thermally regulated transition from a soil-dwelling filamentous form to a yeast-like pathogenic form. To better understand the genetic basis of growth and pathogenicity in Paracoccidioides, we sequenced the genomes of two strains of Paracoccidioides brasiliensis (Pb03 and Pb18 and one strain of Paracoccidioides lutzii (Pb01. These genomes range in size from 29.1 Mb to 32.9 Mb and encode 7,610 to 8,130 genes. To enable genetic studies, we mapped 94% of the P. brasiliensis Pb18 assembly onto five chromosomes. We characterized gene family content across Onygenales and related fungi, and within Paracoccidioides we found expansions of the fungal-specific kinase family FunK1. Additionally, the Onygenales have lost many genes involved in carbohydrate metabolism and fewer genes involved in protein metabolism, resulting in a higher ratio of proteases to carbohydrate active enzymes in the Onygenales than their relatives. To determine if gene content correlated with growth on different substrates, we screened the non-pathogenic onygenale Uncinocarpus reesii, which has orthologs for 91% of Paracoccidioides metabolic genes, for growth on 190 carbon sources. U. reesii showed growth on a limited range of carbohydrates, primarily basic plant sugars and cell wall components; this suggests that Onygenales, including dimorphic fungi, can degrade cellulosic plant material in the soil. In addition, U. reesii grew on gelatin and a wide range of dipeptides and amino acids, indicating a preference for proteinaceous growth substrates over carbohydrates, which may enable these fungi to also degrade animal biomass. These capabilities for degrading plant and animal substrates suggest a duality in lifestyle that could enable pathogenic

  19. RTTN Mutations Cause Primary Microcephaly and Primordial Dwarfism in Humans.

    Science.gov (United States)

    Shamseldin, Hanan; Alazami, Anas M; Manning, Melanie; Hashem, Amal; Caluseiu, Oana; Tabarki, Brahim; Esplin, Edward; Schelley, Susan; Innes, A Micheil; Parboosingh, Jillian S; Lamont, Ryan; Majewski, Jacek; Bernier, Francois P; Alkuraya, Fowzan S

    2015-12-03

    Primary microcephaly is a developmental brain anomaly that results from defective proliferation of neuroprogenitors in the germinal periventricular zone. More than a dozen genes are known to be mutated in autosomal-recessive primary microcephaly in isolation or in association with a more generalized growth deficiency (microcephalic primordial dwarfism), but the genetic heterogeneity is probably more extensive. In a research protocol involving autozygome mapping and exome sequencing, we recruited a multiplex consanguineous family who is affected by severe microcephalic primordial dwarfism and tested negative on clinical exome sequencing. Two candidate autozygous intervals were identified, and the second round of exome sequencing revealed a single intronic variant therein (c.2885+8A>G [p.Ser963(∗)] in RTTN exon 23). RT-PCR confirmed that this change creates a cryptic splice donor and thus causes retention of the intervening 7 bp of the intron and leads to premature truncation. On the basis of this finding, we reanalyzed the exome file of a second consanguineous family affected by a similar phenotype and identified another homozygous change in RTTN as the likely causal mutation. Combined linkage analysis of the two families confirmed that RTTN maps to the only significant linkage peak. Finally, through international collaboration, a Canadian multiplex family affected by microcephalic primordial dwarfism and biallelic mutation of RTTN was identified. Our results expand the phenotype of RTTN-related disorders, hitherto limited to polymicrogyria, to include microcephalic primordial dwarfism with a complex brain phenotype involving simplified gyration. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  20. The role of chemerin in human disease

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    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.

  1. Genes of periodontopathogens expressed during human disease.

    Science.gov (United States)

    Song, Yo-Han; Kozarov, Emil V; Walters, Sheila M; Cao, Sam Linsen; Handfield, Martin; Hillman, Jeffrey D; Progulske-Fox, Ann

    2002-12-01

    Since many bacterial genes are environmentally regulated, the screening for virulence-associated factors using classical genetic and molecular biology approaches can be biased under laboratory growth conditions of a given pathogen, because the required conditions for expression of many virulence factors may not occur during in vitro growth. Thus, technologies have been developed during the past several years to identify genes that are expressed during disease using animal models of human disease. However, animal models are not always truly representative of human disease, and with many pathogens, there is no appropriate animal model. A new technology, in vivo-induced antigen technology (IVIAT) was thus engineered and tested in our laboratory to screen for genes of pathogenic organisms induced specifically in humans, without the use of animal or artificial models of infection. This technology uses pooled sera from patients to probe for genes expressed exclusively in vivo (or ivi, in vivo-induced genes). IVIAT was originally designed for the study of Actinobacillus actinomycetemcomitans pathogenesis, but we have now extended it to other oral pathogens including Porphyromonas gingivalis. One hundred seventy-one thousand (171,000) clones from P. gingivalis strain W83 were screened and 144 were confirmed positive. Over 300,000 A. actinomycetemcomitans clones were probed, and 116 were confirmed positive using a quantitative blot assay. MAT has proven useful in identifying previously unknown in vivo-induced genes that are likely involved in virulence and are thus excellent candidates for use in diagnostic : and therapeutic strategies, including vaccine design.

  2. Preventing fatal diseases increases healthcare costs: cause elimination life table approach

    NARCIS (Netherlands)

    L.G.A. Bonneux (Luc); J.J.M. Barendregt (Jan); W.J. Nusselder (Wilma); P.J. van der Maas (Paul)

    1998-01-01

    textabstractOBJECTIVES: To examine whether elimination of fatal diseases will increase healthcare costs. DESIGN: Mortality data from vital statistics combined with healthcare spending in a cause elimination life table. Costs were allocated to specific diseases through t

  3. Understanding human action: integrating meanings, mechanisms, causes, and contexts

    NARCIS (Netherlands)

    M. Keestra

    2012-01-01

    Humans are capable of understanding an incredible variety of actions performed by other humans. Even though these range from primary biological actions like eating and fleeing, to acts in parliament or in poetry, humans generally can make sense of each other’s actions. Understanding other people’s a

  4. Understanding human action: integrating meanings, mechanisms, causes, and contexts

    NARCIS (Netherlands)

    Keestra, M.; Repko, A.F.; Newell, W.H.; Szostak, R.

    2012-01-01

    Humans are capable of understanding an incredible variety of actions performed by other humans. Even though these range from primary biological actions like eating and fleeing, to acts in parliament or in poetry, humans generally can make sense of each other’s actions. Understanding other people’s

  5. Legionella (Legionnaires' Disease and Pontiac Fever): Causes and Transmission

    Science.gov (United States)

    ... ELITE Program for Laboratories For Media Water System Maintenance Water Management Toolkit Identify Buildings at Increased Risk Considerations ... people can get Legionnaires’ disease by aspiration of drinking water. This happens when water “goes down the ...

  6. Microbiological diagnosis of infections caused by Campylobacter jejuni and Campylobacter coli in humans

    Directory of Open Access Journals (Sweden)

    Natalia Rokosz

    2014-01-01

    Full Text Available Campylobacter jejuni and Campylobacter coli are Gram-negative, microaerophilic bacteria which are worldwide in distribution, causing a zoonotic disease in humans called campylobacteriosis. These infections are mainly caused by eating contaminated food products, most often improperly prepared poultry meat. Campylobacteriosis usually takes the form of gastroenteritis, or inflammation of the intestines, and the characteristic symptoms are watery-mucous diarrhea often with the presence of blood in stool, nausea, vomiting, abdominal pain and fever. The epidemiological data suggest that in Europe, as well as in North America, bacteria of the genus Campylobacter, especially C. jejuni and C. coli, are the most commonly isolated pathogens in infections of the gastrointestinal tract in humans. Epidemiological data indicate that these organisms are a much more common cause of acute diarrhea, mostly in young children, than Salmonella and Yersinia. The lack of specific symptoms makes the diagnosis of campylobacteriosis necessary to carry out specialized microbiological diagnostics. Because so far these studies are performed in our country only in a few laboratories, the overwhelming number of cases of campylobacteriosis are not recorded in Polish epidemiological statistics. The purpose of this paper is to discuss issues related to the microbiological diagnosis of infections caused by C. jejuni and C. coli. It also describes the basic epidemiological and clinical data, as well as current treatment of campylobacteriosis.

  7. Waterborne Exophiala species causing disease in cold-blooded animals

    NARCIS (Netherlands)

    de Hoog, G.S.; Vicente, V.A.; Najafzadeh, M.J.; Harrak, M.J.; Badali, H.; Seyedmousavi, S.

    2011-01-01

    The majority of mesophilic waterborne species of the black yeast genus Exophiala (Chaetothyriales) belong to a single clade judging from SSU rDNA data. Most taxa are also found to cause cutaneous or disseminated infections in cold-blooded, water animals, occasionally reaching epidemic proportions. H

  8. Waterborne Exophiala species causing disease in cold-blooded animals

    NARCIS (Netherlands)

    de Hoog, G.S.; Vicente, V.A.; Najafzadeh, M.J.; Harrak, M.J.; Badali, H.; Seyedmousavi, S.

    2012-01-01

    The majority of mesophilic waterborne species of the black yeast genus Exophiala (Chaetothyriales) belong to a single clade judging from SSU rDNA data. Most taxa are also found to cause cutaneous or disseminated infections in cold-blooded, water animals, occasionally reaching epidemic proportions. H

  9. Sooty Mould Disease Caused by Leptoxyphium kurandae on Kenaf.

    Science.gov (United States)

    Choi, In-Young; Kang, Chan-Ho; Lee, Geon-Hwi; Park, Ji-Hyun; Shin, Hyeon-Dong

    2015-09-01

    In September 2013, we discovered sooty mould growing on kenaf with the extrafloral nectaries in Iksan, Korea and identified the causative fungus as Leptoxyphium kurandae based on morphological characteristics and phylogenetic analyses. This is the first report of sooty mould caused by L. kurandae on kenaf in Korea and globally.

  10. Do cell junction protein mutations cause an airway phenotype in mice or humans?

    Science.gov (United States)

    Chang, Eugene H; Pezzulo, Alejandro A; Zabner, Joseph

    2011-08-01

    Cell junction proteins connect epithelial cells to each other and to the basement membrane. Genetic mutations of these proteins can cause alterations in some epithelia leading to varied phenotypes such as deafness, renal disease, skin disorders, and cancer. This review examines if genetic mutations in these proteins affect the function of lung airway epithelia. We review cell junction proteins with examples of disease mutation phenotypes in humans and in mouse knockout models. We also review which of these genes are expressed in airway epithelium by microarray expression profiling and immunocytochemistry. Last, we present a comprehensive literature review to find the lung phenotype when cell junction and adhesion genes are mutated or subject to targeted deletion. We found that in murine models, targeted deletion of cell junction and adhesion genes rarely result in a lung phenotype. Moreover, mutations in these genes in humans have no obvious lung phenotype. Our research suggests that simply because a cell junction or adhesion protein is expressed in an organ does not imply that it will exhibit a drastic phenotype when mutated. One explanation is that because a functioning lung is critical to survival, redundancy in the system is expected. Therefore mutations in a single gene might be compensated by a related function of a similar gene product. Further studies in human and animal models will help us understand the overlap in the function of cell junction gene products. Finally, it is possible that the human lung phenotype is subtle and has not yet been described.

  11. Causes of death in the human immunodeficiency virus population in Western Jamaica

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    Nikkiah Forbes

    2014-01-01

    Full Text Available Background: Monitoring the causes of death in patients with human immunodeficiency virus (HIV in the era of expanding access to antiretroviral therapy in resource-limited settings has implications as more deaths are reported for reasons other than AIDS. Aims: To determine the causes of mortality in HIV-infected adults in Western Jamaica. Materials and Methods: Patients with HIV infection with a death certificate with a known cause of death between 2005 and 2010 were reviewed. Results: There were 189 patients. Co-morbidities were present in 25.3%. The mean age at death was 42.4 years. Early disease (World Health Organization [WHO] stages 1 or 2 was the presentation in 21.5% while 78.6% presented with advanced disease (WHO stages 3 or 4. The mean CD4 count at diagnosis was 95 cells/mm 3 . In patients presenting with early disease, 14.2% presented with sexually transmitted infections, 22.8% skin manifestations, and 14.2% lymphadenopathy. In patients presenting with late disease, 41.7% had Pneumocystis jirovecii pneumonia (PCP, 18.9% central nervous system (CNS toxoplasmosis, 11.3% HIV-associated nephropathy, and 5% cryptococcal meningitis. At death, 72.6% were in WHO class 4, and 21.2% class 3. The average CD4 count at death was 75.5 cells/mm 3 . Overall, 55.2% of the patients had received highly active antiretroviral therapy. PCP accounted for 42.9% of deaths, 27.3% had CNS opportunistic infections, HIV nephropathy 16.4%, and 4.6% had malignancies. About 52.3% of patients died within 1 year of diagnosis with HIV, while 68.3% died within 2 years. Conclusion: Patients with HIV are presenting with late disease and dying of conditions that are AIDS-related. Efforts to improve early diagnosis and treatment are urgently needed in Jamaica.

  12. Kikuchi's Disease: A Rare Cause of Fever of Unknown Origin.

    Science.gov (United States)

    Jalal-ud-din, Mir; Noor, Muhammad Munir; Ali, Shadab; Ali, Rashid

    2015-04-01

    Kikuchi Fujimoto Disease (KFD) or histiocytic necrotizing lymphadenitis can present with unexplained fever and lymphadenopathy. It is often mistaken for more serious conditions like malignant lymphoma or tuberculosis. First case was described by Kikuchi in Japan, very few cases have been reported in Pakistan. A middle aged female presented with fever and body aches for one month. She was investigated extensively for pyrexia of unknown origin, all of which came out to be normal except a raised ESR. Anti-tuberculous drugs were started on clinical suspicion, with no improvement after a month. Later, a detailed physical examination revealed cervical lymphadenopathy. One of the lymph nodes was excised and biopsied. The histopathology suggested Kikuchi's disease. Oral Prednisolone was started showing improvement. Her fever subsided and lymph nodes disappeared at the follow-up visit. No relapse was encountered in the subsequent visits.

  13. Node of Ranvier Disruption as a Cause of Neurological Diseases

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    Keiichiro Susuki

    2013-07-01

    Full Text Available Dysfunction and/or disruption of nodes of Ranvier are now recognized as key contributors to the pathophysiology of various neurological diseases. One reason is that the excitable nodal axolemma contains a high density of Nav (voltage-gated Na+ channels that are required for the rapid and efficient saltatory conduction of action potentials. Nodal physiology is disturbed by altered function, localization, and expression of voltage-gated ion channels clustered at nodes and juxtaparanodes, and by disrupted axon–glial interactions at paranodes. This paper reviews recent discoveries in molecular/cellular neuroscience, genetics, immunology, and neurology that highlight the critical roles of nodes of Ranvier in health and disease.

  14. "Kissing bugs": potential disease vectors and cause of anaphylaxis.

    Science.gov (United States)

    Klotz, John H; Dorn, Patricia L; Logan, Joy L; Stevens, Lori; Pinnas, Jacob L; Schmidt, Justin O; Klotz, Stephen A

    2010-06-15

    Physicians in the United States should familiarize themselves with "kissing bugs" endemic to their area of practice and appreciate the medical implications of their bites. Bite victims often seek advice from physicians about allergic reactions as well as the risk of contracting Chagas disease. Physicians are generally knowledgeable about the role of kissing bugs in the transmission of Trypanosoma cruzi in Latin America. However, they may be unaware of (1) severe allergic reactions to kissing bug salivary antigens, (2) the widespread occurrence of T. cruzi amongst vertebrate hosts of kissing bugs, and (3) the incidence of T. cruzi among kissing bugs (T. cruzi may infect >50% of sampled bugs). Despite the potential for Chagas disease transmission, the major concern regarding kissing bugs in the United States is anaphylactic reactions to their bites resulting in frequent emergency department visits, especially in areas of endemicity in the Southwest.

  15. Transgenic rabbits as therapeutic protein bioreactors and human disease models.

    Science.gov (United States)

    Fan, Jianglin; Watanabe, Teruo

    2003-09-01

    Genetically modified laboratory animals provide a powerful approach for studying gene expression and regulation and allow one to directly examine structure-function and cause-and-effect relationships in pathophysiological processes. Today, transgenic mice are available as a research tool in almost every research institution. On the other hand, the development of a relatively large mammalian transgenic model, transgenic rabbits, has provided unprecedented opportunities for investigators to study the mechanisms of human diseases and has also provided an alternative way to produce therapeutic proteins to treat human diseases. Transgenic rabbits expressing human genes have been used as a model for cardiovascular disease, AIDS, and cancer research. The recombinant proteins can be produced from the milk of transgenic rabbits not only at lower cost but also on a relatively large scale. One of the most promising and attractive recombinant proteins derived from transgenic rabbit milk, human alpha-glucosidase, has been successfully used to treat the patients who are genetically deficient in this enzyme. Although the pronuclear microinjection is still the major and most popular method for the creation of transgenic rabbits, recent progress in gene targeting and animal cloning has opened new avenues that should make it possible to produce transgenic rabbits by somatic cell nuclear transfer in the future. Based on a computer-assisted search of the studies of transgenic rabbits published in the English literature here, we introduce to the reader the achievements made thus far with transgenic rabbits, with emphasis on the application of these rabbits as human disease models and live bioreactors for producing human therapeutic proteins and on the recent progress in cloned rabbits.

  16. Causes of Parkinson’s disease: Literature Review

    OpenAIRE

    Shafique, Hassan

    2011-01-01

    Hassan Shafique,1 Alex Blagrove,2 Angela Chung,2 Raynarth Logendrarajah1Department of Neuroscience, University of Toronto, Toronto, Ontario, Canada; 2Department of Psychology, University of Toronto, Toronto, Ontario, CanadaAbstract: Parkinson’s disease is one of the most common movement disorders in the world. Parkinson’s affects approximately 1% of all adults over the age of 60. This disorder is the result of the degeneration of dopamineproducing cells in the substantia n...

  17. Depression as the cause and consequence of cerebrovascular diseases

    Directory of Open Access Journals (Sweden)

    Rabi-Žikić Tamara

    2007-01-01

    Full Text Available Inbtroduction: Recent epidemiological, clinical, neuroimaging and neuropathological studies have reported substantial evidence on the complex interactive relationships between depression and cerebrovascular diseases, especially in older populations, and plausible explanations of the etiopathogenetic mechanisms in both directions have been proposed. Poststroke depression Although there is no general consensus regarding its prevalence, it is widely accepted that major depression after stroke is common and that it should be recognized as a key factor in rehabilitation and outcome following stroke. Vascular depression The "vascular depression" hypothesis presupposes that late-onset depression may often result from vascular damage to frontal-subcortical circuits implicated in mood regulation. This concept has stimulated many researches and the obtained results support the proposed hypothesis. Depression as a stroke risk factor Recent large studies have emphasized the role of depression per se in the development of subsequent stroke. Mechanisms proposed to explain the increased risk of cerebrovascular diseases in depressed patients There are a number of plausible mechanisms that could explain why depression may increase the risk of subsequent cerebrovascular disease, the most important being sympathoadrenal hyperactivity, platelet activation, an increase in inflammatory cytokines and an increased risk of arrhythmias. Conclusion: Thorough clinical examinations determining the conventional stroke risk factors in the population with depression, as well as management of depression as part of the overall measures for the reduction of cerebrovascular risk factors are of utmost importance.

  18. HTT-lowering reverses Huntington’s disease immune dysfunction caused by NFκB pathway dysregulation

    Science.gov (United States)

    Träger, Ulrike; Andre, Ralph; Lahiri, Nayana; Magnusson-Lind, Anna; Weiss, Andreas; Grueninger, Stephan; McKinnon, Chris; Sirinathsinghji, Eva; Kahlon, Shira; Pfister, Edith L.; Moser, Roger; Hummerich, Holger; Antoniou, Michael; Bates, Gillian P.; Luthi-Carter, Ruth; Lowdell, Mark W.; Björkqvist, Maria; Ostroff, Gary R.; Aronin, Neil

    2014-01-01

    Huntington’s disease is an inherited neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. The peripheral innate immune system contributes to Huntington’s disease pathogenesis and has been targeted successfully to modulate disease progression, but mechanistic understanding relating this to mutant huntingtin expression in immune cells has been lacking. Here we demonstrate that human Huntington’s disease myeloid cells produce excessive inflammatory cytokines as a result of the cell-intrinsic effects of mutant huntingtin expression. A direct effect of mutant huntingtin on the NFκB pathway, whereby it interacts with IKKγ, leads to increased degradation of IκB and subsequent nuclear translocation of RelA. Transcriptional alterations in intracellular immune signalling pathways are also observed. Using a novel method of small interfering RNA delivery to lower huntingtin expression, we show reversal of disease-associated alterations in cellular function–the first time this has been demonstrated in primary human cells. Glucan-encapsulated small interfering RNA particles were used to lower huntingtin levels in human Huntington’s disease monocytes/macrophages, resulting in a reversal of huntingtin-induced elevated cytokine production and transcriptional changes. These findings improve our understanding of the role of innate immunity in neurodegeneration, introduce glucan-encapsulated small interfering RNA particles as tool for studying cellular pathogenesis ex vivo in human cells and raise the prospect of immune cell-directed HTT-lowering as a therapeutic in Huntington’s disease. PMID:24459107

  19. Cultural Transformations in China and Progresses in Human Rights Cause

    Institute of Scientific and Technical Information of China (English)

    LI JUNRU

    2011-01-01

    Human rights refer to the rights that should be enjoyed by anyone as human beings.However,human beings have not only the natural attributes,but also social attributes,including such high-level social attributes as thinking capability and culture.The role of culture on human beings can be seen in people's understandings on human rights connotation and human rights value.In fact,the different views on human rights issue of various countries worldwide are linked with their different cultures.We cannot change the differences of various countries in cultures,but we can learn about and understand the differences through cultural exchanges so as to enhance recognition on human rights issue.On the issue of human rights,we always insist on dialogue,not confrontation.Practices in the past years prove that in order to make such dialogues more effective,we must enhance cultural exchanges and mutual understandings among various countries.Here,I would like to introduce how the Chinese people deepen their understandings on human rights in the process of cultural transformation.

  20. 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.

  1. Dynamics and distribution of natural and human-caused hypoxia

    Directory of Open Access Journals (Sweden)

    N. N. Rabalais

    2010-02-01

    Full Text Available Water masses can become undersaturated with oxygen when natural processes alone or in combination with anthropogenic processes produce enough organic carbon that is aerobically decomposed faster than the rate of oxygen re-aeration. The dominant natural processes usually involved are photosynthetic carbon production and microbial respiration. The re-supply rate is indirectly related to its isolation from the surface layer. Hypoxic water masses (<2 mg L−1, or approximately 30% saturation can form, therefore, under "natural" conditions, and are more likely to occur in marine systems when the water residence time is extended, water exchange and ventilation are minimal, stratification occurs, and where carbon production and export to the bottom layer are relatively high. Hypoxia has occurred through geological time and naturally occurs in oxygen minimum zones, deep basins, eastern boundary upwelling systems, and fjords.

    Hypoxia development and continuation in many areas of the world's coastal ocean is accelerated by human activities, especially where nutrient loading increased in the Anthropocene. This higher loading set in motion a cascading set of events related to eutrophication. The formation of hypoxic areas has been exacerbated by any combination of interactions that increase primary production and accumulation of organic carbon leading to increased respiratory demand for oxygen below a seasonal or permanent pycnocline. Nutrient loading is likely to increase further as population growth and resource intensification rises, especially with increased dependency on crops using fertilizers, burning of fossil fuels, urbanization, and waste water generation. It is likely that the occurrence and persistence of hypoxia will be even more widespread and have more impacts than presently observed.

    Global climate change will further complicate the causative factors in both natural and human-caused hypoxia. The likelihood of

  2. 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

    for understanding and improving attribution methodologies and for sharing knowledge within the scientific community. We propose harmonized nomenclature, and describe the various approaches for human illness source attribution and their usefulness to address specific public health questions.......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...

  3. Chromatin remodeling by the CHD7 protein is impaired by mutations that cause human developmental disorders.

    Science.gov (United States)

    Bouazoune, Karim; Kingston, Robert E

    2012-11-20

    Mutations in the CHD7 gene cause human developmental disorders including CHARGE syndrome. Genetic studies in model organisms have further established CHD7 as a central regulator of vertebrate development. Functional analysis of the CHD7 protein has been hampered by its large size. We used a dual-tag system to purify intact recombinant CHD7 protein and found that it is an ATP-dependent nucleosome remodeling factor. Biochemical analyses indicate that CHD7 has characteristics distinct from SWI/SNF- and ISWI-type remodelers. Further investigations show that CHD7 patient mutations have consequences that range from subtle to complete inactivation of remodeling activity, and that mutations leading to protein truncations upstream of amino acid 1899 of CHD7 are likely to cause a hypomorphic phenotype for remodeling. We propose that nucleosome remodeling is a key function for CHD7 during developmental processes and provide a molecular basis for predicting the impact of disease mutations on that function.

  4. Catalytic deficiency of human aldolase B in hereditary fructose intolerance caused by a common missense mutation.

    Science.gov (United States)

    Cross, N C; Tolan, D R; Cox, T M

    1988-06-17

    Hereditary fructose intolerance (HFI) is a human autosomal recessive disease caused by a deficiency of aldolase B that results in an inability to metabolize fructose and related sugars. We report here the first identification of a molecular lesion in the aldolase B gene of an affected individual whose defective protein has previously been characterized. The mutation is a G----C transversion in exon 5 that creates a new recognition site for the restriction enzyme Ahall and results in an amino acid substitution (Ala----Pro) at position 149 of the protein within a region critical for substrate binding. Utilizing this novel restriction site and the polymerase chain reaction, the patient was shown to be homozygous for the mutation. Three other HFI patients from pedigrees unrelated to this individual were found to have the same mutation: two were homozygous and one was heterozygous. We suggest that this genetic lesion is a prevailing cause of hereditary fructose intolerance.

  5. [From gene to disease; Dent's disease caused by abnormalities in the CLCN5 and OCRL1 genes

    NARCIS (Netherlands)

    Levtchenko, E.N.; Monnens, L.A.H.; Bokenkamp, A.; Knoers, N.V.A.M.

    2007-01-01

    Dent's disease is an X-linked disorder, characterized by generalized proximal tubular dysfunction, nephrolithiasis, nephrocalcinosis and the development ofend-stage renal disease, generally occurring after the age of thirty. In the majority of cases, the disease is caused by mutations in the CLCN5-g

  6. Human-Wildlife Conflicts in Nepal: Patterns of Human Fatalities and Injuries Caused by Large Mammals.

    Science.gov (United States)

    Acharya, Krishna Prasad; Paudel, Prakash Kumar; Neupane, Prem Raj; Köhl, Michael

    2016-01-01

    Injury and death from wildlife attacks often result in people feeling violent resentment and hostility against the wildlife involved and, therefore, may undermine public support for conservation. Although Nepal, with rich biodiversity, is doing well in its conservation efforts, human-wildlife conflicts have been a major challenge in recent years. The lack of detailed information on the spatial and temporal patterns of human-wildlife conflicts at the national level impedes the development of effective conflict mitigation plans. We examined patterns of human injury and death caused by large mammals using data from attack events and their spatiotemporal dimensions collected from a national survey of data available in Nepal over five years (2010-2014). Data were analyzed using logistic regression and chi-square or Fisher's exact tests. The results show that Asiatic elephants and common leopards are most commonly involved in attacks on people in terms of attack frequency and fatalities. Although one-horned rhinoceros and bears had a higher frequency of attacks than Bengal tigers, tigers caused more fatalities than each of these two species. Attacks by elephants peaked in winter and most frequently occurred outside protected areas in human settlements. Leopard attacks occurred almost entirely outside protected areas, and a significantly greater number of attacks occurred in human settlements. Attacks by one-horned rhinoceros and tigers were higher in the winter, mainly in forests inside protected areas; similarly, attacks by bears occurred mostly within protected areas. We found that human settlements are increasingly becoming conflict hotspots, with burgeoning incidents involving elephants and leopards. We conclude that species-specific conservation strategies are urgently needed, particularly for leopards and elephants. The implications of our findings for minimizing conflicts and conserving these imperiled species are discussed.

  7. Bacterial meningitis and diseases caused by bacterial toxins.

    Science.gov (United States)

    Rings, D M

    1987-03-01

    Bacterial meningitis most commonly occurs in young calves secondary to septicemia. Clinical signs of hyperirritability are usually seen. Meningitis can be confirmed by cerebrospinal fluid analysis and culture or by necropsy. Intoxications by the exotoxins of Clostridium perfringens types C and D, C. botulinum, and C. tetani are difficult to confirm. The clinical signs of these intoxications vary from flaccid paralysis (botulism) to muscular rigidity (tetanus). Treatment of affected cattle has been unrewarding in botulism and enterotoxemia, whereas early aggressive treatment of tetanus cases can often be successfully resolved. Botulism and enterotoxemia can be proved using mouse inoculation tests, whereas tetanus is diagnosed largely by ruling out other diseases.

  8. SCN5A variant that blocks fibroblast growth factor homologous factor regulation causes human arrhythmia

    Science.gov (United States)

    Musa, Hassan; Kline, Crystal F.; Sturm, Amy C.; Murphy, Nathaniel; Adelman, Sara; Wang, Chaojian; Yan, Haidun; Johnson, Benjamin L.; Csepe, Thomas A.; Kilic, Ahmet; Higgins, Robert S. D.; Janssen, Paul M. L.; Fedorov, Vadim V.; Weiss, Raul; Salazar, Christina; Hund, Thomas J.; Pitt, Geoffrey S.; Mohler, Peter J.

    2015-01-01

    Nav channels are essential for metazoan membrane depolarization, and Nav channel dysfunction is directly linked with epilepsy, ataxia, pain, arrhythmia, myotonia, and irritable bowel syndrome. Human Nav channelopathies are primarily caused by variants that directly affect Nav channel permeability or gating. However, a new class of human Nav channelopathies has emerged based on channel variants that alter regulation by intracellular signaling or cytoskeletal proteins. Fibroblast growth factor homologous factors (FHFs) are a family of intracellular signaling proteins linked with Nav channel regulation in neurons and myocytes. However, to date, there is surprisingly little evidence linking Nav channel gene variants with FHFs and human disease. Here, we provide, to our knowledge, the first evidence that mutations in SCN5A (encodes primary cardiac Nav channel Nav1.5) that alter FHF binding result in human cardiovascular disease. We describe a five*generation kindred with a history of atrial and ventricular arrhythmias, cardiac arrest, and sudden cardiac death. Affected family members harbor a novel SCN5A variant resulting in p.H1849R. p.H1849R is localized in the central binding core on Nav1.5 for FHFs. Consistent with these data, Nav1.5 p.H1849R affected interaction with FHFs. Further, electrophysiological analysis identified Nav1.5 p.H1849R as a gain-of-function for INa by altering steady-state inactivation and slowing the rate of Nav1.5 inactivation. In line with these data and consistent with human cardiac phenotypes, myocytes expressing Nav1.5 p.H1849R displayed prolonged action potential duration and arrhythmogenic afterdepolarizations. Together, these findings identify a previously unexplored mechanism for human Nav channelopathy based on altered Nav1.5 association with FHF proteins. PMID:26392562

  9. Is pesticide exposure a cause of obstructive airways disease?

    Directory of Open Access Journals (Sweden)

    Emma Doust

    2014-06-01

    Full Text Available A systematic review was performed to identify any associations between pesticide exposure and the occurrence (both prevalence and incidence of airways disease (asthma and chronic obstructive pulmonary disease and wheezing symptoms. PubMed, MEDLINE, Embase, Scopus, CINAHL, Google Scholar and the Cochrane Database of Systematic Reviews were searched between September 2010 and October 2010 for papers with the inclusion criteria of English language, published after 1990, peer-reviewed and nondietary exposure. From a total of 4390 papers identified, 42 were included after initial assessment of content. After evaluating the included studies for quality, those considered to be at high risk of bias were excluded, leaving a total of 23 relevant papers. Results suggest that exposure to pesticides may be associated with prevalent asthma, but methodological issues, such as cross-sectional/case–control design, measurements of exposure and limited adjustment for confounders, limit the strength of the evidence base in this area. The association between pesticide exposure and asthma appears to be more evident and consistent in children than in adults. Exposure to pesticides may be associated with COPD; however, the strength of evidence for an association with COPD is weaker than for asthma. As the exposure metrics within each health end-point varied across studies, no meta-analyses were carried out.

  10. Adnexal masses caused by pelvic inflammatory disease. MR appearance

    Energy Technology Data Exchange (ETDEWEB)

    Ueda, Hiroyuki; Togashi, Kaori; Kataoka, Milliam L.; Koyama, Takashi; Fujiwara, Toshitaka; Konishi, Junji [Hitachi Medical Corp., Tokyo (Japan); Fujii, Shingo [Kyoto Univ. (Japan). Graduate School of Medicine

    2002-12-01

    The purpose of this study was to describe the morphologic and signal intensity characteristics of inflammatory adnexal masses in magnetic resonance (MR) images. MR images of 15 patients with a total of 20 confirmed inflammatory adnexal masses were analyzed retrospectively. The findings obtained from MR imaging were as follows: lesions have ill-defined borders; ill-defined areas of high intensity signals surround the masses on T{sub 2}-weighted images; a ''rim'' at the innermost layer of the cyst wall exhibits high signal intensity on T{sub 1}-weighted images and low intensity on T{sub 2}-weighted images; secondary changes in the surrounding fat plane and bowel loops are extensive; and adhesions are dense. These findings reflect the basic characteristics of the inflammatory process, which are edema caused by increased permeability and highly vascularized granulation tissue caused by the strong tendency to repair. MR imaging findings well reflect the basic pathological process of inflammation, and inflammatory adnexal masses are associated with relatively specific appearances in MR images. MR imaging can be a problem-solving alternative in the diagnosis of inflammatory adnexal masses. (author)

  11. Conditional Lineage Ablation to Model Human Diseases

    Science.gov (United States)

    Lee, Paul; Morley, Gregory; Huang, Qian; Fischer, Avi; Seiler, Stephanie; Horner, James W.; Factor, Stephen; Vaidya, Dhananjay; Jalife, Jose; Fishman, Glenn I.

    1998-09-01

    Cell loss contributes to the pathogenesis of many inherited and acquired human diseases. We have developed a system to conditionally ablate cells of any lineage and developmental stage in the mouse by regulated expression of the diphtheria toxin A (DTA) gene by using tetracycline-responsive promoters. As an example of this approach, we targeted expression of DTA to the hearts of adult mice to model structural abnormalities commonly observed in human cardiomyopathies. Induction of DTA expression resulted in cell loss, fibrosis, and chamber dilatation. As in many human cardiomyopathies, transgenic mice developed spontaneous arrhythmias in vivo, and programmed electrical stimulation of isolated-perfused transgenic hearts demonstrated a strikingly high incidence of spontaneous and inducible ventricular tachycardia. Affected mice showed marked perturbations of cardiac gap junction channel expression and localization, including a subset with disorganized epicardial activation patterns as revealed by optical action potential mapping. These studies provide important insights into mechanisms of arrhythmogenesis and suggest that conditional lineage ablation may have wide applicability for studies of disease pathogenesis.

  12. Integration of Lightning- and Human-Caused Wildfire Occurrence Models

    DEFF Research Database (Denmark)

    Vilar, Lara; Nieto Solana, Hector; Martín, M. Pilar

    2010-01-01

    Fire risk indices are useful tools for fire prevention actions by fire managers. A fire ignition is either the result of lightning or human activities. In European Mediterranean countries most forest fires are due to human activities. However, lightning is still an important fire ignition source ...

  13. Bud Rot Caused by Phytophthora palmivora: A Destructive Emerging Disease of Oil Palm.

    Science.gov (United States)

    Torres, G A; Sarria, G A; Martinez, G; Varon, F; Drenth, A; Guest, D I

    2016-04-01

    Oomycetes from the genus Phytophthora are among the most important plant pathogens in agriculture. Epidemics caused by P. infestans precipitated the great Irish famine and had a major impact on society and human history. In the tropics, P. palmivora is a pathogen of many plant species including cacao (Theobroma cacao), citrus (Citrus sp.), durian (Durio zibethines), jackfruit (Artrocarpus heterophyllus), rubber (Hevea brasiliensis), and several palm species including coconut (Cocos nucifera), and the African oil palm (Elaeis guineensis) as determined recently. The first localized epidemics of bud rot in oil palm in Colombia were reported in 1964. However, recent epidemics of bud rot have destroyed more than 70,000 ha of oil palm in the Western and Central oil palm growing regions of Colombia. The agricultural, social, and economic implications of these outbreaks have been significant in Colombia. Identification of the pathogen after 100 years of investigating the disease in the world enabled further understanding of infection, expression of a range of symptoms, and epidemiology of the disease. This review examines the identification of P. palmivora as the cause of bud rot in Colombia, its epidemiology, and discusses the importance of P. palmivora as a major threat to oil palm plantings globally.

  14. Alcohol binging causes peliosis hepatis during azathioprine therapy in Crohn's disease

    Institute of Scientific and Technical Information of China (English)

    Christoph Elsing; Joerg Placke; Thomas Herrmann

    2007-01-01

    Patients with inflammatory bowel disease have normal life expectancy and, due to modern immunosuppressive therapies, also a normal quality of life. Since mostly young people are affected, their social behaviour suits this environment. Alcohol binging is an increasingly disturbing factor among young people. We describe a patient with Crohn's disease, treated with azathioprine,who developed peliosis hepatis after three epsiodes of alcohol binging. Liver toxicity was not observed previously during the course of the treatment.Azathioprine-induced peliosis hepatis is thought to be idiosyncratic in humans. From animal studies, however,it is clear that hepatic depletion of glutathione leads to azathioprine toxicity to the sinusoidal endothelial cells. Damage of these cells causes peliosis hepatis.Since alcohol binging leads to hepatic glutathione depletion, we conclude that in our patient the episodes of binging have reduced liver gluathione content and therefore this has increased azathioprine toxicity causing peliosis hepatis. The problem of alcohol binging has not yet been addressed in IBD patients undertaking immunosuppressive therapy. This should be reviewed in future considerations regarding patients advice.

  15. Mitochondrial diseases caused by toxic compound accumulation: from etiopathology to therapeutic approaches.

    Science.gov (United States)

    Di Meo, Ivano; Lamperti, Costanza; Tiranti, Valeria

    2015-10-01

    Mitochondrial disorders are a group of highly invalidating human conditions for which effective treatment is currently unavailable and characterized by faulty energy supply due to defective oxidative phosphorylation (OXPHOS). Given the complexity of mitochondrial genetics and biochemistry, mitochondrial inherited diseases may present with a vast range of symptoms, organ involvement, severity, age of onset, and outcome. Despite the wide spectrum of clinical signs and biochemical underpinnings of this group of dis-orders, some common traits can be identified, based on both pathogenic mechanisms and potential therapeutic approaches. Here, we will review two peculiar mitochondrial disorders, ethylmalonic encephalopathy (EE) and mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), caused by mutations in the ETHE1 and TYMP nuclear genes, respectively. ETHE1 encodes for a mitochondrial enzyme involved in sulfide detoxification and TYMP for a cytosolic enzyme involved in the thymidine/deoxyuridine catabolic pathway. We will discuss these two clinical entities as a paradigm of mitochondrial diseases caused by the accumulation of compounds normally present in traces, which exerts a toxic and inhibitory effect on the OXPHOS system. © 2015 The Authors. Published under the terms of the CC BY 4.0 license.

  16. Integration of Lightning- and Human-Caused Wildfire Occurrence Models

    DEFF Research Database (Denmark)

    Vilar, Lara; Nieto Solana, Hector; Martín, M. Pilar

    2010-01-01

    Fire risk indices are useful tools for fire prevention actions by fire managers. A fire ignition is either the result of lightning or human activities. In European Mediterranean countries most forest fires are due to human activities. However, lightning is still an important fire ignition source...... in some regions. Integration of lightning and human fire occurrence probability into fire risk indices would be necessary to have a complete picture of the causal agents and their relative importance in fire occurrence. We present two methods for the integration of lightning and human fire occurrence...... probability models at 1 × 1 km grid cell resolution in two regions of Spain: Madrid, which presents a high fire incidence due to human activities; and Aragón, one of the most affected regions in Spain by lightning-fires. For validation, independent fire ignition points were used to compute the Receiver...

  17. Fatal Case of Polymicrobial Meningitis Caused by Cryptococcus liquefaciens and Mycobacterium tuberculosis Complex in a Human Immunodeficiency Virus-Infected Patient.

    Science.gov (United States)

    Conde-Pereira, César; Rodas-Rodríguez, Lia; Díaz-Paz, Manuel; Palacios-Rivera, Hilda; Firacative, Carolina; Meyer, Wieland; Alcázar-Castillo, Myriam

    2015-08-01

    We describe a fatal case of polymicrobial meningitis in a human immunodeficiency virus-infected patient from Guatemala caused by Cryptococcus liquefaciens and Mycobacterium tuberculosis complex. Central nervous system infections caused concurrently by these species are extremely rare. This is also the first report of disseminated disease caused by C. liquefaciens.

  18. A murine herpesvirus closely related to ubiquitous human herpesviruses causes T-cell depletion.

    Science.gov (United States)

    Patel, Swapneel J; Zhao, Guoyan; Penna, Vinay R; Park, Eugene; Lauron, Elvin J; Harvey, Ian B; Beatty, Wandy L; Plougastel-Douglas, Beatrice; Poursine-Laurent, Jennifer; Fremont, Daved H; Wang, David; Yokoyama, Wayne M

    2017-02-08

    Mouse models of human herpesvirus infections The human roseoloviruses HHV6A, HHV6B, and HHV7 comprise the Roseolovirus genus of the human Betaherpesvirinae subfamily. Infections with these viruses have been implicated in many diseases; however, it has been challenging to establish infections with Roseoloviruses as direct drivers of pathology because they are nearly ubiquitous and display species-specific tropism. Furthermore, controlled study of infection has been hampered by the lack of experimental models, and until now, a mouse roseolovirus has not been identified. Herein we describe a virus that causes severe thymic necrosis in neonatal mice, characterized by a loss of CD4(+) T-cells. These phenotypes resemble those caused by the previously described mouse thymic virus (MTV), a putative herpesvirus that has not been molecularly characterized. By Next Generation sequencing of infected tissue homogenates, we assembled a contiguous 174Kb genome sequence encoding 128 unique predicted open reading frames (ORFs), many of which were most closely related to herpesvirus genes. Moreover, the structure of the virus genome and phylogenetic analysis of multiple genes strongly suggested that this virus is a betaherpesvirus more closely related to the roseoloviruses, HHV6A, HHV6B, and HHV7, than another murine betaherpesvirus, mouse cytomegalovirus (MCMV). As such, we have named this virus murine roseolovirus (MRV) because these data strongly suggest that MRV is a mouse homolog of HHV6A/HHV6B/HHV7.Importance: Herein we describe the complete genome sequence of a novel murine herpesvirus. By sequence and phylogenetic analyses, we show that it is a betaherpesvirus most closely related to the roseoloviruses, human herpesvirus 6A, 6B, and 7. These data combined with physiological similarities with human roseoloviruses collectively suggest that this virus is a murine roseolovirus (MRV), the first definitively described rodent roseolovirus, to our knowledge. Many biological and

  19. Detection of Secondary Causes and Coexisting Diseases in Hypertensive Patients: OSA and PA Are the Common Causes Associated with Hypertension

    Directory of Open Access Journals (Sweden)

    Lei Wang

    2017-01-01

    Full Text Available Background. Since the control rate of blood pressure is lower in mainland China, the aim of this study is to investigate the proportion of secondary causes and coexisting diseases of hypertension in hypertensive patients. Methods. Data on consecutive patients with hypertension who visited the Hypertension Center. Diseases were detected using an established strict screening protocol. Results. Detection rate of secondary causes and coexisting diseases of hypertension was 39.5% among 3003 hypertensive patients. Obstructive sleep apnea (OSA was the most common, accounting for 24.7% of patients, followed by primary aldosteronism (PA (5.8% and PA + OSA (4.9%. Endocrine hypertension accounted for 12.1% of patients, including 10.7% of patients with PA, 1.1% with hypothyroidism, 0.1% with pheochromocytoma, 0.1% with Cushing’s syndrome, and 0.1% with hyperthyroidism, respectively. Those who smoke, those who are obese, and those who have diabetes accounted for 31.3%, 27.5%, and 16.6% of total patients, respectively. There were overlapping conditions in secondary causes and coexisting diseases of hypertension. OSA was the most common in each age- and BMI-stratified group. Conclusion. Findings from the current study suggest an increasing frequency of secondary forms of hypertension, highlighting the burden of OSA and PA in hypertensive patients.

  20. Mitochondrial dysfunction in psychiatric and neurological diseases: cause(s), consequence(s), and implications of antioxidant therapy.

    Science.gov (United States)

    Kasote, Deepak M; Hegde, Mahabaleshwar V; Katyare, Surendra S

    2013-01-01

    Mitochondrial dysfunction is at the base of development and progression of several psychiatric and neurologic diseases with different etiologies. MtDNA/nDNA mutational damage, failure of endogenous antioxidant defenses, hormonal malfunction, altered membrane permeability, metabolic dysregulation, disruption of calcium buffering capacity and ageing have been found to be the root causes of mitochondrial dysfunction in psychatric and neurodegenerative diseases. However, the overall consequences of mitochondrial dysfunction are only limited to increase in oxidative/nitrosative stress and cellular energy crises. Thus far, extensive efforts have been made to improve mitochondrial function through specific cause-dependent antioxidant therapy. However, owing to complex genetic and interlinked causes of mitochondrial dysfunction, it has not been possible to achieve any common, unique supportive antioxidant therapeutic strategy for the treatment of psychiatric and neurologic diseases. Hence, we propose an antioxidant therapeutic strategy for management of consequences of mitochondrial dysfunction in psychiatric and neurologic diseases. It is expected that this will not only reduces oxidative stress, but also promote anaerobic energy production.

  1. Mapping global potential risk of mango sudden decline disease caused by fungus Ceratocystis fimbriata

    Science.gov (United States)

    Mango Sudden Decline (MSD), sometimes referred to as mango wilt, is an important disease of mango caused by one of the most significant fungal species causing disease in woody plants, Ceratocystis fimbriata. This species is mainly disseminated by the mango bark beetle, Hypocryphalus mangiferae (Steb...

  2. ARTERIAL STIFFNESS AND CHRONIC KIDNEY DISEASE: CAUSES AND CONSEQUENCES

    Directory of Open Access Journals (Sweden)

    J. D. Kobalava

    2015-09-01

    Full Text Available Chronic kidney disease (CKD is associated with increased cardiovascular risk. CKD is characterized by accelerated aging of vessels in which the age-related arterial stiffness increase is exacerbated by a number of uremia-related processes. Increased arterial stiffness is associated with structural and functional disorders, as well as with the increase in cardiovascular mortality in patients with CKD. Increased arterial stiffness is diagnosed at an early stage of CKD. Modern understanding of the mechanisms of increased risk of cardiovascular complications in CKD, the factors contributing to the loss of elasticity of the arteries, arterial stiffness increase consequences are analyzed. Data illustrating the twoway interaction between CKD and arterial stiffness and mechanisms of accelerated progression of arterial stiffness in CKD are presented.

  3. Mitochondrial Disease as a Cause of Neonatal Hemophagocytic Lymphohistiocytosis

    Directory of Open Access Journals (Sweden)

    Kazumasa Fuwa

    2016-01-01

    Full Text Available Diagnosis of mitochondrial respiratory chain disorder (MRCD is often difficult. Its pathogenesis is still unclear. We diagnosed MRCD by measuring the activity of the mitochondrial respiratory chain enzyme, and the patient also had hemophagocytic lymphohistiocytosis (HLH. A preterm female infant was born at 34 weeks of gestation. On day 6, HLH was revealed by bone marrow aspiration. She died on day 10 due to uncontrollable HLH. An autopsy was performed, and we measured the activity of the mitochondrial respiratory chain enzyme in the liver, muscle, and heart. The activity of complex I was decreased in all tissues. As we could not prove another origin of the HLH, she was diagnosed as having HLH caused by MRCD. It is useful to measure the activity of the mitochondrial respiratory chain enzyme for diagnosing MRCD. MRCD, which has a severe clinical course, may be related to HLH.

  4. Immunoregulatory networks in human Chagas disease

    Science.gov (United States)

    Dutra, Walderez O.; Menezes, Cristiane A.S.; Magalhães, Luisa M. D.; Gollob, Kenneth J.

    2014-01-01

    Summary Chagas disease, caused by the infection with Trypanosoma cruzi, is endemic in all Latin America. Due to the increase in population migration, Chagas disease has spread worldwide and is now considered a health issue not only in endemic countries. While most chronically infected individuals remain asymptomatic, approximately 30% of the patients develop a potentially deadly cardiomyopathy. The exact mechanisms that underlie the establishment and maintenance of the cardiac pathology are not clear. However, there is consistent evidence that immunoregulatory cytokines are critical for orchestrating the immune response and, thus, influence disease development or control. While the asymptomatic (indeterminate) form represents a state of balance between the host and the parasite, the establishment of the cardiac form represents the loss of this balance. Analysis of data obtained from several studies have led to the hypothesis that the indeterminate form is associated with an anti-inflammatory cytokine profile, represented by high expression of IL-10, while cardiac form is associated with a high production of IFN-gamma and TNF-alpha in relation to IL-10, leading to an inflammatory profile. Here, we discuss the immunoregulatory events that might influence disease outcome, as well as the mechanisms that influence the establishment of these complex immunoregulatory networks. PMID:24611805

  5. Uniparental disomy and human disease: an overview.

    Science.gov (United States)

    Yamazawa, Kazuki; Ogata, Tsutomu; Ferguson-Smith, Anne C

    2010-08-15

    Uniparental disomy (UPD) refers to the situation in which both homologues of a chromosomal region/segment have originated from only one parent. This can involve the entire chromosome or only a small segment. As a consequence of UPD, or uniparental duplication/deficiency of part of a chromosome, there are two types of developmental risk: aberrant dosage of genes regulated by genomic imprinting and homozygosity of a recessive mutation. UPD models generated by reciprocal and Robertsonian translocation heterozygote intercrosses have been a powerful tool to investigate genomic imprinting in mice, whereas novel UPD patients such as those with cystic fibrosis and Prader-Willi syndrome, triggered the clarification of recessive diseases and genomic imprinting disorders in human. Newly developed genomic technologies as well as conventional microsatellite marker methods have been contributing to the functional and mechanistic investigation of UPD, leading to not only the acquisition of clinically valuable information, but also the further clarification of diverse genetic processes and disease pathogenesis.

  6. Evaluating the Contribution of the Cause of Kidney Disease to Prognosis in CKD

    DEFF Research Database (Denmark)

    Haynes, Richard; Staplin, Natalie; Emberson, Jonathan

    2014-01-01

    BACKGROUND: The relevance of the cause of kidney disease to prognosis among patients with chronic kidney disease is uncertain. STUDY DESIGN: Observational study. SETTINGS & PARTICIPANTS: 6,245 nondialysis participants in the Study of Heart and Renal Protection (SHARP). PREDICTOR: Baseline cause......, whose adjusted risk of death was 2-fold higher than that of the cystic kidney disease group (relative risk, 2.35 [95% CI, 1.73-3.18]). LIMITATIONS: Exclusion of patients with prior myocardial infarction or coronary revascularization. CONCLUSIONS: The cause of kidney disease has substantial prognostic...

  7. 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.

  8. The Microbiota, Chemical Symbiosis, and Human Disease

    Science.gov (United States)

    Redinbo, Matthew R.

    2014-01-01

    Our understanding of mammalian-microbial mutualism has expanded by combing microbial sequencing with evolving molecular and cellular methods, and unique model systems. Here, the recent literature linking the microbiota to diseases of three of the key mammalian mucosal epithelial compartments – nasal, lung and gastrointestinal (GI) tract – is reviewed with a focus on new knowledge about the taxa, species, proteins and chemistry that promote health and impact progression toward disease. The information presented is further organized by specific diseases now associated with the microbiota:, Staphylococcus aureus infection and rhinosinusitis in the nasal-sinus mucosa; cystic fibrosis (CF), chronic obstructive pulmonary disorder (COPD), and asthma in the pulmonary tissues. For the vast and microbially dynamic GI compartment, several disorders are considered, including obesity, atherosclerosis, Crohn’s disease, ulcerative colitis, drug toxicity, and even autism. Our appreciation of the chemical symbiosis ongoing between human systems and the microbiota continues to grow, and suggest new opportunities for modulating this symbiosis using designed interventions. PMID:25305474

  9. IGF1 as predictor of all cause mortality and cardiovascular disease in an elderly population

    DEFF Research Database (Denmark)

    Andreassen, Mikkel; Raymond, Ilan; Kistorp, Caroline;

    2009-01-01

    BACKGROUND: IGF1 is believed to influence ageing and development of cardiovascular disease (CVD) through complex mechanisms. Reduced IGF1 levels might be causally associated with conditions accompanying ageing including development of CVD. However, in animal models reduced GH-IGF1 signalling...... increases lifespan. Reduced IGF1 activity might also be associated with longevity in humans. OBJECTIVE: The objective was to investigate if plasma IGF1 levels were associated with all cause mortality, and the development of chronic heart failure (CHF) and a major CV event. PATIENTS AND DESIGN: A population...... systolic function and without prevalent CVD. Outcomes were ascertained after 5 years using hospital discharge diagnoses. RESULTS: Adjustment for risk factors IGF1 values in the fourth quartile versus values below the fourth quartile was associated with increased mortality (n=103), hazard ratio (HR) 1...

  10. Kcne2 deletion causes early-onset nonalcoholic fatty liver disease via iron deficiency anemia

    Science.gov (United States)

    Lee, Soo Min; Nguyen, Dara; Anand, Marie; Kant, Ritu; Köhncke, Clemens; Lisewski, Ulrike; Roepke, Torsten K.; Hu, Zhaoyang; Abbott, Geoffrey W.

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is an increasing health problem worldwide, with genetic, epigenetic, and environmental components. Here, we describe the first example of NAFLD caused by genetic disruption of a mammalian potassium channel subunit. Mice with germline deletion of the KCNE2 potassium channel β subunit exhibited NAFLD as early as postnatal day 7. Using mouse genetics, histology, liver damage assays and transcriptomics we discovered that iron deficiency arising from KCNE2-dependent achlorhydria is a major factor in early-onset NAFLD in Kcne2─/─ mice, while two other KCNE2-dependent defects did not initiate NAFLD. The findings uncover a novel genetic basis for NAFLD and an unexpected potential factor in human KCNE2-associated cardiovascular pathologies, including atherosclerosis. PMID:26984260

  11. Tailor-made RNAi knockdown against triplet repeat disease-causing alleles.

    Science.gov (United States)

    Takahashi, Masaki; Watanabe, Shoko; Murata, Miho; Furuya, Hirokazu; Kanazawa, Ichiro; Wada, Keiji; Hohjoh, Hirohiko

    2010-12-14

    Nucleotide variations, including SNPs, in the coding regions of disease genes are important targets for RNAi treatment, which is a promising medical treatment for intractable diseases such as triplet repeat diseases. However, the identification of such nucleotide variations and the design of siRNAs conferring disease allele-specific RNAi are quite difficult. In this study we developed a pull-down method to rapidly identify coding SNP (cSNP) haplotypes of triple repeat, disease-causing alleles, and we demonstrated disease allele-specific RNAi that targeted cSNP sites in mutant Huntingtin alleles, each of which possessed a different cSNP haplotype. Therefore, the methods presented here allow for allele-specific RNAi knockdown against disease-causing alleles by using siRNAs specific to disease-linked cSNP haplotypes, and advanced progress toward tailor-made RNAi treatments for triplet repeat diseases.

  12. 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

    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.......e. Leber hereditary optic neuropathy and dominant optic atrophy. The mechanism leading to mRGCs sparing in these blinding disorders, characterized by extensive and selective loss of RGCs, is currently unknown and under investigation. Other studies reported on mRGCs in glaucoma, on genetic variation...

  13. [Alteration of biological rhythms causes metabolic diseases and obesity].

    Science.gov (United States)

    Saderi, Nadia; Escobar, Carolina; Salgado-Delgado, Roberto

    2013-07-16

    The incidence of obesity worldwide has become a serious, constantly growing public health issue that reaches alarming proportions in some countries. To date none of the strategies developed to combat obesity have proved to be decisive, and hence there is an urgent need to address the problem with new approaches. Today, studies in the field of chronobiology have shown that our physiology continually adapts itself to the cyclical changes in the environment, regard-less of whether they are daily or seasonal. This is possible thanks to the existence of a biological clock in our hypothalamus which regulates the expression and/or activity of enzymes and hormones involved in regulating our metabolism, as well as all the homeostatic functions. It has been observed that this clock can be upset as a result of today's modern lifestyle, which involves a drop in physical activity during the day and the abundant ingestion of food during the night, among other factors, which together promote metabolic syndrome and obesity. Hence, the aim of this review is to summarise the recent findings that show the effect that altering the circadian rhythms has on the metabolism and how this can play a part in the development of metabolic diseases.

  14. Indoxyl sulphate and kidney disease: Causes, consequences and interventions.

    Science.gov (United States)

    Ellis, Robert J; Small, David M; Vesey, David A; Johnson, David W; Francis, Ross; Vitetta, Luis; Gobe, Glenda C; Morais, Christudas

    2016-03-01

    In the last decade, chronic kidney disease (CKD), defined as reduced renal function (glomerular filtration rate (GFR) kidney damage (typically manifested as albuminuria) for at least 3 months, has become one of the fastest-growing public health concerns worldwide. CKD is characterized by reduced clearance and increased serum accumulation of metabolic waste products (uremic retention solutes). At least 152 uremic retention solutes have been reported. This review focuses on indoxyl sulphate (IS), a protein-bound, tryptophan-derived metabolite that is generated by intestinal micro-organisms (microbiota). Animal studies have demonstrated an association between IS accumulation and increased fibrosis, and oxidative stress. This has been mirrored by in vitro studies, many of which report cytotoxic effects in kidney proximal tubular cells following IS exposure. Clinical studies have associated IS accumulation with deleterious effects, such as kidney functional decline and adverse cardiovascular events, although causality has not been conclusively established. The aims of this review are to: (i) establish factors associated with increased serum accumulation of IS; (ii) report effects of IS accumulation in clinical studies; (iii) critique the reported effects of IS in the kidney, when administered both in vivo and in vitro; and (iv) summarize both established and hypothetical therapeutic options for reducing serum IS or antagonizing its reported downstream effects in the kidney.

  15. Saffold virus, a human Theiler's-like cardiovirus, is ubiquitous and causes infection early in life.

    Directory of Open Access Journals (Sweden)

    Jan Zoll

    2009-05-01

    Full Text Available The family Picornaviridae contains well-known human pathogens (e.g., poliovirus, coxsackievirus, rhinovirus, and parechovirus. In addition, this family contains a number of viruses that infect animals, including members of the genus Cardiovirus such as Encephalomyocarditis virus (EMCV and Theiler's murine encephalomyelits virus (TMEV. The latter are important murine pathogens that cause myocarditis, type 1 diabetes and chronic inflammation in the brains, mimicking multiple sclerosis. Recently, a new picornavirus was isolated from humans, named Saffold virus (SAFV. The virus is genetically related to Theiler's virus and classified as a new species in the genus Cardiovirus, which until the discovery of SAFV did not contain human viruses. By analogy with the rodent cardioviruses, SAFV may be a relevant new human pathogen. Thus far, SAFVs have sporadically been detected by molecular techniques in respiratory and fecal specimens, but the epidemiology and clinical significance remained unclear. Here we describe the first cultivated SAFV type 3 (SAFV-3 isolate, its growth characteristics, full-length sequence, and epidemiology. Unlike the previously isolated SAFV-1 and -2 viruses, SAFV-3 showed efficient growth in several cell lines with a clear cytopathic effect. The latter allowed us to conduct a large-scale serological survey by a virus-neutralization assay. This survey showed that infection by SAFV-3 occurs early in life (>75% positive at 24 months and that the seroprevalence reaches >90% in older children and adults. Neutralizing antibodies were found in serum samples collected in several countries in Europe, Africa, and Asia. In conclusion, this study describes the first cultivated SAFV-3 isolate, its full-length sequence, and epidemiology. SAFV-3 is a highly common and widespread human virus causing infection in early childhood. This finding has important implications for understanding the impact of these ubiquitous viruses and their possible

  16. Saffold virus, a human Theiler's-like cardiovirus, is ubiquitous and causes infection early in life.

    Science.gov (United States)

    Zoll, Jan; Erkens Hulshof, Sandra; Lanke, Kjerstin; Verduyn Lunel, Frans; Melchers, Willem J G; Schoondermark-van de Ven, Esther; Roivainen, Merja; Galama, Jochem M D; van Kuppeveld, Frank J M

    2009-05-01

    The family Picornaviridae contains well-known human pathogens (e.g., poliovirus, coxsackievirus, rhinovirus, and parechovirus). In addition, this family contains a number of viruses that infect animals, including members of the genus Cardiovirus such as Encephalomyocarditis virus (EMCV) and Theiler's murine encephalomyelits virus (TMEV). The latter are important murine pathogens that cause myocarditis, type 1 diabetes and chronic inflammation in the brains, mimicking multiple sclerosis. Recently, a new picornavirus was isolated from humans, named Saffold virus (SAFV). The virus is genetically related to Theiler's virus and classified as a new species in the genus Cardiovirus, which until the discovery of SAFV did not contain human viruses. By analogy with the rodent cardioviruses, SAFV may be a relevant new human pathogen. Thus far, SAFVs have sporadically been detected by molecular techniques in respiratory and fecal specimens, but the epidemiology and clinical significance remained unclear. Here we describe the first cultivated SAFV type 3 (SAFV-3) isolate, its growth characteristics, full-length sequence, and epidemiology. Unlike the previously isolated SAFV-1 and -2 viruses, SAFV-3 showed efficient growth in several cell lines with a clear cytopathic effect. The latter allowed us to conduct a large-scale serological survey by a virus-neutralization assay. This survey showed that infection by SAFV-3 occurs early in life (>75% positive at 24 months) and that the seroprevalence reaches >90% in older children and adults. Neutralizing antibodies were found in serum samples collected in several countries in Europe, Africa, and Asia. In conclusion, this study describes the first cultivated SAFV-3 isolate, its full-length sequence, and epidemiology. SAFV-3 is a highly common and widespread human virus causing infection in early childhood. This finding has important implications for understanding the impact of these ubiquitous viruses and their possible role in acute

  17. Saffold virus, a human Theiler's-like cardiovirus, is ubiquitous and causes infection early in life.

    Directory of Open Access Journals (Sweden)

    Jan Zoll

    2009-05-01

    Full Text Available The family Picornaviridae contains well-known human pathogens (e.g., poliovirus, coxsackievirus, rhinovirus, and parechovirus. In addition, this family contains a number of viruses that infect animals, including members of the genus Cardiovirus such as Encephalomyocarditis virus (EMCV and Theiler's murine encephalomyelits virus (TMEV. The latter are important murine pathogens that cause myocarditis, type 1 diabetes and chronic inflammation in the brains, mimicking multiple sclerosis. Recently, a new picornavirus was isolated from humans, named Saffold virus (SAFV. The virus is genetically related to Theiler's virus and classified as a new species in the genus Cardiovirus, which until the discovery of SAFV did not contain human viruses. By analogy with the rodent cardioviruses, SAFV may be a relevant new human pathogen. Thus far, SAFVs have sporadically been detected by molecular techniques in respiratory and fecal specimens, but the epidemiology and clinical significance remained unclear. Here we describe the first cultivated SAFV type 3 (SAFV-3 isolate, its growth characteristics, full-length sequence, and epidemiology. Unlike the previously isolated SAFV-1 and -2 viruses, SAFV-3 showed efficient growth in several cell lines with a clear cytopathic effect. The latter allowed us to conduct a large-scale serological survey by a virus-neutralization assay. This survey showed that infection by SAFV-3 occurs early in life (>75% positive at 24 months and that the seroprevalence reaches >90% in older children and adults. Neutralizing antibodies were found in serum samples collected in several countries in Europe, Africa, and Asia. In conclusion, this study describes the first cultivated SAFV-3 isolate, its full-length sequence, and epidemiology. SAFV-3 is a highly common and widespread human virus causing infection in early childhood. This finding has important implications for understanding the impact of these ubiquitous viruses and their possible

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

    Directory of Open Access Journals (Sweden)

    Bo Peng

    2007-03-01

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

  19. Beyond the zebrafish: diverse fish species for modeling human disease

    Directory of Open Access Journals (Sweden)

    Manfred Schartl

    2014-02-01

    Full Text Available In recent years, zebrafish, and to a lesser extent medaka, have become widely used small animal models for human diseases. These organisms have convincingly demonstrated the usefulness of fish for improving our understanding of the molecular and cellular mechanisms leading to pathological conditions, and for the development of new diagnostic and therapeutic tools. Despite the usefulness of zebrafish and medaka in the investigation of a wide spectrum of traits, there is evidence to suggest that other fish species could be better suited for more targeted questions. With the emergence of new, improved sequencing technologies that enable genomic resources to be generated with increasing efficiency and speed, the potential of non-mainstream fish species as disease models can now be explored. A key feature of these fish species is that the pathological condition that they model is often related to specific evolutionary adaptations. By exploring these adaptations, new disease-causing and disease-modifier genes might be identified; thus, diverse fish species could be exploited to better understand the complexity of disease processes. In addition, non-mainstream fish models could allow us to study the impact of environmental factors, as well as genetic variation, on complex disease phenotypes. This Review will discuss the opportunities that such fish models offer for current and future biomedical research.

  20. Acute myeloid leukaemia as a cause of acute ischaemic heart disease

    NARCIS (Netherlands)

    van Haelst, P.L.; Schot, Bart; Hoendermis, E.S.; van den Berg, M.P.

    2006-01-01

    Ischaemic heart disease is almost invariably the result of atherosclerotic degeneration of the coronary arteries. However, other causes of ischaemic heart disease should always be considered. Here we describe two patients with a classic presentation of ischaemic heart disease resulting from acute le

  1. Acute myeloid leukaemia as a cause of acute ischaemic heart disease

    NARCIS (Netherlands)

    van Haelst, P.L.; Schot, Bart; Hoendermis, E.S.; van den Berg, M.P.

    2006-01-01

    Ischaemic heart disease is almost invariably the result of atherosclerotic degeneration of the coronary arteries. However, other causes of ischaemic heart disease should always be considered. Here we describe two patients with a classic presentation of ischaemic heart disease resulting from acute

  2. Acute myeloid leukaemia as a cause of acute ischaemic heart disease

    NARCIS (Netherlands)

    van Haelst, P.L.; Schot, Bart; Hoendermis, E.S.; van den Berg, M.P.

    2006-01-01

    Ischaemic heart disease is almost invariably the result of atherosclerotic degeneration of the coronary arteries. However, other causes of ischaemic heart disease should always be considered. Here we describe two patients with a classic presentation of ischaemic heart disease resulting from acute le

  3. Disease course of lower respiratory tract infection with a bacterial cause

    NARCIS (Netherlands)

    Teepe, Jolien; Broekhuizen, Berna D L; Loens, Katherine; Lammens, Christine; Ieven, Margareta; Goossens, Herman; Little, Paul; Butler, Christopher C.; Coenen, Samuel; Godycki-Cwirko, Maciek; Verheij, Theo

    2016-01-01

    PURPOSE Bacterial pathogens are assumed to cause an illness course different from that of nonbacterial causes of acute cough, but evidence is lacking. We evaluated the disease course of lower respiratory tract infection (LRTI) with a bacterial cause in adults with acute cough. METHODS We conducted a

  4. Hand, foot, and mouth disease caused by coxsackievirus A6, Thailand, 2012.

    Science.gov (United States)

    Puenpa, Jiratchaya; Chieochansin, Thaweesak; Linsuwanon, Piyada; Korkong, Sumeth; Thongkomplew, Siwanat; Vichaiwattana, Preyaporn; Theamboonlers, Apiradee; Poovorawan, Yong

    2013-04-01

    In Thailand, hand, foot, and mouth disease (HFMD) is usually caused by enterovirus 71 or coxsackievirus A16. To determine the cause of a large outbreak of HFMD in Thailand during June-August 2012, we examined patient specimens. Coxsackievirus A6 was the causative agent. To improve prevention and control, causes of HFMD should be monitored.

  5. Bacterial agents as a cause of infertility in humans.

    Science.gov (United States)

    Ruggeri, Melania; Cannas, Sara; Cubeddu, Marina; Molicotti, Paola; Piras, Gennarina Laura; Dessole, Salvatore; Zanetti, Stefania

    2016-07-01

    Infertility is a problem affecting almost 15% of couples. There are many causes for this condition, among which urogenital bacterial infections seem to play an important role. Many studies have explained the mechanisms by which bacteria cause infertility both in men and women. Therefore we undertook this study to evaluate the presence of genito-urinary infections in infertile couples who sought counselling to investigate their condition. Microbiological analysis was performed on semen and vaginal/cervical samples of both partners of each couple. The percentage of individuals affected by a urogenital bacterial infection was between 14 and 20%. More significantly, most of the species isolated both in men and women have been described in the literature as potential causes of infertility.

  6. [Kimura's disease: an unrecognized cause of adult-onset nephrotic syndrome with minimal change disease].

    Science.gov (United States)

    Shehwaro, N; Langlois, A-L; Gueutin, V; Debchi, L; Charlotte, F; Rouvier, P; Rottembourg, J; Izzedine, H

    2014-02-01

    Kimura's disease (KD) is an angiolymphoid proliferative disorder of soft tissue with eosinophilia, with a predilection for head and neck regions in young Oriental men. Kidney disease is thought to be rare in KD. About a case of adult-onset nephrotic syndrome with minimal change disease, we comment Kimura's disease and its associated kidney damage. Kimura disease should be suspected and included in the diagnosis of adult-onset nephrotic syndrome with minimal change disease.

  7. Pulmonary Veno-Occlusive Disease: A Newly Recognized Cause of Severe Pulmonary Hypertension in Dogs.

    Science.gov (United States)

    Williams, K; Andrie, K; Cartoceti, A; French, S; Goldsmith, D; Jennings, S; Priestnall, S L; Wilson, D; Jutkowitz, A

    2016-07-01

    Pulmonary hypertension is a well-known though poorly characterized disease in veterinary medicine. In humans, pulmonary veno-occlusive disease (PVOD) is a rare cause of severe pulmonary hypertension with a mean survival time of 2 years without lung transplantation. Eleven adult dogs (5 males, 6 females; median age 10.5 years, representing various breeds) were examined following the development of severe respiratory signs. Lungs of affected animals were evaluated morphologically and with immunohistochemistry for alpha smooth muscle actin, desmin, CD31, CD3, CD20, and CD204. All dogs had pulmonary lesions consistent with PVOD, consisting of occlusive remodeling of small- to medium-sized pulmonary veins, foci of pulmonary capillary hemangiomatosis (PCH), and accumulation of hemosiderophages; 6 of 11 dogs had substantial pulmonary arterial medial and intimal thickening. Ultrastructural examination and immunohistochemistry showed that smooth muscle cells contributed to the venous occlusion. Increased expression of CD31 was evident in regions of PCH indicating increased numbers of endothelial cells in these foci. Spindle cells strongly expressing alpha smooth muscle actin and desmin co-localized with foci of PCH; similar cells were present but less intensely labeled elsewhere in non-PCH alveoli. B cells and macrophages, detected by immunohistochemistry, were not co-localized with the venous lesions of canine PVOD; small numbers of CD3-positive T cells were occasionally in and around the wall of remodeled veins. These findings indicate a condition in dogs with clinically severe respiratory disease and pathologic features resembling human PVOD, including foci of pulmonary venous remodeling and PCH.

  8. Subcutaneous dirofilariasis caused by (Nochtiella in Sri Lanka: A potential risk of transmitting human dirofilariasis

    Directory of Open Access Journals (Sweden)

    Nayana Gunathilaka

    2017-03-01

    Full Text Available Objective: Dirofilariasis is a parasitic infection caused by filarial nematodes belonging to the genus Dirofilaria . Human dirofilariasis due to Dirofilaria repens has been widely reported from European countries. Sri Lanka is the most affected country in Asia with an infection rate of almost 60% in dog population. However, human infection of D. repens remains undiagnosed and many of the cases are not scientifically documented. Therefore, the objective of the present investigation is to document the presence of dirofilariasis infections in humans. Method: A 1 year and 10 months old boy from Ragama, Gampaha District, Western Province of Sri Lanka, was presented to a private hospital with a painless, non-pruritic and ill-defined subcutaneous nodule on his right hypochondrial region of the anterior abdominal wall for 1 week. On examination, there was a non-tender swelling measuring 2 cm × 2 cm in the anterior abdominal wall, with surrounding mild redness. The patient was referred for ultrasound confirmation. Results: The ultrasound scan revealed a hypoechoic nodular lesion measuring 11 mm × 6 mm in the anterior abdominal wall. Parasitological examination on the excised nodule confirmed the presence of D. repens measuring 10.5 cm in length having characteristic cuticle with longitudinal ridges. Conclusion: It is essential to record the human infections and increase the awareness about this infection, diagnostic tests and vector controlling measures, in order to reduce the disease prevalence through suppressing vector densities, proper diagnosis and patient care.

  9. Megaselia scalaris causing human intestinal myiasis in Egypt.

    Science.gov (United States)

    Mazayad, Said A M; Rifaat, Manal M A

    2005-04-01

    Megaselia scalaris is a worldwide distributed insect of medical importance. In a laboratory-based study, stool samples with undefined maggot infestation were examined and the presence of M. scalaris maggots was confirmed. Binocular stereo-microscopy was used for identification of the maggots. Larvae were allowed to develop into adults onto a human stool culture. The larvae and the emerged flies were identified using standard keys. This may be the first report of M. scalaris as a causative agent of human myiasis in Egypt. Details of the third instar larva, pupa and adults were given.

  10. Bacteroides pyogenes causing serious human wound infection from animal bites.

    Science.gov (United States)

    Lau, Jillian S Y; Korman, Tony M; Yeung, Alex; Streitberg, Richard; Francis, Michelle J; Graham, Maryza

    2016-12-01

    Bacteroides pyogenes is part of the normal oral flora of domestic animals. There is one previous report of human infection, with B. pyogenes bacteremia following a cat bite (Madsen 2011). We report seven severe human infections where B. pyogenes was identified by Bruker matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDTI-TOF MS), but not by VITEK MS and was misidentified by VITEK ANC card. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

  11. Human rotavirus genotypes causing acute watery diarrhea among ...

    African Journals Online (AJOL)

    2014-06-17

    Jun 17, 2014 ... Nigerian Journal of Clinical Practice • Jan-Feb 2015 • Vol 18 • Issue 1. Abstract. Background: Diarrhea is a major cause of childhood morbidity and mortality in the .... Pennap et al. from Zaria, northern Nigeria, a case‑controlled.

  12. Blood type biochemistry and human disease.

    Science.gov (United States)

    Ewald, D Rose; Sumner, Susan C J

    2016-11-01

    Associations between blood type and disease have been studied since the early 1900s when researchers determined that antibodies and antigens are inherited. In the 1950s, the chemical identification of the carbohydrate structure of surface antigens led to the understanding of biosynthetic pathways. The blood type is defined by oligosaccharide structures, which are specific to the antigens, thus, blood group antigens are secondary gene products, while the primary gene products are various glycosyltransferase enzymes that attach the sugar molecules to the oligosaccharide chain. Blood group antigens are found on red blood cells, platelets, leukocytes, plasma proteins, certain tissues, and various cell surface enzymes, and also exist in soluble form in body secretions such as breast milk, seminal fluid, saliva, sweat, gastric secretions, urine, and amniotic fluid. Recent advances in technology, biochemistry, and genetics have clarified the functional classifications of human blood group antigens, the structure of the A, B, H, and Lewis determinants and the enzymes that produce them, and the association of blood group antigens with disease risks. Further research to identify differences in the biochemical composition of blood group antigens, and the relationship to risks for disease, can be important for the identification of targets for the development of nutritional intervention strategies, or the identification of druggable targets. WIREs Syst Biol Med 2016, 8:517-535. doi: 10.1002/wsbm.1355 For further resources related to this article, please visit the WIREs website.

  13. HECT E3s and human disease

    Directory of Open Access Journals (Sweden)

    Staub Olivier

    2007-11-01

    Full Text Available Abstract In a simplified view, members of the HECT E3 family have a modular structure consisting of the C-terminal HECT domain, which is catalytically involved in the attachment of ubiquitin to substrate proteins, and N-terminal extensions of variable length and sequence that mediate the substrate specificity of the respective HECT E3. Although the physiologically relevant substrates of most HECT E3s have remained elusive, it is becoming increasingly clear that HECT E3s play an important role in sporadic and hereditary human diseases including cancer, cardiovascular (Liddle's syndrome and neurological (Angelman syndrome disorders, and/or in disease-relevant processes including bone homeostasis, immune response and retroviral budding. Thus, molecular approaches to target the activity of distinct HECT E3s, regulators thereof, and/or of HECT E3 substrates could prove valuable in the treatment of the respective diseases. Publication history: Republished from Current BioData's Targeted Proteins database (TPdb; http://www.targetedproteinsdb.com.

  14. A Finger Amputation Case Caused by Human Bite

    Directory of Open Access Journals (Sweden)

    Kamil Hakan Doğan

    2014-07-01

    Full Text Available Bite is a type of wound created with animal or human teeth. Bite wounds created by humans are encountered in situations as fighting, rape, murder and child abuse. Bite marks are usually observed on arms, neck, breasts, body, cheeks and legs. The teeth may penetrate to skin on the areas where bone or cartilage tissue lies underneath skin, and tissue loss may occur. Auricles are most frequent regions that occur tissue loss with bites. Finger amputation occurring with human bite is extremely rare. The case presented in this paper is a 28 years old man. In his medical history, the 3rd finger of his left hand was bitten during a fight two months ago. One centimeter shortness at the end point of the distal phalanx of the left 3rd finger because of tissue loss was found in the examination. In his left hand radiograph, bone defect at the middle part of the distal phalanx of 3rd finger was determined. The case has been discussed by comparing similar cases rarely reported in the literature. Keywords: Forensic medicine, human bite, amputation

  15. HUMAN RHINOVIRUS CAUSES SEVERE INFECTION IN PRETERM INFANTS

    NARCIS (Netherlands)

    van Piggelen, Renee O.; van Loon, Anton M.; Krediet, Tanette G.; Verboon-Maciolek, Malgorzata A.

    2010-01-01

    Data of 11 infants (median gestational age and birth weight 30 weeks and 1520 g, respectively) with severe human rhinovirus infection (HRV) are described. Nine of 11 (82%) were preterm infants and 7 of these 9 (78%) became infected during their stay in the neonatal intensive care unit. All infants p

  16. Diet, disease and pigment variation in humans.

    Science.gov (United States)

    Khan, R; Khan, B S Razib

    2010-10-01

    There are several hypotheses which explain the de-pigmentation of humans. The most prominent environmental explanation is that reduced endogenous vitamin D production due to diminished radiation at higher latitudes had a deleterious impact on fitness. This drove de-pigmentation as an adaptive response. A model of natural selection explains the high correlations found between low vitamin D levels and ill health, as vitamin D's role in immune response has clear evolutionary implications. But recent genomic techniques have highlighted the likelihood that extreme de-pigmentation in Eurasia is a feature of the last 10,000years, not the Upper Pleistocene, when modern humans first settled northern Eurasia. Additionally the data imply two independent selection events in eastern and western Eurasia. Therefore new parameters must be added to the model of natural selection so as to explain the relatively recent and parallel adaptive responses. I propose a model of gene-culture co-evolution whereby the spread of agriculture both reduced dietary vitamin D sources and led to more powerful selection on immune response because of the rise of infectious diseases with greater population densities. This model explains the persistence of relatively dark-skinned peoples at relatively high latitudes and the existence of relatively light-skinned populations at low latitudes. It also reinforces the importance of vitamin D as a micronutrient because of the evidence of extremely powerful fitness implications in the recent human past of pigmentation. Copyright 2010 Elsevier Ltd. All rights reserved.

  17. An autosomal locus causing autoimmune disease: Autoimmune polyglandular disease type I assigned to chromosome 21

    NARCIS (Netherlands)

    J. Aaltonen (Johanna); P. Björses (Petra); L.A. Sandkuijl (Lodewijk); J. Perheentupa (Jaakko); L. Peltonen (Leena Johanna)

    1994-01-01

    textabstractAutoimmune polyglandular disease type I (APECED) is an autosomal recessive autoimmune disease characterized by a variable combination of the failure of the endocrine glands. The pathogenesis of this unique autoimmune disease is unknown; unlike many other autoimmune diseases, APECED does

  18. Prediction of disease causing non-synonymous SNPs by the Artificial Neural Network Predictor NetDiseaseSNP.

    Directory of Open Access Journals (Sweden)

    Morten Bo Johansen

    Full Text Available We have developed a sequence conservation-based artificial neural network predictor called NetDiseaseSNP which classifies nsSNPs as disease-causing or neutral. Our method uses the excellent alignment generation algorithm of SIFT to identify related sequences and a combination of 31 features assessing sequence conservation and the predicted surface accessibility to produce a single score which can be used to rank nsSNPs based on their potential to cause disease. NetDiseaseSNP classifies successfully disease-causing and neutral mutations. In addition, we show that NetDiseaseSNP discriminates cancer driver and passenger mutations satisfactorily. Our method outperforms other state-of-the-art methods on several disease/neutral datasets as well as on cancer driver/passenger mutation datasets and can thus be used to pinpoint and prioritize plausible disease candidates among nsSNPs for further investigation. NetDiseaseSNP is publicly available as an online tool as well as a web service: http://www.cbs.dtu.dk/services/NetDiseaseSNP.

  19. Human neurocysticercosis: immunological features involved in the host's susceptibility to become infected and to develop disease.

    Science.gov (United States)

    Sciutto, Edda; Cárdenas, Graciela; Adalid-Peralta, Laura; Fragoso, Gladis; Larralde, Carlos; Fleury, Agnes

    2013-06-01

    Human neurocysticercosis (NC) is a clinically and radiologically heterogeneous disease caused by the establishment of Taenia solium larvae in the central nervous system. Herein, the immunological and endocrinological features involved in resistance to infection and severe forms of the disease are reviewed, and their clinical relevance is discussed.

  20. Tangier disease is caused by mutations in the gene encoding ATP-binding cassette transporter 1.

    Science.gov (United States)

    Rust, S; Rosier, M; Funke, H; Real, J; Amoura, Z; Piette, J C; Deleuze, J F; Brewer, H B; Duverger, N; Denèfle, P; Assmann, G

    1999-08-01

    Tangier disease (TD) was first discovered nearly 40 years ago in two siblings living on Tangier Island. This autosomal co-dominant condition is characterized in the homozygous state by the absence of HDL-cholesterol (HDL-C) from plasma, hepatosplenomegaly, peripheral neuropathy and frequently premature coronary artery disease (CAD). In heterozygotes, HDL-C levels are about one-half those of normal individuals. Impaired cholesterol efflux from macrophages leads to the presence of foam cells throughout the body, which may explain the increased risk of coronary heart disease in some TD families. We report here refining of our previous linkage of the TD gene to a 1-cM region between markers D9S271 and D9S1866 on chromosome 9q31, in which we found the gene encoding human ATP cassette-binding transporter 1 (ABC1). We also found a change in ABC1 expression level on cholesterol loading of phorbol ester-treated THP1 macrophages, substantiating the role of ABC1 in cholesterol efflux. We cloned the full-length cDNA and sequenced the gene in two unrelated families with four TD homozygotes. In the first pedigree, a 1-bp deletion in exon 13, resulting in truncation of the predicted protein to approximately one-fourth of its normal size, co-segregated with the disease phenotype. An in-frame insertion-deletion in exon 12 was found in the second family. Our findings indicate that defects in ABC1, encoding a member of the ABC transporter superfamily, are the cause of TD.

  1. Human Trafficking in Southeast Asia: Causes and Policy Implications

    Science.gov (United States)

    2009-06-01

    itself as a cause is the recent trend of the feminization of both the formal and informal labor sectors.52 In some regions of the world, female...potential 67 Piper, A Problem by a Different Name, 210. 68 Kimberley Thachuk, ed., Transnational ...flourishing nations relying on trafficked labor to maintain profits. Also, the feminization of the migrant labor has led to an increased demand for

  2. Human Coronavirus in the 2014 Winter Season as a Cause of Lower Respiratory Tract Infection.

    Science.gov (United States)

    Kim, Kyu Yeun; Han, Song Yi; Kim, Ho Seong; Cheong, Hyang Min; Kim, Sung Soon; Kim, Dong Soo

    2017-01-01

    During the late autumn to winter season (October to December) in the Republic of Korea, respiratory syncytial virus (RSV) is the most common pathogen causing lower respiratory tract infections (LRTIs). Interestingly, in 2014, human coronavirus (HCoV) caused not only upper respiratory infections but also LRTIs more commonly than in other years. Therefore, we sought to determine the epidemiology, clinical characteristics, outcomes, and severity of illnesses associated with HCoV infections at a single center in Korea. We retrospectively identified patients with positive HCoV respiratory specimens between October 2014 and December 2014 who were admitted to Severance Children's Hospital at Yonsei University Medical Center for LRTI. Charts of the patients with HCoV infection were reviewed and compared with RSV infection. During the study period, HCoV was the third most common respiratory virus and accounted for 13.7% of infections. Coinfection was detected in 43.8% of children with HCoV. Interestingly, one patient had both HCoV-OC43 and HCoV-NL63. Mild pneumonia was most common (60.4%) with HCoV, and when combined with RSV, resulted in bronchiolitis. Two patients required care in the intensive care unit. However, compared with that of RSV infection, the disease course HCoV was short. Infections caused by HCoVs are common, and can cause LRTIs. During an epidemic season, clinicians should be given special consideration thereto. When combined with other medical conditions, such as neurologic or cardiologic diseases, intensive care unit (ICU) care may be necessary.

  3. DNA barcoding of fungi causing infections in humans and animals.

    Science.gov (United States)

    Irinyi, Laszlo; Lackner, Michaela; de Hoog, G Sybren; Meyer, Wieland

    2016-02-01

    Correct species identification is becoming increasingly important in clinical diagnostics. Till now, many mycological laboratories rely on conventional phenotypic identification. But this is slow and strongly operator-dependent. Therefore, to improve the quality of pathogen identification, rapid, reliable, and objective identification methods are essential. One of the most encouraging approaches is molecular barcoding using the internal transcribed spacer (ITS) of the rDNA, which is rapid, easily achievable, accurate, and applicable directly from clinical specimens. It relies on the comparison of a single ITS sequence with a curated reference database. The International Society for Human and Animal Mycology (ISHAM) working group for DNA barcoding has recently established such a database, focusing on the majority of human and animal pathogenic fungi (ISHAM-ITS, freely accessible at http://www.isham.org/ or directly from http://its.mycologylab.org). For some fungi the use of secondary barcodes may be necessary.

  4. Human RECQ helicases: roles in cancer, aging, and inherited disease

    Directory of Open Access Journals (Sweden)

    Sidorova JM

    2014-12-01

    Full Text Available Julia M Sidorova,1,* Raymond J Monnat Jr,1,2,* 1Department of Pathology, 2Department of Genome Sciences, University of Washington, Seattle, WA, USA *The authors contributed equally to this review Abstract: DNA helicases use the energy of ATP hydrolysis to disrupt DNA base pairing and displace proteins from DNA in order to facilitate replication, recombination, transcription, and repair. This article focuses on the human RECQ helicases, five DNA-dependent helicases that play key roles in cellular physiology and disease. Loss of function of three RECQ helicases causes the cancer predisposition syndromes Bloom syndrome, Werner syndrome, and Rothmund–Thomson and related syndromes. We summarize recent work on these syndromes and proteins and discuss disease pathogenesis in light of RECQ helicase biochemical activities and in vivo functions. Keywords: ATP-dependent DNA helicase, Bloom syndrome, Werner syndrome, Rothmund–Thomson syndrome, DNA replication, DNA repair, genetic instability, cancer predisposition syndrome

  5. Therapeutics Targeting FGF Signaling Network in Human Diseases.

    Science.gov (United States)

    Katoh, Masaru

    2016-12-01

    Fibroblast growth factor (FGF) signaling through its receptors, FGFR1, FGFR2, FGFR3, or FGFR4, regulates cell fate, angiogenesis, immunity, and metabolism. Dysregulated FGF signaling causes human diseases, such as breast cancer, chondrodysplasia, gastric cancer, lung cancer, and X-linked hypophosphatemic rickets. Recombinant FGFs are pro-FGF signaling therapeutics for tissue and/or wound repair, whereas FGF analogs and gene therapy are under development for the treatment of cardiovascular disease, diabetes, and osteoarthritis. FGF traps, anti-FGF/FGFR monoclonal antibodies (mAbs), and small-molecule FGFR inhibitors are anti-FGF signaling therapeutics under development for the treatment of cancer, chondrodysplasia, and rickets. Here, I discuss the benefit-risk and cost-effectiveness issues of precision medicine targeting FGFRs, ALK, EGFR, and FLT3. FGFR-targeted therapy should be optimized for cancer treatment, focusing on genomic tests and recurrence.

  6. 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

    Most pathogenic mitochondrial DNA (mtDNA) mutations induce defects in mitochondrial oxidative phosphorylation (OXPHOS). However, phenotypic effects of these mutations show a large degree of variation depending on the tissue affected. These differences are difficult to reconcile with OXPHOS...... 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...... 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....

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

    NARCIS (Netherlands)

    Baarlen, van P.; Belkum, van A.; Thomma, B.P.H.J.

    2007-01-01

    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.

  8. Evolutionary history of human disease genes reveals phenotypic connections and comorbidity among genetic diseases.

    Science.gov (United States)

    Park, Solip; Yang, Jae-Seong; Kim, Jinho; Shin, Young-Eun; Hwang, Jihye; Park, Juyong; Jang, Sung Key; Kim, Sanguk

    2012-01-01

    The extent to which evolutionary changes have impacted the phenotypic relationships among human diseases remains unclear. In this work, we report that phenotypically similar diseases are connected by the evolutionary constraints on human disease genes. Human disease groups can be classified into slowly or rapidly evolving classes, where the diseases in the slowly evolving class are enriched with morphological phenotypes and those in the rapidly evolving class are enriched with physiological phenotypes. Our findings establish a clear evolutionary connection between disease classes and disease phenotypes for the first time. Furthermore, the high comorbidity found between diseases connected by similar evolutionary constraints enables us to improve the predictability of the relative risk of human diseases. We find the evolutionary constraints on disease genes are a new layer of molecular connection in the network-based exploration of human diseases.

  9. Prediction of Disease Causing Non-Synonymous SNPs by the Artificial Neural Network Predictor NetDiseaseSNP

    DEFF Research Database (Denmark)

    Johansen, Morten Bo; Gonzalez-Izarzugaza, Jose Maria; Brunak, Søren

    2013-01-01

    We have developed a sequence conservation-based artificial neural network predictor called NetDiseaseSNP which classifies nsSNPs as disease-causing or neutral. Our method uses the excellent alignment generation algorithm of SIFT to identify related sequences and a combination of 31 features...

  10. Identification of a Novel GJA8 (Cx50) Point Mutation Causes Human Dominant Congenital Cataracts

    Science.gov (United States)

    Ge, Xiang-Lian; Zhang, Yilan; Wu, Yaming; Lv, Jineng; Zhang, Wei; Jin, Zi-Bing; Qu, Jia; Gu, Feng

    2014-02-01

    Hereditary cataracts are clinically and genetically heterogeneous lens diseases that cause a significant proportion of visual impairment and blindness in children. Human cataracts have been linked with mutations in two genes, GJA3 and GJA8, respectively. To identify the causative mutation in a family with hereditary cataracts, family members were screened for mutations by PCR for both genes. Sequencing the coding regions of GJA8, coding for connexin 50, revealed a C > A transversion at nucleotide 264, which caused p.P88T mutation. To dissect the molecular consequences of this mutation, plasmids carrying wild-type and mutant mouse ORFs of Gja8 were generated and ectopically expressed in HEK293 cells and human lens epithelial cells, respectively. The recombinant proteins were assessed by confocal microscopy and Western blotting. The results demonstrate that the molecular consequences of the p.P88T mutation in GJA8 include changes in connexin 50 protein localization patterns, accumulation of mutant protein, and increased cell growth.

  11. A nairovirus isolated from African bats causes haemorrhagic gastroenteritis and severe hepatic disease in mice.

    Science.gov (United States)

    Ishii, Akihiro; Ueno, Keisuke; Orba, Yasuko; Sasaki, Michihito; Moonga, Ladslav; Hang'ombe, Bernard M; Mweene, Aaron S; Umemura, Takashi; Ito, Kimihito; Hall, William W; Sawa, Hirofumi

    2014-12-02

    Bats can carry important zoonotic pathogens. Here we use a combination of next-generation sequencing and classical virus isolation methods to identify novel nairoviruses from bats captured from a cave in Zambia. This nairovirus infection is highly prevalent among giant leaf-nosed bats, Hipposideros gigas (detected in samples from 16 individuals out of 38). Whole-genome analysis of three viral isolates (11SB17, 11SB19 and 11SB23) reveals a typical bunyavirus tri-segmented genome. The strains form a single phylogenetic clade that is divergent from other known nairoviruses, and are hereafter designated as Leopards Hill virus (LPHV). When i.p. injected into mice, the 11SB17 strain causes only slight body weight loss, whereas 11SB23 produces acute and lethal disease closely resembling that observed with Crimean-Congo Haemorrhagic Fever virus in humans. We believe that our LPHV mouse model will be useful for research on the pathogenesis of nairoviral haemorrhagic disease.

  12. Lineage 2 west nile virus as cause of fatal neurologic disease in horses, South Africa.

    Science.gov (United States)

    Venter, Marietjie; Human, Stacey; Zaayman, Dewald; Gerdes, Gertruida H; Williams, June; Steyl, Johan; Leman, Patricia A; Paweska, Janusz Tadeusz; Setzkorn, Hildegard; Rous, Gavin; Murray, Sue; Parker, Rissa; Donnellan, Cynthia; Swanepoel, Robert

    2009-06-01

    Serologic evidence suggests that West Nile virus (WNV) is widely distributed in horses in southern Africa. However, because few neurologic cases have been reported, endemic lineage 2 strains were postulated to be nonpathogenic in horses. Recent evidence suggests that highly neuroinvasive lineage 2 strains exist in humans and mice. To determine whether neurologic cases are being missed in South Africa, we tested 80 serum or brain specimens from horses with unexplained fever (n = 48) and/or neurologic signs (n = 32) for WNV. From March 2007 through June 2008, using reverse transcription-PCR (RT-PCR) and immunoglobulin (Ig) M ELISA, we found WNV RNA or IgM in 7/32 horses with acute neurologic disease; 5 horses died or were euthanized. In 5/7 horses, no other pathogen was detected. DNA sequencing for all 5 RT-PCR-positive cases showed the virus belonged to lineage 2. WNV lineage 2 may cause neurologic disease in horses in South Africa.

  13. Chronic aluminum intake causes Alzheimer's disease: applying Sir Austin Bradford Hill's causality criteria.

    Science.gov (United States)

    Walton, J R

    2014-01-01

    Industrialized societies produce many convenience foods with aluminum additives that enhance various food properties and use alum (aluminum sulfate or aluminum potassium sulfate) in water treatment to enable delivery of large volumes of drinking water to millions of urban consumers. The present causality analysis evaluates the extent to which the routine, life-long intake, and metabolism of aluminum compounds can account for Alzheimer's disease (AD), using Austin Bradford Hill's nine epidemiological and experimental causality criteria, including strength of the relationship, consistency, specificity, temporality, dose-dependent response, biological rationale, coherence with existing knowledge, experimental evidence, and analogy. Mechanisms that underlie the risk of low concentrations of aluminum relate to (1) aluminum's absorption rates, allowing the impression that aluminum is safe to ingest and as an additive in food and drinking water treatment, (2) aluminum's slow progressive uptake into the brain over a long prodromal phase, and (3) aluminum's similarity to iron, in terms of ionic size, allows aluminum to use iron-evolved mechanisms to enter the highly-active, iron-dependent cells responsible for memory processing. Aluminum particularly accumulates in these iron-dependent cells to toxic levels, dysregulating iron homeostasis and causing microtubule depletion, eventually producing changes that result in disconnection of neuronal afferents and efferents, loss of function and regional atrophy consistent with MRI findings in AD brains. AD is a human form of chronic aluminum neurotoxicity. The causality analysis demonstrates that chronic aluminum intake causes AD.

  14. Are 20 human papillomavirus types causing cervical cancer?

    OpenAIRE

    Arbyn, Marc; Tommasino, Massimo; Depuydt, Christophe; Dillner, Joakim

    2014-01-01

    Abstract: In 2012, the International Agency for Research on Cancer concluded that there was consistent and sufficient epidemiological, experimental and mechanistic evidence of carcinogenicity to humans for 12 HPV types (HPV16, HPV18, HPV31, HPV33, HPV35, HPV39, HPV45, HPV51, HPV52, HPV56, HPV58 and HPV59) for cervical cancer. Therefore, these types were considered as 1A carcinogens. They all belong to the family of the -Papillomaviridae, in particular to the species 5 (HPV51), 6 (HPV56), 7 (H...

  15. Capitalizing on the Autophagic Response for Treatment of Liver Disease Caused by Alpha-1-Antitrypsin Deficiency and Other Genetic Diseases

    Directory of Open Access Journals (Sweden)

    Andrew S. Chu

    2014-01-01

    Full Text Available Alpha-1-antitrypsin deficiency (ATD is one of the most common genetic causes of liver disease and is a prototype of liver diseases caused by the pathologic accumulation of aggregated mutant alpha-1-antitrypsin Z (ATZ within liver cells. In the case of ATD-associated liver disease, the resulting “gain-of-function” toxicity can lead to serious clinical manifestations, including cirrhosis and hepatocellular carcinoma. Currently, the only definitive therapy for ATD-associated liver disease is liver transplantation, but recent efforts have demonstrated the exciting potential for novel therapies that target disposal of the mutant protein aggregates by harnessing a cellular homeostasis mechanism called autophagy. In this review, we will summarize research advances on autophagy and genetic liver diseases. We will discuss autophagy enhancer strategies for liver disease due to ATD and another genetic liver disease, inherited hypofibrinogenemia, caused by the proteotoxic effects of a misfolded protein. On the basis of recent evidence that autophagy plays a role in cellular lipid degradation, we also speculate about autophagy enhancer strategies for treatment of hepatic lipid storage diseases such as cholesterol ester storage disease.

  16. Human KATP channelopathies: diseases of metabolic homeostasis

    Science.gov (United States)

    2009-01-01

    Assembly of an inward rectifier K+ channel pore (Kir6.1/Kir6.2) and an adenosine triphosphate (ATP)-binding regulatory subunit (SUR1/SUR2A/SUR2B) forms ATP-sensitive K+ (KATP) channel heteromultimers, widely distributed in metabolically active tissues throughout the body. KATP channels are metabolism-gated biosensors functioning as molecular rheostats that adjust membrane potential-dependent functions to match cellular energetic demands. Vital in the adaptive response to (patho)physiological stress, KATP channels serve a homeostatic role ranging from glucose regulation to cardioprotection. Accordingly, genetic variation in KATP channel subunits has been linked to the etiology of life-threatening human diseases. In particular, pathogenic mutations in KATP channels have been identified in insulin secretion disorders, namely, congenital hyperinsulinism and neonatal diabetes. Moreover, KATP channel defects underlie the triad of developmental delay, epilepsy, and neonatal diabetes (DEND syndrome). KATP channelopathies implicated in patients with mechanical and/or electrical heart disease include dilated cardiomyopathy (with ventricular arrhythmia; CMD1O) and adrenergic atrial fibrillation. A common Kir6.2 E23K polymorphism has been associated with late-onset diabetes and as a risk factor for maladaptive cardiac remodeling in the community-at-large and abnormal cardiopulmonary exercise stress performance in patients with heart failure. The overall mutation frequency within KATP channel genes and the spectrum of genotype–phenotype relationships remain to be established, while predicting consequences of a deficit in channel function is becoming increasingly feasible through systems biology approaches. Thus, advances in molecular medicine in the emerging field of human KATP channelopathies offer new opportunities for targeted individualized screening, early diagnosis, and tailored therapy. PMID:20033705

  17. Major trends in human parasitic diseases in China.

    Science.gov (United States)

    Li, Ting; He, Shenyi; Zhao, Hong; Zhao, Guanghui; Zhu, Xing-Quan

    2010-05-01

    Tremendous progress has been made in the control and prevention of human parasitic diseases in mainland China in the past 30 years because of China's Reform and Opening to the Outside Policies initiated in 1978. However, parasitic diseases remain a major human health problem, with significant morbidity and mortality as well as adverse socioeconomic consequences. Although soil-transmitted parasitic diseases are in the process of being gradually controlled, food-borne parasitic diseases and emerging parasitic diseases are becoming the focus of new campaigns for control and prevention. This article reviews major trends in human parasitic diseases in mainland China, with perspectives for control.

  18. A rare case of human trypanosomiasis caused by Trypanosoma evansi

    Directory of Open Access Journals (Sweden)

    Powar R

    2006-01-01

    Full Text Available Human trypanosoma infections like the ones seen in Africa and South America are unknown in India. The only exception in literature is of two documented cases of a self-limiting febrile illness, being attributed to Trypanosoma lewisi like parasites. We are reporting an unusual case of trypanosomiasis from the rural parts of Chandrapur district in Maharashtra. An adult male farmhand who used to practice veterinary medicine also, presented with history of febrile episodes on and off since five months and drowsiness before admission to this Institute. Though routine blood and other investigations were within normal limits, the peripheral smear showed a large number of trypanosomes which morphologically resembled the species Trypanosoma evansi , the aetiological agent of surra - a form of animal trypanosomiasis. A battery of assays covering the spectrum of parasitology, serology, and molecular biology confirmed the infecting parasite to be T. evansi . Failure to demonstrate the central nervous system (CNS involvement, as evidenced by the absence of parasite in cerebrospinal fluid (CSF advocated the use of suramin - the drug of choice in early stage African trypanosomiasis without any CNS involvement. Suramin achieved cure in our patient. The case is being reported because of its unique nature as the patient was not immunocompromised and showed infestation with a parasite which normally does not affect human beings.

  19. Human-caused fires limit rainfall in tropical Africa

    Science.gov (United States)

    Tosca, M. G., Jr.

    2015-12-01

    It is well established that smoke particles modify clouds, which in turn affects climate. However, no studies have quantified the temporal dynamics of aerosol-cloud interactions with direct observations. Here, for the first time, we use temporally-offset satellite observations from northern Africa between 2006 and 2010 to quantitatively measure the effect of fire aerosols on convective cloud dynamics. We attribute a reduction in cloud fraction during periods of high aerosol optical depths to a smoke-driven inhibition of convection. We find that higher smoke burdens limit upward vertical motion, increase surface pressure, and increase low-level divergence -- meteorological indicators of convective suppression. The resulting decrease in rainfall is substantial and may increase human ignitions during the dry season. These results are corroborated by climate simulations that show a smoke-driven increase in regionally averaged shortwave tropospheric heating and decrease in convective precipitation during the fire season. Our results suggest that, in tropical regions, anthropogenic fire initiates a positive feedback loop where increased aerosol emissions limit convection, dry the surface and enable increased fire activity via human ignition.

  20. 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.

  1. LRPPRC mutations cause early-onset multisystem mitochondrial disease outside of the French-Canadian population.

    Science.gov (United States)

    Oláhová, Monika; Hardy, Steven A; Hall, Julie; Yarham, John W; Haack, Tobias B; Wilson, William C; Alston, Charlotte L; He, Langping; Aznauryan, Erik; Brown, Ruth M; Brown, Garry K; Morris, Andrew A M; Mundy, Helen; Broomfield, Alex; Barbosa, Ines A; Simpson, Michael A; Deshpande, Charu; Moeslinger, Dorothea; Koch, Johannes; Stettner, Georg M; Bonnen, Penelope E; Prokisch, Holger; Lightowlers, Robert N; McFarland, Robert; Chrzanowska-Lightowlers, Zofia M A; Taylor, Robert W

    2015-12-01

    Mitochondrial Complex IV [cytochrome c oxidase (COX)] deficiency is one of the most common respiratory chain defects in humans. The clinical phenotypes associated with COX deficiency include liver disease, cardiomyopathy and Leigh syndrome, a neurodegenerative disorder characterized by bilateral high signal lesions in the brainstem and basal ganglia. COX deficiency can result from mutations affecting many different mitochondrial proteins. The French-Canadian variant of COX-deficient Leigh syndrome is unique to the Saguenay-Lac-Saint-Jean region of Québec and is caused by a founder mutation in the LRPPRC gene. This encodes the leucine-rich pentatricopeptide repeat domain protein (LRPPRC), which is involved in post-transcriptional regulation of mitochondrial gene expression. Here, we present the clinical and molecular characterization of novel, recessive LRPPRC gene mutations, identified using whole exome and candidate gene sequencing. The 10 patients come from seven unrelated families of UK-Caucasian, UK-Pakistani, UK-Indian, Turkish and Iraqi origin. They resemble the French-Canadian Leigh syndrome patients in having intermittent severe lactic acidosis and early-onset neurodevelopmental problems with episodes of deterioration. In addition, many of our patients have had neonatal cardiomyopathy or congenital malformations, most commonly affecting the heart and the brain. All patients who were tested had isolated COX deficiency in skeletal muscle. Functional characterization of patients' fibroblasts and skeletal muscle homogenates showed decreased levels of mutant LRPPRC protein and impaired Complex IV enzyme activity, associated with abnormal COX assembly and reduced steady-state levels of numerous oxidative phosphorylation subunits. We also identified a Complex I assembly defect in skeletal muscle, indicating different roles for LRPPRC in post-transcriptional regulation of mitochondrial mRNAs between tissues. Patient fibroblasts showed decreased steady-state levels

  2. A mouse-adapted SARS-coronavirus causes disease and mortality in BALB/c mice.

    Directory of Open Access Journals (Sweden)

    Anjeanette Roberts

    2007-01-01

    Full Text Available No single animal model for severe acute respiratory syndrome (SARS reproduces all aspects of the human disease. Young inbred mice support SARS-coronavirus (SARS-CoV replication in the respiratory tract and are available in sufficient numbers for statistical evaluation. They are relatively inexpensive and easily accessible, but their use in SARS research is limited because they do not develop illness following infection. Older (12- to 14-mo-old BALB/c mice develop clinical illness and pneumonitis, but they can be hard to procure, and immune senescence complicates pathogenesis studies. We adapted the SARS-CoV (Urbani strain by serial passage in the respiratory tract of young BALB/c mice. Fifteen passages resulted in a virus (MA15 that is lethal for mice following intranasal inoculation. Lethality is preceded by rapid and high titer viral replication in lungs, viremia, and dissemination of virus to extrapulmonary sites accompanied by lymphopenia, neutrophilia, and pathological changes in the lungs. Abundant viral antigen is extensively distributed in bronchial epithelial cells and alveolar pneumocytes, and necrotic cellular debris is present in airways and alveoli, with only mild and focal pneumonitis. These observations suggest that mice infected with MA15 die from an overwhelming viral infection with extensive, virally mediated destruction of pneumocytes and ciliated epithelial cells. The MA15 virus has six coding mutations associated with adaptation and increased virulence; when introduced into a recombinant SARS-CoV, these mutations result in a highly virulent and lethal virus (rMA15, duplicating the phenotype of the biologically derived MA15 virus. Intranasal inoculation with MA15 reproduces many aspects of disease seen in severe human cases of SARS. The availability of the MA15 virus will enhance the use of the mouse model for SARS because infection with MA15 causes morbidity, mortality, and pulmonary pathology. This virus will be of value as

  3. Osler-Weber-Rendu disease: A rare cause of recurrent hemoptysis.

    Science.gov (United States)

    Khoja, Amir M; Jalan, Rahul K; Jain, Dheeraj L; Kajale, Omkar V

    2016-01-01

    Osler-Weber-Rendu disease, also known as hereditary hemorrhagic telangiectasia, is a rare autosomal dominant condition causing systemic fibrovascular dysplasia. It has an incidence of 1-2/100,000. Phenotypic variation is extreme ranging from asymptomatic to severely symptomatic, from cases with no or few mucocutaneous lesions to those with diffuse cutaneous telangiectasia. We discuss a case of Osler-Weber-Rendu disease causing diffuse cutaneous telangiectasia and hemoptysis. The patient presented with complaints of hemoptysis and was extensively examined and investigated before being diagnosed with Osler-Weber-Rendu disease. We successfully managed the patient's hemoptysis by bronchial artery embolization. This case emphasizes the need for careful examination and investigation and to consider such rare diseases when all the common causes of hemoptysis are ruled out. An early and proper diagnosis will lead to more effective management of such a rare disease with few treatment options available.

  4. Osler-Weber-Rendu disease: A rare cause of recurrent hemoptysis

    Directory of Open Access Journals (Sweden)

    Amir M Khoja

    2016-01-01

    Full Text Available Osler-Weber-Rendu disease, also known as hereditary hemorrhagic telangiectasia, is a rare autosomal dominant condition causing systemic fibrovascular dysplasia. It has an incidence of 1-2/100,000. Phenotypic variation is extreme ranging from asymptomatic to severely symptomatic, from cases with no or few mucocutaneous lesions to those with diffuse cutaneous telangiectasia. We discuss a case of Osler-Weber-Rendu disease causing diffuse cutaneous telangiectasia and hemoptysis. The patient presented with complaints of hemoptysis and was extensively examined and investigated before being diagnosed with Osler-Weber-Rendu disease. We successfully managed the patient′s hemoptysis by bronchial artery embolization.  This case emphasizes the need for careful examination and investigation and to consider such rare diseases when all the common causes of hemoptysis are ruled out. An early and proper diagnosis will lead to more effective management of such a rare disease with few treatment options available.

  5. Sleep duration and ischemic heart disease and all-cause mortality

    DEFF Research Database (Denmark)

    Garde, Anne Helene; Hansen, Åse Marie; Holtermann, Andreas;

    2013-01-01

    This prospective study aimed to examine if sleep duration is a risk indicator for ischemic heart disease (IHD) and all-cause mortality, and how perceived stress during work and leisure time and use of tranquilizers/hypnotics modifies the association.......This prospective study aimed to examine if sleep duration is a risk indicator for ischemic heart disease (IHD) and all-cause mortality, and how perceived stress during work and leisure time and use of tranquilizers/hypnotics modifies the association....

  6. Ileitis caused by Yersinia enterocolitica - X-ray differential diagnosis of Crohn's disease

    Energy Technology Data Exchange (ETDEWEB)

    Lingg, G.; Hering, L.; Tanneberger, D.

    1981-12-01

    The article gives a brief description of the characteristic features of the clinical and roentgenological course and the various stages of enteritis caused by Yersinia. Basing on three cases of ileitis caused by Yersinia, the far-reaching similarity with the early changes and even the advanced stages of Crohn's diseases are demonstrated. Attention is drawn to the possibilities of differentiating between the two disease patterns.

  7. Drug Resistance Mechanisms in Bacteria Causing Sexually Transmitted Diseases and Associated with Vaginosis

    OpenAIRE

    Shaskolskiy, Boris; Dementieva, Ekaterina; Leinsoo, Arvo; Runina, Anastassia; Vorobyev, Denis; Plakhova, Xenia; Kubanov, Alexey; Deryabin, Dmitrii; Gryadunov, Dmitry

    2016-01-01

    Here, we review sexually transmitted diseases (STDs) caused by pathogenic bacteria and vaginal infections which result from an overgrowth of opportunistic bacterial microflora. First, we describe the STDs, the corresponding pathogens and the antimicrobials used for their treatment. In addition to the well-known diseases caused by single pathogens (i.e., syphilis, gonococcal infections, and chlamydiosis), we consider polymicrobial reproductive tract infections (especially those that are diffic...

  8. Activating germline mutations in STAT3 cause early-onset multi-organ autoimmune disease.

    Science.gov (United States)

    Flanagan, Sarah E; Haapaniemi, Emma; Russell, Mark A; Caswell, Richard; Lango Allen, Hana; De Franco, Elisa; McDonald, Timothy J; Rajala, Hanna; Ramelius, Anita; Barton, John; Heiskanen, Kaarina; Heiskanen-Kosma, Tarja; Kajosaari, Merja; Murphy, Nuala P; Milenkovic, Tatjana; Seppänen, Mikko; Lernmark, Åke; Mustjoki, Satu; Otonkoski, Timo; Kere, Juha; Morgan, Noel G; Ellard, Sian; Hattersley, Andrew T

    2014-08-01

    Monogenic causes of autoimmunity provide key insights into the complex regulation of the immune system. We report a new monogenic cause of autoimmunity resulting from de novo germline activating STAT3 mutations in five individuals with a spectrum of early-onset autoimmune disease, including type 1 diabetes. These findings emphasize the critical role of STAT3 in autoimmune disease and contrast with the germline inactivating STAT3 mutations that result in hyper IgE syndrome.

  9. Furuncular myiasis caused by Dermatobia hominis, the human botfly.

    Science.gov (United States)

    Maier, Harald; Hönigsmann, Herbert

    2004-02-01

    Myiasis is a common travel-associated dermatosis. Travelers to many parts of Central and South America are susceptible to infestation by Dermatobia hominis. Despite the common name of human botfly, D hominis infests a broad range of mammals and is a severe pest to economically important farm animals in endemic regions. The adult female does not lay the eggs on the host. Instead, the adult female infests hosts indirectly by using blood-feeding arthropods to serve as phoretic vectors to transport the eggs. We present a patient who acquired Dermatobia when bitten by a day-active mosquito during a visit to Guatemala. He had a locally painful, firm furuncular lesion with a central pore that drained serosanguineous exudates. The patient applied an occlusive ointment and recovered the larva after it emerged. In this report we discuss the life cycle of D hominis, the differential diagnosis, and therapeutic approaches.

  10. Human papillomavirus: cause of epithelial lacrimal sac neoplasia?

    DEFF Research Database (Denmark)

    Sjö, Nicolai Christian; von Buchwald, Christian; Cassonnet, Patricia

    2007-01-01

    PURPOSE: Epithelial tumours of the lacrimal sac are rare but important entities that may carry grave prognoses. In this study the prevalence and possible role of human papillomavirus (HPV) infection in epithelial tumours of the lacrimal sac were evaluated. METHODS: Five papillomas and six...... 11 RNA was demonstrated in two papillomas. CONCLUSIONS: By analysing 11 epithelial lacrimal sac papillomas and carcinomas using PCR, DNA ISH and RNA ISH, we found HPV DNA in all investigated transitional epithelium tumours of the lacrimal sac. HPV RNA was present in two of eight epithelial lacrimal...... sac tumours positive for HPV DNA. As RNA degrades fast in paraffin-embedded tissue, only a small fraction of DNA-positive tumours can be expected to be RNA-positive. We therefore suggest that HPV infection is associated with the development of lacrimal sac papillomas and carcinomas....

  11. Human keratin diseases: hereditary fragility of specific epithelial tissues.

    Science.gov (United States)

    Corden, L D; McLean, W H

    1996-12-01

    Keratins are heteropolymeric proteins which form the intermediate filament cytoskeleton in epithelial cells. Since 1991, mutations in several keratin genes have been found to cause a variety of human diseases affecting the epidermis and other epithelial structures. Epidermolysis bullosa simplex (EBS) was the first mechanobullous disease for which the underlying genetic lesion was found, with mutations in both the K5 and K14 genes rendering basal epidermal keratinocytes less resilient to trauma, resulting in skin fragility. The site of mutation in the keratin protein correlates with phenotypic severity in this disorder. Since mutations were identified in the basal cell keratins, the total number of keratin genes associated with diseases has risen to eleven. The rod domains of suprabasal keratins K1 and K10 are mutated in bullous congenital ichthyosiform erythroderma (BCIE; also called epidermolytic hyperkeratosis, EH) and mosaicism for K1/K10 mutations results in a nevoid distribution of EH. An unusual mutation in the VI domain of K1 has also been found to cause diffuse non-epidermolytic palmoplantar keratoderma (DNEPPK). Mutations in palmoplantar specific keratin K9 cause epidermolytic palmoplantar keratoderma (EPPK) and mutations in the late differentiation suprabasal keratin K2e cause ichthyosis bullosa of Siemens (IBS). In the last year or so, mutations were discovered in differentiation specific keratins K6a and K16 causing pachyonychia congenita type 1 and K17 mutations occur in pachyonychia congenita type 2. K16 and K17 mutations have also been reported to produce phenotypes with little or no nail changes: K16 mutations can present as focal non-epidermolytic palmoplantar keratoderma (NEPPK) and K17 mutations can result in a phenotype resembling steatocystoma multiplex. Recently, mutation of mucosal keratin pair K4 and K13 has been shown to underlie white sponge nevus (WSN). This year, the first mutations in a keratin-associated protein, plectin, were shown to

  12. Locus heterogeneity disease genes encode proteins with high interconnectivity in the human protein interaction network.

    Science.gov (United States)

    Keith, Benjamin P; Robertson, David L; Hentges, Kathryn E

    2014-01-01

    Mutations in genes potentially lead to a number of genetic diseases with differing severity. These disease genes have been the focus of research in recent years showing that the disease gene population as a whole is not homogeneous, and can be categorized according to their interactions. Locus heterogeneity describes a single disorder caused by mutations in different genes each acting individually to cause the same disease. Using datasets of experimentally derived human disease genes and protein interactions, we created a protein interaction network to investigate the relationships between the products of genes associated with a disease displaying locus heterogeneity, and use network parameters to suggest properties that distinguish these disease genes from the overall disease gene population. Through the manual curation of known causative genes of 100 diseases displaying locus heterogeneity and 397 single-gene Mendelian disorders, we use network parameters to show that our locus heterogeneity network displays distinct properties from the global disease network and a Mendelian network. Using the global human proteome, through random simulation of the network we show that heterogeneous genes display significant interconnectivity. Further topological analysis of this network revealed clustering of locus heterogeneity genes that cause identical disorders, indicating that these disease genes are involved in similar biological processes. We then use this information to suggest additional genes that may contribute to diseases with locus heterogeneity.

  13. MicroRNAs in Human Diseases: From Autoimmune Diseases to Skin, Psychiatric and Neurodegenerative Diseases.

    Science.gov (United States)

    Ha, Tai-You

    2011-10-01

    MicroRNAs (miRNAs) are small noncoding RNA molecules that negatively regulate gene expression via degradation or translational repression of their target messenger RNAs (mRNAs). Recent studies have clearly demonstrated that miRNAs play critical roles in several biologic processes, including cell cycle, differentiation, cell development, cell growth, and apoptosis and that miRNAs are highly expressed in regulatory T (Treg) cells and a wide range of miRNAs are involved in the regulation of immunity and in the prevention of autoimmunity. It has been increasingly reported that miRNAs are associated with various human diseases like autoimmune disease, skin disease, neurological disease and psychiatric disease. Recently, the identification of mi- RNAs in skin has added a new dimension in the regulatory network and attracted significant interest in this novel layer of gene regulation. Although miRNA research in the field of dermatology is still relatively new, miRNAs have been the subject of much dermatological interest in skin morphogenesis and in regulating angiogenesis. In addition, miRNAs are moving rapidly onto center stage as key regulators of neuronal development and function in addition to important contributions to neurodegenerative disorder. Moreover, there is now compelling evidence that dysregulation of miRNA networks is implicated in the development and onset of human neruodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, Tourette's syndrome, Down syndrome, depression and schizophrenia. In this review, I briefly summarize the current studies about the roles of miRNAs in various autoimmune diseases, skin diseases, psychoneurological disorders and mental stress.

  14. CRISPR-mediated genome editing and human diseases

    Directory of Open Access Journals (Sweden)

    Liquan Cai

    2016-12-01

    Full Text Available CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats technology has emerged as a powerful technology for genome editing and is now widely used in basic biomedical research to explore gene function. More recently, this technology has been increasingly applied to the study or treatment of human diseases, including Barth syndrome effects on the heart, Duchenne muscular dystrophy, hemophilia, β-Thalassemia, and cystic fibrosis. CRISPR/Cas9 (CRISPR-associated protein 9 genome editing has been used to correct disease-causing DNA mutations ranging from a single base pair to large deletions in model systems ranging from cells in vitro to animals in vivo. In addition to genetic diseases, CRISPR/Cas9 gene editing has also been applied in immunology-focused applications such as the targeting of C-C chemokine receptor type 5, the programmed death 1 gene, or the creation of chimeric antigen receptors in T cells for purposes such as the treatment of the acquired immune deficiency syndrome (AIDS or promoting anti-tumor immunotherapy. Furthermore, this technology has been applied to the genetic manipulation of domesticated animals with the goal of producing biologic medical materials, including molecules, cells or organs, on a large scale. Finally, CRISPR/Cas9 has been teamed with induced pluripotent stem (iPS cells to perform multiple tissue engineering tasks including the creation of disease models or the preparation of donor-specific tissues for transplantation. This review will explore the ways in which the use of CRISPR/Cas9 is opening new doors to the treatment of human diseases.

  15. Comparison of severe pneumonia caused by Human metapneumovirus and respiratory syncytial virus in hospitalized children

    Directory of Open Access Journals (Sweden)

    Yuqing Wang

    2014-01-01

    Full Text Available Objectives: The objective of this study is to compare the incidence and clinical characteristics of severe pneumonia caused by Human metapneumovirus (hMPV to respiratory syncytial virus (RSV infection in children. Patients and Methods: A total of 151 children hospitalized with severe pneumonia, were tested for hMPV using reverse-transcription polymerase chain reaction. At the same time, samples were tested for RSV and other common respiratory viruses. Medical records, including clinical, laboratory data, and chest radiography findings, were reviewed for all children. Results: Of the 151 samples, 88 (58.3% were positive for respiratory viruses. Of the 88 positive, there were 6 (4.0% with hMPV, 66 (43.7% with RSV, 13 (8.6% with influenza A, 2 (1.3% with parainfluenza virus III, 1 (0.7% with parainfluenza virus I, 1 (0.7% with adenovirus and 1 (0.7% with influenza B. hMPV-infected patients were significantly older than RSV-infected patients (P < 0.001. Children with hMPV pneumonia had fever more frequently (P = 0.03. Two hMPV-positive patients (33.3% required admission to an intensive care unit, and two patients (33.3% required mechanical ventilation. The duration of illness was 18.33 ± 7.09 days. These characteristics of hMPV infections were similar to patients with RSV infections. Conclusion: Human metapneumovirus is an infrequent viral pathogen causing severe pneumonia in children. Children with hMPV were older than those with RSV. The disease caused by hMPV was similar in presentation and severity to RSV, with a minority of children requiring additional respiratory support.

  16. Human Sperm Immotility Caused by Degeneration in the Epididymis

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To investigate whether sperm immotility was caused by degeneration in the epididymisMethods Five patients with totally immotile sperm were selected in this study. Testic ular biopsy was used to obtain testicular sperm to evaluate sperm motility. The com bined hypoosmotic swelling-eosin Y exclusion test was carried out to determine the sperm head and tail membrane integrity for the ejaculated and the testicular sperm.The ultrastructure of ejaculated sperm was examined by transmission electron microscope.Results No motile sperm were found in the ejaculated semen samples from 5 patients,whereas 2% to 11% motile testicular sperm extracted from the testicular biopsy tissues were observed. The percentage of testicular sperm with intact head and tail membranes was higher than that of the ejaculated sperm (P< 0. 01). Ultrastructure of the ejacu lated sperm showed marked degenerative features. Seminal plasma from patients did not influence the motility of normal donor sperm.Conclusion Sperm could undergo degenerative changes during transit through and /or storage in the epididymis, which led to lose sperm motility in these patients. Using motile testicular sperm would benefit the treatment for such cases.

  17. Oral hypertonic saline causes transient fall of vasopressin in humans

    Energy Technology Data Exchange (ETDEWEB)

    Seckl, J.R.; Williams, D.M.; Lightman, S.L.

    1986-08-01

    After dehydration, oral rehydration causes a fall in plasma arginine vasopressin (AVP) that precedes changes in plasma osmolality. To investigate further the stimulus for this effect, its specificity, and association with thirst, six volunteers were deprived of water for 24 h and given a salt load on two separate occasions. On each study day they then drank rapidly 10 ml/kg of either tap water or hypertonic saline (360 mosmol/kg). There was a significant fall in plasma AVP from 2.0 +/- 0.3 to 1.2 +/- 0.4 pmol/l 5 min after drinking water and from 1.8 +/- 0.3 to 0.9 +/- 0.2 pmol/l after hypertonic saline. Plasma osmolality fell 30-60 min after water and was unchanged after saline. Plasma renin activity, oxytocin, and total protein all remained unchanged. All subjects reported diminished thirst after hypertonic saline. Gargling with water reduced thirst but did not affect plasma AVP. There appears to be a drinking-mediated neuroendocrine reflex that decreases plasma AVP irrespective of the osmolality of the liquid consumed. The sensation of thirst did not correlate with plasma osmolality and was not always related to plasma AVP concentration. AVP was measured by radioimmunoassay.

  18. De Quervain disease caused by abductor pollicis longus tenosynovitis: a report of three cases.

    Science.gov (United States)

    Maruyama, Masahiro; Takahara, Masatoshi; Kikuchi, Noriaki; Ito, Kazuo; Watanabe, Tadayoshi; Ogino, Toshihiko

    2009-01-01

    De Quervain disease is caused by a stenosing tenosynovitis in the first dorsal compartment, and the main aetiology is extensor pollicis brevis (EPB) tenosynovitis. We encountered three cases in which EPB tenosynovitis was absent and abductor pollicis longus (APL) tenosynovitis was confirmed during operation. In the treatment of de Quervain disease, APL tenosynovitis should be paid as much attention as EPB tenosynovitis.

  19. Milk and dairy consumption and risk of cardiovascular diseases and all-cause mortality

    DEFF Research Database (Denmark)

    Guo, Jing; Astrup, Arne; Lovegrove, Julie A

    2017-01-01

    With a growing number of prospective cohort studies, an updated dose-response meta-analysis of milk and dairy products with all-cause mortality, coronary heart disease (CHD) or cardiovascular disease (CVD) have been conducted. PubMed, Embase and Scopus were searched for articles published up...

  20. First report of mango malformation disease caused by Fusarium pseudocircinatum in Mexico

    Science.gov (United States)

    Mango (Mangifera indica L.) malformation disease (MMD) is one of the most important diseases affecting this crop worldwide, causing severe economic loss due to reduction of yield. Subsequent to the first report in India in 1891 (3), MMD has spread worldwide to most mango-growing regions. Several spe...

  1. Causes of Infectious Diseases Which Tend to Get Into Febrile Convulsion

    OpenAIRE

    Blouki Moghaddam; Bidabadi; Hassanzadeh Rad; Dalili

    2015-01-01

    Background Febrile convulsions are seizures associated with fever during childhood. They generally have excellent prognosis. However, as they may signify a serious underlying acute infectious disease, each case must be carefully examined and appropriately investigated. Objectives The aim of this study was to investigate the causes of infectious diseases, which tend to get into febrile convulsion in patients hospitalized in 17th Sh...

  2. Milk and dairy consumption and risk of cardiovascular diseases and all-cause mortality

    DEFF Research Database (Denmark)

    Guo, Jing; Astrup, Arne; Lovegrove, Julie A

    2017-01-01

    With a growing number of prospective cohort studies, an updated dose-response meta-analysis of milk and dairy products with all-cause mortality, coronary heart disease (CHD) or cardiovascular disease (CVD) have been conducted. PubMed, Embase and Scopus were searched for articles published up...

  3. First report of laurel wilt disease caused by Raffaelea lauricola on pondspice in Florida

    Science.gov (United States)

    M. Hughes; J.A. Smith; A.E. Mayfield III; M.C. Minno; K. Shin

    2011-01-01

    Laurel wilt is a fungal vascular disease of redbay (Persea borbonia (L.) Spreng) and other plants in the family Lauraceae in the southeastern United States (1). The disease is caused by Raffaelea lauricola T. C. Harr., Fraedrich & Aghayeva, which is vectored by the exotic redbay ambrosia beetle (Xyleborus glabratus...

  4. Annual all-cause mortality rate for patients with diabetic kidney disease in Singapore

    Directory of Open Access Journals (Sweden)

    Yee Gary Ang

    2016-06-01

    Conclusion: Our study estimated the annual all-cause mortality rate for Singaporean patients with diabetic kidney disease by CKD stages and identified predictors of all-cause mortality. This study has affirmed the poor prognosis of these patients and an urgency to intervene early so as to retard the progression to later stages of CKD.

  5. Mortality in adult congenital heart disease : Are national registries reliable for cause of death?

    NARCIS (Netherlands)

    Zomer, A. Carla; Uiterwaal, Cuno S. P. M.; van der Velde, Enno T.; Tijssen, Jan G. P.; Mariman, Edwin C. M.; Verheugt, Carianne L.; Vaartjes, Ilonca; Pieper, Petronella G.; Meijboom, Folkert J.; Grobbee, Diederick E.; Mulder, Barbara J. M.

    2011-01-01

    Background: Statistics on cause-specific mortality are important for prognostic research. The aim of this study was to assess the utility of the national mortality registry in research on causes of death in adult patients with congenital heart disease (CHD). Methods: The CONCOR registry of over

  6. Heart Disease: A Price Humans Pay for Fertility?

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_166826.html Heart Disease: A Price Humans Pay for Fertility? Study finds ... 22, 2017 (HealthDay News) -- Certain genes linked to heart disease may also improve your chances of having children, ...

  7. Biowarfare, bioterrorism, and animal diseases as bioweapons: Chapter 6 in Disease emergence and resurgence: The wildlife-human connection

    Science.gov (United States)

    Friend, Milton

    2006-01-01

    Linkages between disease in humans and the maladies of animals continue to be a focus for those concerned with disease effects on human health. References to animal diseases, particularly zoonoses such as rabies and glanders, are found in the writings of Greek (Hippocrates, Democritus, Aristotle, Galen, Dioscorides), Byzantine (Oribasius, Actius of Amida), and Roman (Pliny the Elder, Celsus) physicians and naturalists.3 Also, early advances in disease knowledge were closely associated with the study of contagions in animals to the extent that “The most complete ancient accounts of the concepts of contagion and contamination are found in treatises on veterinary medicine.”4,5Opportunities for disease transfer between animals and humans have increased during modern times, partly because of advances in animal husbandry and intensive agriculture that result in increased contacts among humans, domestic animals, and wildlife. Infectious pathogens exploit these contacts, and must be considered in this era of increased world tensions and international terrorism (Fig. 6.1).Disease emergence and resurgence are generally associated with natural processes and unanticipated outcomes related to human behavior and actions. That perspective has been broadened by recent acts of bioterrorism. A new category of deliberately emerging diseases contains emerging microbes that are developed by humans, usually for nefarious use.211 Included are naturally occurring microbial agents and those altered by bioengineering.This chapter highlights the wildlife component of the pathogen-host-environment triad to focus attention on the potential for bioterrorists to use wildlife as a means for infectious disease attacks against society. The value of this focus is that the underlying causes of disease emergence and the optimal prevention or control response frequently differ for disease emergence, resurgence, and deliberately emerging diseases.211 Differences also exist relative to the potential

  8. Dehydration as a Cause of Chronic Kidney Disease: Role of Fructokinase

    Science.gov (United States)

    2015-10-01

    of islet cell fructokinase in the development of diabetes . The liver fructokinase can also be targeted and may be responsible for the fatty liver and...Exercised-Induced Uric Acid Crystalluria: a Perspective on Mesoamerican Nephropathy? Am J Kid Dis (in press) 2. Garcia-Trabanino R, Jarquin E...common causes of end stage renal disease, such as diabetes , hypertension, glomerulonephritis, or polycystic kidney disease. Thus, the disease has been

  9. Modest Visceral Fat Gain Causes Endothelial Dysfunction In Healthy Humans

    Science.gov (United States)

    Romero-Corral, Abel; Sert-Kuniyoshi, Fatima H.; Sierra-Johnson, Justo; Orban, Marek; Gami, Apoor; Davison, Diane; Singh, Prachi; Pusalavidyasagar, Snigdha; Huyber, Christine; Votruba, Susanne; Lopez-Jimenez, Francisco; Jensen, Michael D.; Somers, Virend K.

    2014-01-01

    Objective This study sought to determine the impact of fat gain and its distribution on endothelial function in lean healthy humans. Background Endothelial dysfunction has been identified as an independent predictor of cardiovascular events. Whether fat gain impairs endothelial function is unknown. Methods A randomized controlled study to assess the effects of fat gain on endothelial function. We recruited 43 normal weight healthy volunteers (mean age 29 years; 18 women). Subjects were assigned to gain weight (approximately 4 kg) (n=35) or to maintain weight (n=8). Endothelial function (brachial artery flow mediated dilation -FMD) was measured at baseline, after fat gain (8 weeks) and after weight loss (16 weeks) for fat-gainers and at baseline and follow-up (8 weeks) for weight-maintainers. Body composition was measured by DXA and abdominal CT scans. Results After an average weight gain of 4.1 kg, fat-gainers significantly increased their total, visceral and subcutaneous fat. Blood pressure and overnight polysomnography did not change after fat gain or loss. FMD remained unchanged in weight-maintainers. FMD decreased in fat-gainers (9.1 ± 3% vs. 7.8 ± 3.2%, p =0.003), but recovered to baseline when subjects shed the gained weight. There was a significant correlation between the decrease in FMD and the increase in visceral fat gain (rho = −0.42, p=0.004), but not with subcutaneous fat gain (rho = −0.22, p=0.15). Conclusions In normal weight healthy young subjects, modest fat gain results in impaired endothelial function, even in the absence of changes in blood pressure. Endothelial function recovers after weight loss. Increased visceral rather than subcutaneous fat predicts endothelial dysfunction. PMID:20705223

  10. Human telomere biology: A contributory and interactive factor in aging, disease risks, and protection.

    Science.gov (United States)

    Blackburn, Elizabeth H; Epel, Elissa S; Lin, Jue

    2015-12-04

    Telomeres are the protective end-complexes at the termini of eukaryotic chromosomes. Telomere attrition can lead to potentially maladaptive cellular changes, block cell division, and interfere with tissue replenishment. Recent advances in the understanding of human disease processes have clarified the roles of telomere biology, especially in diseases of human aging and in some aging-related processes. Greater overall telomere attrition predicts mortality and aging-related diseases in inherited telomere syndrome patients, and also in general human cohorts. However, genetically caused variations in telomere maintenance either raise or lower risks and progression of cancers, in a highly cancer type-specific fashion. Telomere maintenance is determined by genetic factors and is also cumulatively shaped by nongenetic influences throughout human life; both can interact. These and other recent findings highlight both causal and potentiating roles for telomere attrition in human diseases.

  11. A nonsense mutation in the acid α-glucosidase gene causes Pompe disease in Finnish and Swedish Lapphunds.

    Directory of Open Access Journals (Sweden)

    Eija H Seppälä

    Full Text Available Pompe disease is a recessively inherited and often fatal disorder caused by the deficiency of acid α-glucosidase, an enzyme encoded by the GAA gene and needed to break down glycogen in lysosomes. This glycogen storage disease type II has been reported also in Swedish Lapphund dogs. Here we describe the genetic defect in canine Pompe disease and show that three related breeds from Scandinavia carry the same mutation. The affected dogs are homozygous for the GAA c.2237G>A mutation leading to a premature stop codon at amino acid position 746. The corresponding mutation has previously been reported in humans and causes infantile Pompe disease in combination with a second fully deleterious mutation. The affected dogs from both the Finnish as well as the Swedish breed mimic infantile-onset Pompe disease genetically, but also clinico-pathologically. Therefore this canine model provides a valuable tool for preclinical studies aimed at the development of gene therapy in Pompe disease.

  12. Addison's Disease Caused by Tuberculosis with Atypical Hyperpigmentation and Active Pulmonary Tuberculosis.

    Science.gov (United States)

    Namikawa, Hiroki; Takemoto, Yasuhiko; Kainuma, Shigeto; Umeda, Sakurako; Makuuchi, Ayako; Fukumoto, Kazuo; Kobayashi, Masanori; Kinuhata, Shigeki; Isaka, Yoshihiro; Toyoda, Hiromitsu; Kamata, Noriko; Tochino, Yoshihiro; Hiura, Yoshikazu; Morimura, Mina; Shuto, Taichi

    2017-01-01

    We herein report a case of Addison's disease caused by tuberculosis characterized by atypical hyperpigmentation, noted as exacerbation of the pigmentation of freckles and the occurrence of new freckles, that was diagnosed in the presence of active pulmonary tuberculosis. The clinical condition of the patient was markedly ameliorated by the administration of hydrocortisone and anti-tuberculosis agents. When exacerbation of the pigmentation of the freckles and/or the occurrence of new freckles are noted, Addison's disease should be considered as part of the differential diagnosis. In addition, the presence of active tuberculosis needs to be assumed whenever we treat patients with Addison's disease caused by tuberculosis, despite its rarity.

  13. Reg gene family and human diseases

    Institute of Scientific and Technical Information of China (English)

    Yu-Wei Zhang; Liu-Song Ding; Mao-De Lai

    2003-01-01

    Regenerating gene (Reg or REG) family, within the superfamily of C-type lectin, is mainly involved in the liver,pancreatic, gastric and intestinal cell proliferation or differentiation. Considerable attention has focused on Reg family and its structurally related molecules. Over the last 15 years, 17 members of the Reg family have been cloned and sequenced. They have been considered as members of a conserved protein family sharing structural and some functional properties being involved in injury, inflammation,diabetes and carcinogenesis. We previously identified Reg Ⅳ as a strong candidate for a gene that was highly expressed in colorectal adenoma when compared to normal mucosa based on suppression subtractive hybridization (SSH),reverse Northern blot, semi-quantitative reverse transcriptase PCR (RT-PCR)and Northern blot. In situ hybridization results further support that overexpression of Reg Ⅳ may be an early event in colorectal carcinogenesis. We suggest that detection of Reg Ⅳ overexpression might be useful in the early diagnosis of carcinomatous transformation of adenoma.This review summarizes the roles of Reg family in diseases in the literature as well as our recent results of Reg Ⅳ in colorectal cancer. The biological properties of Reg family and its possible roles in human diseases are discussed. We particularly focus on the roles of Reg family as sensitive reactants of tissue injury, prognostic indicators of tumor survival and early biomarkers of carcinogenesis. In addition to our current understanding of Reg gene functions, we postulate that there might be relationships between Reg family and microsatellite instability, apoptosis and cancer with a poor prognosis. Investigation of the correlation between tumor Reg expression and survival rate, and analysis of the Reg gene status in human maliganancies, are required to elucidate the biologic consequences of Reg gene expression, the implications for Reg gene regulation of cell growth, tumorigenesis

  14. Are 20 human papillomavirus types causing cervical cancer?

    Science.gov (United States)

    Arbyn, Marc; Tommasino, Massimo; Depuydt, Christophe; Dillner, Joakim

    2014-12-01

    In 2012, the International Agency for Research on Cancer concluded that there was consistent and sufficient epidemiological, experimental and mechanistic evidence of carcinogenicity to humans for 12 HPV types (HPV16, HPV18, HPV31, HPV33, HPV35, HPV39, HPV45, HPV51, HPV52, HPV56, HPV58 and HPV59) for cervical cancer. Therefore, these types were considered as 1A carcinogens. They all belong to the family of the α-Papillomaviridae, in particular to the species α5 (HPV51), α6 (HPV56), α7 (HPV18, HPV39, HPV45, HPV59) and α9 (HPV16, HPV31, HPV33, HPV35, HPV52, HPV58). Less evidence is available for a thirteenth type (HPV68, α7), which is classified as a 2A carcinogen (probably carcinogenic). Moreover, seven other phylogenetically related types (HPV26, HPV53, HPV66, HPV67, HPV68, HPV70 and HPV73) were identified as single HPV infections in certain rare cases of cervical cancer and were considered possibly carcinogenic (2B carcinogens). Recently, Halec et al [7] demonstrated that the molecular signature of HPV-induced carcinogenesis (presence of type-specific spliced E6*| mRNA; increased expression of p16; and decreased expression of cyclin D1, p53 and Rb) was similar in cervical cancers containing single infections with one of the eight afore-mentioned 2A or 2B carcinogens to those in cancers with single infections with group 1 carcinogens. Ninety six percent of cervical cancers are attributable to one of the 13 most common HPV types (groups 1 and 2A). Including the additional seven HPV types (group 2B) added 2.6%, to reach a total of 98.7% of all HPV-positive cervical cancers. From recently updated meta-analyses, it was shown that HPV68, HPV26, HPV66, HPV67, HPV73 and HPV82 were significantly more common in cancer cases than in women with normal cervical cytology, suggesting that for these HPV types, an upgrading of the carcinogen classification could be considered. However, there is no need to include them in HPV screening tests or vaccines, given their rarity in

  15. Ending versus controlling versus employing addiction in the tobacco-caused disease endgame: moral psychological perspectives

    Science.gov (United States)

    Kozlowski, Lynn T

    2013-01-01

    Even though interest in reducing or eliminating tobacco-caused diseases is a common goal in tobacco control, many experts hold different views on addiction as a target of intervention. Some consider tobacco-caused addiction as a tobacco-caused disease to be eliminated alongside the other diseases. Some consider tobacco-caused addiction as a much lower priority disease to be eliminated, and a subset of this group is prepared to employ addiction to tobacco (nicotine) as a tool to reduce other tobacco-caused disease. These varying attitudes towards ending, controlling or employing tobacco addiction to reduce damage from tobacco use constitute quite different approaches to tobacco control and cause conflict among those in tobacco control. Moral psychological analyses argue that there is more than scientific evidence involved in supporting this continuum of approaches. Divergent values also influence positions in tobacco control. Attention to these values as well as the scientific evidence should be included in policy and practice in tobacco control. It is not that one constellation of values is necessarily superior, but debates need to be informed by and engage discussions of these values as well as the scientific evidence. PMID:23591503

  16. Intensity of human prion disease surveillance predicts observed disease incidence

    NARCIS (Netherlands)

    G.M. Klug (Genevieve); H. Wand (Handan); M. Simpson (Marion); A. Boyd (Alison); M. Law (Matthew); C. Masters (Colin); R. Mateǰ (Radoslav); R. Howley (Rachel); M. Farrell (Michael); M. Breithaupt; I. Zerr (Inga); C.M. van Duijn (Cock); C.A. Ibrahim-Verbaas (Carla); J. Mackenzie; R.G. Will (Robert); J-P. Brandel (Jean-Philippe); A. Alperovitch (Annick); H. Budka (Herbert); G.G. Kovacs (Gabor); G.H. Jansen (Gerard); M. Coulthard (Michael); S.J. Collins (Steven)

    2013-01-01

    textabstractBackground: Prospective national screening and surveillance programmes serve a range of public health functions. Objectively determining their adequacy and impact on disease may be problematic for rare disorders. We undertook to assess whether objective measures of disease surveillance

  17. Lack of Neuronal IFN-β-IFNAR Causes Lewy Body- and Parkinson's Disease-like Dementia

    DEFF Research Database (Denmark)

    Ejlerskov, Patrick; Hultberg, Jeanette Göransdotter; Wang, JunYang;

    2015-01-01

    -causing mutant proteins. Mice lacking Ifnb function exhibited motor and cognitive learning impairments with accompanying α-synuclein-containing Lewy bodies in the brain, as well as a reduction in dopaminergic neurons and defective dopamine signaling in the nigrostriatal region. Lack of IFN-β signaling caused...... neuron loss in a familial Parkinson's disease model. These results indicate a protective role for IFN-β in neuronal homeostasis and validate Ifnb mutant mice as a model for sporadic Lewy body and Parkinson's disease dementia.......Neurodegenerative diseases have been linked to inflammation, but whether altered immunomodulation plays a causative role in neurodegeneration is not clear. We show that lack of cytokine interferon-β (IFN-β) signaling causes spontaneous neurodegeneration in the absence of neurodegenerative disease...

  18. Exonic rearrangements in the known Parkinson's disease-causing genes are a rare cause of the disease in South African patients.

    Science.gov (United States)

    van der Merwe, Celia; Carr, Jonathan; Glanzmann, Brigitte; Bardien, Soraya

    2016-04-21

    Parkinson's disease (PD) is a neurodegenerative movement disorder characterized by the loss of dopaminergic neurons in the substantia nigra of the midbrain. To date, a number of PD-causing genes have been found, including SNCA, LRRK2, VPS35, PARK2, PINK1, DJ-1, ATP13A2, and most recently CHCHD2. Mutations in these genes range from point mutations to larger exonic rearrangements including deletions and duplications. This study aimed to detect possible copy number variation (CNV) in the known PD-causing genes in a cohort of South African patients with PD. Multiplex Ligation-dependent Probe Amplification (MLPA) analysis was performed on a total of 210 South African PD patients, and possible CNVs were verified using quantitative real time PCR. No homozygous or compound heterozygous exon rearrangements in the genes analysed were found in the patient group. A heterozygous PARK2 exon 4 deletion was found in a sporadic patient with an age at onset of 51 years. Sanger sequencing did not reveal any additional mutations in PARK2 in this patient. Combining our results with that of previous studies in a South African cohort, the frequency of exonic rearrangements in the known PD-causing genes is only 1.8% (8/439 patients). In conclusion, CNV in the known PD-causing genes are a rare cause of PD in a South African cohort, and there may be as yet unknown genetic causes of PD that are specific to patients of African ethnicity.

  19. Familial Alzheimer's disease: genetic analysis related to disease heterogeneity, Down syndrome and human brain evolution.

    Science.gov (United States)

    Schapiro, M B; Rapoport, S I

    1989-01-01

    Etiologically heterogeneous subgroups of patients with Alzheimer's disease (AD) exist and need to be distinguished so as to better identify genetic causes of familial cases. Furthermore, the presence of AD neuropathology in Down syndrome (trisomy 21) subjects older than 35 years suggests that AD in some cases is caused by dysregulation of expression of genes on chromosome 21. Cerebral metabolic abnormalities in life, and the distribution of AD neuropathology in the post-mortem brain, indicate that AD involves the association neocortices and subcortical regions with which they evolved during evolution of the human brain. Accordingly, understanding the molecular basis of this evolution should elucidate the genetic basis of AD, whereas knowing the genetics of AD should be informative about the genomic changes which promoted brain evolution.

  20. Changes in the Leading Cause of Death: Recent Patterns in Heart Disease and Cancer Mortality.

    Science.gov (United States)

    Heron, Melonie; Anderson, Robert N

    2016-08-01

    Data from the National Vital Statistics System •Heart disease has consistently been the leading cause of death in the United States and remained so in 2014. •The gap between the number of heart disease and cancer deaths generally widened from 1950 through 1968, narrowed from 1968 through 2012, and then slightly widened again from 2012 through 2014. •The mortality burden of cancer has surpassed that of heart disease in several states. In 2000, there were only 2 states where cancer was the leading cause of death; in 2014, there were 22. •Heart disease remained the leading cause of death for the non-Hispanic white and non-Hispanic black populations in 2014. •Cancer is now the leading cause of death for the non-Hispanic Asian or Pacific Islander and Hispanic populations. The timing of the leading-cause crossover varied by group. For the total U.S. population, heart disease has been the leading cause of death for decades, with cancer the second leading cause (1). However, the ranking of these causes has varied across demographic group and geographic unit over time. Rankings are based on the number of deaths and reflect mortality burden rather than risk of death (2). This report highlights changes in the mortality burden of heart disease and cancer and presents findings by state, race, and Hispanic origin. All material appearing in this report is in the public domain and may be reproduced or copied without permission; citation as to source, however, is appreciated.

  1. Paget's disease of the skull causing hyperprolactinemia and erectile dysfunction: a case report

    Directory of Open Access Journals (Sweden)

    Hepherd Rachel

    2008-07-01

    Full Text Available Abstract Introduction Hyperprolactinemia is an uncommon cause of erectile dysfunction in men. Paget's disease of the skull is a relatively common disease. This case proposes a rare example of a causative link between the two and how treatment of the Paget's disease with bisphosphonates helped the patient regain erectile function. Case presentation A 67-year-old man with Paget's disease of the skull presented with prostatitis, erectile dysfunction, and hyperprolactinemia. Radio-isotope scanning showed increased vascularity around the sphenoid bone. Treatment with intravenous bisphosphonates improved the active Paget's disease as indicated by declining alkaline phosphatase levels and the patient's erectile function while serum prolactin levels became normal and serum testosterone levels remained unchanged. Conclusion It is possible that hyperprolactinemia is unrecognised in other patients with Paget's disease of the skull. Normalizing elevated prolactin levels by using bisphosphonates in treating Paget's disease appears to be more appropriate than traditional treatment for hyperprolactinemia.

  2. Human endogenous retrovirus-K contributes to motor neuron disease.

    Science.gov (United States)

    Li, Wenxue; Lee, Myoung-Hwa; Henderson, Lisa; Tyagi, Richa; Bachani, Muzna; Steiner, Joseph; Campanac, Emilie; Hoffman, Dax A; von Geldern, Gloria; Johnson, Kory; Maric, Dragan; Morris, H Douglas; Lentz, Margaret; Pak, Katherine; Mammen, Andrew; Ostrow, Lyle; Rothstein, Jeffrey; Nath, Avindra

    2015-09-30

    The role of human endogenous retroviruses (HERVs) in disease pathogenesis is unclear. We show that HERV-K is activated in a subpopulation of patients with sporadic amyotrophic lateral sclerosis (ALS) and that its envelope (env) protein may contribute to neurodegeneration. The virus was expressed in cortical and spinal neurons of ALS patients, but not in neurons from control healthy individuals. Expression of HERV-K or its env protein in human neurons caused retraction and beading of neurites. Transgenic animals expressing the env gene developed progressive motor dysfunction accompanied by selective loss of volume of the motor cortex, decreased synaptic activity in pyramidal neurons, dendritic spine abnormalities, nucleolar dysfunction, and DNA damage. Injury to anterior horn cells in the spinal cord was manifested by muscle atrophy and pathological changes consistent with nerve fiber denervation and reinnervation. Expression of HERV-K was regulated by TAR (trans-activation responsive) DNA binding protein 43, which binds to the long terminal repeat region of the virus. Thus, HERV-K expression within neurons of patients with ALS may contribute to neurodegeneration and disease pathogenesis. Copyright © 2015, American Association for the Advancement of Science.

  3. Two family members with a syndrome of headache and rash caused by human parvovirus B19

    Directory of Open Access Journals (Sweden)

    Antonio Carlos M. Pereira

    Full Text Available Human parvovirus B19 infection can cause erythema infectiosum (EI and several other clinical presentations. Central nervous system (CNS involvement is rare, and only a few reports of encephalitis and aseptic meningitis have been published. Here, we describe 2 cases of B19 infection in a family presenting different clinical features. A 30 year old female with a 7-day history of headache, malaise, myalgias, joint pains, and rash was seen. Physical examination revealed a maculopapular rash on the patient's body, and arthritis of the hands. She completely recovered in 1 week. Two days before, her 6 year old son had been admitted to a clinic with a 1-day history of fever, headache, abdominal pain and vomiting. On admission, he was alert, and physical examination revealed neck stiffness, Kerning and Brudzinski signs, and a petechial rash on his trunk and extremities. Cerebrospinal fluid analysis was normal. He completely recovered in 5 days. Acute and convalescent sera of both patients were positive for specific IgM antibody to B19. Human parvovirus B19 should be considered in the differential diagnosis of aseptic meningitis, particularly during outbreaks of erythema infectiosum. The disease may mimic meningococcemia and bacterial meningitis.

  4. Two family members with a syndrome of headache and rash caused by human parvovirus B19

    Directory of Open Access Journals (Sweden)

    Antonio Carlos M. Pereira

    2001-02-01

    Full Text Available Human parvovirus B19 infection can cause erythema infectiosum (EI and several other clinical presentations. Central nervous system (CNS involvement is rare, and only a few reports of encephalitis and aseptic meningitis have been published. Here, we describe 2 cases of B19 infection in a family presenting different clinical features. A 30 year old female with a 7-day history of headache, malaise, myalgias, joint pains, and rash was seen. Physical examination revealed a maculopapular rash on the patient's body, and arthritis of the hands. She completely recovered in 1 week. Two days before, her 6 year old son had been admitted to a clinic with a 1-day history of fever, headache, abdominal pain and vomiting. On admission, he was alert, and physical examination revealed neck stiffness, Kerning and Brudzinski signs, and a petechial rash on his trunk and extremities. Cerebrospinal fluid analysis was normal. He completely recovered in 5 days. Acute and convalescent sera of both patients were positive for specific IgM antibody to B19. Human parvovirus B19 should be considered in the differential diagnosis of aseptic meningitis, particularly during outbreaks of erythema infectiosum. The disease may mimic meningococcemia and bacterial meningitis.

  5. IgG4-related disease and other causes of inflammatory meningeal disease.

    Science.gov (United States)

    Carruthers, Robert; Carruthers, Mollie; Della-Torre, Emanuel

    2014-09-01

    Immunoglobulin-4 (IgG4-) related disease is a newly described treatable condition that has recently expanded the differential diagnosis of inflammatory meningeal disorders. This review will discuss the main clinical and pathophysiological features of IgG4-related meningeal disease in the context of meningeal inflammatory disorders in general. Particular attention will be dedicated to the differential diagnosis and the different therapeutic approaches.

  6. Protein Tau: Prime Cause of Synaptic and Neuronal Degeneration in Alzheimer's Disease

    Science.gov (United States)

    Crespo-Biel, Natalia; Theunis, Clara; Van Leuven, Fred

    2012-01-01

    The microtubule-associated protein Tau (MAPT) is a major component of the pathogenesis of a wide variety of brain-damaging disorders, known as tauopathies. These include Alzheimer's disease (AD), denoted as secondary tauopathy because of the obligatory combination with amyloid pathology. In all tauopathies, protein Tau becomes aberrantly phosphorylated, adopts abnormal conformations, and aggregates into fibrils that eventually accumulate as threads in neuropil and as tangles in soma. The argyrophilic neurofibrillary threads and tangles, together denoted as NFT, provide the postmortem pathological diagnosis for all tauopathies. In AD, neurofibrillary threads and tangles (NFTs) are codiagnostic with amyloid depositions but their separated and combined contributions to clinical symptoms remain elusive. Importantly, NFTs are now considered a late event and not directly responsible for early synaptic dysfunctions. Conversely, the biochemical and pathological timeline is not exactly known in human tauopathy, but experimental models point to smaller Tau-aggregates, termed oligomers or multimers, as synaptotoxic in early stages. The challenge is to molecularly define these Tau-isoforms that cause early cognitive and synaptic impairments. Here, we discuss relevant studies and data obtained in our mono- and bigenic validated preclinical models, with the perspective of Tau as a therapeutic target. PMID:22720188

  7. Protein Tau: Prime Cause of Synaptic and Neuronal Degeneration in Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Natalia Crespo-Biel

    2012-01-01

    Full Text Available The microtubule-associated protein Tau (MAPT is a major component of the pathogenesis of a wide variety of brain-damaging disorders, known as tauopathies. These include Alzheimer's disease (AD, denoted as secondary tauopathy because of the obligatory combination with amyloid pathology. In all tauopathies, protein Tau becomes aberrantly phosphorylated, adopts abnormal conformations, and aggregates into fibrils that eventually accumulate as threads in neuropil and as tangles in soma. The argyrophilic neurofibrillary threads and tangles, together denoted as NFT, provide the postmortem pathological diagnosis for all tauopathies. In AD, neurofibrillary threads and tangles (NFTs are codiagnostic with amyloid depositions but their separated and combined contributions to clinical symptoms remain elusive. Importantly, NFTs are now considered a late event and not directly responsible for early synaptic dysfunctions. Conversely, the biochemical and pathological timeline is not exactly known in human tauopathy, but experimental models point to smaller Tau-aggregates, termed oligomers or multimers, as synaptotoxic in early stages. The challenge is to molecularly define these Tau-isoforms that cause early cognitive and synaptic impairments. Here, we discuss relevant studies and data obtained in our mono- and bigenic validated preclinical models, with the perspective of Tau as a therapeutic target.

  8. Analysis of the Legionella longbeachae genome and transcriptome uncovers unique strategies to cause Legionnaires' disease.

    Directory of Open Access Journals (Sweden)

    Christel Cazalet

    2010-02-01

    Full Text Available Legionella pneumophila and L. longbeachae are two species of a large genus of bacteria that are ubiquitous in nature. L. pneumophila is mainly found in natural and artificial water circuits while L. longbeachae is mainly present in soil. Under the appropriate conditions both species are human pathogens, capable of causing a severe form of pneumonia termed Legionnaires' disease. Here we report the sequencing and analysis of four L. longbeachae genomes, one complete genome sequence of L. longbeachae strain NSW150 serogroup (Sg 1, and three draft genome sequences another belonging to Sg1 and two to Sg2. The genome organization and gene content of the four L. longbeachae genomes are highly conserved, indicating strong pressure for niche adaptation. Analysis and comparison of L. longbeachae strain NSW150 with L. pneumophila revealed common but also unexpected features specific to this pathogen. The interaction with host cells shows distinct features from L. pneumophila, as L. longbeachae possesses a unique repertoire of putative Dot/Icm type IV secretion system substrates, eukaryotic-like and eukaryotic domain proteins, and encodes additional secretion systems. However, analysis of the ability of a dotA mutant of L. longbeachae NSW150 to replicate in the Acanthamoeba castellanii and in a mouse lung infection model showed that the Dot/Icm type IV secretion system is also essential for the virulence of L. longbeachae. In contrast to L. pneumophila, L. longbeachae does not encode flagella, thereby providing a possible explanation for differences in mouse susceptibility to infection between the two pathogens. Furthermore, transcriptome analysis revealed that L. longbeachae has a less pronounced biphasic life cycle as compared to L. pneumophila, and genome analysis and electron microscopy suggested that L. longbeachae is encapsulated. These species-specific differences may account for the different environmental niches and disease epidemiology of these

  9. Human disease resulting from exposure to electromagnetic fields.

    Science.gov (United States)

    Carpenter, David O

    2013-01-01

    Electromagnetic fields (EMFs) include everything from cosmic rays through visible light to the electric and magnetic fields associated with electricity. While the high frequency fields have sufficient energy to cause cancer, the question of whether there are human health hazards associated with communication radiofrequency (RF) EMFs and those associated with use of electricity remains controversial. The issue is more important than ever given the rapid increase in the use of cell phones and other wireless devices. This review summarizes the evidence stating that excessive exposure to magnetic fields from power lines and other sources of electric current increases the risk of development of some cancers and neurodegenerative diseases, and that excessive exposure to RF radiation increases risk of cancer, male infertility, and neurobehavioral abnormalities. The relative impact of various sources of exposure, the great range of standards for EMF exposure, and the costs of doing nothing are also discussed.

  10. Targeting Splicing in the Treatment of Human Disease

    Directory of Open Access Journals (Sweden)

    Marc Suñé-Pou

    2017-02-01

    Full Text Available The tightly regulated process of precursor messenger RNA (pre-mRNA alternative splicing (AS is a key mechanism in the regulation of gene expression. Defects in this regulatory process affect cellular functions and are the cause of many human diseases. Recent advances in our understanding of splicing regulation have led to the development of new tools for manipulating splicing for therapeutic purposes. Several tools, including antisense oligonucleotides and trans-splicing, have been developed to target and alter splicing to correct misregulated gene expression or to modulate transcript isoform levels. At present, deregulated AS is recognized as an important area for therapeutic intervention. Here, we summarize the major hallmarks of the splicing process, the clinical implications that arise from alterations in this process, and the current tools that can be used to deliver, target, and correct deficiencies of this key pre-mRNA processing event.

  11. Estrogen receptor polymorphisms: significance to human physiology, disease and therapy.

    Science.gov (United States)

    Figtree, Gemma A; Noonan, Jonathon E; Bhindi, Ravinay; Collins, Peter

    2009-01-01

    Other than its well-recognized effects on reproductive physiology, estrogen has important actions in a wide variety of other body systems with important examples including bone, blood vessels and the heart. These effects are seen in both females and males. Investigators have hypothesized those genetic variants in the genes coding for estrogen signaling proteins may cause variable sensitivity to the hormone and influence an individual's estrogen-sensitive phenotypes. The most obvious candidate genes are the estrogen receptors alpha and (ERalpha and beta). However, the regulation of these genes is complex and not well understood. Furthermore, their coding exons, and regulatory sequences are dispersed across large segments of the genome. A number of common polymorphisms have been identified in both ERalpha and ERbeta, with variable degrees of evidence of their direct biological significance and their association with human disease. The identification of genetic variations associated with altered estrogen response is of potential public health importance. Insights may be gained into the pathogenesis of estrogen sensitive diseases such as osteoporosis, breast cancer and cardiovascular disease contributing to the development and application of newer therapies for these disorders. Furthermore, genetic variants that alter sensitivity to estrogen may affect both therapeutic and harmful responses to exogenous estrogen administered in the form of the oral contraceptive pill or hormone replacement therapy. This clinical significance has led to the publication of a number of patents which will be reviewed.

  12. Thymic Epithelial Cell Development and Its Dysfunction in Human Diseases

    Directory of Open Access Journals (Sweden)

    Lina Sun

    2014-01-01

    Full Text Available Thymic epithelial cells (TECs are the key components in thymic microenvironment for T cells development. TECs, composed of cortical and medullary TECs, are derived from a common bipotent progenitor and undergo a stepwise development controlled by multiple levels of signals to be functionally mature for supporting thymocyte development. Tumor necrosis factor receptor (TNFR family members including the receptor activator for NFκB (RANK, CD40, and lymphotoxin β receptor (LTβR cooperatively control the thymic medullary microenvironment and self-tolerance establishment. In addition, fibroblast growth factors (FGFs, Wnt, and Notch signals are essential for establishment of functional thymic microenvironment. Transcription factors Foxn1 and autoimmune regulator (Aire are powerful modulators of TEC development, differentiation, and self-tolerance. Dysfunction in thymic microenvironment including defects of TEC and thymocyte development would cause physiological disorders such as tumor, infectious diseases, and autoimmune diseases. In the present review, we will summarize our current understanding on TEC development and the underlying molecular signals pathways and the involvement of thymus dysfunction in human diseases.

  13. AFSC/NMML: Known human-caused marine mammal injury and mortalities from 2007 to present

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The National Marine Fisheries Service (NMFS) is required under the MMPA to estimate the annual human-caused mortality and serious injury of marine mammal stocks by...

  14. The implications of relationships between human diseases and metabolic subpathways.

    Directory of Open Access Journals (Sweden)

    Xia Li

    Full Text Available One of the challenging problems in the etiology of diseases is to explore the relationships between initiation and progression of diseases and abnormalities in local regions of metabolic pathways. To gain insight into such relationships, we applied the "k-clique" subpathway identification method to all disease-related gene sets. For each disease, the disease risk regions of metabolic pathways were then identified and considered as subpathways associated with the disease. We finally built a disease-metabolic subpathway network (DMSPN. Through analyses based on network biology, we found that a few subpathways, such as that of cytochrome P450, were highly connected with many diseases, and most belonged to fundamental metabolisms, suggesting that abnormalities of fundamental metabolic processes tend to cause more types of diseases. According to the categories of diseases and subpathways, we tested the clustering phenomenon of diseases and metabolic subpathways in the DMSPN. The results showed that both disease nodes and subpathway nodes displayed slight clustering phenomenon. We also tested correlations between network topology and genes within disease-related metabolic subpathways, and found that within a disease-related subpathway in the DMSPN, the ratio of disease genes and the ratio of tissue-specific genes significantly increased as the number of diseases caused by the subpathway increased. Surprisingly, the ratio of essential genes significantly decreased and the ratio of housekeeping genes remained relatively unchanged. Furthermore, the coexpression levels between disease genes and other types of genes were calculated for each subpathway in the DMSPN. The results indicated that those genes intensely influenced by disease genes, including essential genes and tissue-specific genes, might be significantly associated with the disease diversity of subpathways, suggesting that different kinds of genes within a disease-related subpathway may play

  15. Human pluripotent stem cells: applications and challenges in neurological diseases

    Directory of Open Access Journals (Sweden)

    Youssef eHIBAOUI

    2012-07-01

    Full Text Available The ability to generate human pluripotent stem cells (hPSCs holds great promise for the understanding and the treatment of human neurological diseases in modern medicine. The hPSCs are considered for their in vitro use as research tools to provide relevant cellular model for human diseases, drug discovery and toxicity assays and for their in vivo use in regenerative medicine applications. In this review, we highlight recent progress, promises and challenges of hPSC applications in human neurological disease modelling and therapies.

  16. Modeling human disease using organotypic cultures

    DEFF Research Database (Denmark)

    Schweiger, Pawel J; Jensen, Kim B

    2016-01-01

    Reliable disease models are needed in order to improve quality of healthcare. This includes gaining better understanding of disease mechanisms, developing new therapeutic interventions and personalizing treatment. Up-to-date, the majority of our knowledge about disease states comes from in vivo...

  17. Infantile onset spinocerebellar ataxia caused by compound heterozygosity for Twinkle mutations and modeling of Twinkle mutations causing recessive disease

    Science.gov (United States)

    Gulsuner, Suleyman; Stapleton, Gail A.; Walsh, Tom; Lee, Ming K.; Mandell, Jessica B.; Morales, Augusto; Klevit, Rachel E.; King, Mary-Claire; Rogers, R. Curtis

    2016-01-01

    Mutations in nuclear genes required for the replication and maintenance of mitochondrial DNA cause progressive multisystemic neuromuscular disorders with overlapping phenotypes. Biallelic mutations in C10orf2, encoding the Twinkle mitochondrial DNA helicase, lead to infantile-onset cerebellar ataxia (IOSCA), as well as milder and more severe phenotypes. We present a 13-year-old girl with ataxia, severe hearing loss, optic atrophy, peripheral neuropathy, and hypergonadotropic hypogonadism. Whole-exome sequencing revealed that the patient is compound heterozygous for previously unreported variants in the C10orf2 gene: a paternally inherited frameshift variant (c.333delT; p.L112Sfs*3) and a maternally inherited missense variant (c.904C>T; p.R302W). The identification of novel C10orf2 mutations extends the spectrum of mutations in the Twinkle helicase causing recessive disease, in particular the intermediate IOSCA phenotype. Structural modeling suggests that the p.R302W mutation and many other recessively inherited Twinkle mutations impact the position or interactions of the linker region, which is critical for the oligomeric ring structure and activity of the helicase. This study emphasizes the utility of whole-exome sequencing for the genetic diagnosis of a complex multisystemic disorder. PMID:27551684

  18. Alzheimer's Disease: A Pathogenetic Autoimmune Disorder Caused by Herpes Simplex in a Gene-Dependent Manner

    Directory of Open Access Journals (Sweden)

    C. J. Carter

    2010-01-01

    Full Text Available Herpes simplex is implicated in Alzheimer's disease and viral infection produces Alzheimer's disease like pathology in mice. The virus expresses proteins containing short contiguous amino acid stretches (5–9aa “vatches” = viralmatches homologous to APOE4, clusterin, PICALM, and complement receptor 1, and to over 100 other gene products relevant to Alzheimer's disease, which are also homologous to proteins expressed by other pathogens implicated in Alzheimer's disease. Such homology, reiterated at the DNA level, suggests that gene association studies have been tracking infection, as well as identifying key genes, demonstrating a role for pathogens as causative agents. Vatches may interfere with the function of their human counterparts, acting as dummy ligands, decoy receptors, or via interactome interference. They are often immunogenic, and antibodies generated in response to infection may target their human counterparts, producing protein knockdown, or generating autoimmune responses that may kill the neurones in which the human homologue resides, a scenario supported by immune activation in Alzheimer's disease. These data may classify Alzheimer's disease as an autoimmune disorder created by pathogen mimicry of key Alzheimer's disease-related proteins. It may well be prevented by vaccination and regular pathogen detection and elimination, and perhaps stemmed by immunosuppression or antibody adsorption-related therapies.

  19. Genomic signatures of human and animal disease in the zoonotic pathogen Streptococcus suis.

    Science.gov (United States)

    Weinert, Lucy A; Chaudhuri, Roy R; Wang, Jinhong; Peters, Sarah E; Corander, Jukka; Jombart, Thibaut; Baig, Abiyad; Howell, Kate J; Vehkala, Minna; Välimäki, Niko; Harris, David; Chieu, Tran Thi Bich; Van Vinh Chau, Nguyen; Campbell, James; Schultsz, Constance; Parkhill, Julian; Bentley, Stephen D; Langford, Paul R; Rycroft, Andrew N; Wren, Brendan W; Farrar, Jeremy; Baker, Stephen; Hoa, Ngo Thi; Holden, Matthew T G; Tucker, Alexander W; Maskell, Duncan J

    2015-03-31

    Streptococcus suis causes disease in pigs worldwide and is increasingly implicated in zoonotic disease in East and South-East Asia. To understand the genetic basis of disease in S. suis, we study the genomes of 375 isolates with detailed clinical phenotypes from pigs and humans from the United Kingdom and Vietnam. Here, we show that isolates associated with disease contain substantially fewer genes than non-clinical isolates, but are more likely to encode virulence factors. Human disease isolates are limited to a single-virulent population, originating in the 1920, s when pig production was intensified, but no consistent genomic differences between pig and human isolates are observed. There is little geographical clustering of different S. suis subpopulations, and the bacterium undergoes high rates of recombination, implying that an increase in virulence anywhere in the world could have a global impact over a short timescale.

  20. Elevated C-reactive protein, depression, somatic diseases, and all-cause mortality

    DEFF Research Database (Denmark)

    Wium-Andersen, Marie Kim; Orsted, David Dynnes; Nordestgaard, Børge Grønne

    2014-01-01

    population. End points included hospitalization or death with depression and somatic diseases, prescription antidepressant medication use, and all-cause mortality. RESULTS: A doubling in plasma CRP yielded an observed odds ratio (OR) of 1.28 (95% confidence interval [CI]: 1.23-1.33) for hospitalization...... of cancer (p = .002), ischemic heart disease (p = 4 × 10(-99)), chronic obstructive pulmonary disease (p = 6 × 10(-86)), and all-cause mortality (p = .001) examined in the same individuals. CONCLUSIONS: Elevated CRP was associated with increased risk of depression in individuals in the general population......BACKGROUND: Elevated levels of plasma C-reactive protein (CRP) have been associated with many diseases including depression, but it remains unclear whether this association is causal. We tested the hypothesis that CRP is causally associated with depression, and compared these results to those...

  1. Taxonomy of fungi causing mucormycosis and entomophthoramycosis (zygomycosis) and nomenclature of the disease: molecular mycologic perspectives.

    Science.gov (United States)

    Kwon-Chung, Kyung J

    2012-02-01

    Molecular phylogenetic analysis confirmed the phylum Zygomycota to be polyphyletic, and the taxa conventionally classified in Zygomycota are now distributed among the new phylum Glomeromycota and 4 subphyla incertae sedis (uncertain placement). Because the nomenclature of the disease zygomycosis was based on the phylum Zygomycota (Zygomycetes) in which the etiologic agents had been classified, the new classification profoundly affects the name of the disease. Zygomycosis was originally described as a convenient and inclusive name for 2 clinicopathologically different diseases, mucormycosis caused by members of Mucorales and entomophthoramycosis caused by species in the order Entomophthorales of Zygomycota. Without revision of original definition, the name "zygomycosis," however, has more often been used as a synonym only for mucormycosis. This article reviews the progress and changes in taxonomy and nomenclature of Zygomycota and the disease zygomycosis. The article also reiterates the reasons why the classic names "mucormycosis" and "entomophthoramycosis" are more appropriate than "zygomycosis."

  2. Polycystic Thyroid Disease in Pediatric Patients: An Uncommon Cause of Hypothyroidism.

    Science.gov (United States)

    Naranjo, Isaac Daimiel; Robinot, David Coca; Rojo, Jaime Cruz; Ponferrada, Miguel Rasero

    2016-01-01

    Polycystic thyroid disease has been described as a rare cause of hypothyroidism. This uncommon entity has been reported in adults within areas with high iodine intake. Sonographic findings of multiple small thin-walled simple thyroid cysts in the context of hypothyroidism without thyroid autoantibodies are highly suggestive of this diagnosis. To our knowledge, we report the first 2 cases of polycystic thyroid disease in pediatric patients in Europe.

  3. Echinococcal disease of the bone: An unusual cause of a pathological fracture

    Directory of Open Access Journals (Sweden)

    Matthew Goodier

    2010-12-01

    Full Text Available Echinococcosis is caused by the larva of the tapeworm, Echinococcus granulosus or Echinococcus multiloccularis and is endemic in many rural areas of Southern Africa. Echinococcosis of the bone is an unusual manifestation of echinococcal disease and a rare cause of a lytic lesion of bone. This report describes a 30-yr old female who presented with an Echinococcal cyst of the right radius complicated by a pathological fracture.

  4. Cluster of infections caused by methicillin-resistant Staphylococcus pseudintermedius in humans in a tertiary hospital.

    Science.gov (United States)

    Starlander, Gustaf; Börjesson, Stefan; Grönlund-Andersson, Ulrika; Tellgren-Roth, Christian; Melhus, Asa

    2014-08-01

    The dog-associated Staphylococcus pseudintermedius is a rare pathogen in humans. Here we describe a cluster of infections caused by the methicillin-resistant S. pseudintermedius clone ST71-J-t02-II-III. It involved four elderly patients at a tertiary hospital. Three patients had wound infections, and the strain had a tendency to cause bullous skin lesions.

  5. Mutations in the glucose-6-phosphatase gene that cause glycogen storage disease type 1a

    Energy Technology Data Exchange (ETDEWEB)

    Chou, J.Y.; Lei, K.J.; Shelly, L.L. [National Institutes of Health, Bethesda, MD (United States)

    1994-09-01

    Glycogen storage disease (GSD) type la (von Gierke disease) is caused by the deficiency of glucose-6-phosphatase (G6Pase), the key enzyme in glucose homeostasis. The disease presents with clinical manifestations of severe hypoglycemia, hepatomegaly, growth retardation, lactic acidemia, hyperlipidemia, and hyperuricemia. We have succeeded in isolating a murine G6Pase cDNA from a normal mouse liver cDNA library by differentially screening method. We then isolated the human G6Pase cDNA and gene. To date, we have characterized the G6Pase genes of twelve GSD type la patients and uncovered a total of six different mutations. The mutations are comprised of R83C (an Arg at codon 83 to a Cys), Q347X (a Gly at codon 347 to a stop codon), 459insTA (a two basepair insertion at nucleotide 459 yielding a truncated G6Pase of 129 residues), R295C (an Arg at codon 295 to a Cys), G222R (a Gly at codon 222 to an Arg) and {delta}F327 (a codon deletion for Phe-327 at nucleotides 1058 to 1060). The relative incidences of these mutations are 37.5% (R83C), 33.3% (Q347X), 16.6% (459insTA), 4.2% (G222R), 4.2% (R295C) and 4.2% ({delta}F327). Site-directed mutagenesis and transient expression assays demonstrated that the R83C, Q347X, R295C, and {delta}F327 mutations abolished whereas the G222R mutation greatly reduced G6Pase activity. We further characterized the structure-function requirements of amino acids 83, 222, and 295 in G6Pase catalysis. The identification of mutations in GSD type la patients has unequivocally established the molecular basis of the type la disorder. Knowledge of the mutations may be applied to prenatal diagnosis and opens the way for developing and evaluating new therapeutic approaches.

  6. Strength of Occipital Hair as an Explanation for Pilonidal Sinus Disease Caused by Intruding Hair.

    Science.gov (United States)

    Doll, Dietrich; Bosche, Friederike D; Stauffer, Verena K; Sinicina, Inga; Hoffmann, Sebastian; van der Zypen, Dominic; Luedi, Markus M

    2017-09-01

    Pilonidal sinus disease is thought to be caused by intrusion of hair into healthy skin; loose hair in the intergluteal fold is thought to promote disease. However, compelling evidence to support these postulates is lacking; the cause of pilonidal sinus disease remains uncertain. To determine whether particular properties of hair are associated with susceptibility to pilonidal sinus disease, we compared physical properties of hairs of patients with pilonidal sinus disease with hairs from control subjects who were matched for sex, BMI, and age. This was an experimental study with establishment of a mechanical strength test for single hairs to quantify the maximum vertical force that a hair could exert, following tests of strength of occipital, lumbar, and intergluteal hair. Hair from patients with pilonidal sinus disease and matched control subjects were harvested from patients of the St. Marienhospital Vechta Department of Procto-Surgery. A total of 17 adult patients with pilonidal sinus disease and 217 control subjects were included. ANOVA and intraclass and interclass variations of data gained from mechanical strength tests of occipital, lumbar, and intergluteal hair were included. Vertical hair strength was significantly greater in patients with pilonidal sinus disease. Occipital hair exhibited 20% greater, glabella sacralis 1.1 times greater, and intergluteal hair 2 times greater strength in patients with pilonidal sinus disease than in matched control subjects (all p = 0.0001). In addition, patients with pilonidal sinus disease presented with significantly more hair at the glabella sacralis and in the intergluteal fold. The study was limited by its relatively small number of patients from a specific cohort of European patients. Occipital hair exhibited considerable vertical strength. Because occipital hair exerted the greatest force and cut hair fragments were found in the pilonidal nest in large quantities, these data suggest that pilonidal sinus disease is

  7. Pictures of you: Dot stimuli cause motor contagion in presence of a still human form.

    Science.gov (United States)

    Sparks, S; Sidari, M; Lyons, M; Kritikos, A

    2016-10-01

    In this study, we investigate which visual cues induce participants to encode a non-human motion stimulus in their motor system. Participants performed reach-to-grasp actions to a target after observing a dot moving in a direct or higher-arcing path across a screen. Dot motion occurred in the presence of a meaningless (scrambled human model) stimulus, a still human model, or a human model performing a direct or exaggeratedly curved reach to a target. Our results show that observing the dot displacement causes motor contagion (changes in the height of the observer's hand trajectory) when a human form was visually present in the background (either moving or still). No contagion was evident, however, when this human context was absent (i.e., human image scrambled and not identifiable). This indicates that visual cues suggestive of human agency can determine whether or not moving stimuli are encoded in the motor system.

  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. Diffuse cystic lung disease of unexplained cause with coexistent small airway disease: a possible causal relationship?

    Science.gov (United States)

    Rowan, Camilla; Hansell, David M; Renzoni, Elisabetta; Maher, Toby M; Wells, Athol U; Polkey, Michael I; Rehal, Pauline K; Ibrahim, Wanis H; Kwong, Georges Ng Man; Colby, Thomas V; Pistolesi, Massimo; Bigazzi, Francesca; Comin, Camilla E; Nicholson, Andrew G

    2012-02-01

    Diffuse "true" cystic lung disease is rare, and the specificity of high-resolution computed tomography (HRCT) has reduced the need for biopsy. We present 5 patients with similar clinical and HRCT features of cystic lung disease that were sufficiently atypical to warrant surgical lung biopsies that showed coexistent small airway diseases (SAD). There were 4 female patients and 1 male patient with a mean age of 43 years. All were never smokers. Four had symptoms such as dyspnea (1), cough (2), or both (1). HRCTs showed variably sized thin-walled cystic airspaces without zonal distribution, some with prominent vessels in their walls. One case was unilateral. Surgical lung biopsy showed cystic change comprising localized loss of alveolar density with coexistent SADs [chronic bronchiolitis (n=2), eosinophilic bronchiolitis, probable asthma (n=1), and diffuse idiopathic neuroendocrine cell hyperplasia (n=2)]. Two patients who were tested for Birt-Hogg-Dube-related gene mutations proved negative, and all lacked other features of Birt-Hogg-Dube. We hypothesize that chronic damage to small airways may lead to cystic degeneration in a minority of patients. Precedents in relation to Sjogren syndrome and hypersensitivity pneumonitis raise the possibility of a causal association between pathologies in these 2 anatomic compartments, although HRCT data in relation to common SADs indicate that this would be a rare phenomenon. The driving factor remains unknown.

  10. The spectrum of nephrocutaneous diseases and associations: Genetic causes of nephrocutaneous disease.

    Science.gov (United States)

    Wofford, Jay; Fenves, Andrew Z; Jackson, J Mark; Kimball, Alexa B; Menter, Alan

    2016-02-01

    There are a significant number of diseases and treatment considerations of considerable importance relating to the skin and renal systems. This emphasizes the need for dermatologists in practice or in clinical training to be aware of these associations. Part I of this 2-part continuing medical education article reviews the genetic syndromes with both renal and cutaneous involvement that are most important for the dermatologist to be able to identify, manage, and appropriately refer to nephrology colleagues. Part II reviews the inflammatory syndromes with relevant renal manifestations and therapeutic agents commonly used by dermatologists that have drug-induced effects on or require close consideration of renal function. In addition, we will likewise review therapeutic agents commonly used by nephrologists that have drug-induced effects on the skin that dermatologists are likely to encounter in clinical practice. In both parts of this continuing medical education article, we discuss diagnosis, management, and appropriate referral to our nephrology colleagues in the context of each nephrocutaneous association. There are a significant number of dermatoses associated with renal abnormalities and disease, emphasizing the need for dermatologists to be keenly aware of their presence in order to avoid overlooking important skin conditions with potentially devastating renal complications. This review discusses important nephrocutaneous disease associations with recommendations for the appropriate urgency of referral to nephrology colleagues for diagnosis, surveillance, and early management of potential renal sequelae.

  11. A previously unknown reovirus of bat origin is associated with an acute respiratory disease in humans.

    Science.gov (United States)

    Chua, Kaw Bing; Crameri, Gary; Hyatt, Alex; Yu, Meng; Tompang, Mohd Rosli; Rosli, Juliana; McEachern, Jennifer; Crameri, Sandra; Kumarasamy, Verasingam; Eaton, Bryan T; Wang, Lin-Fa

    2007-07-03

    Respiratory infections constitute the most widespread human infectious disease, and a substantial proportion of them are caused by unknown etiological agents. Reoviruses (respiratory enteric orphan viruses) were first isolated from humans in the early 1950s and so named because they were not associated with any known disease. Here, we report a previously unknown reovirus (named "Melaka virus") isolated from a 39-year-old male patient in Melaka, Malaysia, who was suffering from high fever and acute respiratory disease at the time of virus isolation. Two of his family members developed similar symptoms approximately 1 week later and had serological evidence of infection with the same virus. Epidemiological tracing revealed that the family was exposed to a bat in the house approximately 1 week before the onset of the father's clinical symptoms. Genome sequence analysis indicated a close genetic relationship between Melaka virus and Pulau virus, a reovirus isolated in 1999 from fruit bats in Tioman Island, Malaysia. Screening of sera collected from human volunteers on the island revealed that 14 of 109 (13%) were positive for both Pulau and Melaka viruses. This is the first report of an orthoreovirus in association with acute human respiratory diseases. Melaka virus is serologically not related to the different types of mammalian reoviruses that were known to infect humans asymptomatically. These data indicate that bat-borne reoviruses can be transmitted to and cause clinical diseases in humans.

  12. [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.

  13. Gastrointestinal stromal tumor causing small bowel intussusception in a patient with Crohn's disease

    Institute of Scientific and Technical Information of China (English)

    George E Theodoropoulos; Dimitrios Linardoutsos; Dimitrios Tsamis; Paraskevas Stamopoulos; Dimitrios Giannopoulos; Flora Zagouri; Nikolaos V Michalopoulos

    2009-01-01

    We report a case of jejunoileal intussusception in a 42-year-old patient with Crohn's disease caused by a gastrointestinal stromal tumor. The patient complained of vague diffuse abdominal pain for a period of 4 mo. Intussusception was suspected at computer tomography and magnetic resonance imaging scans. Segmental resection of the small intestine was performed. Pathological examination of the surgical specimen revealed a gastrointestinal stromal tumor as well as aphthous ulcerations and areas of inflammation, which were characteristic of Crohn's disease. This is the first report of small bowel intussusception due to a gastrointestinal stromal tumor coexisting with Crohn's disease.

  14. A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome.

    Science.gov (United States)

    Wiseman, Frances K; Al-Janabi, Tamara; Hardy, John; Karmiloff-Smith, Annette; Nizetic, Dean; Tybulewicz, Victor L J; Fisher, Elizabeth M C; Strydom, André

    2015-09-01

    Down syndrome, which arises in individuals carrying an extra copy of chromosome 21, is associated with a greatly increased risk of early-onset Alzheimer disease. It is thought that this risk is conferred by the presence of three copies of the gene encoding amyloid precursor protein (APP)--an Alzheimer disease risk factor--although the possession of extra copies of other chromosome 21 genes may also play a part. Further study of the mechanisms underlying the development of Alzheimer disease in people with Down syndrome could provide insights into the mechanisms that cause dementia in the general population.

  15. A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome

    Science.gov (United States)

    Wiseman, Frances K.; Al-Janabi, Tamara; Hardy, John; Karmiloff-Smith, Annette; Nizetic, Dean; Tybulewicz, Victor L. J.; Fisher, Elizabeth M. C.; Strydom, André

    2015-01-01

    Down syndrome, which arises in individuals carrying an extra copy of chromosome 21, is associated with a greatly increased risk of early-onset Alzheimer disease. It is thought that this risk is conferred by the presence of three copies of the gene encoding amyloid precursor protein (APP) — an Alzheimer disease risk factor — although the possession of extra copies of other chromosome 21 genes may also play a part. Further study of the mechanisms underlying the development of Alzheimer disease in people with Down syndrome could provide insights into the mechanisms that cause dementia in the general population. PMID:26243569

  16. Chronic exposure to low benzo[a]pyrene level causes neurodegenerative disease-like syndromes in zebrafish (Danio rerio).

    Science.gov (United States)

    Gao, Dongxu; Wu, Meifang; Wang, Chonggang; Wang, Yuanchuan; Zuo, Zhenghong

    2015-10-01

    Previous epidemiological and animal studies report that exposure to environmental pollutant exposure links to neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. Benzo[a]pyrene (BaP), a neurotoxic polycyclic aromatic hydrocarbon, has been increasingly released into the environment during recent decades. So far, the role of BaP on the development of neurodegenerative diseases remaind unclear. This study aimed to determine whether chronic exposure to low dose BaP would cause neurodegenerative disease-like syndromes in zebrafish (Danio rerio). We exposed zebrafish, from early embryogenesis to adults, to environmentally relevant concentrations of BaP for 230 days. Our results indicated that BaP decreased the brain weight to body weight ratio, locomotor activity and cognitive ability; induced the loss of dopaminergic neurons; and resulted in neurodegeneration. In addition, obvious cell apoptosis in the brain was found. Furthermore, the neurotransmitter levels of dopamine and 3,4-dihydroxyphenylacetic acid, the mRNA levels of the genes encoding dopamine transporter, Parkinson protein 7, phosphatase and tensin-induced putative kinase 1, ubiquitin carboxy-terminal hydrolase L1, leucine-rich repeat serine/threonine kinase 2, amyloid precursor protein b, presenilin 1 and presenilin 2 were significantly down-regulated by BaP exposure. These findings suggest that chronic exposure to low dose BaP could cause the behavioral, neuropathological, neurochemical, and genetic features of neurodegenerative diseases. This study provides clues that BaP may constitute an important environmental risk factor for neurodegenerative diseases in humans.

  17. Helicobacter pylori Eradication Causes Perturbation of the Human Gut Microbiome in Young Adults.

    Directory of Open Access Journals (Sweden)

    Theresa Wan-Chen Yap

    Full Text Available Accumulating evidence shows that Helicobacter pylori protects against some metabolic and immunological diseases in which the development of these diseases coincide with temporal or permanent dysbiosis. The aim of this study was to assess the effect of H. pylori eradication on the human gut microbiome.As part of the currently on-going ESSAY (Eradication Study in Stable Adults/Youths study, we collected stool samples from 17 H. pylori-positive young adult (18-30 years-old volunteers. The same cohort was followed up 6, 12 and 18 months-post H. pylori eradication. The impact of H. pylori on the human gut microbiome pre- and post-eradication was investigated using high throughput 16S rRNA gene (V3-V4 region sequencing using the Illumina Miseq followed by data analysis using Qiime pipeline.We compared the composition and diversity of bacterial communities in the fecal microbiome of the H. pylori-positive volunteers, before and after H. pylori eradication therapy. The 16S rRNA gene was sequenced at an average of 150,000-170,000 reads/sample. The microbial diversity were similar pre- and post-H. pylori eradication with no significant differences in richness and evenness of bacterial species. Despite that the general profile of the gut microbiome was similar pre- and post-eradication, some changes in the bacterial communities at the phylum and genus levels were notable, particularly the decrease in relative abundance of Bacterioidetes and corresponding increase in Firmicutes after H. pylori eradication. The significant increase of short-chain fatty acids (SCFA-producing bacteria genera could also be associated with increased risk of metabolic disorders.Our preliminary stool metagenomics study shows that eradication of H. pylori caused perturbation of the gut microbiome and may indirectly affect the health of human. Clinicians should be aware of the effect of broad spectrum antibiotics used in H. pylori eradication regimen and be cautious in the clinical

  18. A shift in paradigm towards human biology-based systems for cholestatic-liver diseases.

    Science.gov (United States)

    Noor, Fozia

    2015-12-01

    Cholestatic-liver diseases (CLDs) arise from diverse causes ranging from genetic factors to drug-induced cholestasis. The so-called diseases of civilization (obesity, diabetes, metabolic disorders, non-alcoholic liver disease, cardiovascular diseases, etc.) are intricately implicated in liver and gall bladder diseases. Although CLDs have been extensively studied, there seem to be important gaps in the understanding of human disease. Despite the fact that many animal models exist and substantial clinical data are available, translation of this knowledge towards therapy has been disappointingly limited. Recent advances in liver cell culture such as in vivo-like 3D cultivation of human primary hepatic cells, human induced pluripotent stem cell-derived hepatocytes; and cutting-edge analytical techniques such as 'omics' technologies and high-content screenings could play a decisive role in deeper mechanistic understanding of CLDs. This Topical Review proposes a roadmap to human biology-based research using omics technologies providing quantitative information on mechanisms in an adverse outcome/disease pathway framework. With modern sensitive tools, a shift in paradigm in human disease research seems timely and even inevitable to overcome species barriers in translation.

  19. Complete staghorn calculus in polycystic kidney disease: infection is still the cause.

    Science.gov (United States)

    Mao, Zhiguo; Xu, Jing; Ye, Chaoyang; Chen, Dongping; Mei, Changlin

    2013-08-01

    Kidney stones in patients with autosomal dominant polycystic kidney disease are common, regarded as the consequence of the combination of anatomic abnormality and metabolic risk factors. However, complete staghorn calculus is rare in polycystic kidney disease and predicts a gloomy prognosis of kidney. For general population, recent data showed metabolic factors were the dominant causes for staghorn calculus, but for polycystic kidney disease patients, the cause for staghorn calculus remained elusive. We report a case of complete staghorm calculus in a polycystic kidney disease patient induced by repeatedly urinary tract infections. This 37-year-old autosomal dominant polycystic kidney disease female with positive family history was admitted in this hospital for repeatedly upper urinary tract infection for 3 years. CT scan revealed the existence of a complete staghorn calculus in her right kidney, while there was no kidney stone 3 years before, and the urinary stone component analysis showed the composition of calculus was magnesium ammonium phosphate. UTI is an important complication for polycystic kidney disease and will facilitate the formation of staghorn calculi. As staghorn calculi are associated with kidney fibrosis and high long-term renal deterioration rate, prompt control of urinary tract infection in polycystic kidney disease patient will be beneficial in preventing staghorn calculus formation.

  20. A novel sponge disease caused by a consortium of micro-organisms

    Science.gov (United States)

    Sweet, Michael; Bulling, Mark; Cerrano, Carlo

    2015-09-01

    In healthy sponges, microbes have been shown to account for up to 40 % of tissues. The majority of these are thought to originate from survivors evading digestion and immune responses of the sponge and growing and residing in the microenvironments of the mesophyll. Although a large percentage of these microbes are likely commensals, they may also include potentially pathogenic agents, which under specific conditions, such as temperature stress, may cause disease. Here we report a novel disease (sponge necrosis syndrome) that is severely affecting populations of the sponge Callyspongia ( Euplacella) aff biru. Both ITS fungal and 16S rDNA bacterial diversities were assessed in healthy and diseased individuals, highlighting six potential primary causal agents for this new disease: two bacteria, a Rhodobacteraceae sp. and a cyanobacterium, Hormoscilla spongeliae (formally identified as Oscillatoria spongeliae), and four fungi, a Ascomycota sp., a Pleosporales sp., a Rhabdocline sp., and a Clasosporium sp. Furthermore, histological analysis showed the dominance of fungal hyphae rather than bacteria throughout the disease lesion, which was absent or rare in healthy tissues. Inoculation trails showed that only a combination of one bacterium and one fungus could replicate the disease, fulfilling Henle-Koch's postulates and showing that this sponge disease is caused by a poly-microbial consortium.

  1. Medical disease as a cause of maternal mortality: the pre-imminence of cardiovascular pathology.

    Science.gov (United States)

    Mocumbi, A O; Sliwa, K; Soma-Pillay, P

    2016-01-01

    Maternal mortality ratio in low- to middle-income countries (LMIC) is 14 times higher than in high-income countries. This is partially due to lack of antenatal care, unmet needs for family planning and education, as well as low rates of birth managed by skilled attendants. While direct causes of maternal death such as complications of hypertension, obstetric haemorrhage and sepsis remain the largest cause of maternal death in LMICs, cardiovascular disease emerges as an important contributor to maternal mortality in both developing countries and the developed world, hampering the achievement of the millennium development goal 5, which aimed at reducing by three-quarters the maternal mortality ratio until the end of 2015. Systematic search for cardiac disease is usually not performed during pregnancy in LMICs despite hypertensive disease, rheumatic heart disease and cardiomyopathies being recognised as major health problems in these settings. New concern has been rising due to both the HIV/AIDS epidemic and the introduction of highly active antiretroviral therapy. Undetected or untreated congenital heart defects, undiagnosed pulmonary hypertension, uncontrolled heart failure and complications of sickle cell disease may also be important challenges. This article discusses issues related to the role of cardiovascular disease in determining a substantial portion of maternal morbidity and mortality. It also presents an algorhitm to be used for suspected and previously known cardiac disease in pregnancy in the context of LIMCs.

  2. Podocyte-specific overexpression of wild type or mutant trpc6 in mice is sufficient to cause glomerular disease.

    Directory of Open Access Journals (Sweden)

    Paola Krall

    Full Text Available Mutations in the TRPC6 calcium channel (Transient receptor potential channel 6 gene have been associated with familiar forms of Focal and Segmental Glomerulosclerosis (FSGS affecting children and adults. In addition, acquired glomerular diseases are associated with increased expression levels of TRPC6. However, the exact role of TRPC6 in the pathogenesis of FSGS remains to be elucidated. In this work we describe the generation and phenotypic characterization of three different transgenic mouse lines with podocyte-specific overexpression of the wild type or any of two mutant forms of Trpc6 (P111Q and E896K previously related to FSGS. Consistent with the human phenotype a non-nephrotic range of albuminuria was detectable in almost all transgenic lines. The histological analysis demonstrated that the transgenic mice developed a kidney disease similar to human FSGS. Differences of 2-3 folds in the presence of glomerular lesions were found between the non transgenic and transgenic mice expressing Trpc6 in its wild type or mutant forms specifically in podocytes. Electron microscopy of glomerulus from transgenic mice showed extensive podocyte foot process effacement. We conclude that overexpression of Trpc6 (wild type or mutated in podocytes is sufficient to cause a kidney disease consistent with FSGS. Our results contribute to reinforce the central role of podocytes in the etiology of FSGS. These mice constitute an important new model in which to study future therapies and outcomes of this complex disease.

  3. 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

  4. 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.

  5. [Coeliac disease as a possible cause of some gynecological and obstetric abnormalities].

    Science.gov (United States)

    Fiolková, K; Biringer, K; Hrtánková, M; Fiolka, R; Danko, J

    To bring a review of available literature sources on the prevalence of coeliac disease and its possible impact on gynecological and obstetric disorders. Review article. Gynecology and Obstetrics Clinic, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia. Analysis of literary sources. Coeliac disease is an autoimmune enteropathy caused by abnormal immune system response to gluten. Over the last decade when the prevalence of the disease increases rapidly confirming the relationship between coeliac disease and a range of reproductive disorders. Problems in this area are mostly confirmed in untreated women. Among the atypical symptoms of coeliac disease also include infertility such as delayed onset of menstruation, early menopause, secondary amenorrhea, infertility and pregnancy complications, such as recurrent abortions, intrauterine fetal growth restriction, small fetus for gestational age, low birth weight and premature birth.

  6. Modelling the economic impact of three lameness causing diseases using herd and cow level evidence

    DEFF Research Database (Denmark)

    Ettema, Jehan Frans; Østergaard, Søren; Kristensen, Anders Ringgaard

    2010-01-01

    profitability of such actions. An existing approach of modelling lameness as one health disorder in a dynamic, stochastic and mechanistic simulation model has been improved in two ways. First of all, three underlying diseases causing lameness were modelled: digital dermatitis, interdigital hyperplasia and claw......, marginal posterior probability distributions for disease prevalence in the specific herd are created in a Bayesian network. Random draws from these distributions are used by the simulation model to describe disease risk. Hereby field data on prevalence is used systematically and uncertainty around herd...... specific risk is represented. Besides the fact that estimated profitability of halving disease risk depended on the hyper-distributions used, the estimates differed for herds with different levels of diseases risk and reproductive efficiency....

  7. Protein kinase CK2 in human diseases

    DEFF Research Database (Denmark)

    Guerra, Barbara; Issinger, Olaf-Georg

    2008-01-01

    in various disease processes including cancer has been gained in recent years, and the present review may help to further elucidate its aberrant role in many disease states. Its peculiar structural features [3-9] may be advantageous in designing tailor-made compounds with the possibility to specifically...

  8. S-phase-dependent cell cycle disturbances caused by Aleutian mink disease parvovirus

    DEFF Research Database (Denmark)

    Oleksiewicz, M.B.; Alexandersen, Søren

    1997-01-01

    We examined replication of the autonomous parovirus Aleutian mink disease parovirus (ADV) in relation to cell cycle progression of permissive Crandell feline kidney (CRFK) cells. Flow cytometric analysis showed that ADV caused a composite, binary pattern of cell cycle arrest. ADV-induced cell cyc...

  9. Genome sequence of Fusarium oxysporum f. sp. melonis, a fungus causing wilt disease on melon

    Science.gov (United States)

    This manuscript reports the genome sequence of F. oxysporum f. sp. melonis, a fungal pathogen that causes Fusarium wilt disease on melon (Cucumis melo). The project is part of a large comparative study designed to explore the genetic composition and evolutionary origin of this group of horizontally ...

  10. Causes of Death Data in the Global Burden of Disease Estimates for Ischemic and Hemorrhagic Stroke

    DEFF Research Database (Denmark)

    Truelsen, Thomas; Krarup, Lars-Henrik; Iversen, Helle K

    2015-01-01

    BACKGROUND: Stroke mortality estimates in the Global Burden of Disease (GBD) study are based on routine mortality statistics and redistribution of ill-defined codes that cannot be a cause of death, the so-called 'garbage codes' (GCs). This study describes the contribution of these codes to stroke...

  11. Loss of stability and hydrophobicity of presenilin 1 mutations causing Alzheimer's Disease

    DEFF Research Database (Denmark)

    Somavarapu, Arun Kumar; Kepp, Kasper Planeta

    2016-01-01

    Nearly 200 mutations in the gene coding for presenilin 1 (PSEN1) cause early-onset Alzheimer's Disease, yet the molecular mechanism remains obscure. As a meta-analysis, we compiled available clinical and biochemical data for PSEN1 variants and correlated these to chemical properties of the mutants...

  12. In search of the causes of Parkinson?s disease, seasons 1 to 4

    OpenAIRE

    Elbaz, Alexis

    2011-01-01

    In search of the causes of Parkinson?s disease, seasons 1 to 4 (Elbaz, Alexis) INSERM, U708, Neuroepidemiology - 75005 - Paris - FRANCE (Elbaz, Alexis) UPMC Univ Paris 06, UMR_S708, Neuroepidemiology - 75005 - Paris - FRANCE (Elbaz, Alexis) FRANCE Registration: 2011-04-16 Received: 2011-03-30 Accepted: 2011-04-15 ePublished: 2011-05-31

  13. The haematocrit - an important factor causing impaired haemostasis in patients with cyanotic congenital heart disease

    DEFF Research Database (Denmark)

    Jensen, A S; Johansson, P I; Idorn, L;

    2013-01-01

    BACKGROUND: Patients with cyanotic congenital heart disease(CCHD) have haemostatic abnormalities, which result in an increased risk of bleeding. The cause is unknown, but recent studies have indicated that an elevated haematocrit, which is present in cyanotic patients, could be an important factor...

  14. Erdheim-Chester disease: a rare cause of recurrent fever of unknown origin mimicking lymphoma.

    Science.gov (United States)

    Mariampillai, Anusiyanthan; Sivapiragasam, Abirami; Kumar, Amit; Hindenburg, Alexander; Cunha, Burke A; Zhou, Jianhong

    2014-01-01

    We report the case of a patient with recurrent fever of unknown origin (FUO) with prominent back pain, hepatosplenomegaly, and abdominal/pelvic adenopathy suggesting lymphoma. A bone biopsy showed histiocytic infiltration. Studies for lymphoma were negative, but immunohistochemical stains were diagnostic of Erdheim-Chester disease (ECD). ECD should be included as a rare cause of recurrent FUO with bone involvement.

  15. MRPL44 mutations cause a slowly progressive multisystem disease with childhood-onset hypertrophic cardiomyopathy

    NARCIS (Netherlands)

    Distelmaier, F.; Haack, T.B.; Catarino, C.B.; Gallenmuller, C.; Rodenburg, R.J.T.; Strom, T.M.; Baertling, F.; Meitinger, T.; Mayatepek, E.; Prokisch, H.; Klopstock, T.

    2015-01-01

    Defects in mitochondrial translation may lead to combined respiratory chain deficiency and typically cause childhood-onset multisystem disease. Only recently, a homozygous missense mutation (c.467T > G, p.Leu156Arg) in MRPL44, encoding a protein of the large subunit of the mitochondrial ribosome,

  16. Outbreak of Legionnaire’s Disease Caused by Legionella pneumophila Serogroups 1 and 13

    Science.gov (United States)

    Amemura-Maekawa, Junko; Ohya, Hitomi; Furukawa, Ichiro; Suzuki, Miyuki; Masaoka, Tomoka; Aikawa, Kastuhiro; Hibi, Kazumi; Morita, Masatomo; Lee, Ken-ichi; Ohnishi, Makoto; Kura, Fumiaki

    2017-01-01

    In Japan, hot springs and public baths are the major sources of legionellosis. In 2015, an outbreak of Legionnaires’ disease occurred among 7 patients who had visited a spa house. Laboratory investigation indicated that L. pneumophila serogroup 1 and 13 strains caused the outbreak and that these strains were genetically related. PMID:28098535

  17. Infection and disease progress of motile Aeromonas septicemia caused by virulent Aeromonas hydrophila in channel catfish

    Science.gov (United States)

    Motile Aeromonas septicemia (MAS), caused by virulent clonal isolates of Aeromonas hydrophila (vAh), is emerging as a major disease in channel catfish (Ictalurus punctatus) aquaculture in the Southeastern United States. Predisposing conditions leading to vAh infection in catfish were however largely...

  18. 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.

  19. Oxygen-dependent injury by a human plasma factor associated with minimal change disease

    NARCIS (Netherlands)

    Cheung, PK; Baller, JFW; Bakker, WW

    1998-01-01

    The mechanism by which a human plasma factor associated with proteinuria is able to cause experimental glomerular albumin leakage is unknown. This factor (called 100KF) is able to induce glomerular alterations in the rat kidney, similar to those seen in minimal change disease, including loss of glom

  20. Fifty-eight cases of ocular ischemic diseases caused by carotid artery stenosis

    Institute of Scientific and Technical Information of China (English)

    LUO Rong-jiang; LIU Shao-rui; LI Xiao-min; ZHUO Ye-hong; TIAN Zhen

    2010-01-01

    Background The blood supply to the eye comes from the retinal central vascular system of the ophthalmic artery and the ciliary vascular system. The ophthalmic artery stems from the ipsilateral internal carotid artery. If occlusion or stenosis occurs in the carotid artery, the blood perfusion to the ophthalmic artery becomes insufficient, leading to signs and symptoms of anterior and posterior ocular ischemia. The objective of this study was to evaluate the clinical characteristics and risk factors of ocular ischemic diseases caused by carotid artery stenosis.Methods This study was a retrospective review of 145 patients with carotid artery stenosis. Fifty-eight patients who had symptoms of ocular ischemic disease caused by carotid artery stenosis formed group A and the other 87 patients who only had carotid artery stenosis formed group B. We analyzed the causes and course of disease, and relative risk factors,by comparing the two groups.Results The degree of carotid artery stenosis in group A was higher than that in group B. And group A had a greater decrease of ophthalmic artery flow. Male, hypertension, hyperlipidemia, and smoking were significantly related to carotid artery stenosis. Amaurosis fugax was the most common ocular symptom in group A. The ocular ischemic diseases mainly included ischemic optic neuropathy, central/branch retinal artery occlusion, ophthalmoplegia externa, and ocular ischemic syndrome.Conclusions Carotid artery stenosis correlates with ocular ischemic diseases. Ophthalmologists must observe for ocular symptoms, which were the onset symptoms in some patients.