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Sample records for inherited skin diseases

  1. The Molecular Revolution in Cutaneous Biology: Era of Molecular Diagnostics for Inherited Skin Diseases.

    PubMed

    McGrath, John A

    2017-05-01

    The discovery of pathogenic mutations in inherited skin diseases represents one of the major landmarks of late 20th century molecular genetics. Mutation data can provide accurate diagnoses, improve genetic counseling, help define disease mechanisms, establish disease models, and provide a basis for translational research and testing of novel therapeutics. The process of detecting disease mutations, however, has not always been straightforward. Traditional approaches using genetic linkage or candidate gene analysis have often been limited, costly, and slow to yield new insights, but the advent of next-generation sequencing (NGS) technologies has altered the landscape of current gene discovery and mutation detection approaches. Copyright © 2017 The Author. Published by Elsevier Inc. All rights reserved.

  2. Insights into desmosome biology from inherited human skin disease and cardiocutaneous syndromes.

    PubMed

    Nitoiu, Daniela; Etheridge, Sarah L; Kelsell, David P

    2014-06-01

    The importance of desmosomes in tissue homeostasis is highlighted by natural and engineered mutations in desmosomal genes, which compromise the skin or heart and in some instances both. Desmosomal gene mutations account for 45-50% of cases of arrhythmogenic right ventricular cardiomyopathy, and are mutated in an array of other disorders such as striate palmoplantar keratoderma, hypotrichosis with or without skin vesicles and lethal acantholytic epidermolysis bullosa. Recently, we reported loss-of-function mutations in the human ADAM17 gene, encoding for the 'sheddase' ADAM17, a transmembrane protein which cleaves extracellular domains of substrate proteins including TNF-α, growth factors and desmoglein (DSG) 2. Patients present with cardiomyopathy and an inflammatory skin and bowel syndrome with defective DSG processing. In contrast, the dominantly inherited tylosis with oesophageal cancer appears to result from gain-of-function in ADAM17 due to increased processing via iRHOM2. This review discusses the heterogeneity of mutations in desmosomes and their regulatory proteins.

  3. Mitochondrial inheritance and disease.

    PubMed

    Fine, P E

    1978-09-23

    Spontaneously occurring variants of the D.N.A. content of mitochondria may be responsible for human disease. Among the prime candidates for such a mitochondrial aetiology are certain drug-induced blood dyscrasias, particularly that due to chloramphenicol. Because mitochondria are generally inherited from the female parent, such disorders should be clustered among matroclinally related individuals. The clinical manifestations of such diseases are a function of the manner in which mitochondria are allocated to somatic cells and tissues during development.

  4. ‘…Re-written in the skin’ – Clues to skin biology and aging from inherited disease

    PubMed Central

    Monnat, Raymond J.

    2015-01-01

    The growing diversity of heritable skin diseases, a practical challenge to clinicians and dermatonosologists alike, has nonetheless served as a rich source of insight into skin biology and disease mechanisms. I summarize below some key insights from the recent gene-driven phase of research on Werner syndrome, a heritable adult progeroid syndrome with prominent dermatologic features, constitutional genomic instability and an elevated risk of cancer. I also indicate how new insights into skin biology, disease and aging may come from unexpected sources. PMID:25810110

  5. PGD for inherited cardiac diseases.

    PubMed

    Kuliev, Anver; Pomerantseva, Ekaterina; Polling, Dana; Verlinsky, Oleg; Rechitsky, Svetlana

    2012-04-01

    Preimplantation genetic diagnosis (PGD) has been applied for more than 200 different inherited conditions, with expanding application to common disorders with genetic predisposition. One of the recent indications for PGD has been inherited cardiac disease, for which no preclinical diagnosis and preventive management may exist and which may lead to premature or sudden death. This paper presents the first, as far as is known, cumulative experience of PGD for inherited cardiac diseases, including familial hypertrophic and dilated cardiomyopathy, cardioencephalomyopathy and Emery-Dreifuss muscular dystrophy. A total of 18 PGD cycles were performed, resulting in transfer in 15 of them, which yielded nine unaffected pregnancies and the births of seven disease- or disease predisposition-free children. The data open the prospect of PGD for inherited cardiac diseases, allowing couples carrying cardiac disease predisposing genes to reproduce without much fear of having offspring with these genes, which are at risk for premature or sudden death. Preimplantation genetic diagnosis (PGD) is currently an established clinical procedure in assisted reproduction and genetic practices. Its application has been expanding beyond traditional indications of prenatal diagnosis and currently includes common disorders with genetic predisposition, such as inherited forms of cancer. This applies also to the diseases with no current prospect of treatment, which may manifest despite presymptomatic diagnosis and follow up, when PGD may provide the only relief for the at-risk couples to reproduce. One of the recent indications for PGD has been inherited cardiac disease, for which no preclinical diagnosis and preventive management may exist and which may lead to premature or sudden death. We present here our first cumulative experience of PGD for inherited cardiac diseases, including familial hypertrophic and dilated cardiomyopathy, cardioencephalomyopathy and Emery-Dreifuss muscular dystrophy. A

  6. Transgenerational inheritance of metabolic disease.

    PubMed

    Stegemann, Rachel; Buchner, David A

    2015-07-01

    Metabolic disease encompasses several disorders including obesity, type 2 diabetes, and dyslipidemia. Recently, the incidence of metabolic disease has drastically increased, driven primarily by a worldwide obesity epidemic. Transgenerational inheritance remains controversial, but has been proposed to contribute to human metabolic disease risk based on a growing number of proof-of-principle studies in model organisms ranging from Caenorhabditis elegans to Mus musculus to Sus scrofa. Collectively, these studies demonstrate that heritable risk is epigenetically transmitted from parent to offspring over multiple generations in the absence of a continued exposure to the triggering stimuli. A diverse assortment of initial triggers can induce transgenerational inheritance including high-fat or high-sugar diets, low-protein diets, various toxins, and ancestral genetic variants. Although the mechanistic basis underlying the transgenerational inheritance of disease risk remains largely unknown, putative molecules mediating transmission include small RNAs, histone modifications, and DNA methylation. Due to the considerable impact of metabolic disease on human health, it is critical to better understand the role of transgenerational inheritance of metabolic disease risk to open new avenues for therapeutic intervention and improve upon the current methods for clinical diagnoses and treatment.

  7. Transgenerational Inheritance of Metabolic Disease

    PubMed Central

    Stegemann, Rachel; Buchner, David A.

    2015-01-01

    Metabolic disease encompasses several disorders including obesity, type 2 diabetes, and dyslipidemia. Recently, the incidence of metabolic disease has drastically increased, driven primarily by a worldwide obesity epidemic. Transgenerational inheritance remains controversial, but has been proposed to contribute to human metabolic disease risk based on a growing number of proof-of-principle studies in model organisms ranging from C. elegans to M. musculus to S. scrofa. Collectively, these studies demonstrate that heritable risk is epigenetically transmitted from parent to offspring over multiple generations in the absence of a continued exposure to the triggering stimuli. A diverse assortment of initial triggers can induce transgenerational inheritance including high-fat or high-sugar diets, low-protein diets, various toxins, and ancestral genetic variants. Although the mechanistic basis underlying the transgenerational inheritance of disease risk remains largely unknown, putative molecules mediating transmission include small RNAs, histone modifications, and DNA methylation. Due to the considerable impact of metabolic disease on human health, it is critical to better understand the role of transgenerational inheritance of metabolic disease risk to open new avenues for therapeutic intervention and improve upon the current methods for clinical diagnoses and treatment. PMID:25937492

  8. Epigenetic Inheritance of Disease and Disease Risk

    PubMed Central

    Bohacek, Johannes; Mansuy, Isabelle M

    2013-01-01

    Epigenetic marks in an organism can be altered by environmental factors throughout life. Although changes in the epigenetic code can be positive, some are associated with severe diseases, in particular, cancer and neuropsychiatric disorders. Recent evidence has indicated that certain epigenetic marks can be inherited, and reshape developmental and cellular features over generations. This review examines the challenging possibility that epigenetic changes induced by environmental factors can contribute to some of the inheritance of disease and disease risk. This concept has immense implications for the understanding of biological functions and disease etiology, and provides potential novel strategies for diagnosis and treatment. Examples of epigenetic inheritance relevant to human disease, such as the detrimental effects of traumatic stress or drug/toxic exposure on brain functions, are reviewed. Different possible routes of transmission of epigenetic information involving the germline or germline-independent transfer are discussed, and different mechanisms for the maintenance and transmission of epigenetic information like chromatin remodeling and small noncoding RNAs are considered. Future research directions and remaining major challenges in this field are also outlined. Finally, the adaptive value of epigenetic inheritance, and the cost and benefit of allowing acquired epigenetic marks to persist across generations is critically evaluated. PMID:22781843

  9. Multicentre consensus recommendations for skin care in inherited epidermolysis bullosa.

    PubMed

    El Hachem, May; Zambruno, Giovanna; Bourdon-Lanoy, Eva; Ciasulli, Annalisa; Buisson, Christiane; Hadj-Rabia, Smail; Diociaiuti, Andrea; Gouveia, Carolina F; Hernández-Martín, Angela; de Lucas Laguna, Raul; Dolenc-Voljč, Mateja; Tadini, Gianluca; Salvatori, Guglielmo; De Ranieri, Cristiana; Leclerc-Mercier, Stephanie; Bodemer, Christine

    2014-05-20

    Inherited epidermolysis bullosa (EB) comprises a highly heterogeneous group of rare diseases characterized by fragility and blistering of skin and mucous membranes. Clinical features combined with immunofluorescence antigen mapping and/or electron microscopy examination of a skin biopsy allow to define the EB type and subtype. Molecular diagnosis is nowadays feasible in all EB subtypes and required for prenatal diagnosis. The extent of skin and mucosal lesions varies greatly depending on EB subtype and patient age. In the more severe EB subtypes lifelong generalized blistering, chronic ulcerations and scarring sequelae lead to multiorgan involvement, major morbidity and life-threatening complications. In the absence of a cure, patient management remains based on preventive measures, together with symptomatic treatment of cutaneous and extracutaneous manifestations and complications. The rarity and complexity of EB challenge its appropriate care. Thus, the aim of the present study has been to generate multicentre, multidisciplinary recommendations on global skin care addressed to physicians, nurses and other health professionals dealing with EB, both in centres of expertise and primary care setting. Almost no controlled trials for EB treatment have been performed to date. For this reason, recommendations were prepared by a multidisciplinary team of experts from different European EB centres based on available literature and expert opinion. They have been subsequently revised by a panel of external experts, using an online-modified Delphi method to generate consensus. Recommendations are reported according to the age of the patients. The major topics treated comprise the multidisciplinary approach to EB patients, global skin care including wound care, management of itching and pain, and early diagnosis of squamous cell carcinoma. Aspects of therapeutic patient education, care of disease burden and continuity of care are also developed. The recommendations are

  10. Molecular basis of inherited skin-blistering disorders, and therapeutic implications.

    PubMed

    Aumailley, Monique; Has, Cristina; Tunggal, Lucy; Bruckner-Tuderman, Leena

    2006-10-13

    Epidermolysis bullosa (EB) and associated skin-fragility syndromes are a group of inherited skin diseases characterised by trauma-induced blistering of the skin and mucous membranes. Mutations in at least 14 distinct genes encoding molecular components of the epidermis or the dermal-epidermal junction (DEJ) can cause blistering skin diseases that differ by clinical presentation and severity of the symptoms. Despite great advances in discerning the genetic basis of this group of diseases, the molecular pathways leading to symptoms are not yet fully understood. Unravelling these pathways by molecular analysis of the structure and in vitro assessment of functional properties of the human proteins involved, combined with genetic models in lower organisms, should pave the way for specific cures for inherited skin fragility.

  11. Skin Diseases: Skin Health and Skin Diseases

    MedlinePlus

    ... and dryness. Sunlight is a major cause of skin aging. ( See "Skin and Sun—Not a Good Mix") . ... person has smoked. Many products claim to revitalize aging skin or reduce wrinkles, but the Food and Drug ...

  12. Center for Inherited Disease Research (CIDR)

    Cancer.gov

    The Center for Inherited Disease Research (CIDR) Program at The Johns Hopkins University provides high-quality next generation sequencing and genotyping services to investigators working to discover genes that contribute to common diseases.

  13. Multicentre consensus recommendations for skin care in inherited epidermolysis bullosa

    PubMed Central

    2014-01-01

    Background Inherited epidermolysis bullosa (EB) comprises a highly heterogeneous group of rare diseases characterized by fragility and blistering of skin and mucous membranes. Clinical features combined with immunofluorescence antigen mapping and/or electron microscopy examination of a skin biopsy allow to define the EB type and subtype. Molecular diagnosis is nowadays feasible in all EB subtypes and required for prenatal diagnosis. The extent of skin and mucosal lesions varies greatly depending on EB subtype and patient age. In the more severe EB subtypes lifelong generalized blistering, chronic ulcerations and scarring sequelae lead to multiorgan involvement, major morbidity and life-threatening complications. In the absence of a cure, patient management remains based on preventive measures, together with symptomatic treatment of cutaneous and extracutaneous manifestations and complications. The rarity and complexity of EB challenge its appropriate care. Thus, the aim of the present study has been to generate multicentre, multidisciplinary recommendations on global skin care addressed to physicians, nurses and other health professionals dealing with EB, both in centres of expertise and primary care setting. Methods Almost no controlled trials for EB treatment have been performed to date. For this reason, recommendations were prepared by a multidisciplinary team of experts from different European EB centres based on available literature and expert opinion. They have been subsequently revised by a panel of external experts, using an online-modified Delphi method to generate consensus. Results Recommendations are reported according to the age of the patients. The major topics treated comprise the multidisciplinary approach to EB patients, global skin care including wound care, management of itching and pain, and early diagnosis of squamous cell carcinoma. Aspects of therapeutic patient education, care of disease burden and continuity of care are also developed

  14. Inherited Retinal Degenerative Disease Registry

    ClinicalTrials.gov

    2016-03-21

    Eye Diseases Hereditary; Retinal Disease; Achromatopsia; Bardet-Biedl Syndrome; Bassen-Kornzweig Syndrome; Batten Disease; Best Disease; Choroidal Dystrophy; Choroideremia; Cone Dystrophy; Cone-Rod Dystrophy; Congenital Stationary Night Blindness; Enhanced S-Cone Syndrome; Fundus Albipunctatus; Goldmann-Favre Syndrome; Gyrate Atrophy; Juvenile Macular Degeneration; Kearns-Sayre Syndrome; Leber Congenital Amaurosis; Refsum Syndrome; Retinitis Pigmentosa; Retinitis Punctata Albescens; Retinoschisis; Rod-Cone Dystrophy; Rod Dystrophy; Rod Monochromacy; Stargardt Disease; Usher Syndrome

  15. Viral Skin Diseases.

    PubMed

    Ramdass, Priya; Mullick, Sahil; Farber, Harold F

    2015-12-01

    In the vast world of skin diseases, viral skin disorders account for a significant percentage. Most viral skin diseases present with an exanthem (skin rash) and, oftentimes, an accompanying enanthem (lesions involving the mucosal membrane). In this article, the various viral skin diseases are explored, including viral childhood exanthems (measles, rubella, erythema infectiosum, and roseola), herpes viruses (herpes simplex virus, varicella zoster virus, Kaposi sarcoma herpes virus, viral zoonotic infections [orf, monkeypox, ebola, smallpox]), and several other viral skin diseases, such as human papilloma virus, hand, foot, and mouth disease, molluscum contagiosum, and Gianotti-Crosti syndrome. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. How Is Wilson Disease Inherited?

    MedlinePlus

    ... Connect with Wilson Disease Association Send Email Physician Contacts List of Physicians and Institutions in Your Area View Contacts Support Contacts Individuals who can offer Support and Information View ...

  17. Oxidative Stress in Inherited Mitochondrial Diseases

    PubMed Central

    Hayashi, Genki; Cortopassi, Gino

    2015-01-01

    Mitochondria are a source of reactive oxygen species (ROS). Mitochondrial diseases are the result of inherited defects in mitochondrially-expressed genes. One potential pathomechanism for mitochondrial disease is oxidative stress. Oxidative stress can occur as the result of increased ROS production, or decreased ROS protection. The role of oxidative stresses in the five most common inherited mitochondrial diseases; Friedreich's ataxia (FA), LHON, MELAS, MERRF and Leigh Syndrome (LS) is discussed. Published reports for oxidative stress involvement in pathomechanism in these five mitochondrial diseases are reviewed. The strongest for oxidative stress pathomechanism among the five diseases was in Friedreich's ataxia. In addition, a meta-analysis was carried out to provide an unbiased evaluation of the role of oxidative stress in the five diseases, by searching for oxidative stress citation count frequency within each disease. Of the five most common mitochondrial diseases, the strongest support for oxidative stress is in Friedreich's ataxia (6.42%), followed by LHON (2.45%), MELAS (2.18%), MERRF (1.71%), and LS (1.03%). The increased frequency of oxidative stress citations was significant relative to the mean of the total pool of five diseases (p<0.01) and the mean of the four non-Friedreich's diseases (p<0.0001). Thus there is support for oxidative stress in all five most common mitochondrial diseases, but the strongest, significant support is for Friedreich's ataxia. PMID:26073122

  18. Prevalence of specific anti-skin autoantibodies in a cohort of patients with inherited epidermolysis bullosa

    PubMed Central

    2013-01-01

    Background Inherited epidermolysis bullosa (EB) is a group of skin diseases characterized by blistering of the skin and mucous membranes. There are four major types of EB (EB simplex, junctional EB, dystrophic EB and Kindler syndrome) caused by different gene mutations. Dystrophic EB is derived from mutations in the type VII collagen gene (COL7A1), encoding a protein which is the predominant component of the anchoring fibrils at the dermal-epidermal junction. For the first time in literature, we have evaluated the presence of anti-skin autoantibodies in a wider cohort of patients suffering from inherited EB and ascertained whether they may be a marker of disease activity. Methods Sera from patients with inherited EB, 17 with recessive dystrophic EB (RDEB), 10 with EB simplex (EBS) were analysed. As much as 20 patients with pemphigus vulgaris, 21 patients with bullous pemphigoid and 20 healthy subjects were used as controls. Anti-skin autoantibodies were tested in all samples with the Indirect Immunofluorescence (IIF) method and the currently available ELISA method in order to detect anti-type VII collagen, anti-BP180 and anti-BP230 autoantibodies. Results The mean concentrations of anti-type VII collagen autoantibodies titres, anti-BP180 and anti-BP230 autoantibodies were statistically higher in RDEB patients than in EBS patients. The sensitivity and specificity of the anti-type VII collagen ELISA test were 88.2% and 96.7%. The Birmingham Epidermolysis Bullosa Severity score, which is used to evaluate the severity of the disease, correlated with anti-skin autoantibodies titres. Conclusions The precise pathogenic role of circulating anti-skin autoantibodies in RDEB is unclear. There is a higher prevalence of both anti-type VII collagen and other autoantibodies in patients with RDEB, but their presence can be interpreted as an epiphenomenon. PMID:24007552

  19. Microbiome and skin diseases.

    PubMed

    Zeeuwen, Patrick L J M; Kleerebezem, Michiel; Timmerman, Harro M; Schalkwijk, Joost

    2013-10-01

    This article reviews recent findings on the skin microbiome. It provides an update on the current understanding of the role of microbiota in healthy skin and in inflammatory and allergic skin diseases. Advances in computing and high-throughput sequencing technology have enabled in-depth analysis of microbiota composition and functionality of human skin. Most data generated to date are related to the skin microbiome of healthy volunteers, but recent studies have also addressed the dynamics of the microbiome in diseased and injured skin. Currently, reports are emerging that evaluate the strategies to manipulate the skin microbiome, intending to modulate diseases and/or their symptoms. The microbiome of normal human skin was found to have a high diversity and high interpersonal variation. Microbiota compositions of diseased lesional skin (in atopic dermatitis and psoriasis) showed distinct differences compared with healthy skin. The function of microbial colonization in establishing immune system homeostasis has been reported, whereas host-microbe interactions and genetically determined variation of stratum corneum properties might be linked to skin dysbiosis. Both are relevant for cutaneous disorders with aberrant immune responses and/or disturbed skin barrier function. Modulation of skin microbiota composition to restore host-microbiota homeostasis could be future strategies to treat or prevent disease.

  20. [Skin diseases of swine].

    PubMed

    von Altrock, A; Höltig, D

    2013-01-01

    Skin alterations can be caused by both environmental conditions and diseases of the organism. Some diseases may only manifest in the skin while others represent signs of a generalized infection. Regarding their origin, skin diseases can be divided into congenital, infectious, and nutritional disorders, and those resulting from housing scarcities. Additionally, there are skin diseases with unknown causes. Skin diseases in a swine herd can result in economic losses through decreased feed efficiency and growth rate and increased mortality. The knowledge of causes and symptoms as well as the selection of appropriate further laboratory investigations provide a valid diagnosis and enable a quick and effective therapy. This description of several skin diseases should provide a background.

  1. Inherited ion channel diseases: a brief review.

    PubMed

    Lieve, Krystien V V; Wilde, Arthur A M

    2015-10-01

    Ion channelopathies are diseases caused by dysfunctional ion channels that may lead to sudden death. These diseases can be either acquired or inherited. The main phenotypes observed in patients carrying these heritable arrhythmia syndromes are congenital long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, and short QT syndrome. In the recent years, tremendous progress has been made in the recognition, mechanisms, and treatment of these diseases. The goal of this review is to provide an overview of the main phenotypes, genetic underpinnings, risk stratification, and treatment options for these so-called cardiac ion channelopathies.

  2. Inherited Retinal Degenerative Disease Clinical Trial Network

    DTIC Science & Technology

    2012-10-01

    the total number of individuals affected by retinitis pigmentosa (RP) and other forms of rare inherited retinal degenerative diseases is estimated at...for autosomal dominant retinitis pigmentosa ). As new interventions become available for clinical evaluation, the creation of such a network will...dominant retinitis pigmentosa at six sites- the CTEC site at University of Utah and five recruitment sites- the Retina Foundation of the Southwest

  3. [Skin diseases and obesity].

    PubMed

    Guerra-Segovia, Carolina; Ocampo-Candiani, Jorge

    2015-01-01

    Obesity is a public health problem worldwide. It predominates in industrialized countries; however, it is prevalent in all nations. It is defined as a condition of excess adipose tissue and is the result of changes in lifestyle, excessive consumption of energy-dense foods with poor nutritional value, physical inactivity and the reduction of open space where one can practice a sport. Although obesity is associated with multiple diseases, it is important to stress that the metabolic changes caused by it affect skin physiology and play a predisposing factor for the development of skin diseases. Very little has been studied on the impact of obesity on the skin. The purpose of this article is to review the most frequently skin diseases in obesity. Some skin pathologies in obesity are caused by changes in skin physiology, others are related to insulin resistance or constitute an exacerbating factor for dermatitis. This article covers the clinical features of obesity related skin disease and its management.

  4. Genetic sequence analysis of inherited bleeding diseases

    PubMed Central

    Peyvandi, Flora; Kunicki, Tom

    2013-01-01

    The genes encoding the coagulation factor proteins were among the first human genes to be characterized over 25 years ago. Since then, significant progress has been made in the translational application of this information for the 2 commonest severe inherited bleeding disorders, hemophilia A and B. For these X-linked disorders, genetic characterization of the disease-causing mutations is now incorporated into the standard of care and genetic information is used for risk stratification of treatment complications. With electronic databases detailing >2100 unique mutations for hemophilia A and >1100 mutations for hemophilia B, these diseases are among the most extensively characterized inherited diseases in humans. Experience with the genetics of the rare bleeding disorders is, as expected, less well advanced. However, here again, electronic mutation databases have been developed and provide excellent guidance for the application of genetic analysis as a confirmatory approach to diagnosis. Most recently, progress has also been made in identifying the mutant loci in a variety of inherited platelet disorders, and these findings are beginning to be applied to the genetic diagnosis of these conditions. Investigation of patients with bleeding phenotypes without a diagnosis, using genome-wide strategies, may identify novel genes not previously recognized as playing a role in hemostasis. PMID:24124085

  5. Occupational skin diseases.

    PubMed

    Diepgen, Thomas L

    2012-05-01

    Occupational skin diseases are the most commonly reported notifiable occupational diseases. In Germany, 23 596 out of a total of 71 263 reported occupational diseases in 2010 were classified as occupational skin diseases (BK No. 5101: "severe or recurrent skin diseases which have forced the person to discontinue all occupational activities that caused or could cause the development, worsening, or recurrence of the disease"). Contact dermatitis (allergic, irritant) of the hands is the most common skin disease and atopic skin diathesis is often an important co-factor. The number of work-related skin diseases is many times higher than the number of notified occupational dermatoses. This CME article explains the legal framework of occupational diseases, the tasks and obligations of the legal statutory work insurance. Typical allergens and irritants of high risk professions are also presented as are the important steps from diagnosis to compensation. Early prevention of occupational skin diseases is very important to avoid severe chronic hand eczema. Therefore the "dermatologist's report" is crucial. Other occupational dermatoses (outside of BK 5101) are briefly mentioned. In recent years the number of notifications of occupational skin cancer due to occupational UV-irradiation has increased. According to recent epidemiological findings, there is a significant and consistent positive association between occupational UV-irradiation and squamous cell carcinoma. Therefore, an important criterion for a new occupational disease is fulfilled. © The Authors • Journal compilation © Blackwell Verlag GmbH, Berlin.

  6. Arrhythmogenic inherited heart muscle diseases in children.

    PubMed

    Towbin, J A; Bowles, N E

    2001-01-01

    The left ventricle (LV) plays a central role in the maintenance of health of children and adults due to its role as the major pump of the heart. In cases of LV dysfunction, a significant percentage of affected individuals develop signs and symptoms of congestive heart failure, leading to the need for therapeutic intervention. Therapy for these patients include anticongestive medications and, in some, placement of devices such as aortic balloon pump or left ventricular assist device, or cardiac transplantation. In the majority of patients the origin is unknown, leading to the term idiopathic dilated cardiomyopathy. During the past decade, the basis of LV dysfunction has begun to unravel. In approximately 30% to 40% of cases, the disorder is inherited; autosomal dominant inheritance is most common (although X-linked, autosomal recessive and mitochondrial inheritance occurs). In the remaining patients, the disorder is presumed to be acquired, with inflammatory heart disease playing an important role. In the case of familial dilated cardiomyopathy, the genetic basis is beginning to unfold. To date, 2 genes for X-linked familial dilated cardiomyopathy (dystrophin, G4.5) have been identified and 4 genes for the autosomal dominant form (actin, desmin, lamin A/C, delta-sarcoglycan) have been described. In 1 form of inflammatory heart disease, coxsackievirus myocarditis, inflammatory mediators, and dystrophin cleavage play a role in the development of LV dysfunction. This review describes the molecular genetics of LV dysfunction and provide evidence for a "final common pathway" responsible for the phenotype.

  7. The Genetics of Human Skin Disease

    PubMed Central

    DeStefano, Gina M.; Christiano, Angela M.

    2014-01-01

    The skin is composed of a variety of cell types expressing specific molecules and possessing different properties that facilitate the complex interactions and intercellular communication essential for maintaining the structural integrity of the skin. Importantly, a single mutation in one of these molecules can disrupt the entire organization and function of these essential networks, leading to cell separation, blistering, and other striking phenotypes observed in inherited skin diseases. Over the past several decades, the genetic basis of many monogenic skin diseases has been elucidated using classical genetic techniques. Importantly, the findings from these studies has shed light onto the many classes of molecules and essential genetic as well as molecular interactions that lend the skin its rigid, yet flexible properties. With the advent of the human genome project, next-generation sequencing techniques, as well as several other recently developed methods, tremendous progress has been made in dissecting the genetic architecture of complex, non-Mendelian skin diseases. PMID:25274756

  8. Rheumatologic Skin Disease.

    PubMed

    Kalus, Andrea

    2015-11-01

    In common rheumatologic diseases skin findings are an important diagnostic clue for astute clinicians. Skin manifestations can help identify systemic disease or may require therapy uniquely targeted at the cutaneous problem. This article discusses 3 common rheumatologic conditions seen in adults by dermatologists: cutaneous lupus, dermatomyositis, and morphea. The focus is on the cutaneous findings and clinical presentation. Some approaches to treatment are explored. Clues to help identify systemic disease are also highlighted.

  9. The Mode of Inheritance of Scheuermann's Disease

    PubMed Central

    Zaidman, A. M.; Zaidman, M. N.; Strokova, E. L.; Korel, A. V.; Kalashnikova, E. V.; Rusova, T. V.; Mikhailovsky, M. V.

    2013-01-01

    The mode of Scheuermann's disease inheritance and its phenotypic traits in probands and their relatives were studied in 90 pedigrees (90 probands and 385 relatives). The disorder was identified as a genetically related pathology inherited by autosomal dominant type, controlled by a mutant major gene, as a kyphotic deformity without signs of vertebral bodies' anomaly and torsion. Morphological and biochemical studies showed disturbance in the structure of vertebral growth plate anterior aspects at the level of deformity, defects in proliferation and differentiation of chondrocytes, and change in proteoglycan spectrum in cells and matrix. Twelve candidate genes were studied in chondrocytes isolated from vertebral growth plates of patients with Scheuermann's disease. The study results included disorder in the IHH gene expression and preservation of the expression of PAX1, two aggrecan isoforms, link protein, types I and II collagen, lumican, versican, growth hormone and growth factor receptor genes, and proliferation gene. Preservation of the SOX9 gene (transcription gene) probably indicates posttranscriptional genetic disorders. The study is under way. PMID:24102061

  10. The mode of inheritance of Scheuermann's disease.

    PubMed

    Zaidman, A M; Zaidman, M N; Strokova, E L; Korel, A V; Kalashnikova, E V; Rusova, T V; Mikhailovsky, M V

    2013-01-01

    The mode of Scheuermann's disease inheritance and its phenotypic traits in probands and their relatives were studied in 90 pedigrees (90 probands and 385 relatives). The disorder was identified as a genetically related pathology inherited by autosomal dominant type, controlled by a mutant major gene, as a kyphotic deformity without signs of vertebral bodies' anomaly and torsion. Morphological and biochemical studies showed disturbance in the structure of vertebral growth plate anterior aspects at the level of deformity, defects in proliferation and differentiation of chondrocytes, and change in proteoglycan spectrum in cells and matrix. Twelve candidate genes were studied in chondrocytes isolated from vertebral growth plates of patients with Scheuermann's disease. The study results included disorder in the IHH gene expression and preservation of the expression of PAX1, two aggrecan isoforms, link protein, types I and II collagen, lumican, versican, growth hormone and growth factor receptor genes, and proliferation gene. Preservation of the SOX9 gene (transcription gene) probably indicates posttranscriptional genetic disorders. The study is under way.

  11. Genetic testing for inherited cardiac disease.

    PubMed

    Wilde, Arthur A M; Behr, Elijah R

    2013-10-01

    Over the past 2 decades, investigators in the field of cardiac genetics have evolved a complex understanding of the pathophysiological basis of inherited cardiac diseases, which predispose individuals to sudden cardiac death. In this Review, we describe the current status of gene discovery and the associations between phenotype and genotype in the cardiac channelopathies and cardiomyopathies. The various indications for genetic testing and its utility in the clinic are assessed in relation to diagnosis, cascade testing, guiding management, and prognosis. Some common problems exist across all phenotypes: the variable penetrance and expressivity of genetic disease, and the difficulty of assessing the functional and clinical effects of novel mutations. These issues will be of particular importance as the next-generation sequencing technologies are used by genetics laboratories to provide results from large panels of genes. The accurate interpretation of these results will be the main challenge for the future.

  12. Three lay mental models of disease inheritance.

    PubMed

    Henderson, B J; Maguire, B T

    2000-01-01

    Genetics are coming to play an increasing role in biomedical understanding of common diseases. The implication of such findings is that at-risk individuals may be offered predictive genetic tests. How do individuals make decisions about predictive tests and what information do they need to make informed choices? Richards [Richards, M.P.M., 1993. The new genetics: some issues for social scientists. Sociology of Health and Illness 15, 567-586] has argued the first step in understanding and helping people to make these decisions is to investigate lay beliefs of genetics. This study examined mental models of inheritance in a sample of 72 lay people. Through analysis of open-ended questionnaires we found three mental models which loosely corresponded to three phases of historical development in the science of genetics. These we labelled the Constitutional, Mendelian and Molecular Models. Predictions for individuals holding each model are made for the comprehension of genetic information in a testing situation.

  13. Smoking and skin disease.

    PubMed

    Thomsen, S F; Sørensen, L T

    2010-06-01

    Tobacco smoking is a serious and preventable health hazard that can cause or exacerbate a number of diseases and shorten life expectancy, but the role of smoking as an etiologic factor in the development of skin disease is largely unknown. Although epidemiological evidence is sparse, findings suggest that tobacco smoking is a contributing factor in systemic lupus erythematosus, psoriasis, palmoplantar pustulosis, cutaneous squamous cell carcinoma, hidradenitis suppurativa, and genital warts. In contrast, smoking may confer some protective effects and mitigate other skin diseases, notably pemphigus vulgaris, pyoderma gangrenosum, aphthous ulcers, and Behçet's disease. Various degenerative dermatologic conditions are also impacted by smoking, such as skin wrinkling and dysregulated wound healing, which can result in post-surgical complications and delayed or even arrested healing of chronic wounds. Most likely, alteration of inflammatory cell function and extracellular matrix turnover caused by smoking-induced oxidative stress are involved in the pathophysiologic mechanisms.

  14. Natural repair mechanisms in correcting pathogenic mutations in inherited skin disorders.

    PubMed

    Jonkman, M F; Castellanos Nuijts, M; van Essen, A J

    2003-11-01

    This review assesses molecular aspects of the rescue of disease-causing mutations in genodermatoses by means of naturally occurring secondary genetic phenomena. Such data have important implications for the design of gene therapy approaches for inherited skin diseases. Reversal of the phenotype depends on three elements: the number of cells involved; the degree of gene reversal; and the specific timing of the reversion. If reversion occurs in somatic cells, revertant mosaicism may occur. This is the situation in which a patient's skin is generally affected by the genodermatosis, but islands of normal skin stand out. These reflect the presence of revertant cells that are sufficient to restore a normal local skin phenotype. Reversion of the original mutation may also be partial, in which case the phenotype may display no, or only limited, improvement. Nevertheless, the phenotype may ameliorate with age if the reverted cells preferentially expand in time or if the time of onset of reversion is after birth. In essence, the complexities of naturally occurring rescue processes are important to understand because the inherent mechanisms may provide clues and insight into optimal therapeutic gene manipulation, and the possibility of mimicking nature in the management of patients with diverse genodermatoses.

  15. Preimplantation genetic diagnosis of inherited disease.

    PubMed

    Ao, A

    1996-12-01

    Research on diagnosis of inherited disease in human embryo before implantation was initiated to help those couples who would prefer to select embryos at this stage rather than during pregnancy. Following in vitro fertilization (IVF), one to two cells were removed from 3 day cleavage stage embryo and cells were analysed for genetic defects. Embryos diagnosed as unaffected were returned to the uterus and thus the resulting pregnancies were assured to be normal. First babies born after the preimplantation diagnosis were using DNA amplification of Y-linked sequences by PCR to avoid X-linked disease. Several pregnancies were obtained by identifying sex of embryos using dual fluorescent in situ hybridization (FISH) with fluorochrome labelled DNA sequences specific for X- and Y-chromosomes to interphase nuclei. Development of single cell PCR for single gene defects led to diagnose several genetic disorders. Preimplantation diagnosis was successfully achieved for predominant delta 508 deletion causing cystic fibrosis, and pregnancies were also diagnosed for Lesch-Nyhan syndrome, Tay-Sachs and Duchenne muscular dystrophy.

  16. Inherited human diseases of heterotopic bone formation

    PubMed Central

    Shore, Eileen M.; Kaplan, Frederick S.

    2013-01-01

    Human disorders of hereditary and nonhereditary heterotopic ossification are conditions in which osteogenesis occurs outside of the skeleton, within soft tissues of the body. The resulting extraskeletal bone is normal. The aberration lies within the mechanisms that regulate cell-fate determination, directing the inappropriate formation of cartilage or bone, or both, in tissues such as skeletal muscle and adipose tissue. Specific gene mutations have been identified in two rare inherited disorders that are clinically characterized by extensive and progressive extraskeletal bone formation—fibrodysplasia ossificans progressiva and progressive osseous heteroplasia. In fibrodysplasia ossificans progressiva, activating mutations in activin receptor type-1, a bone morphogenetic protein type I receptor, induce heterotopic endochondral ossification, which results in the development of a functional bone organ system that includes skeletal-like bone and bone marrow. In progressive osseous heteroplasia, the heterotopic ossification leads to the formation of mainly intramembranous bone tissue in response to inactivating mutations in the GNAS gene. Patients with these diseases variably show malformation of normal skeletal elements, identifying the causative genes and their associated signaling pathways as key mediators of skeletal development in addition to regulating cell-fate decisions by adult stem cells. PMID:20703219

  17. Chemokines and skin diseases.

    PubMed

    Sugaya, Makoto

    2015-04-01

    Chemokines are small molecules that induce chemotaxis and activation of certain subsets of leukocytes. The expression patterns of chemokines and chemokine receptors are specific to certain organs and cells. Therefore, chemokines are important to elucidate the mechanism of organ-specific human diseases. CCL17 expressed by Langerhans cells, blood endothelial cells, and fibroblasts plays a key role in attracting Th2 cells and tumor cells of adult T-cell leukemia/lymphoma and mycosis fungoides/Sézary syndrome into the skin, developing various Th2-type inflammatory skin diseases as well as cutaneous lymphoma. CCL11 and CCL26 expressed by skin-resident cells, such as fibroblasts, blood endothelial cells, and keratinocytes, induce infiltration of CCR3-expressing cells such as Th2 cells and eosinophils. CCL11 may also serve as an autocrine as well as a paracrine in anaplastic large cell lymphoma. CX3CL1 expressed on blood endothelial cells leads to infiltration of CX3CR1(+) immune cells, such as mast cells, neutrophils, and macrophages, playing important roles in wound healing, tumor immunity, and vasculitis. Biologics targeting chemokines and their receptors are promising strategies for various skin diseases that are resistant to the current therapy.

  18. Environmentally Induced Epigenetic Transgenerational Inheritance of Reproductive Disease.

    PubMed

    Nilsson, Eric E; Skinner, Michael K

    2015-12-01

    Reproductive disease and fertility issues have dramatically increased in the human population over the last several decades, suggesting environmental impacts. Epigenetics provides a mechanistic link by which an organism can respond to environmental factors. Interestingly, environmentally induced epigenetic alterations in the germ line can promote aberrant gene expression and disease generationally. Environmentally induced epigenetic transgenerational inheritance is defined as germ-line transmission of altered epigenetic information between generations in the absence of continued environmental exposures. This form of nongenetic inheritance has been shown to directly influence fertility and reproductive disease. This review describes the studies in a variety of species that impact reproductive disease and abnormalities. Observations suggest serious attention be paid to the possibility that ancestral exposures to environmental insults promotes transgenerational inheritance of reproductive disease susceptibility. Environmentally induced epigenetic transgenerational inheritance appears to be an important contributing factor to reproductive disease in many organisms, including humans.

  19. Ex vivo gene therapy cures a blistering skin disease.

    PubMed

    Featherstone, Carol; Uitto, Jouni

    2007-06-01

    A recent publication that describes gene therapy treatment of a patient with an inherited blistering skin disease, epidermolysis bullosa, demonstrates for the first time that gene therapy can cure a disease of solid tissue. The treatment relies on ex vivo transduction of autologous epidermal stem cells with a normal copy of the defective gene, followed by reconstitution of the patient's skin with epithelial sheets that are grown from these genetically corrected cells. This approach holds promise for treatment not only of inherited disorders of the skin but also of other solid tissues that are becoming amenable to tissue engineering.

  20. New patterns of inheritance in mitochondrial disease.

    PubMed

    Schwartz, Marianne; Vissing, John

    2003-10-17

    With the identification of a patient with mutated mitochondrial DNA (mtDNA) of paternal origin, it has been unequivocally proven that not only does paternal mtDNA survive in the zygote, but it can also contribute substantially to the mtDNA pool of adult, human skeletal muscle. The questions are: how often does paternal mtDNA inheritance occur and what mechanisms are involved? In this paper, we will review current knowledge on the fate of sperm mitochondria after fertilization and discuss the impact paternal inheritance may have on our understanding of mitochondrial biology.

  1. Elusive inheritance: Transgenerational effects and epigenetic inheritance in human environmental disease.

    PubMed

    Martos, Suzanne N; Tang, Wan-Yee; Wang, Zhibin

    2015-07-01

    Epigenetic mechanisms involving DNA methylation, histone modification, histone variants and nucleosome positioning, and noncoding RNAs regulate cell-, tissue-, and developmental stage-specific gene expression by influencing chromatin structure and modulating interactions between proteins and DNA. Epigenetic marks are mitotically inherited in somatic cells and may be altered in response to internal and external stimuli. The idea that environment-induced epigenetic changes in mammals could be inherited through the germline, independent of genetic mechanisms, has stimulated much debate. Many experimental models have been designed to interrogate the possibility of transgenerational epigenetic inheritance and provide insight into how environmental exposures influence phenotypes over multiple generations in the absence of any apparent genetic mutation. Unexpected molecular evidence has forced us to reevaluate not only our understanding of the plasticity and heritability of epigenetic factors, but of the stability of the genome as well. Recent reviews have described the difference between transgenerational and intergenerational effects; the two major epigenetic reprogramming events in the mammalian lifecycle; these two events making transgenerational epigenetic inheritance of environment-induced perturbations rare, if at all possible, in mammals; and mechanisms of transgenerational epigenetic inheritance in non-mammalian eukaryotic organisms. This paper briefly introduces these topics and mainly focuses on (1) transgenerational phenotypes and epigenetic effects in mammals, (2) environment-induced intergenerational epigenetic effects, and (3) the inherent difficulties in establishing a role for epigenetic inheritance in human environmental disease.

  2. Interdisciplinary psychosocial care for families with inherited cardiovascular diseases.

    PubMed

    Caleshu, Colleen; Kasparian, Nadine A; Edwards, Katharine S; Yeates, Laura; Semsarian, Christopher; Perez, Marco; Ashley, Euan; Turner, Christian J; Knowles, Joshua W; Ingles, Jodie

    2016-10-01

    Inherited cardiovascular diseases pose unique and complex psychosocial challenges for families, including coming to terms with life-long cardiac disease, risk of sudden death, grief related to the sudden death of a loved one, activity restrictions, and inheritance risk to other family members. Psychosocial factors impact not only mental health but also physical health and cooperation with clinical recommendations. We describe an interdisciplinary approach to the care of families with inherited cardiovascular disease, in which psychological care provided by specialized cardiac genetic counselors, nurses, and psychologists is embedded within the cardiovascular care team. We report illustrative cases and the supporting literature to demonstrate common scenarios, as well as practical guidance for clinicians working in the inherited cardiovascular disease setting.

  3. Research on Skin Diseases - USSR -

    DTIC Science & Technology

    1960-09-28

    0T3: 60-31,799 M K\\& £^§ JPRS: 3995 28 September I960 RESEARCH ON SKIN DISEASES USSR - by G. Ya. Travin and D. N. Plishkin L \\s i- £ is...departments» JPRS: 3995 CSO: Ii22k-D RESEARCH ON SKIN DISEASES - USSR - Table of Contents ÜäS£ Ths Incidence of Skin Diseases in Leningrad, USSR...1 The Characteristics of Skin Disease Morbidity in 19$7 at Sverdlovsk, USSR 7 - a - TIE INCIDENCE OF SKIN DISEASES IN LENINGRAD, USSR /Following

  4. Medical Problems in Obstetrics: Inherited Metabolic Disease.

    PubMed

    Murphy, Elaine

    2015-07-01

    An increasing number of women with rare inherited disorders of metabolism are becoming pregnant. Although, in general, outcomes for women and their children are good, there are a number of issues that need to be considered. Currently, limited specific guidance on the management of these conditions in pregnancy is available. Prepregnancy counselling with information on inheritance, options for reproduction, teratogenicity risk, potential impact on maternal health and long-term health of children should be offered. With appropriate specialist management, the teratogenic risk of conditions such as maternal phenylketonuria (PKU) can be eliminated, and the risk of metabolic decompensation in disorders of energy metabolism or intoxication significantly reduced. Multidisciplinary management, and close liaison between obstetricians and other specialists, is required for those women in whom there is cardiac, renal, respiratory, joint or other organ involvement.

  5. Pregnancy in women with inherited metabolic disease

    PubMed Central

    2015-01-01

    An increasing number of women with rare inherited disorders of metabolism are becoming pregnant. Whilst, in general, outcomes for women and their children are good, there are issues that need to be considered. Due to the rarity of many conditions, there is limited specific guidance available on best management. Prepregnancy counselling with information on inheritance, options for reproduction, teratogenicity risk, potential impact on maternal health and long-term health of children should be offered. With appropriate specialist management, the teratogenic risk of conditions such as maternal phenylketonuria (PKU) can be eliminated, and the risk of metabolic decompensation in other disorders of intoxication or energy metabolism significantly reduced. Newer therapies, such as enzyme replacement therapy, appear to be safe in pregnancy, but specific advice should be sought. Multidisciplinary management, and close liaison between obstetricians and other specialists is required for women in whom there is cardiac, renal, respiratory, joint or other organ involvement. PMID:27512458

  6. Mitochondrial inheritance in a mitochondrially mediated disease.

    PubMed

    Egger, J; Wilson, J

    1983-07-21

    Mendelian inheritance involves the transmission to successive generations of DNA contained in genes in the nucleus, but DNA is also contained in mitochondria, where it is believed to be responsible for the encoding of certain mitochondrial enzymes. Since nearly all mitochondrial DNA is maternally transmitted, one might expect a nonmendelian pattern of inheritance in mitochondrial cytopathy, a syndrome in which there are abnormalities in mitochondrial structure and deficiencies in a variety of mitochondrial enzymes. We studied the pedigrees of 6 affected families whose members we had examined personally and of 24 families described in the literature. In 27 families, exclusively maternal transmission occurred; in 3 there was also paternal transmission in one generation. Altogether, 51 mothers but only 3 fathers had transmitted the condition. These results are consistent with mitochondrial transmission of mitochondrial cytopathy; the inheritance and enzyme defects of mitochondrial cytopathy can be considered in the light of recent evidence that subunits of respiratory-enzyme complexes are encoded solely by mitochondrial DNA. The occasional paternal transmission may be explained if certain enzyme subunits that are encoded by nuclear DNA are affected.

  7. Compensation for occupational skin diseases.

    PubMed

    Song, Han-Soo; Ryou, Hyun-chul

    2014-06-01

    The Korean list of occupational skin diseases was amended in July 2013. The past list was constructed according to the causative agent and the target organ, and the items of that list had not been reviewed for a long period. The revised list was reconstructed to include diseases classified by the International Classification of Diseases (10th version). Therefore, the items of compensable occupational skin diseases in the amended list in Korea comprise contact dermatitis; chemical burns; Stevens-Johnson syndrome; tar-related skin diseases; infectious skin diseases; skin injury-induced cellulitis; and skin conditions resulting from physical factors such as heat, cold, sun exposure, and ionized radiation. This list will be more practical and convenient for physicians and workers because it follows a disease-based approach. The revised list is in accordance with the International Labor Organization list and is refined according to Korean worker's compensation and the actual occurrence of occupational skin diseases. However, this revised list does not perfectly reflect the actual status of skin diseases because of the few cases of occupational skin diseases, incomplete statistics of skin diseases, and insufficient scientific evidence. Thus, the list of occupational diseases should be modified periodically on the basis of recent evidence and statistics.

  8. Genetic manipulation for inherited neurodegenerative diseases: myth or reality?

    PubMed Central

    Yu-Wai-Man, Patrick

    2016-01-01

    Rare genetic diseases affect about 7% of the general population and over 7000 distinct clinical syndromes have been described with the majority being due to single gene defects. This review will provide a critical overview of genetic strategies that are being pioneered to halt or reverse disease progression in inherited neurodegenerative diseases. This field of research covers a vast area and only the most promising treatment paradigms will be discussed with a particular focus on inherited eye diseases, which have paved the way for innovative gene therapy paradigms, and mitochondrial diseases, which are currently generating a lot of debate centred on the bioethics of germline manipulation. PMID:27002113

  9. Environmentally induced epigenetic transgenerational inheritance of disease susceptibility.

    PubMed

    Nilsson, Eric E; Skinner, Michael K

    2015-01-01

    Environmental insults, such as exposure to toxicants or nutritional abnormalities, can lead to epigenetic changes that are in turn related to increased susceptibility to disease. The focus of this review is on the transgenerational inheritance of such epigenetic abnormalities (epimutations), and how it is that these inherited epigenetic abnormalities can lead to increased disease susceptibility, even in the absence of continued environmental insult. Observations of environmental toxicant specificity and exposure-specific disease susceptibility are discussed. How epimutations are transmitted across generations and how epigenetic changes in the germline are translated into an increased disease susceptibility in the adult is reviewed with regard to disease etiology.

  10. Rare inherited kidney diseases: challenges, opportunities, and perspectives.

    PubMed

    Devuyst, Olivier; Knoers, Nine V A M; Remuzzi, Giuseppe; Schaefer, Franz

    2014-05-24

    At least 10% of adults and nearly all children who receive renal-replacement therapy have an inherited kidney disease. These patients rarely die when their disease progresses and can remain alive for many years because of advances in organ-replacement therapy. However, these disorders substantially decrease their quality of life and have a large effect on health-care systems. Since the kidneys regulate essential homoeostatic processes, inherited kidney disorders have multisystem complications, which add to the usual challenges for rare disorders. In this review, we discuss the nature of rare inherited kidney diseases, the challenges they pose, and opportunities from technological advances, which are well suited to target the kidney. Mechanistic insights from rare disorders are relevant for common disorders such as hypertension, kidney stones, cardiovascular disease, and progression of chronic kidney disease.

  11. Keratins and skin disease.

    PubMed

    Knöbel, Maria; O'Toole, Edel A; Smith, Frances J D

    2015-06-01

    Mutations in keratin genes cause a diverse spectrum of skin, hair and mucosal disorders. Cutaneous disorders include epidermolysis bullosa simplex, palmoplantar keratoderma, epidermolytic ichthyosis and pachyonychia congenita. Both clinical and laboratory observations confirm a major role for keratins in maintaining epidermal cell-cell adhesion. When normal tissue homeostasis is disturbed, for example, during wound healing and cancer, keratins play an important non-mechanical role. Post-translational modifications including glycosylation and phosphorylation of keratins play an important role in protection of epithelial cells from injury. Keratins also play a role in modulation of the immune response. A current focus in the area of keratins and disease is the development of new treatments including small inhibitory RNA (siRNA) to mutant keratins and small molecules to modulate keratin expression.

  12. Occupational Skin Diseases in Korea

    PubMed Central

    Kim, Min-Gi

    2010-01-01

    Skin disease is the most common occupational disease, but the reported number is small in Korea due to a difficulty of detection and diagnosis in time. We described various official statistics and data from occupational skin disease surveillance system, epidemiological surveys and cases published in scientific journals. Until 1981, 2,222 cases of occupational skin disease were reported by Korean employee's regular medical check-up, accounting for 4.9% of the total occupational diseases. There was no subsequent official statistics to figure out occupational skin diseases till 1998. From 1999, the Korea Occupational Safety and Health Agency (KOSHA) published the number of occupational skin diseases through the statistics of Cause Investigation for Industrial Accidents. A total of 301 cases were reported from 1999 to 2007. Recent one study showed the figures of compensated occupational skin diseases. Many of them belonged to daily-paid workers in the public service, especially forestry workers. Also, it described the interesting cases such as vitiligo and trichloroethylene-induced Stevens-Johnson Syndrome. Skin diseases are still important though the number of cases has decreased, and therefore it is recommended to grasp the status of occupational skin diseases through continuous surveillance system and to make policy protecting high-risk group. PMID:21258591

  13. Drink, dames & disease: Erasmus Darwin on inheritance.

    PubMed

    Wilson, Philip K

    2007-12-01

    Dr Erasmus Darwin (1731-1802) readily acknowledged that diseases including gout, consumption, scrofula, epilepsy, and insanity were hereditarily transferred. He also viewed a particular interconnectedness between intemperance (alcoholism) and other hereditary diseases. Darwin's view of 'hereditary' incorporated a malleable admixture of nature and nurture causes. Consistent with his deistic beliefs that development on the Earth followed no fixed plan, Darwin argued that hereditary diseases were not predestined. To overcome or prevent disease, Darwin argued that one must learn how best to exert power over nature and to improve nurture.

  14. Skin Diseases in the Tropics.

    ERIC Educational Resources Information Center

    Mahe, Antoine; And Others

    1994-01-01

    Common skin diseases are prevalent in tropical countries because of extreme weather conditions, mediocre hygiene, and lack of adequate treatment of infectious dermatoses. This guide describes the major endemic skin diseases and their signs for the purpose of helping unspecialized health agents train themselves and determine when a patient should…

  15. Environmentally induced epigenetic transgenerational inheritance of ovarian disease.

    PubMed

    Nilsson, Eric; Larsen, Ginger; Manikkam, Mohan; Guerrero-Bosagna, Carlos; Savenkova, Marina I; Skinner, Michael K

    2012-01-01

    The actions of environmental toxicants and relevant mixtures in promoting the epigenetic transgenerational inheritance of ovarian disease was investigated with the use of a fungicide, a pesticide mixture, a plastic mixture, dioxin and a hydrocarbon mixture. After transient exposure of an F0 gestating female rat during embryonic gonadal sex determination, the F1 and F3 generation progeny adult onset ovarian disease was assessed. Transgenerational disease phenotypes observed included an increase in cysts resembling human polycystic ovarian disease (PCO) and a decrease in the ovarian primordial follicle pool size resembling primary ovarian insufficiency (POI). The F3 generation granulosa cells were isolated and found to have a transgenerational effect on the transcriptome and epigenome (differential DNA methylation). Epigenetic biomarkers for environmental exposure and associated gene networks were identified. Epigenetic transgenerational inheritance of ovarian disease states was induced by all the different classes of environmental compounds, suggesting a role of environmental epigenetics in ovarian disease etiology.

  16. Environmentally Induced Epigenetic Transgenerational Inheritance of Ovarian Disease

    PubMed Central

    Nilsson, Eric; Larsen, Ginger; Manikkam, Mohan; Guerrero-Bosagna, Carlos; Savenkova, Marina I.; Skinner, Michael K.

    2012-01-01

    The actions of environmental toxicants and relevant mixtures in promoting the epigenetic transgenerational inheritance of ovarian disease was investigated with the use of a fungicide, a pesticide mixture, a plastic mixture, dioxin and a hydrocarbon mixture. After transient exposure of an F0 gestating female rat during embryonic gonadal sex determination, the F1 and F3 generation progeny adult onset ovarian disease was assessed. Transgenerational disease phenotypes observed included an increase in cysts resembling human polycystic ovarian disease (PCO) and a decrease in the ovarian primordial follicle pool size resembling primary ovarian insufficiency (POI). The F3 generation granulosa cells were isolated and found to have a transgenerational effect on the transcriptome and epigenome (differential DNA methylation). Epigenetic biomarkers for environmental exposure and associated gene networks were identified. Epigenetic transgenerational inheritance of ovarian disease states was induced by all the different classes of environmental compounds, suggesting a role of environmental epigenetics in ovarian disease etiology. PMID:22570695

  17. Endocrine disruptor induction of epigenetic transgenerational inheritance of disease.

    PubMed

    Skinner, Michael K

    2014-12-01

    Environmental exposures such as toxicants, nutrition and stress have been shown to promote the epigenetic transgenerational inheritance of disease susceptibility. Endocrine disruptors are one of the largest groups of specific toxicants shown to promote this form of epigenetic inheritance. These environmental compounds that interfere with normal endocrine signaling are one of the largest classes of toxicants we are exposed to on a daily level. The ability of ancestral exposures to promote disease susceptibility significantly increases the potential biohazards of these toxicants. Therefore, what your great-grandmother was exposed to during pregnancy may influence your disease development, even in the absence of any exposure, and you are going to pass this on to your grandchildren. This non-genetic form of inheritance significantly impacts our understanding of biology from the origins of disease to evolutionary biology. The current review will describe the previous studies and endocrine disruptors shown to promote the epigenetic transgenerational inheritance of disease. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. Window panes of eternity. Health, disease, and inherited risk.

    PubMed Central

    Scriver, C. R.

    1982-01-01

    Personal health reflects harmony between individual and experience; it is optimal homeostasis. Disease is an outcome of incongruity leading to dishomeostasis. Relative to earlier times, disease in modern society has higher "heritability" (in the broad meaning of the term). Inherited risks are facts compatible with anticipation and prevention of disease. This viewpoint has major implications for medical practice, deployment of health services, themes of research, and education of health care personnel and citizens. PMID:6763817

  19. Travel-associated skin disease.

    PubMed

    Morris-Jones, Rachael; Morris-Jones, Stephen

    2012-09-01

    Travel associated skin disease is extremely common and a frequent cause of the returning traveller seeking medical attention. Widespread cutaneous eruptions usually represent reactive rashes, indicating an underlying systemic infection or allergic reaction. Patients with disseminated or spreading rashes following travel often present with fever and malaise. In contrast, those presenting with localised skin disease such as a blister, nodule, plaque, ulcer etc are usually well in themselves but have sustained a bite/sting/penetrating injury or introduction of infection directly into the skin at the affected site. As a general rule widespread rashes are investigated with blood tests/serology and localised lesions with a skin biopsy for culture and histology.

  20. Sun exposed skin disease.

    PubMed

    Lehmann, Percy

    2011-01-01

    A wide variety of dermatoses may arise in exposed areas and are at the same time induced or exacerbated by irradiation from the sun. The spectrum may range from acute sunburn to chronic effects of sun damage, including elastosis and ultraviolet-induced skin cancer. Inflammatory ultraviolet-induced dermatoses have a confusing nomenclature and classification that often leads to difficulties in the differential diagnosis. Modern nosology differentiates primary from secondary photodermatoses. Primary photodermatoses are believed to be mainly irradiation-induced and immunologically mediated. If the pathophysiology is not clearly defined, they are also called idiopathic. In cases of a known photosensitizer, local and systemic phototoxic or photoallergic reactions can be differentiated. Secondary photodermatoses have an established pathophysiology; for example, an enzyme defect such as occurs in the porphyrias or xeroderma pigmentosum, which leads to the abnormal sun sensitivity. Finally, preexisting dermatoses may be exacerbated by irradiation from the sun, as in systemic lupus erythematosus or Darier disease. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. An Update on Laboratory Diagnosis of Liver Inherited Diseases

    PubMed Central

    Elce, Ausilia; Amato, Felice

    2013-01-01

    Liver inherited diseases are a group of genetically determined clinical entities that appear with an early chronic liver involvement. They include Wilson's disease (hepatolenticular degeneration), hereditary hemochromatosis, and alpha-1-antitrypsin deficiency. In addition, cystic fibrosis, although it is not specifically a liver disease, may cause a severe liver involvement in a significant percentage of cases. For all these pathologies, the disease gene is known, and molecular analysis may contribute to the unequivocal diagnosis. This approach could avoid the patient invasive procedures and limit complications associated with a delay in diagnosis. We review liver inherited diseases on the basis of the genetic defect, focusing on the contribution of molecular analysis in the multistep diagnostic workup. PMID:24222913

  2. Genetic manipulation for inherited neurodegenerative diseases: myth or reality?

    PubMed

    Yu-Wai-Man, Patrick

    2016-10-01

    Rare genetic diseases affect about 7% of the general population and over 7000 distinct clinical syndromes have been described with the majority being due to single gene defects. This review will provide a critical overview of genetic strategies that are being pioneered to halt or reverse disease progression in inherited neurodegenerative diseases. This field of research covers a vast area and only the most promising treatment paradigms will be discussed with a particular focus on inherited eye diseases, which have paved the way for innovative gene therapy paradigms, and mitochondrial diseases, which are currently generating a lot of debate centred on the bioethics of germline manipulation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  3. Mitochondrial dynamics and inherited peripheral nerve diseases.

    PubMed

    Pareyson, Davide; Saveri, Paola; Sagnelli, Anna; Piscosquito, Giuseppe

    2015-06-02

    Peripheral nerves have peculiar energetic requirements because of considerable length of axons and therefore correct mitochondria functioning and distribution along nerves is fundamental. Mitochondrial dynamics refers to the continuous change in size, shape, and position of mitochondria within cells. Abnormalities of mitochondrial dynamics produced by mutations in proteins involved in mitochondrial fusion (mitofusin-2, MFN2), fission (ganglioside-induced differentiation-associated protein-1, GDAP1), and mitochondrial axonal transport usually present with a Charcot-Marie-Tooth disease (CMT) phenotype. MFN2 mutations cause CMT type 2A by altering mitochondrial fusion and trafficking along the axonal microtubule system. CMT2A is an axonal autosomal dominant CMT type which in most cases is characterized by early onset and rather severe course. GDAP1 mutations also alter fission, fusion and transport of mitochondria and are associated either with recessive demyelinating (CMT4A) and axonal CMT (AR-CMT2K) and, less commonly, with dominant, milder, axonal CMT (CMT2K). OPA1 (Optic Atrophy-1) is involved in fusion of mitochondrial inner membrane, and its heterozygous mutations lead to early-onset and progressive dominant optic atrophy which may be complicated by other neurological symptoms including peripheral neuropathy. Mutations in several proteins fundamental for the axonal transport or forming the axonal cytoskeleton result in peripheral neuropathy, i.e., CMT, distal hereditary motor neuropathy (dHMN) or hereditary sensory and autonomic neuropathy (HSAN), as well as in hereditary spastic paraplegia. Indeed, mitochondrial transport involves directly or indirectly components of the kinesin superfamily (KIF5A, KIF1A, KIF1B), responsible of anterograde transport, and of the dynein complex and related proteins (DYNC1H1, dynactin, dynamin-2), implicated in retrograde flow. Microtubules, neurofilaments, and chaperones such as heat shock proteins (HSPs) also have a fundamental

  4. Seizures in dominantly inherited Alzheimer disease.

    PubMed

    Zarea, Aline; Charbonnier, Camille; Rovelet-Lecrux, Anne; Nicolas, Gaël; Rousseau, Stéphane; Borden, Alaina; Pariente, Jeremie; Le Ber, Isabelle; Pasquier, Florence; Formaglio, Maite; Martinaud, Olivier; Rollin-Sillaire, Adeline; Sarazin, Marie; Croisile, Bernard; Boutoleau-Bretonnière, Claire; Ceccaldi, Mathieu; Gabelle, Audrey; Chamard, Ludivine; Blanc, Frédéric; Sellal, François; Paquet, Claire; Campion, Dominique; Hannequin, Didier; Wallon, David

    2016-08-30

    To assess seizure frequency in a large French cohort of autosomal dominant early-onset Alzheimer disease (ADEOAD) and to determine possible correlations with causative mutations. A national multicentric study was performed in patients with ADEOAD harboring a pathogenic mutation within PSEN1, PSEN2, APP, or a duplication of APP, and a minimal follow-up of 5 years. Clinical, EEG, and imaging data were systematically recorded. We included 132 patients from 77 families: 94 PSEN1 mutation carriers (MCs), 16 APP duplication carriers, 15 APP MCs, and 7 PSEN2 MCs. Seizure frequency was 47.7% after a mean follow-up of 8.4 years (range 5-25). After 5-year follow-up and using a Cox model analysis, the percentages of patients with seizures were respectively 19.1% (10.8%-26.7%) for PSEN1, 28.6% (0%-55.3%) for PSEN2, 31.2% (4.3%-50.6%) for APP duplications, and no patient for APP mutation. APP duplication carriers showed a significantly increased seizure risk compared to both APP MCs (hazard ratio [HR] = 5.55 [95% confidence interval 1.87-16.44]) and PSEN1 MCs (HR = 4.46 [2.11-9.44]). Among all PSEN1 mutations, those within the domains of protein hydrophilic I, transmembrane II (TM-II), TM-III, TM-IV, and TM-VII were associated with a significant increase in seizure frequency compared to other domains (HR = 4.53 [1.93-10.65], p = 0.0005). Seizures are a common feature of ADEOAD. In this population, risk was significantly higher in the APP duplication group than in all other groups. Within PSEN1, 5 specific domains were associated with a higher seizure risk indicating specific correlations between causative mutation and seizures. © 2016 American Academy of Neurology.

  5. Skin Diseases: Cross-section of human skin

    MedlinePlus

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

  6. Skin Diseases and the Adolescent

    ERIC Educational Resources Information Center

    Bauer, Marjorie

    1970-01-01

    Discusses such concerns as acne, syphilis, drug abuse, and tatoos. Indicates need for physician not only to treat skin diseases but to help adolescents to accept themselves and find constructive directions. (CJ)

  7. Skin Diseases and the Adolescent

    ERIC Educational Resources Information Center

    Bauer, Marjorie

    1970-01-01

    Discusses such concerns as acne, syphilis, drug abuse, and tatoos. Indicates need for physician not only to treat skin diseases but to help adolescents to accept themselves and find constructive directions. (CJ)

  8. [Gene transfer as treatment for metabolic inherited liver diseases

    PubMed

    Godoy, J L

    2000-01-01

    OBJECTIVE: To study gene transfer looking for its future clinical application in the treatment of metabolic inherited liver diseases. METHODS: Bibliographic review about the subject. RESULTS AND CONCLUSIONS: Gene transfer into the liver would be an alternative to liver transplantation to treat some inherited metabolic diseases. Various vectors have been employed for gene transfer, including retrovirus vectors, whose integration into the chromosomal DNA would allow stable long term expression of the transgene. The integration of retrovirus vectors into the genoma of the target cell is only possible during mitosis. Therefore, these vectors must be delivered during hepatic regeneration induced by partial hepatectomy, for example. Another obstacle to be overcome is the extra hepatic dissemination of retrovirus, in particular to the germinals cells, due to the risk of changing the genetical heritage of the progeniture.

  9. Gene editing for skin diseases: designer nucleases as tools for gene therapy of skin fragility disorders.

    PubMed

    March, Oliver P; Reichelt, Julia; Koller, Ulrich

    2017-03-07

    The current treatment of inherited blistering skin diseases, such as epidermolysis bullosa (EB) is largely restricted to wound care and pain management. More effective therapeutic strategies are urgently required and targeting the genetic basis of these severe diseases is now within reach. Here we describe current gene editing tools and their potential to correct gene function in monogenetic blistering skin diseases. We present the features of the most frequently used gene editing techniques TALEN and CRISPR/Cas9, determining their preferential application under specific genetic conditions, including the type of mutational inheritance, the targeting site within the gene or the possibility to specifically target the mutation. Both tools have traits beneficial in specific situations. Promising developments in the field engender gene editing as a potentially powerful therapeutic option for future clinical applications. This article is protected by copyright. All rights reserved.

  10. Insulin resistance and skin diseases.

    PubMed

    Napolitano, Maddalena; Megna, Matteo; Monfrecola, Giuseppe

    2015-01-01

    In medical practice, almost every clinician may encounter patients with skin disease. However, it is not always easy for physicians of all specialties to face the daily task of determining the nature and clinical implication of dermatologic manifestations. Are they confined to the skin, representing a pure dermatologic event? Or are they also markers of internal conditions relating to the patient's overall health? In this review, we will discuss the principal cutaneous conditions which have been linked to metabolic alterations. Particularly, since insulin has an important role in homeostasis and physiology of the skin, we will focus on the relationships between insulin resistance (IR) and skin diseases, analyzing strongly IR-associated conditions such as acanthosis nigricans, acne, and psoriasis, without neglecting emerging and potential scenarios as the ones represented by hidradenitis suppurativa, androgenetic alopecia, and hirsutism.

  11. Insulin Resistance and Skin Diseases

    PubMed Central

    Napolitano, Maddalena; Megna, Matteo; Monfrecola, Giuseppe

    2015-01-01

    In medical practice, almost every clinician may encounter patients with skin disease. However, it is not always easy for physicians of all specialties to face the daily task of determining the nature and clinical implication of dermatologic manifestations. Are they confined to the skin, representing a pure dermatologic event? Or are they also markers of internal conditions relating to the patient's overall health? In this review, we will discuss the principal cutaneous conditions which have been linked to metabolic alterations. Particularly, since insulin has an important role in homeostasis and physiology of the skin, we will focus on the relationships between insulin resistance (IR) and skin diseases, analyzing strongly IR-associated conditions such as acanthosis nigricans, acne, and psoriasis, without neglecting emerging and potential scenarios as the ones represented by hidradenitis suppurativa, androgenetic alopecia, and hirsutism. PMID:25977937

  12. Targeting autophagy in skin diseases.

    PubMed

    Yu, Teng; Zuber, Joshua; Li, Jinchao

    2015-01-01

    Autophagy is a major intracellular degradative process by which cytoplasmic materials are sequestered in double-membraned vesicles and degraded upon fusion with lysosomes. Under normal circumstances, basal autophagy is necessary to maintain cellular homeostasis by scavenging dysfunctional or damaged organelles or proteins. In addition to its vital homeostatic role, this degradation pathway has been implicated in many different cellular processes such as cell apoptosis, inflammation, pathogen clearance, and antigen presentation and thereby has been linked to a variety of human disorders, including metabolic conditions, neurodegenerative diseases, cancers, and infectious diseases. The skin, the largest organ of the body, serves as the first line of defense against many different environmental insults; however, only a few studies have examined the effect of autophagy on the pathogenesis of skin diseases. This review provides an overview of the mechanisms of autophagy and highlights recent findings relevant to the role of autophagy in skin diseases and strategies for therapeutic modulation.

  13. Cannabis and skin diseases.

    PubMed

    Tennstedt, Dominique; Saint-Remy, Anaïs

    2011-01-01

    From time out of mind, man has grown hemp for both "industrial" and "recreational" use (it is then referred to as cannabis). Of course, cannabis has strong psychoactive properties and is one of the most commonly used "soft drugs" in the world. Clinicians should know the adverse effects on mucous membranes and on skin, which may sometimes entail an absolutely necessary stopping of consumption. Raynaud's phenomenon, as well as arteritis due to cannabis consumption may be extremely severe and result in worrying situations for both clinicians and patients.

  14. [Skin cancer as occupational disease].

    PubMed

    Bauer, A

    2016-11-01

    The incidence of epithelial skin neoplasms, such as squamous cell carcinoma and basal cell carcinoma is significantly increasing worldwide. Leisure time solar UV exposure is causative in the overwhelming majority of cases in the general population; however, occupational exposure is responsible for a certain percentage of cases. Employees with a relevant exposure to polycyclic aromatic hydrocarbons in soot, raw paraffin, coal tar, anthracene, pitch or similar substances, to sunlight in outdoor occupations as well as to arsenic and ionizing radiation have a significantly increased risk to develop occupational skin cancer compared to the general population. In the official occupational disease list in the appendix of the German by-law on occupational diseases, the following occupational diseases concerning skin cancer are listed: BK 5102 "skin cancer and carcinoma in situ caused by soot, raw paraffin, coal tar, anthracene, pitch or similar substances" (e.g. various solid paraffins, asphalt and mazut as well as mineral oils, grease, cylinder and drilling oils), BK 5103 "squamous cell carcinoma or multiple actinic keratosis caused by natural UV radiation", BK 1108 "diseases caused by arsenic and its compounds" and BK 2402 "diseases caused by ionizing radiation". For further occupational exposure to carcinogenic substances and potential occupationally acquired skin tumors, no official lists are currently available. These cancers might be considered under a special opt out paragraph in the German Social Law (§ 9 para 2 SGB VII). Tumors in scars after occupational skin trauma or occupational burns are compensated as consequences of work accidents. The current official list of occupational skin cancers and new developments for expert opinions are described in this article.

  15. X-linked Inheritance in Females with Chronic Granulomatous Disease

    PubMed Central

    Mills, Elaine L.; Rholl, Kenneth S.; Quie, Paul G.

    1980-01-01

    Chronic granulomatous disease in males is familial and its transmission is is usually clearly x-linked. The mode of inheritance in females with the syndrome is unknown and the carrier state difficult to identify. Defective polymorphonuclear leukocyte bactericidal activity in this disease is associated with an absence of the respiratory burst generated in stimulated phagocytes and may be detected by the chemiluminescence assay. Polymorphonuclear leukocytes from three of four females with chronic granulomatous disease had extremely low chemiluminescence production, their asymptomatic mothers had intermediate values, and their fathers were normal. Polymorphonuclear neutrophils of two affected males in these kinships generated no chemiluminescence, whereas two of seven female relatives had intermediate values, and all nonaffected males had normal values. In the three families in which leukocytes were studied by nitroblue tetrazolium reduction, two populations of neutrophils were demonstrated for the female patients and/or their mothers. The wide phenotypic variability for clinical disease, evidence of two leukocyte populations in the patients or their mothers, and low but detectable leukocyte chemiluminescence in the affected females is consistent with the Lyon hypothesis of x-chromosome inactivation in these families. The findings suggest an x-linked inheritance in these females with chronic granulomatous disease. Images PMID:7400319

  16. Role of Genetic Testing in Inherited Cardiovascular Disease: A Review.

    PubMed

    Cirino, Allison L; Harris, Stephanie; Lakdawala, Neal K; Michels, Michelle; Olivotto, Iacopo; Day, Sharlene M; Abrams, Dominic J; Charron, Philippe; Caleshu, Colleen; Semsarian, Christopher; Ingles, Jodie; Rakowski, Harry; Judge, Daniel P; Ho, Carolyn Y

    2017-08-09

    Genetic testing is a valuable tool for managing inherited cardiovascular disease in patients and families, including hypertrophic, dilated, and arrhythmogenic cardiomyopathies and inherited arrhythmias. By identifying the molecular etiology of disease, genetic testing can improve diagnostic accuracy and refine family management. However, unique features associated with genetic testing affect the interpretation and application of results and differentiate it from traditional laboratory-based diagnostics. Clinicians and patients must have accurate and realistic expectations about the yield of genetic testing and its role in management. Familiarity with the rationale, implications, benefits, and limitations of genetic testing is essential to achieve the best possible outcomes. Successfully incorporating genetic testing into clinical practice requires (1) recognizing when inherited cardiovascular disease may be present, (2) identifying appropriate individuals in the family for testing, (3) selecting the appropriate genetic test, (4) understanding the complexities of result interpretation, and (5) effectively communicating the results and implications to the patient and family. Obtaining a detailed family history is critical to identify families who will benefit from genetic testing, determine the best strategy, and interpret results. Instead of focusing on an individual patient, genetic testing requires consideration of the family as a unit. Consolidation of care in centers with a high level of expertise is recommended. Clinicians without expertise in genetic testing will benefit from establishing referral or consultative networks with experienced clinicans in specialized multidisciplinary clinics. Genetic testing provides a foundation for transitioning to more precise and individualized management. By distinguishing phenotypic subgroups, identifying disease mechanisms, and focusing family care, gene-based diagnosis can improve management. Successful integration of

  17. Nutrition and skin diseases in veterinary medicine.

    PubMed

    Hensel, Patrick

    2010-01-01

    Veterinarians are confronted with a variety of food and nutrition-related skin diseases, with cutaneous food adverse reaction the most common in small animal dermatology. In addition to canine atopic dermatitis, cutaneous food adverse reaction has been an area of interest for extensive research for the last decade. Nutritional deficiencies and toxicoses are rare these days due to commercially available high-quality diets; however, poorly stored diets, inadequate husbandry of exotic pets, or problems in a farm animal environment may result in zinc, vitamin A, vitamin C, and fatty acid, or copper deficiency. Inherited deficiencies due to abnormal zinc absorption through the gastrointestinal tract must be considered in Nordic breed dogs and goats. Copyright © 2010 Elsevier Inc. All rights reserved.

  18. Germline Mutation in EXPH5 Implicates the Rab27B Effector Protein Slac2-b in Inherited Skin Fragility

    PubMed Central

    McGrath, John A.; Stone, Kristina L.; Begum, Rumena; Simpson, Michael A.; Dopping-Hepenstal, Patricia J.; Liu, Lu; McMillan, James R.; South, Andrew P.; Pourreyron, Celine; McLean, W.H. Irwin; Martinez, Anna E.; Mellerio, Jemima E.; Parsons, Maddy

    2012-01-01

    The Rab GTPase Rab27B and one of its effector proteins, Slac2-b (also known as EXPH5, exophilin-5), have putative roles in intracellular vesicle trafficking but their relevance to human disease is not known. By using whole-exome sequencing, we identified a homozygous frameshift mutation in EXPH5 in three siblings with inherited skin fragility born to consanguineous Iraqi parents. All three individuals harbor the mutation c.5786delC (p.Pro1929Leufs∗8) in EXPH5, which truncates the 1,989 amino acid Slac2-b protein by 52 residues. The clinical features comprised generalized scale-crusts and occasional blisters, mostly induced by trauma, as well as mild diffuse pigmentary mottling on the trunk and proximal limbs. There was no increased bleeding tendency, no neurologic abnormalities, and no increased incidence of infection. Analysis of an affected person's skin showed loss of Slac2-b immunostaining (C-terminal antibody), disruption of keratinocyte adhesion within the lower epidermis, and an increased number of perinuclear vesicles. A role for Slac2-b in keratinocyte biology was supported by findings of cytoskeletal disruption (mainly keratin intermediate filaments) and decreased keratinocyte adhesion in both keratinocytes from an affected subject and after shRNA knockdown of Slac2-b in normal keratinocytes. Slac2-b was also shown to colocalize with Rab27B and β4 integrin to early adhesion initiation sites in spreading normal keratinocytes. Collectively, our findings identify an unexpected role for Slac2-b in inherited skin fragility and expand the clinical spectrum of human disorders of GTPase effector proteins. PMID:23176819

  19. Skin diseases of the nose.

    PubMed

    Yigider, Ayse Pelin; Kayhan, Fatma Tulin; Yigit, Ozgur; Kavak, Ayse; Cingi, Cemal

    2016-05-01

    The goal of this study was to review the main lesion types of the nasal skin and appropriate treatment strategies rather than to present a comprehensive list of all diseases that affect the skin that can involve the nose. We reviewed the main nasal skin lesion types and available treatment strategies. Nasal skin lesions were classified as benign, premalignant, or malignant. Benign lesions of the nose include nonmalignant tumoral lesions (i.e., freckles, comedo, adenoma sebaceum [Pringle disease], hydrocystoma, fibrous papules, sebaceous hyperplasia, and rhinophyma), autoimmune and inflammatory conditions (i.e., pemphigus, sarcoidosis, systemic lupus erythematosus, facial eosinophilic granuloma, rosacea, herpes zoster infection, leishmaniasis, and leprosy), and vascular lesions (i.e., telangiectasis, hemangioma, and spider nevus). Premalignant lesions are actinic keratosis and keratoacanthoma; and malignant tumors are melanoma, basal cell carcinoma, and squamous cell carcinoma. Regardless of whether or not they are malignant, all facial lesions can yield significant cosmetic discomfort that should be evaluated carefully before commencing any curative or corrective intervention. In general, benign lesions are treated with dermabrasive modalities, such as trichloroacetic acid, phenol, salicylate, and laser ablation. Electrocautery, cryosurgery, and surgical excision are also used, although these methods may result in scar formation, which can sometimes be more problematic than the original lesion itself. Any disease that affects the skin, especially those diseases that are triggered by ultraviolet exposure, can involve the face and nose. Cosmetic defects due both to the lesion itself and the intervention must be discussed with the patient, preferably in the presence of a first-degree relative, before commencement of treatment. As a result of heterogeneity of skin lesions of the nose, appropriate education of general practitioners as well as otorhinolaryngologists is

  20. The skin in Parkinson's disease.

    PubMed

    Flint, A

    1977-09-01

    The characteristic oily skin in individuals with parkinsonism has long been observed by clinicians. The oiliness seems to be associated with periods when the disease is most active. This seborrhea has been observed particularly in post-encephalitic parkinsonism, as well as in idiopathic paralysis agitans. It also occurs in phenothiazine-induced parkinsonism.

  1. Autosomal Dominant Inherited Cowden's Disease in a Family.

    PubMed

    Ha, Jun-Wook

    2013-01-01

    Cowden's disease, also known as a kind of phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome, is an uncommon autosomal dominant inherited complex disorder with various hamartomatous growths of multiple organs involving all three germ cell layers. It usually manifests with polyps throughout the gastrointestinal tract, ranging anywhere from 30% to 85%, and more common extra intestinal findings. Mucocutaneous lesions like facial trichilemmomas, acral keratoses, papillomatous papules and macrocephaly, and malignancies including breast, thyroid and endometrial carcinoma are the hallmark of the disease. Here we report on familial Cowden's diseases case of a 52-year-old male proband with mucocutaneous lesions and mutation on the PTEN gene obtained by extrapolating from gastrointestinal polyposis as a starter and his daughter who developed thyroid cancer.

  2. Psychoneuroimmunologic aspects of skin diseases.

    PubMed

    Lugović-Mihić, Liborija; Ljubesić, Luka; Mihić, Josip; Vuković-Cvetković, Vlasta; Troskot, Nina; Situm, Mirna

    2013-09-01

    As mental and psychological issues are important in the development of many dermatologic diseases, these factors are of special interest in research. Psychoneuroimmunology is the study of interaction between psychological processes and the nervous and immune systems of the human body, and it was comprehensively described for the first time about 30 years ago. Communication between the mind and the skin involves the psycho-immuno-endocrine-cutaneous system, encompassing the activities of the brain, the immune system and the skin, with participation of different neuropeptides, interleukins, and immune system messengers. Many common dermatologic diseases have some form of psychomediated pathogenesis that partially accounts for the development of skin lesions. There is a link between emotional stressors (acute or chronic), psychiatric diseases, and dermatoses (e.g., psoriasis, atopic dermatitis, urticaria, viral warts, herpes simplex, vitiligo, acnes, alopecia, prurigo, etc.) and different cytokines and mediators produced in the skin and involved in their pathogenesis. A prominent role is played by those agents that belong to the hypothalamic-pituitary-adrenal axis.

  3. Genome editing: the breakthrough technology for inherited retinal disease?

    PubMed

    Smith, Andrew J; Carter, Stephen P; Kennedy, Breandán N

    2017-10-01

    Genetic alterations resulting in a dysfunctional retinal pigment epithelium and/or degenerating photoreceptors cause impaired vision. These juxtaposed cells in the retina of the posterior eye are crucial for the visual cycle or phototransduction. Deficits in these biochemical processes perturb neural processing of images capturing the external environment. Notably, there is a distinct lack of clinically approved pharmacological, cell- or gene-based therapies for inherited retinal disease. Gene editing technologies are rapidly advancing as a realistic therapeutic option. Areas covered: Recent discovery of endonuclease-mediated gene editing technologies has culminated in a surge of investigations into their therapeutic potential. In this review, the authors discuss gene editing technologies and their applicability in treating inherited retinal diseases, the limitations of the technology and the research obstacles to overcome before editing a patient's genome becomes a viable treatment option. Expert opinion: The ability to strategically edit a patient's genome constitutes a treatment revolution. However, concerns remain over the safety and efficacy of either transplanting iPSC-derived retinal cells following ex vivo gene editing, or with direct gene editing in vivo. Ultimately, further refinements to improve efficacy and safety profiles are paramount for gene editing to emerge as a widely available treatment option.

  4. Maternal inheritance and mitochondrial DNA variants in familial Parkinson's disease.

    PubMed

    Simon, David K; Pankratz, Nathan; Kissell, Diane K; Pauciulo, Michael W; Halter, Cheryl A; Rudolph, Alice; Pfeiffer, Ronald F; Nichols, William C; Foroud, Tatiana

    2010-04-01

    Mitochondrial function is impaired in Parkinson's disease (PD) and may contribute to the pathogenesis of PD, but the causes of mitochondrial impairment in PD are unknown. Mitochondrial dysfunction is recapitulated in cell lines expressing mitochondrial DNA (mtDNA) from PD patients, implicating mtDNA variants or mutations, though the role of mtDNA variants or mutations in PD risk remains unclear. We investigated the potential contribution of mtDNA variants or mutations to the risk of PD. We examined the possibility of a maternal inheritance bias as well as the association between mitochondrial haplogroups and maternal inheritance and disease risk in a case-control study of 168 multiplex PD families in which the proband and one parent were diagnosed with PD. 2-tailed Fisher Exact Tests and McNemar's tests were used to compare allele frequencies, and a t-test to compare ages of onset. The frequency of affected mothers of the proband with PD (83/167, 49.4%) was not significantly different from the frequency of affected females of the proband generation (115/259, 44.4%) (Odds Ratio 1.22; 95%CI 0.83-1.81). After correcting for multiple tests, there were no significant differences in the frequencies of mitochondrial haplogroups or of the 10398G complex I gene polymorphism in PD patients compared to controls, and no significant associations with age of onset of PD. Mitochondrial haplogroup and 10398G polymorphism frequencies were similar in probands having an affected father as compared to probands having an affected mother. These data fail to demonstrate a bias towards maternal inheritance in familial PD. Consistent with this, we find no association of common haplogroup-defining mtDNA variants or for the 10398G variant with the risk of PD. However, these data do not exclude a role for mtDNA variants in other populations, and it remains possible that other inherited mitochondrial DNA variants, or somatic mDNA mutations, contribute to the risk of familial PD.

  5. Maternal inheritance and mitochondrial DNA variants in familial Parkinson's disease

    PubMed Central

    2010-01-01

    Background Mitochondrial function is impaired in Parkinson's disease (PD) and may contribute to the pathogenesis of PD, but the causes of mitochondrial impairment in PD are unknown. Mitochondrial dysfunction is recapitulated in cell lines expressing mitochondrial DNA (mtDNA) from PD patients, implicating mtDNA variants or mutations, though the role of mtDNA variants or mutations in PD risk remains unclear. We investigated the potential contribution of mtDNA variants or mutations to the risk of PD. Methods We examined the possibility of a maternal inheritance bias as well as the association between mitochondrial haplogroups and maternal inheritance and disease risk in a case-control study of 168 multiplex PD families in which the proband and one parent were diagnosed with PD. 2-tailed Fisher Exact Tests and McNemar's tests were used to compare allele frequencies, and a t-test to compare ages of onset. Results The frequency of affected mothers of the proband with PD (83/167, 49.4%) was not significantly different from the frequency of affected females of the proband generation (115/259, 44.4%) (Odds Ratio 1.22; 95%CI 0.83 - 1.81). After correcting for multiple tests, there were no significant differences in the frequencies of mitochondrial haplogroups or of the 10398G complex I gene polymorphism in PD patients compared to controls, and no significant associations with age of onset of PD. Mitochondrial haplogroup and 10398G polymorphism frequencies were similar in probands having an affected father as compared to probands having an affected mother. Conclusions These data fail to demonstrate a bias towards maternal inheritance in familial PD. Consistent with this, we find no association of common haplogroup-defining mtDNA variants or for the 10398G variant with the risk of PD. However, these data do not exclude a role for mtDNA variants in other populations, and it remains possible that other inherited mitochondrial DNA variants, or somatic mDNA mutations, contribute

  6. The Role of the Skin Barrier in Occupational Skin Diseases.

    PubMed

    Kasemsarn, Pranee; Bosco, Joanna; Nixon, Rosemary L

    2016-01-01

    Occupational skin diseases (OSDs) are the second most common occupational diseases worldwide. Occupational contact dermatitis (OCD) is the most frequent OSD, and comprises irritant contact dermatitis (ICD), allergic contact dermatitis (ACD), contact urticaria and protein contact dermatitis. There are many endogenous and exogenous factors which affect the development of OCD, including age, sex, ethnicity, atopic skin diathesis, certain occupations and environmental factors. One of the most important contributing causes is skin barrier dysfunction. The skin provides a first-line defense from environmental assaults and incorporates physical, chemical and biological protection. Skin barrier disturbance plays a crucial role in various skin diseases such as atopic dermatitis (AD), ichthyosis, ICD and ACD. Genetic factors, such as filaggrin gene (FLG) mutations, and external factors, such as skin irritants interfering with stratum corneum structure and composition, may lead to abnormalities in skin barrier function and increased vulnerability to skin diseases. FLG encodes the cornified envelope protein, filaggrin, which is involved in skin barrier function. FLG mutation is associated with the development of OCD. High-risk occupations for OCD include health care workers, hairdressers and construction workers. There are often multiple contributing causes to OCD, as workers are exposed to both irritants and allergens. AD is also associated with skin barrier disruption and plays an important role in OCD. ICD often precedes and facilitates the development of ACD, with impairment of the skin barrier contributing to the concurrence of ICD and ACD in many workers with OCD.

  7. Early-onset colorectal cancer: a sporadic or inherited disease?

    PubMed

    Stigliano, Vittoria; Sanchez-Mete, Lupe; Martayan, Aline; Anti, Marcello

    2014-09-21

    Colorectal cancer is the third most common cancer diagnosed worldwide. Although epidemiology data show a marked variability around the world, its overall incidence rate shows a slow but steady decrease, mainly in developed countries. Conversely, early-onset colorectal cancer appears to display an opposite trend with an overall prevalence in United States and European Union ranging from 3.0% and 8.6%. Colorectal cancer has a substantial proportion of familial cases. In particular, early age at onset is especially suggestive of hereditary predisposition. The clinicopathological and molecular features of colorectal cancer cases show a marked heterogeneity not only between early- and late-onset cases but also within the early-onset group. Two distinct subtypes of early-onset colorectal cancers can be identified: a "sporadic" subtype, usually without family history, and an inherited subtype arising in the context of well defined hereditary syndromes. The pathogenesis of the early-onset disease is substantially well characterized in the inherited subtype, which is mainly associated to the Lynch syndrome and occasionally to other rare mendelian diseases, whereas in the "sporadic" subtype the origin of the disease may be attributed to the presence of various common/rare genetic variants, so far largely unidentified, displaying variable penetrance. These variants are thought to act cumulatively to increase the risk of colorectal cancer, and presumably to also anticipate its onset. Efforts are ongoing in the attempt to unravel the intricate genetic basis of this "sporadic" early-onset disease. A better knowledge of molecular entities and pathways may impact on family-tailored prevention and clinical management strategies.

  8. [Skin changes in rheumatic diseases].

    PubMed

    Dobrić, Ivan

    2005-01-01

    The Intruduction includes those eflorescences that might be useful for diagnostics in rheumatology. Further in the text we have described four groups of rheumatic disorders. The first group: rheumatic diseases (lupus erythematosus, dermatomyositis, systemic scleroderma, the mixed connective tissue disease, allergic vasculitis, polyarteritis) which are the most common from the dermatological point of view. The second group: rheumatic diseases (Wegener's granulomatosis, rheumatoid arthritis, Sjögren, Reiter and Behçet syndrome and Kawasaki's disease) which are rarely of interest to our dermatologists. In this group there is also psoriatic arthritis, which is not rare in dermatology but its diagnostics and treatment belong to rheumatologists' field of expertise. The third group: infections (rheumatic fever, diseminated gonococcal infection, subacute bacterial endocarditis, Lyme disesease). The fourth group: metabolic disorders (gout). The diseases of the first group are described completely. In the second, third and fourth group of the diseases we have included only skin changes.

  9. Generation of Transgenic Monkeys with Human Inherited Genetic Disease

    PubMed Central

    Chan, Anthony W.S; Yang, Shang-Hsun

    2009-01-01

    Modeling human diseases using nonhuman primates including chimpanzee, rhesus, cynomolgus, marmoset and squirrel monkeys has been reported in the past decades. Due to the high similarity between nonhuman primates and humans, including genome constitution, cognitive behavioral functions, anatomical structure, metabolic, reproductive, and brain functions; nonhuman primates have played an important role in understanding physiological functions of the human body, clarifying the underlying mechanism of human diseases, and the development of novel treatments for human diseases. However, nonhuman primate research has been restricted to cognitive, behavioral, biochemical and pharmacological approaches of human diseases due to the limitation of gene transfer technology in nonhuman primates. The recent advancement in transgenic technology that has led to the generation of the first transgenic monkey in 2001 and a transgenic monkey model of Huntington's disease (HD) in 2008 has changed that focus. The creation of transgenic HD monkeys that replicate key pathological features of human HD patients further suggests the crucial role of nonhuman primates in the future development of biomedicine. These successes have opened the door to genetic manipulation in nonhuman primates and a new era in modeling human inherited genetic disorders. We focused on the procedures in creating transgenic Huntington's disease monkeys, but our work can be applied to transgenesis in other nonhuman primate species. PMID:19467335

  10. Peripheral neuropathy in complex inherited diseases: an approach to diagnosis.

    PubMed

    Rossor, Alexander M; Carr, Aisling S; Devine, Helen; Chandrashekar, Hoskote; Pelayo-Negro, Ana Lara; Pareyson, Davide; Shy, Michael E; Scherer, Steven S; Reilly, Mary M

    2017-08-09

    Peripheral neuropathy is a common finding in patients with complex inherited neurological diseases and may be subclinical or a major component of the phenotype. This review aims to provide a clinical approach to the diagnosis of this complex group of patients by addressing key questions including the predominant neurological syndrome associated with the neuropathy, for example, spasticity, the type of neuropathy and the other neurological and non-neurological features of the syndrome. Priority is given to the diagnosis of treatable conditions. Using this approach, we associated neuropathy with one of three major syndromic categories: (1) ataxia, (2) spasticity and (3) global neurodevelopmental impairment. Syndromes that do not fall easily into one of these three categories can be grouped according to the predominant system involved in addition to the neuropathy, for example, cardiomyopathy and neuropathy. We also include a separate category of complex inherited relapsing neuropathy syndromes, some of which may mimic Guillain-Barré syndrome, as many will have a metabolic aetiology and be potentially treatable. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  11. Charcot-Marie-Tooth disease and other inherited neuropathies.

    PubMed

    Saporta, Mario A

    2014-10-01

    Inherited peripheral neuropathies are among the most common genetic neuromuscular disorders worldwide. However, their diagnosis can be challenging due to genotypic and phenotypic variability. Charcot-Marie-Tooth disease (CMT), the most common form, is associated with mutations or copy-number variations in over 70 genes, representing proteins with fundamental roles in the development and function of Schwann cells and peripheral axons. Other genetic peripheral neuropathies are associated with multisystem manifestations, including familial amyloid neuropathy and neuropathies associated with metabolic or other genetic syndromes. This article reviews the most recent discoveries in the field and how they are changing the way neurologists diagnose this specific group of peripheral neuropathies. In the past few years, several large cohort studies on the molecular diagnosis of CMT have been published, providing guidelines for genetic testing in clinical practice. In the same period, next-generation sequencing technology has accelerated the discovery of new CMT genes, expanding our knowledge on genotype-phenotype correlations. Recent advances in sequencing technology and genotype-phenotype correlation studies are changing the way neurologists diagnose inherited neuropathies. New therapeutic strategies for familial amyloid neuropathy are paving the way for innovative treatments for genetic neuropathies.

  12. Gene Therapy for Skin Diseases

    PubMed Central

    Gorell, Emily; Nguyen, Ngon; Lane, Alfred; Siprashvili, Zurab

    2014-01-01

    The skin possesses qualities that make it desirable for gene therapy, and studies have focused on gene therapy for multiple cutaneous diseases. Gene therapy uses a vector to introduce genetic material into cells to alter gene expression, negating a pathological process. This can be accomplished with a variety of viral vectors or nonviral administrations. Although results are promising, there are several potential pitfalls that must be addressed to improve the safety profile to make gene therapy widely available clinically. PMID:24692191

  13. Genetics in Parkinson disease: Mendelian versus non-Mendelian inheritance.

    PubMed

    Hernandez, Dena G; Reed, Xylena; Singleton, Andrew B

    2016-10-01

    Parkinson's disease is a common, progressive neurodegenerative disorder, affecting 3% of those older than 75 years of age. Clinically, Parkinson's disease (PD) is associated with resting tremor, postural instability, rigidity, bradykinesia, and a good response to levodopa therapy. Over the last 15 years, numerous studies have confirmed that genetic factors contribute to the complex pathogenesis of PD. Highly penetrant mutations producing rare, monogenic forms of the disease have been discovered in singular genes such as SNCA, Parkin, DJ-1, PINK 1, LRRK2, and VPS35. Unique variants with incomplete penetrance in LRRK2 and GBA have been shown to be strong risk factors for PD in certain populations. Additionally, over 20 common variants with small effect sizes are now recognized to modulate the risk for PD. Investigating Mendelian forms of PD has provided precious insight into the pathophysiology that underlies the more common idiopathic form of disease; however, no treatment methodologies have developed. Furthermore, for identified common risk alleles, the functional basis underlying risk principally remains unknown. The challenge over the next decade will be to strengthen the findings delivered through genetic discovery by assessing the direct, biological consequences of risk variants in tandem with additional high-content, integrated datasets. This review discusses monogenic risk factors and mechanisms of Mendelian inheritance of Parkinson disease. Highly penetrant mutations in SNCA, Parkin, DJ-1, PINK 1, LRRK2 and VPS35 produce rare, monogenic forms of the disease, while unique variants within LRRK2 and GBA show incomplete penetrance and are strong risk factors for PD. Additionally, over 20 common variants with small effect sizes modulate disease risk. The challenge over the next decade is to strengthen genetic findings by assessing direct, biological consequences of risk variants in tandem with high-content, integrated datasets. This article is part of a special

  14. Current and future therapies for inherited cholestatic liver diseases

    PubMed Central

    van der Woerd, Wendy L; Houwen, Roderick HJ; van de Graaf, Stan FJ

    2017-01-01

    Familial intrahepatic cholestasis (FIC) comprises a group of rare cholestatic liver diseases associated with canalicular transport defects resulting predominantly from mutations in ATP8B1, ABCB11 and ABCB4. Phenotypes range from benign recurrent intrahepatic cholestasis (BRIC), associated with recurrent cholestatic attacks, to progressive FIC (PFIC). Patients often suffer from severe pruritus and eventually progressive cholestasis results in liver failure. Currently, first-line treatment includes ursodeoxycholic acid in patients with ABCB4 deficiency (PFIC3) and partial biliary diversion in patients with ATP8B1 or ABCB11 deficiency (PFIC1 and PFIC2). When treatment fails, liver transplantation is needed which is associated with complications like rejection, post-transplant hepatic steatosis and recurrence of disease. Therefore, the need for more and better therapies for this group of chronic diseases remains. Here, we discuss new symptomatic treatment options like total biliary diversion, pharmacological diversion of bile acids and hepatocyte transplantation. Furthermore, we focus on emerging mutation-targeted therapeutic strategies, providing an outlook for future personalized treatment for inherited cholestatic liver diseases. PMID:28223721

  15. Mitochondrial dysfunction in inherited renal disease and acute kidney injury.

    PubMed

    Emma, Francesco; Montini, Giovanni; Parikh, Samir M; Salviati, Leonardo

    2016-05-01

    Mitochondria are increasingly recognized as key players in genetic and acquired renal diseases. Most mitochondrial cytopathies that cause renal symptoms are characterized by tubular defects, but glomerular, tubulointerstitial and cystic diseases have also been described. For example, defects in coenzyme Q10 (CoQ10) biosynthesis and the mitochondrial DNA 3243 A>G mutation are important causes of focal segmental glomerulosclerosis in children and in adults, respectively. Although they sometimes present with isolated renal findings, mitochondrial diseases are frequently associated with symptoms related to central nervous system and neuromuscular involvement. They can result from mutations in nuclear genes that are inherited according to classic Mendelian rules or from mutations in mitochondrial DNA, which are transmitted according to more complex rules of mitochondrial genetics. Diagnosis of mitochondrial disorders involves clinical characterization of patients in combination with biochemical and genetic analyses. In particular, prompt diagnosis of CoQ10 biosynthesis defects is imperative because of their potentially reversible nature. In acute kidney injury (AKI), mitochondrial dysfunction contributes to the physiopathology of tissue injury, whereas mitochondrial biogenesis has an important role in the recovery of renal function. Potential therapies that target mitochondrial dysfunction or promote mitochondrial regeneration are being developed to limit renal damage during AKI and promote repair of injured tissue.

  16. Mitochondrial dysfunction in inherited renal disease and acute kidney injury

    PubMed Central

    Emma, Francesco; Montini, Giovanni; Parikh, Samir M.; Salviati, Leonardo

    2017-01-01

    Mitochondria are increasingly recognized as key players in genetic and acquired renal diseases. Most mitochondrial cytopathies that cause renal symptoms are characterized by tubular defects, but glomerular, tubulointerstitial and cystic diseases have also been described. For example, defects in coenzyme Q10 (CoQ10) biosynthesis and the mitochondrial DNA 3243 A>G mutation are important causes of focal segmental glomerulosclerosis in children and in adults, respectively. Although they sometimes present with isolated renal findings, mitochondrial diseases are frequently associated with symptoms related to central nervous system and neuromuscular involvement. They can result from mutations in nuclear genes that are inherited according to classic Mendelian rules or from mutations in mitochondrial DNA, which are transmitted according to more complex rules of mitochondrial genetics. Diagnosis of mitochondrial disorders involves clinical characterization of patients in combination with biochemical and genetic analyses. In particular, prompt diagnosis of CoQ10 biosynthesis defects is imperative because of their potentially reversible nature. In acute kidney injury (AKI), mitochondrial dysfunction contributes to the physiopathology of tissue injury, whereas mitochondrial biogenesis has an important role in the recovery of renal function. Potential therapies that target mitochondrial dysfunction or promote mitochondrial regeneration are being developed to limit renal damage during AKI and promote repair of injured tissue. PMID:26804019

  17. Molecular findings from 537 individuals with inherited retinal disease

    PubMed Central

    Ellingford, Jamie M; Barton, Stephanie; Bhaskar, Sanjeev; O'Sullivan, James; Williams, Simon G; Lamb, Janine A; Panda, Binay; Sergouniotis, Panagiotis I; Gillespie, Rachel L; Daiger, Stephen P; Hall, Georgina; Gale, Theodora; Lloyd, I Christopher; Bishop, Paul N; Ramsden, Simon C; Black, Graeme C M

    2016-01-01

    Background Inherited retinal diseases (IRDs) are a clinically and genetically heterogeneous set of disorders, for which diagnostic second-generation sequencing (next-generation sequencing, NGS) services have been developed worldwide. Methods We present the molecular findings of 537 individuals referred to a 105-gene diagnostic NGS test for IRDs. We assess the diagnostic yield, the spectrum of clinical referrals, the variant analysis burden and the genetic heterogeneity of IRD. We retrospectively analyse disease-causing variants, including an assessment of variant frequency in Exome Aggregation Consortium (ExAC). Results Individuals were referred from 10 clinically distinct classifications of IRD. Of the 4542 variants clinically analysed, we have reported 402 mutations as a cause or a potential cause of disease in 62 of the 105 genes surveyed. These variants account or likely account for the clinical diagnosis of IRD in 51% of the 537 referred individuals. 144 potentially disease-causing mutations were identified as novel at the time of clinical analysis, and we further demonstrate the segregation of known disease-causing variants among individuals with IRD. We show that clinically analysed variants indicated as rare in dbSNP and the Exome Variant Server remain rare in ExAC, and that genes discovered as a cause of IRD in the post-NGS era are rare causes of IRD in a population of clinically surveyed individuals. Conclusions Our findings illustrate the continued powerful utility of custom-gene panel diagnostic NGS tests for IRD in the clinic, but suggest clear future avenues for increasing diagnostic yields. PMID:27208204

  18. Dermatitis Herpetiformis: Skin Manifestation of Celiac Disease

    MedlinePlus

    ... a chronic, intensely itchy, blistering skin manifestation of gluten-sensitive enteropathy, commonly known as celiac disease. DH ... external manifestation of an abnormal immune response to gluten, in which IgA antibodies form against the skin ...

  19. Complex Inheritance of Melanoma and Pigmentation of Coat and Skin in Grey Horses

    PubMed Central

    Druml, Thomas; Seltenhammer, Monika; Sundström, Elisabeth; Pielberg, Gerli Rosengren; Andersson, Leif

    2013-01-01

    Abstract The dominant phenotype of greying with age in horses, caused by a 4.6-kb duplication in intron 6 of STX17, is associated with a high incidence of melanoma and vitiligo-like skin depigmentation. However, the progressive greying and the incidence of melanoma, vitiligo-like depigmentation, and amount of speckling in these horses do not follow a simple inheritance pattern. To understand their inheritance, we analysed the melanoma grade, grey level, vitiligo grade, and speckling grade of 1,119 Grey horses (7,146 measurements) measured in six countries over a 9-year period. We estimated narrow sense heritability (h2), and we decomposed this parameter into polygenic heritability (h2 POLY), heritability due to the Grey (STX17) mutation (h2 STX17), and heritability due to agouti (ASIP) locus (h2 ASIP). A high heritability was found for greying (h2 = 0.79), vitiligo (h2 = 0.63), and speckling (h2 = 0.66), while a moderate heritability was estimated for melanoma (h2 = 0.37). The additive component of ASIP was significantly different from zero only for melanoma (h2 ASIP = 0.02). STX17 controlled large proportions of phenotypic variance (h2 STX17 = 0.18–0.55) and overall heritability (h2 STX17/h2 = 0.28–0.83) for all traits. Genetic correlations among traits were estimated as moderate to high, primarily due to the effects of the STX17 locus. Nevertheless, the correlation between progressive greying and vitiligo-like depigmentation remained large even after taking into account the effects of STX17. We presented a model where four traits with complex inheritance patterns are strongly influenced by a single mutation. This is in line with evidence of recent studies in domestic animals indicating that some complex traits are, in addition to the large number of genes with small additive effects, influenced by genes of moderate-to-large effect. Furthermore, we demonstrated that the STX17 mutation explains to a large extent the moderate to high

  20. Complex inheritance of melanoma and pigmentation of coat and skin in Grey horses.

    PubMed

    Curik, Ino; Druml, Thomas; Seltenhammer, Monika; Sundström, Elisabeth; Pielberg, Gerli Rosengren; Andersson, Leif; Sölkner, Johann

    2013-01-01

    The dominant phenotype of greying with age in horses, caused by a 4.6-kb duplication in intron 6 of STX17, is associated with a high incidence of melanoma and vitiligo-like skin depigmentation. However, the progressive greying and the incidence of melanoma, vitiligo-like depigmentation, and amount of speckling in these horses do not follow a simple inheritance pattern. To understand their inheritance, we analysed the melanoma grade, grey level, vitiligo grade, and speckling grade of 1,119 Grey horses (7,146 measurements) measured in six countries over a 9-year period. We estimated narrow sense heritability (h(2)), and we decomposed this parameter into polygenic heritability (h(2) (POLY)), heritability due to the Grey (STX17) mutation (h(2) (STX17)), and heritability due to agouti (ASIP) locus (h(2) (ASIP)). A high heritability was found for greying (h(2) = 0.79), vitiligo (h(2) = 0.63), and speckling (h(2) = 0.66), while a moderate heritability was estimated for melanoma (h(2) = 0.37). The additive component of ASIP was significantly different from zero only for melanoma (h(2) (ASIP) = 0.02). STX17 controlled large proportions of phenotypic variance (h(2) (STX17) = 0.18-0.55) and overall heritability (h(2) (STX17)/h(2) = 0.28-0.83) for all traits. Genetic correlations among traits were estimated as moderate to high, primarily due to the effects of the STX17 locus. Nevertheless, the correlation between progressive greying and vitiligo-like depigmentation remained large even after taking into account the effects of STX17. We presented a model where four traits with complex inheritance patterns are strongly influenced by a single mutation. This is in line with evidence of recent studies in domestic animals indicating that some complex traits are, in addition to the large number of genes with small additive effects, influenced by genes of moderate-to-large effect. Furthermore, we demonstrated that the STX17 mutation explains to a large

  1. In silico Mapping of Protein Unfolding Mutations for Inherited Disease

    PubMed Central

    McCafferty, Caitlyn L.; Sergeev, Yuri V.

    2016-01-01

    The effect of disease-causing missense mutations on protein folding is difficult to evaluate. To understand this relationship, we developed the unfolding mutation screen (UMS) for in silico evaluation of the severity of genetic perturbations at the atomic level of protein structure. The program takes into account the protein-unfolding curve and generates propensities using calculated free energy changes for every possible missense mutation at once. These results are presented in a series of unfolding heat maps and a colored protein 3D structure to show the residues critical to the protein folding and are available for quick reference. UMS was tested with 16 crystal structures to evaluate the unfolding for 1391 mutations from the ProTherm database. Our results showed that the computational accuracy of the unfolding calculations was similar to the accuracy of previously published free energy changes but provided a better scale. Our residue identity control helps to improve protein homology models. The unfolding predictions for proteins involved in age-related macular degeneration, retinitis pigmentosa, and Leber’s congenital amaurosis matched well with data from previous studies. These results suggest that UMS could be a useful tool in the analysis of genotype-to-phenotype associations and next-generation sequencing data for inherited diseases. PMID:27905547

  2. Inheritance of Pigeonpea Sterility Mosaic Disease Resistance in Pigeonpea

    PubMed Central

    Daspute, Abhijit; Fakrudin, B.; Bhairappanavar, Shivarudrappa. B.; Kavil, S. P.; Narayana, Y. D.; Muniswamy; Kaumar, Anil; Krishnaraj, P. U.; Yerimani, Abid; Khadi, B. M.

    2014-01-01

    A comprehensive study was conducted using PPSMV resistant (BSMR 736) and susceptible (ICP 8863) genotypes to develop a segregating population and understand the inheritance of PPSMV resistance. The observed segregation was comparable to 13 (susceptible): 3 (resistant). Hence, the inheritance was controlled by two genes, SV1 and SV2, with inhibitory gene interaction. PMID:25289002

  3. Gluten intolerance and skin diseases.

    PubMed

    Humbert, Philippe; Pelletier, Fabien; Dreno, Brigitte; Puzenat, Eve; Aubin, François

    2006-01-01

    Gluten sensitivity with or without coeliac disease (CD) symptoms and intestinal pathology has been suggested as a potentially treatable cause of various diseases. CD is a chronic disease which improves on withdrawal of wheat gliadins and barley, rye and oat prolamins from the diet. There have been numerous reports linking CD with several skin conditions. A body of evidence shows that dermatitis herpetiformis is actually a cutaneous manifestation of CD. Autoimmune diseases, allergic diseases, psoriasis and miscellaneous diseases have also been described with gluten intolerance. Dermatologists should be familiar with the appraisal of gluten sensitive enteropathy and should be able to search for an underlying gluten intolerance (GI). Serological screening by means of antigliadin, antiendomysial and transglutaminase antibodies should be performed. HLA typing is often useful in association with serologic tests. Intestinal biopsy is usually needed to establish the diagnosis of CD or GI. Thus, gluten intolerance gives rise to a variety of dermatological manifestations which may benefit from a gluten-free diet.

  4. Alzheimer disease: from inherited to sporadic AD-crossing the biomarker bridge.

    PubMed

    Hampel, Harald; Lista, Simone

    2012-11-05

    Whether dominantly inherited variants of Alzheimer disease (AD) and 'sporadic' forms exhibit similar pathophysiological and biomarker signatures remains unresolved. A landmark study has proposed a biomarker progression model of dominantly inherited AD, but a complex systems biology and physiology approach is required to translate these findings to sporadic disease.

  5. Diseases of the Earth's skin

    NASA Astrophysics Data System (ADS)

    The German Government's Scientific Advisory Council on Global Climate Change recently diagnosed a score of ailments of the “Earth's skin,” according to the German Research Service. Like numerous viral and bacterial diseases, many of the earthidermal diseases are named for the regions where scientists first discovered them. For some symptoms, the German Council has also recommended therapeutic treatments, such as terracing of slopes near rivers. It remains to be seen whether universities worldwide will start cranking out specialists in Earth dermatology. But judging by the condition of many regions of the world, it appears this field may offer great growth potential for the Earth sciences, which is welcome news in the current tight job market.

  6. Morgellons Disease: Managing a Mysterious Skin Condition

    MedlinePlus

    Morgellons disease: Managing a mysterious skin condition Morgellons disease is mysterious and controversial. Here you'll find answers to common questions about Morgellons disease — and suggestions for coping with it. By ...

  7. Skin protection in the prevention of skin diseases.

    PubMed

    Elsner, Peter

    2007-01-01

    Occupational skin diseases comprise a wide spectrum of conditions. Under epidemiological aspects, occupational contact dermatitis that is usually manifested on the hands is the most frequent occupational skin disease with an estimated average incidence rate of 0.7-1.5 cases per 1,000 workers per year. Irritant dermatitis is due to individual susceptibility and the exposure to irritants such as wet work combined with detergents or other hydrophilic irritants or solvents at the workplace. Chronic irritant dermatitis is a risk factor for delayed-type sensitization and subsequently allergic contact dermatitis. It is therefore the prevention of chronic or cumulative irritant dermatitis that is the decisive factor in the prevention of occupational skin disease. Within prevention programs at the workplace, skin protection plays an important, but limited role. Others are technical and organizational means to avoid or reduce skin exposure to irritants and allergens. Educational measures to increase the awareness of workers for workplace hazards and to motivate them to use skin protection measures appropriately are just as important as the careful selection of skin protection materials.

  8. Wearable defibrillator in congenital structural heart disease and inherited arrhythmias.

    PubMed

    Rao, Mohan; Goldenberg, Ilan; Moss, Arthur J; Klein, Helmut; Huang, David T; Bianco, Nicole R; Szymkiewicz, Steven J; Zareba, Wojciech; Brenyo, Andrew; Buber, Jonathan; Barsheshet, Alon

    2011-12-01

    Patients with congenital structural heart disease (CSHD) and inherited arrhythmias (IAs) are at high risk of ventricular tachyarrhythmias and sudden cardiac death. The present study was designed to evaluate the short- and long-term outcomes of patients with CSHD and IA who received a wearable cardioverter-defibrillator (WCD) for the prevention of sudden cardiac death. The study population included 162 patients with CSHD (n = 43) and IA (n = 119) who were prospectively followed up in a nationwide registry from 2005 to 2010. The mortality rates were compared using Kaplan-Meier survival analysis. The mean age of the study patients was 38 ± 27 years. The patients with CSHD had a greater frequency of left ventricular dysfunction (ejection fraction <30%) than did the patients with IA (37% vs 5%, respectively; p = 0.002). The predominant indication for WCD was pending genetic testing in the IA group and transplant listing in the CSHD group. Compliance with the WCD was similar in the 2 groups (91%). WCD shocks successfully terminated 3 ventricular tachyarrhythmias in the patients with IA during a median follow-up of 29 days of therapy (corresponding to 23 appropriate WCD shocks per 100 patient-years). No arrhythmias occurred in the patients with CSHD during a median follow-up of 27 days. No patients died while actively wearing the WCD. At 1 year of follow-up, the survival rates were significantly lower among the patients with CSHD (87%) than among the patients with IA (97%, p = 0.02). In conclusion, our data suggest that the WCD can be safely used in high-risk adult patients with IA and CSHD. Patients with IA showed a greater rate of ventricular tachyarrhythmias during therapy but significantly lower long-term mortality rates. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Endocrine Dysfunctions in Patients with Inherited Metabolic Diseases

    PubMed Central

    Erdöl, Şahin; Sağlam, Halil

    2016-01-01

    Objective: Inherited metabolic diseases (IMDs) can affect many organ systems, including the endocrine system. There are limited data regarding endocrine dysfunctions related to IMDs in adults, however, no data exist in pediatric patients with IMDs. The aim of this study was to investigate endocrine dysfunctions in patients with IMDs by assessing their demographic, clinical, and laboratory data. Methods: Data were obtained retrospectively from the medical reports of patients with IMDs who were followed by the division of pediatric metabolism and nutrition between June 2011 and November 2013. Results: In total, 260 patients [139 males (53%) and 121 females (47%)] with an IMD diagnosis were included in the study. The mean age of the patients was 5.94 (range; 0.08 to 49) years and 95.8% (249 of 260 patients) were in the pediatric age group. Growth status was evaluated in 258 patients and of them, 27 (10.5%) had growth failure, all cases of which were attributed to non-endocrine reasons. There was a significant correlation between growth failure and serum albumin levels below 3.5 g/dL (p=0.002). Only three of 260 (1.1%) patients had endocrine dysfunction. Of these, one with lecithin-cholesterol acyltransferase deficiency and another with Kearns-Sayre syndrome had diabetes, and one with glycerol kinase deficiency had glucocorticoid deficiency. Conclusion: Endocrine dysfunction in patients with IMDs is relatively rare. For this reason, there is no need to conduct routine endocrine evaluations in most patients with IMDs unless a careful and detailed history and a physical examination point to an endocrine dysfunction. PMID:27086477

  10. Skin microbiome and skin disease: the example of rosacea.

    PubMed

    Picardo, Mauro; Ottaviani, Monica

    2014-01-01

    The imbalance and/or the perturbation of the microbial populations that colonize the skin and that contribute to its defense may represent one of the causes of the development of noninfectious skin diseases. Atopic dermatitis, psoriasis, acne, and rosacea can be listed among these kinds of pathologies. In particular, considering that microbes have been long addressed as having a role in rosacea, this common dermatosis can be an interesting model to evaluate the correlation between microbiome alterations and the occurrence of clinical manifestations. Different microorganisms have been suggested to have a role in rosacea, but no direct correlation with the incidence of the pathology has been clearly defined. Skin microbiome composition is crucial for the correct skin immune functions and recent findings indicate an abnormal activation of innate immune system associated with the rosacea. The enhanced expression of toll-like receptor 2 in the epidermis of rosacea patients can represent a possible explanation for the amplified inflammatory response to external stimuli observed during the disease. In addition, significantly higher small intestinal bacterial overgrowth prevalence in rosacea subjects has been found and its eradication has been associated with a regression of the skin lesions. In conclusion, both skin and gut microbiome seem to have a role, even if synergistic with other factors, in the pathogenesis of rosacea. A deeper knowledge of human microbiome composition and microbe-host interactions will contribute to clarify the mechanism of development of rosacea and possibly will provide innovative therapeutic approaches.

  11. Plants used to treat skin diseases

    PubMed Central

    Tabassum, Nahida; Hamdani, Mariya

    2014-01-01

    Skin diseases are numerous and a frequently occurring health problem affecting all ages from the neonates to the elderly and cause harm in number of ways. Maintaining healthy skin is important for a healthy body. Many people may develop skin diseases that affect the skin, including cancer, herpes and cellulitis. Some wild plants and their parts are frequently used to treat these diseases. The use of plants is as old as the mankind. Natural treatment is cheap and claimed to be safe. It is also suitable raw material for production of new synthetic agents. A review of some plants for the treatment of skin diseases is provided that summarizes the recent technical advancements that have taken place in this area during the past 17 years. PMID:24600196

  12. Induced pluripotent stem cells in the inherited cardiomyopathies: From disease mechanisms to novel therapies.

    PubMed

    Ross, Samantha Barratt; Fraser, Stuart T; Semsarian, Christopher

    2016-11-01

    Inherited cardiomyopathies lead to diverse clinical outcomes including heart failure, arrhythmias, and sudden death. Mutations in over 100 genes have been implicated in the pathogenesis of genetic heart diseases, including the main inherited cardiomyopathies, such as hypertrophic, dilated, and arrhythmogenic right ventricular cardiomyopathies. Understanding how these gene mutations lead to clinical disease and the various secondary genetic and environmental factors, which may modify the clinical phenotype, are key areas of research ultimately influencing diagnosis and management of patients. The emergence of patient-derived induced pluripotent stem cells (iPSCs), which can be differentiated into functional cardiomyocytes (CMs) in vitro, may provide an exciting new approach to understand disease mechanisms underpinning inherited heart diseases. This review will focus specifically on the key role of iPSC-based studies in the inherited cardiomyopathies, both in their potential utility as well as the significant challenges they present. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Inherited Thrombophilia in Pediatric Venous Thromboembolic Disease: Why and Who to Test

    PubMed Central

    van Ommen, C. Heleen; Nowak-Göttl, Ulrike

    2017-01-01

    Venous thromboembolic disease in childhood is a multifactorial disease. Risk factors include acquired clinical risk factors such as a central venous catheter and underlying disease and inherited thrombophilia. Inherited thrombophilia is defined as a genetically determined tendency to develop venous thromboembolism. In contrast to adults, acquired clinical risk factors play a larger role than inherited thrombophilia in the development of thrombotic disease in children. The contributing role of inherited thrombophilia is not clear in many pediatric thrombotic events, especially catheter-related thrombosis. Furthermore, identification of inherited thrombophilia will not often influence acute management of the thrombotic event as well as the duration of anticoagulation. In some patients, however, detection of inherited thrombophilia may lead to identification of other family members who can be counseled for their thrombotic risk. This article discusses the potential arguments for testing of inherited thrombophilia, including factor V Leiden mutation, prothrombin mutation, and deficiencies of antithrombin, protein C, or protein S and suggests some patient groups in childhood, which may be tested. PMID:28352625

  14. Inherited Thrombophilia in Pediatric Venous Thromboembolic Disease: Why and Who to Test.

    PubMed

    van Ommen, C Heleen; Nowak-Göttl, Ulrike

    2017-01-01

    Venous thromboembolic disease in childhood is a multifactorial disease. Risk factors include acquired clinical risk factors such as a central venous catheter and underlying disease and inherited thrombophilia. Inherited thrombophilia is defined as a genetically determined tendency to develop venous thromboembolism. In contrast to adults, acquired clinical risk factors play a larger role than inherited thrombophilia in the development of thrombotic disease in children. The contributing role of inherited thrombophilia is not clear in many pediatric thrombotic events, especially catheter-related thrombosis. Furthermore, identification of inherited thrombophilia will not often influence acute management of the thrombotic event as well as the duration of anticoagulation. In some patients, however, detection of inherited thrombophilia may lead to identification of other family members who can be counseled for their thrombotic risk. This article discusses the potential arguments for testing of inherited thrombophilia, including factor V Leiden mutation, prothrombin mutation, and deficiencies of antithrombin, protein C, or protein S and suggests some patient groups in childhood, which may be tested.

  15. Crohn’s disease and skin

    PubMed Central

    Gravina, AG; Federico, A; Ruocco, E; Lo Schiavo, A; Romano, F; Miranda, A; Sgambato, D; Dallio, M; Ruocco, V; Loguercio, C

    2015-01-01

    Crohn’s disease is a chronic inflammatory bowel disease potentially involving any segment of the gastrointestinal tract. Extra-intestinal manifestations may occur in 6%–40% of patients, and disorders of the skin are among the most common. This manuscript will review skin manifestations associated to Crohn’s disease, with a particular focus on lesions associated to anti-tumour necrosis factor therapy. PMID:27087942

  16. A Novel and Likely Inherited Lymphoproliferative Disease in British Shorthair Kittens.

    PubMed

    Aberdein, D; Munday, J S; Fairley, R A; Vernau, W; Thompson, K G

    2015-11-01

    An unusual lymphoproliferative disease was identified in multiple closely related British Shorthair (BSH) kittens, suggesting an inherited predisposition to disease. Affected kittens typically developed rapidly progressive and marked generalized lymphadenopathy, moderate splenomegaly, and regenerative and likely hemolytic anemia from 6 weeks of age. Microscopic findings were suggestive of multicentric T-cell lymphoma, but additional testing revealed a polyclonal population of CD3+/CD4-/CD8- "double negative" T cells (DNT cells). This is a novel disease presentation with similarities to the human disorder autoimmune lymphoproliferative syndrome (ALPS), a rare inherited disease causing lymphoproliferation and variable manifestations of autoimmunity. The human disease is most commonly due to the presence of Fas gene mutations causing defective lymphocyte apoptosis, and further investigations of both the mode of inheritance and genetic basis for disease in affected cats are currently in progress.

  17. Risk assessment of skin in rheumatic disease.

    PubMed

    Firth, Jill

    Patients with a rheumatic disease are considered to be at high risk of developing skin problems because of their restricted mobility, vascular complications and the type of medication they are taking.

  18. Reflectance Confocal Microscopy for Inflammatory Skin Diseases.

    PubMed

    Agozzino, M; Gonzalez, S; Ardigò, M

    2016-10-01

    In vivo reflectance confocal microscopy (RCM) is a relatively novel non-invasive tool for microscopic evaluation of the skin used prevalently for diagnosis and management of skin tumour. Its axial resolution, its non-invasive and easy clinical application represents the goals for a large diffusion of this technique. During the last 15 years, RCM has been demonstrated to be able to increase the sensibility and sensitivity of dermoscopy in the diagnosis of skin tumours integrating in real time clinic, dermoscopic and microscopic information useful for the definition of malignancy. Despite to date, no large comparative studies on inflammatory skin diseases has been published in the literature, several papers already showed that RCM has a potential for the evaluation of the descriptive features of the most common inflammatory skin diseases as psoriasis, lupus erythematosus, contact dermatitis and others. The aim of the application of this technique in non-neoplastic skin diseases has been prevalently focused on the possibility of clinical diagnosis confirmation, as well as therapeutic management. Moreover, the use of RCM as driver for an optimised skin biopsy has been also followed in order to reduce the number of unsuccessful histopathological examination. In this review article we describe the confocal features of the major groups of inflammatory skin disorders focusing on psoriasiform dermatitis, interface dermatitis and spongiotic dermatitis.

  19. Psychosocial effect of common skin diseases.

    PubMed Central

    Barankin, Benjamin; DeKoven, Joel

    2002-01-01

    OBJECTIVE: To increase awareness of the psychosocial effect of acne, atopic dermatitis, and psoriasis. QUALITY OF EVIDENCE: A literature review was based on a MEDLINE search (1966 to 2000). Selected articles from the dermatologic and psychiatric literature, as well as other relevant medical journals, were reviewed and used as the basis for discussion of how skin disease affects patients' lives and of appropriate management. Studies in the medical literature provide mainly level III evidence predominantly based on descriptive studies and expert opinion. MAIN MESSAGE: Dermatologic problems can result in psychosocial effects that seriously affect patients' lives. More than a cosmetic nuisance, skin disease can produce anxiety, depression, and other psychological problems that affect patients' lives in ways comparable to arthritis or other disabling illnesses. An appreciation for the effects of sex, age, and location of lesions is important, as well as the bidirectional relationship between skin disease and psychological distress. This review focuses on the effects of three common skin diseases seen by family physicians: acne, atopic dermatitis, and psoriasis. CONCLUSION: How skin disease affects psychosocial well-being is underappreciated. Increased understanding of the psychiatric comorbidity associated with skin disease and a biopsychosocial approach to management will ultimately improve patients' lives. PMID:12046366

  20. Hydrocarbons (jet fuel JP-8) induce epigenetic transgenerational inheritance of obesity, reproductive disease and sperm epimutations.

    PubMed

    Tracey, Rebecca; Manikkam, Mohan; Guerrero-Bosagna, Carlos; Skinner, Michael K

    2013-04-01

    Environmental compounds have been shown to promote epigenetic transgenerational inheritance of disease. The current study was designed to determine if a hydrocarbon mixture involving jet fuel (JP-8) promotes epigenetic transgenerational inheritance of disease. Gestating F0 generation female rats were transiently exposed during the fetal gonadal development period. The direct exposure F1 generation had an increased incidence of kidney abnormalities in both females and males, prostate and pubertal abnormalities in males, and primordial follicle loss and polycystic ovarian disease in females. The first transgenerational generation is the F3 generation, and the jet fuel lineage had an increased incidence of primordial follicle loss and polycystic ovarian disease in females, and obesity in both females and males. Analysis of the jet fuel lineage F3 generation sperm epigenome identified 33 differential DNA methylation regions, termed epimutations. Observations demonstrate hydrocarbons can promote epigenetic transgenerational inheritance of disease and sperm epimutations, potential biomarkers for ancestral exposures.

  1. [Xeroderma pigmentosum (XP) : A genetic disease sheds light on UV-induced skin cancer].

    PubMed

    Emmert, B; Hallier, E; Schön, M P; Emmert, S

    2011-02-01

    The recessively inherited nucleotide excision repair (NER) defect syndrome xeroderma pigmentosum (XP) serves as a model disease for UV-induced skin cancer. XP is characterized by sun-sensitivity, freckling, and poikilodermic skin changes in sun-exposed areas, and a more than 1000-fold increased risk of skin cancer including melanoma as well as basal and squamous cell carcinomas. Seven XP complementation groups (XP-A to XP-G) are known to date representing the defective genes in XP patients. An additional "variant" form (XPV) which is clinically indistinguishable from the complementation groups exhibits defective translesional synthesis. An enhanced understanding of skin cancer development in general can help to identify individuals at an increased risk who should take special precautions, for example to avoid occupational exposures. The position of skin cancer induced by UV-light as an occupational disease in the ordinance on industrial diseases (BKV) is currently a topic of research and discussion in Germany.

  2. Skin diseases in internationally adopted children.

    PubMed

    Rigal, Émilie; Nourrisson, Céline; Sciauvaud, Julie; Pascal, Julie; Texier, Charlotte; Corbin, Violaine; Poirier, Véronique; Beytout, Jean; Labbe, André; Lesens, Olivier

    2016-08-01

    Internationally adopted children often present diseases contracted in the country of origin. Skin diseases are common in new arrivals, and diagnosis may prove challenging for GPs or even dermatologists if they are inexperienced in the extensive geographic and ethnic diversity of international adoptees. To analyse the frequency and characteristics of skin diseases in international adoptees. In total, 142 adoptees were evaluated for a cross-sectional cohort study. The most frequent diseases observed at arrival were dermatological conditions. Of the adoptees, 70% presented at least one skin disease, of which 57.5% were infectious; Tinea capitis being the most frequent (n = 42). The recovery rate of Tinea capitis was 89% (n = 32/36). Ten cases of scabies were diagnosed. Other diseases included viral skin infection (n = 22), with 16 cases of Molluscum contagiosum and bacterial infection. Skin diseases are very common in internationally adopted children. There is a need for close collaboration between dermatologists and paediatricians to diagnose such infections, as well as clear guidelines to treat them.

  3. An insight into the global burden of skin diseases.

    PubMed

    Hollestein, Loes M; Nijsten, Tamar

    2014-06-01

    The skin conditions expert group of the Global Burden of Disease 2010 study estimated the global burden of skin conditions worldwide. Health loss due to 15 skin diseases between 1990 and 2010 for 187 countries was quantified. All skin conditions combined were the fourth leading cause of non-fatal disease burden at the global level. The burden of skin conditions was high in both high- and low-income countries, indicating that prevention of skin diseases should be prioritized.

  4. Skin diseases in rural Yucatan, Mexico.

    PubMed

    Paek, So Yeon; Koriakos, Angie; Saxton-Daniels, Stephanie; Pandya, Amit G

    2012-07-01

    There are no known reports of the frequency of skin diseases endemic to rural Yucatan, Mexico. The aim of this study was to report the prevalence of dermatologic conditions in rural villages in that region. We conducted a retrospective descriptive study of all cases of skin disease diagnosed by a team of American board-certified dermatologists during consultations in January 2009, August 2009, and June 2010, in the state of Yucatan, Mexico. Traveling clinics were held in eight different rural locations. Age, sex, and diagnosis, according to history and physical examination, were recorded for each patient. A total of 1071 cases of skin disease were seen in 858 patients. The frequency of parasitic, viral, and fungal infections was 34.5%. Dermatitis and eczema (24.6%) were the next most prevalent conditions, followed by disorders of skin appendages (12.2%), photosensitivity disorders (5.4%), papulosquamous disorders (3.2%), urticaria and erythema (1.5%), bacterial infections of the skin and subcutaneous tissue (1.2%), and neoplastic disorders (2.1%). The most frequently seen single diagnoses were viral warts (12.2%), scabies (8.7%), acne (7.4%), dermatophytosis (6.8%), contact dermatitis (3.5%), and nummular eczema (3.5%). Infectious diseases, acne, and eczemas are the most common skin disorders seen in dermatology clinics in rural Yucatan, Mexico. Our findings may be useful in the development of public health initiatives targeting rural communities in this region. © 2012 The International Society of Dermatology.

  5. Age at onset in Huntington's disease: effect of line of inheritance and patient's sex.

    PubMed Central

    Roos, R A; Vegter-van der Vlis, M; Hermans, J; Elshove, H M; Moll, A C; van de Kamp, J J; Bruyn, G W

    1991-01-01

    The Leiden Roster for Huntington's disease (HD) contained data on 2617 cases up to July 1988. The age at onset (AO) was known in 1084 cases and in 1020 of these both their AO and the sex of the affected parent was known. The mean AO was higher for females than for males and higher for maternal than for paternal cases. However, in the group born before 1925 only females with maternal inheritance had a higher mean AO. Data on influence of sex and line of inheritance were present for the grandparents as well as for the great grandparents. Influence of the line of inheritance from the grandparents was particularly present for the grandmother-father (MP) lineage; regarding the great grandparents a significant difference was found between the MPM and PMP lineage. The results obtained for juvenile HD cases were comparable to those previously published. In late onset cases (over 50 years) no maternal preponderance in inheritance was found. PMID:1833547

  6. Pathophysiological Mechanisms in Sclerosing Skin Diseases

    PubMed Central

    Eckes, Beate; Wang, Fang; Moinzadeh, Pia; Hunzelmann, Nicolas; Krieg, Thomas

    2017-01-01

    Sclerosing skin diseases represent a large number of distinct disease entities, which include systemic sclerosis, localized scleroderma, and scleredema adultorum. These pathologies have a common clinical appearance and share histological features. However, the specific interplay between cytokines and growth factors, which activate different mesenchymal cell populations and production of different extracellular matrix components, determines the biomechanical properties of the skin and the clinical features of each disease. A better understanding of the mechanisms underlying these events is prerequisite for developing novel targeted therapeutic approaches. PMID:28868289

  7. Guiametabolica.org: empowerment through internet tools in inherited metabolic diseases

    PubMed Central

    2012-01-01

    Web-based interventions are effective on the patient empowerment. Guiametabolica.org constitutes an interface for people involved in inherited metabolic diseases, trying to facilitate access to information and contact with professionals and other patients, offering a platform to develop support groups. Guiametabolica.org is widely considered for Spanish-speaking patients and caregivers with inherited metabolic diseases. Preliminary evaluations show changes in their habits, decrease in their senses of isolation and improvement regarding self-efficacy. Specific inherited metabolic diseases websites, especially participative websites, should be considered as a complement to more traditional clinical approaches. Their contribution lies in patient’s general well-being, without interfering with traditional care. PMID:22909005

  8. Laser treatment for skin disease

    NASA Astrophysics Data System (ADS)

    Bloznelyte-Plesniene, Laima; Cepulis, Vytautas; Ponomarev, Igor V.

    1996-12-01

    The correct selection of patients is the most difficult part of the laser treatment. Since 1985 the total number of patients treated by us using different laser systems was 1544. High power lasers: Nd:YAG and CO2 lasers were used by us for surgical treatment. Low power lasers: Helium-Neon, Copper vapor, gold vapor and dye lasers were applied by us to PDT or to treatment of port wine hemangiomas. this paper reports our efforts in selecting the patients with different skin lesions for the treatment with different laser systems.

  9. Inherited neurovascular diseases affecting cerebral blood vessels and smooth muscle.

    PubMed

    Sam, Christine; Li, Fei-Feng; Liu, Shu-Lin

    2015-10-01

    Neurovascular diseases are among the leading causes of mortality and permanent disability due to stroke, aneurysm, and other cardiovascular complications. Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and Marfan syndrome are two neurovascular disorders that affect smooth muscle cells through accumulation of granule and osmiophilic materials and defective elastic fiber formations respectively. Moyamoya disease, hereditary hemorrhagic telangiectasia (HHT), microcephalic osteodysplastic primordial dwarfism type II (MOPD II), and Fabry's disease are disorders that affect the endothelium cells of blood vessels through occlusion or abnormal development. While much research has been done on mapping out mutations in these diseases, the exact mechanisms are still largely unknown. This paper briefly introduces the pathogenesis, genetics, clinical symptoms, and current methods of treatment of the diseases in the hope that it can help us better understand the mechanism of these diseases and work on ways to develop better diagnosis and treatment.

  10. Skin equivalents: skin from reconstructions as models to study skin development and diseases.

    PubMed

    Ali, N; Hosseini, M; Vainio, S; Taïeb, A; Cario-André, M; Rezvani, H R

    2015-08-01

    While skin is readily available for sampling and direct studies of its constituents, an important intermediate step is to design in vitro and/or in vivo models to address scientific or medical questions in dermatology and skin biology. Pioneered more than 30 years ago, human skin equivalents (HSEs) have been refined with better cell culture techniques and media, together with sophisticated cell biology tools including genetic engineering and cell reprogramming. HSEs mimic key elements of human skin biology and have been instrumental in demonstrating the importance of cell-cell interactions in skin homeostasis and the role of a complex cellular microenvironment to coordinate epidermal proliferation, differentiation and pigmentation. HSEs have a wide field of applications from cell biology to dermocosmetics, modelling diseases, drug development, skin ageing, pathophysiology and regenerative medicine. In this article we critically review the major current approaches used to reconstruct organotypic skin models and their application with a particular emphasis on skin biology and pathophysiology of skin disorders. © 2015 British Association of Dermatologists.

  11. [Progress in research on pathogenic genes and gene therapy for inherited retinal diseases].

    PubMed

    Zhu, Ling; Cao, Cong; Sun, Jiji; Gao, Tao; Liang, Xiaoyang; Nie, Zhipeng; Ji, Yanchun; Jiang, Pingping; Guan, Minxin

    2017-02-10

    Inherited retinal diseases (IRDs), including retinitis pigmentosa, Usher syndrome, Cone-Rod degenerations, inherited macular dystrophy, Leber's congenital amaurosis, Leber's hereditary optic neuropathy are the most common and severe types of hereditary ocular diseases. So far more than 200 pathogenic genes have been identified. With the growing knowledge of the genetics and mechanisms of IRDs, a number of gene therapeutic strategies have been developed in the laboratory or even entered clinical trials. Here the progress of IRD research on the pathogenic genes and therapeutic strategies, particularly gene therapy, are reviewed.

  12. Rare diseases, rare presentations: recognizing atypical inherited kidney disease phenotypes in the age of genomics.

    PubMed

    Ars, Elisabet; Torra, Roser

    2017-10-01

    A significant percentage of adults (10%) and children (20%) on renal replacement therapy have an inherited kidney disease (IKD). The new genomic era, ushered in by the next generation sequencing techniques, has contributed to the identification of new genes and facilitated the genetic diagnosis of the highly heterogeneous IKDs. Consequently, it has also allowed the reclassification of diseases and has broadened the phenotypic spectrum of many classical IKDs. Various genetic, epigenetic and environmental factors may explain 'atypical' phenotypes. In this article, we examine different mechanisms that may contribute to phenotypic variability and also provide case examples that illustrate them. The aim of the article is to raise awareness, among nephrologists and geneticists, of rare presentations that IKDs may show, to facilitate diagnosis.

  13. Eosinophilic Skin Diseases: A Comprehensive Review.

    PubMed

    Long, Hai; Zhang, Guiying; Wang, Ling; Lu, Qianjin

    2016-04-01

    Eosinophilic skin diseases, commonly termed as eosinophilic dermatoses, refer to a broad spectrum of skin diseases characterized by eosinophil infiltration and/or degranulation in skin lesions, with or without blood eosinophilia. The majority of eosinophilic dermatoses lie in the allergy-related group, including allergic drug eruption, urticaria, allergic contact dermatitis, atopic dermatitis, and eczema. Parasitic infestations, arthropod bites, and autoimmune blistering skin diseases such as bullous pemphigoid, are also common. Besides these, there are several rare types of eosinophilic dermatoses with unknown origin, in which eosinophil infiltration is a central component and affects specific tissue layers or adnexal structures of the skin, such as the dermis, subcutaneous fat, fascia, follicles, and cutaneous vessels. Some typical examples are eosinophilic cellulitis, granuloma faciale, eosinophilic pustular folliculitis, recurrent cutaneous eosinophilic vasculitis, and eosinophilic fasciitis. Although tissue eosinophilia is a common feature shared by these disorders, their clinical and pathological properties differ dramatically. Among these rare entities, eosinophilic pustular folliculitis may be associated with human immunodeficiency virus (HIV) infection or malignancies, and some other diseases, like eosinophilic fasciitis and eosinophilic cellulitis, may be associated with an underlying hematological disorder, while others are considered idiopathic. However, for most of these rare eosinophilic dermatoses, the causes and the pathogenic mechanisms remain largely unknown, and systemic, high-quality clinical investigations are needed for advances in better strategies for clinical diagnosis and treatment. Here, we present a comprehensive review on the etiology, pathogenesis, clinical features, and management of these rare entities, with an emphasis on recent advances and current consensus.

  14. Dioxin (TCDD) induces epigenetic transgenerational inheritance of adult onset disease and sperm epimutations.

    PubMed

    Manikkam, Mohan; Tracey, Rebecca; Guerrero-Bosagna, Carlos; Skinner, Michael K

    2012-01-01

    Environmental compounds can promote epigenetic transgenerational inheritance of adult-onset disease in subsequent generations following ancestral exposure during fetal gonadal sex determination. The current study examined the ability of dioxin (2,3,7,8-tetrachlorodibenzo[p]dioxin, TCDD) to promote epigenetic transgenerational inheritance of disease and DNA methylation epimutations in sperm. Gestating F0 generation females were exposed to dioxin during fetal day 8 to 14 and adult-onset disease was evaluated in F1 and F3 generation rats. The incidences of total disease and multiple disease increased in F1 and F3 generations. Prostate disease, ovarian primordial follicle loss and polycystic ovary disease were increased in F1 generation dioxin lineage. Kidney disease in males, pubertal abnormalities in females, ovarian primordial follicle loss and polycystic ovary disease were increased in F3 generation dioxin lineage animals. Analysis of the F3 generation sperm epigenome identified 50 differentially DNA methylated regions (DMR) in gene promoters. These DMR provide potential epigenetic biomarkers for transgenerational disease and ancestral environmental exposures. Observations demonstrate dioxin exposure of a gestating female promotes epigenetic transgenerational inheritance of adult onset disease and sperm epimutations.

  15. Highly consistent patterns for inherited human diseases at the molecular level.

    PubMed

    López-Bigas, Núria; Blencowe, Benjamin J; Ouzounis, Christos A

    2006-02-01

    Over 1600 mammalian genes are known to cause an inherited disorder, when subjected to one or more mutations. These disease genes represent a unique resource for the identification and quantification of relationships between phenotypic attributes of a disease and the molecular features of the associated disease genes, including their ascribed annotated functional classes and expression patterns. Such analyses can provide a more global perspective and a deeper understanding of the probable causes underlying human hereditary diseases. In this perspective and critical view of disease genomics, we present a comparative analysis of genes reported to cause inherited diseases in humans in terms of their causative effects on physiology, their genetics and inheritance modes, the functional processes they are involved in and their expression profiles across a wide spectrum of tissues. Our analysis reveals that there are more extensive correlations between these attributes of genetic disease genes than previously appreciated. For instance, the functional pattern of genes causing dominant and recessive diseases is markedly different. Also, the function of the genes and their expression correlate with the type of disease they cause when mutated. The results further indicate that a comparative genomics approach for the analysis of genes linked to human genetic diseases will facilitate the elucidation of the underlying molecular and cellular mechanisms.

  16. Influence of skin diseases on fingerprint recognition.

    PubMed

    Drahansky, Martin; Dolezel, Michal; Urbanek, Jaroslav; Brezinova, Eva; Kim, Tai-hoon

    2012-01-01

    There are many people who suffer from some of the skin diseases. These diseases have a strong influence on the process of fingerprint recognition. People with fingerprint diseases are unable to use fingerprint scanners, which is discriminating for them, since they are not allowed to use their fingerprints for the authentication purposes. First in this paper the various diseases, which might influence functionality of the fingerprint-based systems, are introduced, mainly from the medical point of view. This overview is followed by some examples of diseased finger fingerprints, acquired both from dactyloscopic card and electronic sensors. At the end of this paper the proposed fingerprint image enhancement algorithm is described.

  17. Influence of Skin Diseases on Fingerprint Recognition

    PubMed Central

    Drahansky, Martin; Dolezel, Michal; Urbanek, Jaroslav; Brezinova, Eva; Kim, Tai-hoon

    2012-01-01

    There are many people who suffer from some of the skin diseases. These diseases have a strong influence on the process of fingerprint recognition. People with fingerprint diseases are unable to use fingerprint scanners, which is discriminating for them, since they are not allowed to use their fingerprints for the authentication purposes. First in this paper the various diseases, which might influence functionality of the fingerprint-based systems, are introduced, mainly from the medical point of view. This overview is followed by some examples of diseased finger fingerprints, acquired both from dactyloscopic card and electronic sensors. At the end of this paper the proposed fingerprint image enhancement algorithm is described. PMID:22654483

  18. Effects of climate changes on skin diseases.

    PubMed

    Balato, Nicola; Megna, Matteo; Ayala, Fabio; Balato, Anna; Napolitano, Maddalena; Patruno, Cataldo

    2014-02-01

    Global climate is changing at an extraordinary rate. Climate change (CC) can be caused by several factors including variations in solar radiation, oceanic processes, and also human activities. The degree of this change and its impact on ecological, social, and economical systems have become important matters of debate worldwide, representing CC as one of the greatest challenges of the modern age. Moreover, studies based on observations and predictive models show how CC could affect human health. On the other hand, only a few studies focus on how this change may affect human skin. However, the skin is the most exposed organ to environment; therefore, it is not surprising that cutaneous diseases are inclined to have a high sensitivity to climate. The current review focuses on the effects of CC on skin diseases showing the numerous factors that are contributing to modify the incidence, clinical pattern and natural course of some dermatoses.

  19. The New Human Genetics. How Gene Splicing Helps Researchers Fight Inherited Disease.

    ERIC Educational Resources Information Center

    Pines, Maya

    The science of genetics is perceived to offer hope that a large number of the 3,000 inherited diseases which afflict human beings may be prevented or controlled. This document addresses some of the advances that have been made in this field. It includes an introduction and sections on: "The Beginning of Human Genetics"; "Unlocking the Secrets of…

  20. Viral skin diseases of the rabbit.

    PubMed

    Meredith, Anna L

    2013-09-01

    This article describes the viral skin diseases affecting the domestic rabbit, the most important being myxomatosis. Transmission and pathogenesis, clinical signs, diagnosis, treatment, and control are described and the article will be of interest to veterinary practitioners who treat rabbits. Shope fibroma virus, Shope papilloma virus, and rabbitpox are also discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Skin Manifestations of Inflammatory Bowel Disease

    PubMed Central

    Huang, Brian L.; Chandra, Stephanie; Shih, David Quan

    2012-01-01

    Inflammatory bowel disease (IBD) is a disease that affects the intestinal tract via an inflammatory process. Patients who suffer from IBD often have diseases that affect multiple other organ systems as well. These are called extraintestinal manifestations and can be just as, if not more debilitating than the intestinal inflammation itself. The skin is one of the most commonly affected organ systems in patients who suffer from IBD. The scientific literature suggests that a disturbance of the equilibrium between host defense and tolerance, and the subsequent over-activity of certain immune pathways are responsible for the cutaneous disorders seen so frequently in IBD patients. The purpose of this review article is to give an overview of the types of skin diseases that are typically seen with IBD and their respective pathogenesis, proposed mechanisms, and treatments. These cutaneous disorders can manifest as metastatic lesions, reactive processes to the intestinal inflammation, complications of IBD itself, or side effects from IBD treatments; these can be associated with IBD via genetic linkage, common autoimmune processes, or other mechanisms that will be discussed in this article. Ultimately, it is important for healthcare providers to understand that skin manifestations should always be checked and evaluated for in patients with IBD. Furthermore, skin disorders can predate gastrointestinal symptoms and thus may serve as important clinical indicators leading physicians to earlier diagnosis of IBD. PMID:22347192

  2. Managing Amphibian Disease with Skin Microbiota.

    PubMed

    Woodhams, Douglas C; Bletz, Molly; Kueneman, Jordan; McKenzie, Valerie

    2016-03-01

    The contribution of emerging amphibian diseases to the sixth mass extinction is driving innovative wildlife management strategies, including the use of probiotics. Bioaugmentation of the skin mucosome, a dynamic environment including host and microbial components, may not provide a generalized solution. Multi-omics technologies and ecological context underlie effective implementation.

  3. Managing Amphibian Disease with Skin Microbiota.

    PubMed

    Woodhams, Douglas C; Bletz, Molly; Kueneman, Jordan; McKenzie, Valerie

    2016-01-16

    The contribution of emerging amphibian diseases to the sixth mass extinction is driving innovative wildlife management strategies, including the use of probiotics. Bioaugmentation of the skin mucosome, a dynamic environment including host and microbial components, may not provide a generalized solution. Multi-omics technologies and ecological context underlie effective implementation.

  4. Stem cells for investigation and treatment of inherited retinal disease

    PubMed Central

    Tucker, Budd A.; Mullins, Robert F.; Stone, Edwin M.

    2014-01-01

    Vision is the most important human sense. It facilitates every major activity of daily living ranging from basic communication, mobility and independence to an appreciation of art and nature. Heritable diseases of the retina, such as age-related macular degeneration and retinitis pigmentosa, are the leading cause of blindness in the developed world, collectively affecting as many as one-third of all people over the age of 75, to some degree. For decades, scientists have dreamed of preventing vision loss or of restoring the vision of patients affected with retinal degeneration through some type of drug, gene or cell-based transplantation approach. In this review, we will discuss the current literature pertaining to retinal transplantation. We will focus on the use of induced pluripotent stem cells for interrogation of disease pathophysiology, analysis of drug and gene therapeutics and as a source of autologous cells for cell replacement. PMID:24647603

  5. Stem cells for investigation and treatment of inherited retinal disease.

    PubMed

    Tucker, Budd A; Mullins, Robert F; Stone, Edwin M

    2014-09-15

    Vision is the most important human sense. It facilitates every major activity of daily living ranging from basic communication, mobility and independence to an appreciation of art and nature. Heritable diseases of the retina, such as age-related macular degeneration and retinitis pigmentosa, are the leading cause of blindness in the developed world, collectively affecting as many as one-third of all people over the age of 75, to some degree. For decades, scientists have dreamed of preventing vision loss or of restoring the vision of patients affected with retinal degeneration through some type of drug, gene or cell-based transplantation approach. In this review, we will discuss the current literature pertaining to retinal transplantation. We will focus on the use of induced pluripotent stem cells for interrogation of disease pathophysiology, analysis of drug and gene therapeutics and as a source of autologous cells for cell replacement.

  6. [Skin diseases in geriatric patients. Epidemiologic data].

    PubMed

    Makrantonaki, E; Liakou, A I; Eckardt, R; Zens, M; Steinhagen-Thiessen, E; Zouboulis, C C

    2012-12-01

    The incidence of skin diseases more common in older patients, e.g. inflammatory and autoimmune diseases, benign and malignant tumors and paraneoplastic syndromes, is increasing worldwide rapidly mainly due to early or lifelong UV-overexposure and to an aging population. In order to transform this demographic change into a chance a better understanding of the pathomechanisms of these diseases, an early diagnosis and therapy are essential steps. In addition, a joint effort to raise public awareness, patient education, preventive measures and consistent monitoring of high-risk groups is of great importance. In this article, the relationship between aging and associated skin diseases will be presented with a particular focus on the epidemiology and risk factors.

  7. Endocrine manifestations related to inherited metabolic diseases in adults

    PubMed Central

    2012-01-01

    Most inborn errors of metabolism (IEM) are recessive, genetically transmitted diseases and are classified into 3 main groups according to their mechanisms: cellular intoxication, energy deficiency, and defects of complex molecules. They can be associated with endocrine manifestations, which may be complications from a previously diagnosed IEM of childhood onset. More rarely, endocrinopathies can signal an IEM in adulthood, which should be suspected when an endocrine disorder is associated with multisystemic involvement (neurological, muscular, hepatic features, etc.). IEM can affect all glands, but diabetes mellitus, thyroid dysfunction and hypogonadism are the most frequent disorders. A single IEM can present with multiple endocrine dysfunctions, especially those involving energy deficiency (respiratory chain defects), and metal (hemochromatosis) and storage disorders (cystinosis). Non-autoimmune diabetes mellitus, thyroid dysfunction and/or goiter and sometimes hypoparathyroidism should steer the diagnosis towards a respiratory chain defect. Hypogonadotropic hypogonadism is frequent in haemochromatosis (often associated with diabetes), whereas primary hypogonadism is reported in Alström disease and cystinosis (both associated with diabetes, the latter also with thyroid dysfunction) and galactosemia. Hypogonadism is also frequent in X-linked adrenoleukodystrophy (with adrenal failure), congenital disorders of glycosylation, and Fabry and glycogen storage diseases (along with thyroid dysfunction in the first 3 and diabetes in the last). This is a new and growing field and is not yet very well recognized in adulthood despite its consequences on growth, bone metabolism and fertility. For this reason, physicians managing adult patients should be aware of these diagnoses. PMID:22284844

  8. Genetics in Parkinson disease: Mendelian vs. non-Mendelian inheritance

    PubMed Central

    Hernandez, Dena G.; Reed, Xylena; Singleton, Andrew B.

    2016-01-01

    Parkinson’s disease is a common, progressive neurodegenerative disorder, affecting 3% of those older than 75 years of age. Clinically PD is associated with resting tremor, postural instability, rigidity, bradykinesia and a good response to levodopa therapy. Over the last fifteen years, numerous studies have confirmed that genetic factors contribute to the complex pathogenesis of PD. Highly penetrant mutations producing rare, monogenic forms of the disease have been discovered in singular genes such as SNCA, Parkin, DJ-1, PINK 1, LRRK2 and VPS35. Unique variants with incomplete penetrance in LRRK2 and GBA have been shown to be strong risk factors for PD in certain populations. Additionally, over 20 common variants with small effect sizes are now recognized to modulate the risk for PD. Investigating Mendelian forms of PD has provided precious insight into the pathophysiology that underlies the more common idiopathic form of disease; however, no treatment methodologies have developed. Furthermore, for identified common risk alleles, the functional basis underlying risk principally remains unknown. The challenge over the next decade will be to strengthen the findings delivered through genetic discovery by assessing the direct, biological consequences of risk variants in tandem with additional high-content, integrated datasets. PMID:27090875

  9. Tropical skin diseases in British military personnel.

    PubMed

    Bailey, Mark S

    2013-09-01

    Skin complaints are common in travellers to foreign countries and are responsible for up to 25% of medical consultations by military personnel during deployments in the tropics. They also have relatively high rates of field hospital admission, medical evacuation and referral to UK Role 4 healthcare facilities. Non-infectious tropical skin diseases include sunburn, heat rash, arthropod bites, venomous bites, contact dermatitis and phytophotodermatitis. During tropical deployments skin infections that commonly occur in military personnel may become more frequent, severe and difficult to treat. Several systemic tropical infections have cutaneous features that can be useful in making early diagnoses. Tropical skin infections such as cutaneous larva migrans, cutaneous myiasis, cutaneous leishmaniasis and leprosy do occur in British troops and require specialist clinical management. This illustrated review focuses on the most significant tropical skin diseases that have occurred in British military personnel in recent years. Clinical management of these conditions on deployments would be improved and medical evacuations could be reduced if a military dermatology 'reach-back' service (including a telemedicine facility) was available.

  10. DANDRUFF: THE MOST COMMERCIALLY EXPLOITED SKIN DISEASE

    PubMed Central

    Ranganathan, S; Mukhopadhyay, T

    2010-01-01

    The article discuss in detail about the prevalence, pathophysiology, clinical manifestations of dandruff including the etio-pathology. The article also discusses in detail about various treatment methods available for dandruff. The status of dandruff being amphibious – a disease/disorder, and relatively less medical intervention is sought after for the treatment, dandruff is the most commercially exploited skin and scalp disorder/disease by personal care industries. PMID:20606879

  11. Inherited dyslipidaemic disorders contributing to coronary heart disease.

    PubMed

    Attaullah, Salma; Bangash, Rahim; Amanullah; Ahmed, Zahoor; Rehman, Jamilur

    2008-01-01

    Lipoprotein (a) [Lp (a)] is an established independent risk factor for premature myocardial infarction (MI)/coronary artery disease (CAD). The study was conducted to determine the value of Lp (a) in prediction of CAD or MI in the offspring at risk. A total of 160 subjects were investigated. Serum Lp (a) was measured by ELISA, serum total cholesterol, triglycerides (TG) and HDL-Cholesterol by enzymatic colorimetric methods using standard kits. Differences in levels of total Lp (a) and cholesterol were observed between patients and controls. Both Lp (a) (16.23 +/-1.95 mg/dL) and cholesterol (175.00 +/- 7.60 mg/dL) of group A (patients) were higher than the corresponding controls. However an opposite trend in results was noted for serum HDL-Cholesterol in patients vs. controls. Persons found to have elevated levels of Lp (a) should focus on controlling the known modifiable risk factor for heart disease, especially smoking, hypercholesterolemia, obesity, hypertension and sedentary life style.

  12. Dioxin induction of transgenerational inheritance of disease in zebrafish.

    PubMed

    Baker, Tracie R; King-Heiden, Tisha C; Peterson, Richard E; Heideman, Warren

    2014-12-01

    Dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin; TCDD) is an aryl hydrocarbon receptor (AHR) agonist, an endocrine disruptor, and a potent global pollutant. TCDD exposure is associated with diseases of almost every organ system, and its toxicity is highly conserved across vertebrates. While the acute developmental effects of dioxin exposure have been extensively studied, the ability of early sublethal exposure to produce toxicity in adulthood or subsequent generations is poorly understood. This type of question is difficult to study because of the time frame of the effects. With human subjects, such a study could span more than a lifetime. We have chosen zebrafish (Danio rerio) as a model because they are vertebrates with short generation times and consistent genetic backgrounds. Zebrafish have very modest housing needs, facilitating single and multigenerational studies with minimal time and expense. We have used this model to identify transgenerational effects of TCDD on skeletal development, sex ratio, and male-mediated decreases in reproductive capacity. Here we compare these findings with transgenerational effects described in laboratory rodent species. We propose that the zebrafish is a cost-effective model system for evaluating the transgenerational effects of toxic chemicals and their role in the fetal basis of adult disease.

  13. Current Status of Gene Therapy for Inherited Lung Diseases

    PubMed Central

    Driskell, Ryan R.; Engelhardt, John F.

    2007-01-01

    Gene therapy as a treatment modality for pulmonary disorders has attracted significant interest over the past decade. Since the initiation of the first clinical trials for cystic fibrosis lung disease using recombinant adenovirus in the early 1990s, the field has encountered numerous obstacles including vector inflammation, inefficient delivery, and vector production. Despite these obstacles, enthusiasm for lung gene therapy remains high. In part, this enthusiasm is fueled through the diligence of numerous researchers whose studies continue to reveal great potential of new gene transfer vectors that demonstrate increased tropism for airway epithelia. Several newly identified serotypes of adeno-associated virus have demonstrated substantial promise in animal models and will likely surface soon in clinical trials. Furthermore, an increased understanding of vector biology has also led to the development of new technologies to enhance the efficiency and selectivity of gene delivery to the lung. Although the promise of gene therapy to the lung has yet to be realized, the recent concentrated efforts in the field that focus on the basic virology of vector development will undoubtedly reap great rewards over the next decade in treating lung diseases. PMID:12524461

  14. CYSTIC FIBROSIS: AN INHERITED DISEASE AFFECTING MUCIN-PRODUCING ORGANS

    PubMed Central

    Ehre, Camille; Ridley, Caroline; Thornton, David J

    2014-01-01

    Our current understanding of cystic fibrosis (CF) has revealed that the biophysical properties of mucus play a considerable role in the pathogenesis of the disease in view of the fact that most mucus-producing organs are affected in CF patients. In this review, we discuss the potential causal relationship between altered cystic fibrosis transmembrane conductance regulator (CFTR) function and the production of mucus with abnormal biophysical properties in the intestine and lungs, highlighting what has been learned from cell cultures and animal models that mimic CF pathogenesis. A similar cascade of events, including mucus obstruction, infection and inflammation, is common to all epithelia affected by impaired surface hydration. Hence, the main structural components of mucus, namely the polymeric, gel-forming mucins, are critical to the onset of the disease. Defective CFTR leads to epithelial surface dehydration, altered pH/electrolyte composition and mucin concentration. Further, it can influence mucin transition from the intracellular to extracellular environment, potentially resulting in aberrant mucus gel formation. While defective HCO3− production has long been identified as a feature of CF, it has only recently been considered as a key player in the transition phase of mucins. We conclude by examining the influence of mucins on the biophysical properties of CF sputum and discuss existing and novel therapies aimed at removing mucus from the lungs. PMID:24685676

  15. Data Mining and Pattern Recognition Models for Identifying Inherited Diseases: Challenges and Implications

    PubMed Central

    Iddamalgoda, Lahiru; Das, Partha S.; Aponso, Achala; Sundararajan, Vijayaraghava S.; Suravajhala, Prashanth; Valadi, Jayaraman K.

    2016-01-01

    Data mining and pattern recognition methods reveal interesting findings in genetic studies, especially on how the genetic makeup is associated with inherited diseases. Although researchers have proposed various data mining models for biomedical approaches, there remains a challenge in accurately prioritizing the single nucleotide polymorphisms (SNP) associated with the disease. In this commentary, we review the state-of-art data mining and pattern recognition models for identifying inherited diseases and deliberate the need of binary classification- and scoring-based prioritization methods in determining causal variants. While we discuss the pros and cons associated with these methods known, we argue that the gene prioritization methods and the protein interaction (PPI) methods in conjunction with the K nearest neighbors' could be used in accurately categorizing the genetic factors in disease causation. PMID:27559342

  16. Air pollution and skin diseases: Adverse effects of airborne particulate matter on various skin diseases.

    PubMed

    Kim, Kyung Eun; Cho, Daeho; Park, Hyun Jeong

    2016-05-01

    Environmental air pollution encompasses various particulate matters (PMs). The increased ambient PM from industrialization and urbanization is highly associated with morbidity and mortality worldwide, presenting one of the most severe environmental pollution problems. This article focuses on the correlation between PM and skin diseases, along with related immunological mechanisms. Recent epidemiological studies on the cutaneous impacts of PM showed that PM affects the development and exacerbation of skin diseases. PM induces oxidative stress via production of reactive oxygen species and secretion of pro-inflammatory cytokines such as TNF-α, IL-1α, and IL-8. In addition, the increased production of ROS such as superoxide and hydroxyl radical by PM exposure increases MMPs including MMP-1, MMP-2, and MMP-9, resulting in the degradation of collagen. These processes lead to the increased inflammatory skin diseases and skin aging. In addition, environmental cigarette smoke, which is well known as an oxidizing agent, is closely related with androgenetic alopecia (AGA). Also, ultrafine particles (UFPs) including black carbon and polycyclic aromatic hydrocarbons (PAHs) enhance the incidence of skin cancer. Overall, increased PM levels are highly associated with the development of various skin diseases via the regulation of oxidative stress and inflammatory cytokines. Therefore, anti-oxidant and anti-inflammatory drugs may be useful for treating PM-induced skin diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Histone methylation: a dynamic mark in health, disease and inheritance

    PubMed Central

    Greer, Eric L.; Shi, Yang

    2014-01-01

    Organisms require an appropriate balance of stability and reversibility in gene expression programs, to maintain cell identity or to enable responses to stimuli; epigenetic regulation is integral to this dynamic control. Post-translational modification of histones by methylation is an important and widespread type of chromatin modification that is known to influence biological processes in the context of development and cellular responses. We provide a broad overview of how histone methylation is regulated and leads to biological outcomes, to evaluate how histone methylation contributes to stable or reversible control. The importance of maintaining or reprogramming histone methylation appropriately is illustrated by links to disease and aging, or possibly transmission of traits across generations. PMID:22473383

  18. Recent advances in the molecular analysis of inherited disease.

    PubMed

    Malcolm, S

    1990-12-12

    Many important human genes have been cloned during the last ten years. In some cases, using reverse genetic techniques [Orkin, S. H. (1986) Cell 47, 845-850], disease-causing genes have been isolated whose product was previously unknown. Important examples include the dystrophin protein which, when mutated, gives rise to either Duchenne or Becker muscular dystrophy [Koenig, M., Hoffman, E. P., Bertelson, C. J., Monaco, A. P., Feener, C. and Kunkel, L. M. (1987) Cell 50, 509-517; Monaco, A. P., Bertelson, C. J., Liechti-Gallati, S. & Kunkel, L. M. (1988) Genomics 2, 90-95; Koenig, M., Monaco, A. P. & Kunkel, L. M. (1988) Cell 53, 219-228] and the cystic fibrosis transmembrane conductance regulator (CFTR) [Riordan, J. R., Rommens, J. M., Kerem, B.-S., Alon, N., Rozmahel, R., Grzelczak, Z., Zielenski, J., Lok, S., Plavsic, N., Chou, J.-L., Drumm, M. L., Ianuzzi, M. C., Collins, F. S. & Tsui, L.-C. (1989) Science 245, 1066-1073]. Recently the technology for systematically detecting single base-pair changes by chemical methods, enzymatic methods or direct DNA sequencing has greatly expanded and simplified. In addition to providing structural information about these clinically important genes and information on disease-causing mutations, these studies have led to an increased understanding of mechanisms of mutation, to the discovery of novel genetic mechanisms and to important clinical applications of carrier detection and pre-natal diagnosis. The recent rapid progress has been made possible by the development of DNA amplification using the polymerase chain reaction (pcr) invented by Saiki and colleagues [Saiki, R. K., Chang, C-A., Levenson, C. H., Warren, T. C., Boehm, C. D., Kazazian, H. H. & Ehrlich, H. A. (1988) N. Engl. J. Med. 319, 537-541].

  19. Reflectance confocal microscopy for inflammatory skin diseases.

    PubMed

    Ardigò, M; Prow, T; Agozzino, M; Soyer, P; Berardesca, E

    2015-10-01

    Reflectance confocal microscopy evaluation of inflammatory skin diseases represents a relatively new indication that, during the last 5 years, has shown an increasing interest with consequent progressive increment of publications in literature. The success of RCM in this filed of dermatology is directly related to the high needing of non-invasive techniques able to reduce the number of skin biopsies and support the clinical diagnosis and patient's management. RCM demonstrated to visualize microscopic descriptors of inflammatory and pigmentary skin conditions with good reproducibility between observer and high grade of correspondence with optical histology. Moreover, RCM has shown to provide sufficient data to support clinical diagnosis and differential diagnosis of inflammatory and pigmentary skin diseases. Recently, several works published in literature have opened the prospective to use RCM also for therapeutic follow-up in order to monitor the improvement of the microscopic parameters and help to prevent treatment side effects. In this review article we present some examples of RCM application in inflammatory and pigmentary diseases.

  20. 9 CFR 311.6 - Diamond-skin disease.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Diamond-skin disease. 311.6 Section... CERTIFICATION DISPOSAL OF DISEASED OR OTHERWISE ADULTERATED CARCASSES AND PARTS § 311.6 Diamond-skin disease. Carcasses of hogs affected with diamond-skin disease when localized and not associated with systemic...

  1. 9 CFR 311.6 - Diamond-skin disease.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Diamond-skin disease. 311.6 Section... CERTIFICATION DISPOSAL OF DISEASED OR OTHERWISE ADULTERATED CARCASSES AND PARTS § 311.6 Diamond-skin disease. Carcasses of hogs affected with diamond-skin disease when localized and not associated with systemic...

  2. 9 CFR 311.6 - Diamond-skin disease.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Diamond-skin disease. 311.6 Section... CERTIFICATION DISPOSAL OF DISEASED OR OTHERWISE ADULTERATED CARCASSES AND PARTS § 311.6 Diamond-skin disease. Carcasses of hogs affected with diamond-skin disease when localized and not associated with systemic...

  3. 9 CFR 311.6 - Diamond-skin disease.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Diamond-skin disease. 311.6 Section... CERTIFICATION DISPOSAL OF DISEASED OR OTHERWISE ADULTERATED CARCASSES AND PARTS § 311.6 Diamond-skin disease. Carcasses of hogs affected with diamond-skin disease when localized and not associated with systemic...

  4. 9 CFR 311.6 - Diamond-skin disease.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Diamond-skin disease. 311.6 Section... CERTIFICATION DISPOSAL OF DISEASED OR OTHERWISE ADULTERATED CARCASSES AND PARTS § 311.6 Diamond-skin disease. Carcasses of hogs affected with diamond-skin disease when localized and not associated with systemic...

  5. Oxidative stress and autoimmune skin disease.

    PubMed

    Shah, Amit Aakash; Sinha, Animesh A

    2013-01-01

    Antioxidants play the important role in our body of neutralizing free radicals and peroxides that are formed during normal physiologic events. While these reactive oxygen species are necessary for numerous biological processes, when created in excess they can have deleterious effects. The skin as an organ is constantly under attack by reactive oxygen species from both endogenous and exogenous sources. The pathophysiology of many autoimmune diseases is unknown and recently oxidative stress has come to light as a possible triggering mechanism. Recent investigations attempting to link autoimmune skin diseases and oxidative stress have had varying degrees of success. In this article, we review the current literature regarding antioxidants in alopecia areata, pemphigus vulgaris and other blistering diseases, vitiligo, and psoriasis, and suggest possible future studies and treatment options.

  6. Immunology and Skin in Health and Disease

    PubMed Central

    Richmond, Jillian M.; Harris, John E.

    2014-01-01

    The skin is a complex organ that, in addition to providing a strong barrier against external insults, serves as an arena for a wide variety of inflammatory processes, including immunity against infections, tumor immunity, autoimmunity, and allergy. A variety of cells collaborate to mount functional immune responses, which are initiated by resident populations and evolve through the recruitment of additional cell populations to the skin. Inflammatory responses are quite diverse, resulting in a wide range of signs and symptoms that depend on the initiating signals, characteristics of the infiltrating cell populations, and cytokines that are produced (cytokines are secreted protein that allows for cell–cell communication; usually refers to communication between immune–immune cells or stromal–immune cells). In this work, we will review the skin architecture and resident and recruited cell populations and discuss how these populations contribute to inflammation using human diseases and treatments when possible to illustrate their importance within a clinical context. PMID:25452424

  7. Mutation databases for inherited renal disease: are they complete, accurate, clinically relevant, and freely available?

    PubMed

    Savige, Judy; Dagher, Hayat; Povey, Sue

    2014-07-01

    This study examined whether gene-specific DNA variant databases for inherited diseases of the kidney fulfilled the Human Variome Project recommendations of being complete, accurate, clinically relevant and freely available. A recent review identified 60 inherited renal diseases caused by mutations in 132 genes. The disease name, MIM number, gene name, together with "mutation" or "database," were used to identify web-based databases. Fifty-nine diseases (98%) due to mutations in 128 genes had a variant database. Altogether there were 349 databases (a median of 3 per gene, range 0-6), but no gene had two databases with the same number of variants, and 165 (50%) databases included fewer than 10 variants. About half the databases (180, 54%) had been updated in the previous year. Few (77, 23%) were curated by "experts" but these included nine of the 11 with the most variants. Even fewer databases (41, 12%) included clinical features apart from the name of the associated disease. Most (223, 67%) could be accessed without charge, including those for 50 genes (40%) with the maximum number of variants. Future efforts should focus on encouraging experts to collaborate on a single database for each gene affected in inherited renal disease, including both unpublished variants, and clinical phenotypes. © 2014 WILEY PERIODICALS, INC.

  8. The Human Variome Project: ensuring the quality of DNA variant databases in inherited renal disease.

    PubMed

    Savige, Judy; Dalgleish, Raymond; Cotton, Richard Gh; den Dunnen, Johan T; Macrae, Finlay; Povey, Sue

    2015-11-01

    A recent review identified 60 common inherited renal diseases caused by DNA variants in 132 different genes. These diseases can be diagnosed with DNA sequencing, but each gene probably also has a thousand normal variants. Many more normal variants have been characterised by individual laboratories than are reported in the literature or found in publicly accessible collections. At present, testing laboratories must assess each novel change they identify for pathogenicity, even when this has been done elsewhere previously, and the distinction between normal and disease-associated variants is particularly an issue with the recent surge in exomic sequencing and gene discovery projects. The Human Variome Project recommends the establishment of gene-specific DNA variant databases to facilitate the sharing of DNA variants and decisions about likely disease causation. Databases improve diagnostic accuracy and testing efficiency, and reduce costs. They also help with genotype-phenotype correlations and predictive algorithms. The Human Variome Project advocates databases that use standardised descriptions, are up-to-date, include clinical information and are freely available. Currently, the genes affected in the most common inherited renal diseases correspond to 350 different variant databases, many of which are incomplete or have insufficient clinical details for genotype-phenotype correlations. Assistance is needed from nephrologists to maximise the usefulness of these databases for the diagnosis and management of inherited renal disease.

  9. Skin Diseases: Skin and Sun—Not a good mix

    MedlinePlus

    ... higher. A higher number means longer, stronger protection. Buy products with an SPF of 15 or higher. ... protection, too . The incidence of skin cancer in African Americans and other dark-skinned people is much lower ...

  10. Pesticide methoxychlor promotes the epigenetic transgenerational inheritance of adult-onset disease through the female germline.

    PubMed

    Manikkam, Mohan; Haque, M Muksitul; Guerrero-Bosagna, Carlos; Nilsson, Eric E; Skinner, Michael K

    2014-01-01

    Environmental compounds including fungicides, plastics, pesticides, dioxin and hydrocarbons can promote the epigenetic transgenerational inheritance of adult-onset disease in future generation progeny following ancestral exposure during the critical period of fetal gonadal sex determination. This study examined the actions of the pesticide methoxychlor to promote the epigenetic transgenerational inheritance of adult-onset disease and associated differential DNA methylation regions (i.e. epimutations) in sperm. Gestating F0 generation female rats were transiently exposed to methoxychlor during fetal gonadal development (gestation days 8 to 14) and then adult-onset disease was evaluated in adult F1 and F3 (great-grand offspring) generation progeny for control (vehicle exposed) and methoxychlor lineage offspring. There were increases in the incidence of kidney disease, ovary disease, and obesity in the methoxychlor lineage animals. In females and males the incidence of disease increased in both the F1 and the F3 generations and the incidence of multiple disease increased in the F3 generation. There was increased disease incidence in F4 generation reverse outcross (female) offspring indicating disease transmission was primarily transmitted through the female germline. Analysis of the F3 generation sperm epigenome of the methoxychlor lineage males identified differentially DNA methylated regions (DMR) termed epimutations in a genome-wide gene promoters analysis. These epimutations were found to be methoxychlor exposure specific in comparison with other exposure specific sperm epimutation signatures. Observations indicate that the pesticide methoxychlor has the potential to promote the epigenetic transgenerational inheritance of disease and the sperm epimutations appear to provide exposure specific epigenetic biomarkers for transgenerational disease and ancestral environmental exposures.

  11. The clinical spectrum of inherited diseases involved in the synthesis and remodeling of complex lipids. A tentative overview.

    PubMed

    Garcia-Cazorla, Àngels; Mochel, Fanny; Lamari, Foudil; Saudubray, Jean-Marie

    2015-01-01

    Over one hundred diseases related to inherited defects of complex lipids synthesis and remodeling are now reported. Most of them were described within the last 5 years. New descriptions and phenotypes are expanding rapidly. While the associated clinical phenotype is currently difficult to outline, with only a few patients identified, it appears that all organs and systems may be affected. The main clinical presentations can be divided into (1) Diseases affecting the central and peripheral nervous system. Complex lipid synthesis disorders produce prominent motor manifestations due to upper and/or lower motoneuron degeneration. Motor signs are often complex, associated with other neurological and extra-neurological signs. Three neurological phenotypes, spastic paraparesis, neurodegeneration with brain iron accumulation and peripheral neuropathies, deserve special attention. Many apparently well clinically defined syndromes are not distinct entities, but rather clusters on a continuous spectrum, like for the PNPLA6-associated diseases, extending from Boucher-Neuhauser syndrome via Gordon Holmes syndrome to spastic ataxia and pure hereditary spastic paraplegia; (2) Muscular/cardiac presentations; (3) Skin symptoms mostly represented by syndromic (neurocutaneous) and non syndromic ichthyosis; (4) Retinal dystrophies with syndromic and non syndromic retinitis pigmentosa, Leber congenital amaurosis, cone rod dystrophy, Stargardt disease; (5) Congenital bone dysplasia and segmental overgrowth disorders with congenital lipomatosis; (6) Liver presentations characterized mainly by transient neonatal cholestatic jaundice and non alcoholic liver steatosis with hypertriglyceridemia; and (7) Renal and immune presentations. Lipidomics and molecular functional studies could help to elucidate the mechanism(s) of dominant versus recessive inheritance observed for the same gene in a growing number of these disorders.

  12. Human skin pigmentation, migration and disease susceptibility

    PubMed Central

    Jablonski, Nina G.; Chaplin, George

    2012-01-01

    Human skin pigmentation evolved as a compromise between the conflicting physiological demands of protection against the deleterious effects of ultraviolet radiation (UVR) and photosynthesis of UVB-dependent vitamin D3. Living under high UVR near the equator, ancestral Homo sapiens had skin rich in protective eumelanin. Dispersals outside of the tropics were associated with positive selection for depigmentation to maximize cutaneous biosynthesis of pre-vitamin D3 under low and highly seasonal UVB conditions. In recent centuries, migrations and high-speed transportation have brought many people into UVR regimes different from those experienced by their ancestors and, accordingly, exposed them to new disease risks. These have been increased by urbanization and changes in diet and lifestyle. Three examples—nutritional rickets, multiple sclerosis (MS) and cutaneous malignant melanoma (CMM)—are chosen to illustrate the serious health effects of mismatches between skin pigmentation and UVR. The aetiology of MS in particular provides insight into complex and contingent interactions of genetic and environmental factors necessary to trigger lethal disease states. Low UVB levels and vitamin D deficiencies produced by changes in location and lifestyle pose some of the most serious disease risks of the twenty-first century. PMID:22312045

  13. Skin function and skin disorders in Parkinson's disease.

    PubMed

    Fischer, M; Gemende, I; Marsch, W C; Fischer, P A

    2001-01-01

    Cutaneous symptoms (seborrhoea and hyperhidrosis) in Parkinson's disease were investigated. In 70 treated patients with Parkinson's disease and 22 control subjects, non-invasive bioengineering methods (sebumetry, corneometry, pH) were carried out on the forehead, sternum and forearm. In addition, concomitant dermatoses and medication were recorded. 18.6% of the patients had seborrhoea on the forehead (>220 microg/cm2), 51.4% showed normal sebum values (100-220 microg/cm2) and 30% a sebostasis (<100 microg/cm2). Males has significantly higher sebum values than females. No relationship between the seborrhoea and the therapy for Morbus Parkinson was found. Patients with hyperhidrosis (n = 36) had significantly lower pH values (p < 0.05) on the forehead than those without hyperhidrosis. 22 patients (31.9%) reported a cold/hot flush and a further 13 (18.8%) had clinical rosacea. Seborrhoea is rare in treated Parkinsonian patients but hyperhidrosis is frequently found. Furthermore, a particular lack of vasostability (flush) appears to be an autonomic dysregulation in the skin related to Morbus Parkinson, which has not been studied to any extent to date.

  14. Inherited Neuropathies

    PubMed Central

    Li, Jun

    2013-01-01

    With a prevalence of 1 in 2500 people, inherited peripheral nerve diseases, collectively called Charcot-Marie-Tooth disease (CMT), are among the most common inherited neurologic disorders. Patients with CMT typically present with chronic muscle weakness and atrophy in limbs, sensory loss in the feet and hands, and foot deformities. Clinical similarities between patients often require genetic testing to achieve a precise diagnosis. In this article, the author reviews the clinical and pathologic features of CMT, and demonstrates how electrodiagnostic and genetic tools are used to assist in the diagnosis and symptomatic management of the diseases. Several cases are presented to illustrate the diagnostic processes. PMID:23117945

  15. Gene therapy for inherited muscle diseases: where genetics meets rehabilitation medicine.

    PubMed

    Braun, Robynne; Wang, Zejing; Mack, David L; Childers, Martin K

    2014-11-01

    The development of clinical vectors to correct genetic mutations that cause inherited myopathies and related disorders of skeletal muscle is advancing at an impressive rate. Adeno-associated virus vectors are attractive for clinical use because (1) adeno-associated viruses do not cause human disease and (2) these vectors are able to persist for years. New vectors are now becoming available as gene therapy delivery tools, and recent preclinical experiments have demonstrated the feasibility, safety, and efficacy of gene therapy with adeno-associated virus for long-term correction of muscle pathology and weakness in myotubularin-deficient canine and murine disease models. In this review, recent advances in the application of gene therapies to treat inherited muscle disorders are presented, including Duchenne muscular dystrophy and x-linked myotubular myopathy. Potential areas for therapeutic synergies between rehabilitation medicine and genetics are also discussed.

  16. Gene therapy for inherited muscle diseases: Where genetics meets rehabilitation medicine

    PubMed Central

    Braun, Robynne; Wang, Zejing; Mack, David L.; Childers, Martin K.

    2014-01-01

    The development of clinical vectors to correct genetic mutations that cause inherited myopathies and related disorders of skeletal muscle is advancing at an impressive rate. Adeno-associated virus (AAV) vectors are attractive for clinical use because (i) AAVs do not cause human disease, and (ii) these vectors are able to persist for years. New vectors are now becoming available as gene therapy delivery tools, and recent preclinical experiments have demonstrated the feasibility, safety and efficacy of gene therapy with AAV for long-term correction of muscle pathology and weakness in myotubularin-deficient canine and murine disease models. In this review, we present recent advances in the application of gene therapies to treat inherited muscle disorders including Duchenne Muscular Dystrophy and X-linked Myotubular Myopathy. Potential areas for therapeutic synergies between rehabilitation medicine and genetics are also discussed. PMID:25313664

  17. Infections and skin diseases mimicking diaper dermatitis.

    PubMed

    Van Gysel, Dirk

    2016-07-01

    Diaper dermatitis is a common condition that often prompts parents to seek medical attention. Irritant diaper dermatitis is by far the most common cause, but numerous potentially serious diseases can present with changes of the skin in the diaper area. The differential diagnosis can include psoriasis, metabolic disorders, rare immune diseases and infection. Clinical examination can be helpful in distinguishing the underlying cause. General screening laboratory tests, as well as select testing when a specific condition is suspected, can be used to challenge or confirm the putative diagnosis.

  18. Oedematous skin disease of buffalo in Egypt.

    PubMed

    Selim, S A

    2001-05-01

    This review covers a historical view and etiology of oedematous skin disease which affects buffalo in Egypt, the microbiology of Corynebacterium pseudotuberculosis causing the disease: its virulence; clinical signs; mechanism of pathogenesis; histopathology; mode of transmission; immunological aspects; treatment and control. It is concluded that C. pseudotuberculosis serotype II is the main cause of OSD and exotoxin phospholipase D and its lipid contents of the cell wall are the major causes of pathogenesis. After declaring the role of Hippobosca equina in transmission of the causative agent among buffaloes, control of OSD is now available.

  19. Identifying strains that contribute to complex diseases through the study of microbial inheritance.

    PubMed

    Faith, Jeremiah J; Colombel, Jean-Frédéric; Gordon, Jeffrey I

    2015-01-20

    It has been 35 y since Carl Woese reported in PNAS how sequencing ribosomal RNA genes could be used to distinguish the three domains of life on Earth. During the past decade, 16S rDNA sequencing has enabled the now frequent enumeration of bacterial communities that populate the bodies of humans representing different ages, cultural traditions, and health states. A challenge going forward is to quantify the contributions of community members to wellness, disease risk, and disease pathogenesis. Here, we explore a theoretical framework for studies of the inheritance of bacterial strains and discuss the advantages and disadvantages of various study designs for assessing the contribution of strains to complex diseases.

  20. Brain-water diffusion coefficients reflect the severity of inherited prion disease

    PubMed Central

    Hyare, H.; Wroe, S.; Siddique, D.; Webb, T.; Fox, N. C.; Stevens, J.; Collinge, J.; Yousry, T.; Thornton, J. S.

    2010-01-01

    Objective: Inherited prion diseases are progressive neurodegenerative conditions, characterized by cerebral spongiosis, gliosis, and neuronal loss, caused by mutations within the prion protein (PRNP) gene. We wished to assess the potential of diffusion-weighted MRI as a biomarker of disease severity in inherited prion diseases. Methods: Twenty-five subjects (mean age 45.2 years) with a known PRNP mutation including 19 symptomatic patients, 6 gene-positive asymptomatic subjects, and 7 controls (mean age 54.1 years) underwent conventional and diffusion-weighted MRI. An index of normalized brain volume (NBV) and region of interest (ROI) mean apparent diffusion coefficient (ADC) for the head of caudate, putamen, and pulvinar nuclei were recorded. ADC histograms were computed for whole brain (WB) and gray matter (GM) tissue fractions. Clinical assessment utilized standardized clinical scores. Mann-Whitney U test and regression analyses were performed. Results: Symptomatic patients exhibited an increased WB mean ADC (p = 0.006) and GM mean ADC (p = 0.024) compared to controls. Decreased NBV and increased mean ADC measures significantly correlated with clinical measures of disease severity. Using a stepwise multivariate regression procedure, GM mean ADC was an independent predictor of Clinician's Dementia Rating score (p = 0.001), Barthel Index of activities of daily living (p = 0.001), and Rankin disability score (p = 0.019). Conclusions: Brain volume loss in inherited prion diseases is accompanied by increased cerebral apparent diffusion coefficient (ADC), correlating with increased disease severity. The association between gray matter ADC and clinical neurologic status suggests this measure may prove a useful biomarker of disease activity in inherited prion diseases. GLOSSARY ADAS-Cog = Alzheimer's Disease Assessment Scale–Cognitive subscale; ADC = apparent diffusion coefficient; ADL = Barthel Activities of Daily Living scale; BET = brain extraction tool; BPRS

  1. "COV'COP" allows to detect CNVs responsible for inherited diseases among amplicons sequencing data.

    PubMed

    Derouault, P; Parfait, B; Moulinas, R; Barrot, C-C; Sturtz, F; Merillou, S; Lia, A-S

    2017-01-30

    In order to help molecular geneticists to rapidly identify CNVs responsible for inherited diseases among amplicons sequencing data generated by NGS, we designed a user-friendly tool "Cov'Cop". Using the run's coverage file provided by the sequencer, Cov'Cop simultaneously analyzes all the patients of the run using a two-stage algorithm containing correction and normalization levels and provides an easily understandable output, showing with various colors, potentially deleted and duplicated amplicons.

  2. IgG4-related skin disease.

    PubMed

    Tokura, Y; Yagi, H; Yanaguchi, H; Majima, Y; Kasuya, A; Ito, T; Maekawa, M; Hashizume, H

    2014-11-01

    IgG4-related disease (IgG4-RD) is a recently established clinical entity characterized by high levels of circulating IgG4, and tissue infiltration of IgG4(+) plasma cells. IgG4-RD exhibits a distinctive fibroinflammatory change involving multiple organs, such as the pancreas and salivary and lacrimal glands. The skin lesions of IgG4-RD have been poorly characterized and may stem not only from direct infiltration of plasma cells but also from IgG4-mediated inflammation. Based on the documented cases together with ours, we categorized the skin lesions into seven subtypes: (1) cutaneous plasmacytosis (multiple papulonodules or indurations on the trunk and proximal part of the limbs), (2) pseudolymphoma and angiolymphoid hyperplasia with eosinophilia (plaques and papulonodules mainly on the periauricular, cheek and mandible regions), (3) Mikulicz disease (palpebral swelling, sicca syndrome and exophthalmos), (4) psoriasis-like eruption (strikingly mimicking psoriasis vulgaris), (5) unspecified maculopapular or erythematous eruptions, (6) hypergammaglobulinaemic purpura (bilateral asymmetrical palpable purpuric lesions on the lower extremities) and urticarial vasculitis (prolonged urticarial lesions occasionally with purpura) and (7) ischaemic digit (Raynaud phenomenon and digital gangrene). It is considered that subtypes 1-3 are induced by direct infiltration of IgG4(+) plasma cells, while the other types (4-7) are caused by secondary mechanisms. IgG4-related skin disease is defined as IgG4(+) plasma-cell-infiltrating skin lesions that form plaques, nodules or tumours (types 1-3), but may manifest secondary lesions caused by IgG4(+) plasma cells and/or IgG4 (types 4-7).

  3. Global skin diseases on Instagram hashtags.

    PubMed

    Braunberger, Taylor; Mounessa, Jessica; Rudningen, Kyle; Dunnick, Cory A; Dellavalle, Robert P

    2017-05-15

    Recently named one of the most influential phone applications, Instagram continues to grow in popularity [1]. Instagram consists of images and video posts, making it ideal for education and communication within the visual field of dermatology. In this study, we seek to determine the presence of dermatology-related content with regard to the most common cutaneous diseases of the world. We searched the account types and hashtags associated with the eight most common skin diseases globally as identified by the Global Burden of Disease (GBD) study by Hollenstein et al.: eczema, psoriasis, acne,pruritus, alopecia, decubitus ulcer, urticaria, andscabies [9]. The majority of Instagram accounts included patient experiences (n=73), private accounts(n=52), and disease advocacy and awareness groups(n=20), (total n=221). We further investigated over 2 million skin disease hashtags. The greatest numbersof hashtags were the following: #acne (n = 1,622,626),#alopecia (n = 317,566), and #eczema (n = 196,115). Our results demonstrate that patients interact withone another through Instagram. As social networking platforms become more frequently used as a source of information for patients and patient support, medical professionals must gain awareness of content available through Instagram and consider it as a means to educate the public.

  4. Epigenetic transgenerational inheritance of vinclozolin induced mouse adult onset disease and associated sperm epigenome biomarkers.

    PubMed

    Guerrero-Bosagna, Carlos; Covert, Trevor R; Haque, Md M; Settles, Matthew; Nilsson, Eric E; Anway, Matthew D; Skinner, Michael K

    2012-12-01

    The endocrine disruptor vinclozolin has previously been shown to promote epigenetic transgenerational inheritance of adult onset disease in the rat. The current study was designed to investigate the transgenerational actions of vinclozolin on the mouse. Transient exposure of the F0 generation gestating female during gonadal sex determination promoted transgenerational adult onset disease in F3 generation male and female mice, including spermatogenic cell defects, testicular abnormalities, prostate abnormalities, kidney abnormalities and polycystic ovarian disease. Pathology analysis demonstrated 75% of the vinclozolin lineage animals developed disease with 34% having two or more different disease states. Interestingly, the vinclozolin induced transgenerational disease was observed in the outbred CD-1 strain, but not the inbred 129 mouse strain. Analysis of the F3 generation sperm epigenome identified differential DNA methylation regions that can potentially be utilized as epigenetic biomarkers for transgenerational exposure and disease.

  5. [Skin Diseases in Primary Psychiatric Disorders].

    PubMed

    Mavrogiorgou, P; Juckel, G

    2016-10-01

    Somatic diseases in psychiatric disorders are frequently seen in clinical practice. Several international studies have shown that patients with a primary psychiatric disorder are at increased risk for developing severe somatic comorbidities in comparison to the normal population. Whereas there has been accumulation of knowledge on cardiovascular comorbidities, the relationship between skin and psychiatric disorders is less understood. There are only a few systematic studies on this subject and, in addition, there is lack of knowledge about underlying neurobiological and immunological mechanisms. Impairments and disorders of the skin are often an (early) sign of a psychiatric disorder. Somatic treatment of skin diseases should be initiated as early as possible in patients with psychiatric disorders. This review article focuses on dermatological diagnoses that are related to primary psychiatric disorders such as psychotic and affective disorders as well as addiction disorders, and presents the most important aspects of epidemiology, symptomatology and possible pathophysiology. © Georg Thieme Verlag KG Stuttgart · New York.

  6. Medicinal plants used in treatment of inflammatory skin diseases

    PubMed Central

    2013-01-01

    Skin is an organ providing contact with the environment and protecting the human body from unfavourable external factors. Skin inflammation, reflected adversely in its functioning and appearance, also unfavourably affects the psyche, the condition of which is important during treatment of chronic skin diseases. The use of plants in treatment of inflammatory skin diseases results from their influence on different stages of inflammation. The paper presents results of the study regarding the anti-inflammatory activity of the plant raw material related to its influence on skin. The mechanism of action, therapeutic indications and side effects of medicinal plants used for treatment of inflammatory diseases of the skin are described. PMID:24278070

  7. Genetic testing for inherited heart diseases: longitudinal impact on health-related quality of life.

    PubMed

    Ingles, Jodie; Yeates, Laura; O'Brien, Lisa; McGaughran, Julie; Scuffham, Paul A; Atherton, John; Semsarian, Christopher

    2012-05-03

    Purpose:A genetic diagnosis is an extremely useful tool in the management and care of families with inherited heart diseases, particularly in allowing clarification of risk status of asymptomatic family members. The psychosocial consequences of genetic testing in this group are poorly understood. This longitudinal pilot study sought to determine changes in health-related quality of life in patients and asymptomatic family members undergoing genetic testing for inherited heart diseases.Methods:Individuals attending two specialized multidisciplinary cardiac genetic clinics in Australia were invited to participate. Patients undergoing proband or predictive genetic testing for an inherited cardiomyopathy or primary arrhythmogenic disorder were eligible. The Medical Outcomes Short Form-36 (version 2) was administered before the genetic result was given, and follow-up surveys were completed 1-3, 6, and 12 months after the result was given.Results:A total of 54 individuals with hypertrophic cardiomyopathy, familial dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, and long QT syndrome completed baseline and at least one follow-up survey, including 33 probands and 21 asymptomatic relatives. Physical and mental component scores analyzed at baseline and 1-3 months were found to be unchanged in all groups. Furthermore, no significant differences were observed up to 12 months after result.Conclusion:In this longitudinal pilot study, no change in health-related quality of life was observed up to 12 months after the result was given in patients and their asymptomatic family members undergoing genetic testing for an inherited heart disease.Genet Med 2012 advance online publication 3 May 2012.

  8. Oral mucosal manifestations of autoimmune skin diseases.

    PubMed

    Mustafa, Mayson B; Porter, Stephen R; Smoller, Bruce R; Sitaru, Cassian

    2015-10-01

    A group of autoimmune diseases is characterised by autoantibodies against epithelial adhesion structures and/or tissue-tropic lymphocytes driving inflammatory processes resulting in specific pathology at the mucosal surfaces and the skin. The most frequent site of mucosal involvement in autoimmune diseases is the oral cavity. Broadly, these diseases include conditions affecting the cell-cell adhesion causing intra-epithelial blistering and those where autoantibodies or infiltration lymphocytes cause a loss of cell-matrix adhesion or interface inflammation. Clinically, patients present with blistering, erosions and ulcers that may affect the skin as well as further mucosal surfaces of the eyes, nose and genitalia. While the autoimmune disease may be suspected based on clinical manifestations, demonstration of tissue-bound and circulating autoantibodies, or lymphocytic infiltrates, by various methods including histological examination, direct and indirect immunofluorescence microscopy, immunoblotting and quantitative immunoassay is a prerequisite for definitive diagnosis. Given the frequency of oral involvement and the fact that oral mucosa is the initially affected site in many cases, the informed practitioner should be well acquainted with diagnostic and therapeutic aspects of autoimmune dermatosis with oral involvement. This paper reviews the pathogenesis and clinical presentation of these conditions in the oral cavity with a specific emphasis on their differential diagnosis and current management approaches.

  9. Occupational skin diseases in automotive industry workers.

    PubMed

    Yakut, Yunus; Uçmak, Derya; Akkurt, Zeynep Meltem; Akdeniz, Sedat; Palanci, Yilmaz; Sula, Bilal

    2014-03-01

    Studies on occupational skin diseases in workers of the automotive industry are few. To investigate the prevalence of occupational skin diseases in workers of the automotive industry. Between September and December 2011, a total of 405 workers from the automotive repair industry in Diyarbakır were interviewed. They were active workers in the repair industry who had been employed for at least six months. Business owners, sellers of spare parts and accounting officers were not included. The employees were examined at their workplaces and the working conditions were observed. Detailed dermatological examination was performed. The mean age of the 405 workers who participated in the study was 27.7 ± 10.3. The mean working time of employees was 13.3 ± 10.4 years. All of the employees were male. Dermatological diseases were not detected in 144 out of 405 workers (35.6%) and at least one condition was diagnosed in 261 (64.4%). The most frequent diagnosis was callus, hyperkeratosis, clavus (27.7%), followed by nail changes (16.8%) and superficial mycoses (12.1%). Contact dermatitis was seen at a rate of 5.9%. Traumatic lesions such as hyperkeratotic lesions and nail changes were found most frequently. Traumatic lesions were common among individuals who did not use gloves. Most nail changes were localized leuconychia, a finding not reported in the studies on automotive industry workers. In accordance with the literature, irritant contact dermatitis was observed in patients with a history of atopy and who had been working for a long time. Occupational skin diseases comprise an important field in dermatology, deserving much attention. Further studies on occupational dermatology are necessary.

  10. Update of the G2D tool for prioritization of gene candidates to inherited diseases

    PubMed Central

    Perez-Iratxeta, Carolina; Bork, Peer; Andrade-Navarro, Miguel A.

    2007-01-01

    G2D (genes to diseases) is a web resource for prioritizing genes as candidates for inherited diseases. It uses three algorithms based on different prioritization strategies. The input to the server is the genomic region where the user is looking for the disease-causing mutation, plus an additional piece of information depending on the algorithm used. This information can either be the disease phenotype (described as an online Mendelian inheritance in man (OMIM) identifier), one or several genes known or suspected to be associated with the disease (defined by their Entrez Gene identifiers), or a second genomic region that has been linked as well to the disease. In the latter case, the tool uses known or predicted interactions between genes in the two regions extracted from the STRING database. The output in every case is an ordered list of candidate genes in the region of interest. For the first two of the three methods, the candidate genes are first retrieved through sequence homology search, then scored accordingly to the corresponding method. This means that some of them will correspond to well-known characterized genes, and others will overlap with predicted genes, thus providing a wider analysis. G2D is publicly available at http://www.ogic.ca/projects/g2d_2/ PMID:17478516

  11. Phototherapy and photochemotherapy of skin diseases

    SciTech Connect

    Parrish, J.A.

    1981-07-01

    One important aspect of photomedicine is the use of nonionizing electromagnetic radiation with and without exogenous photosensitizers to treat diseases. Phototoxicity (cell injury by photons) is a likely mechanism for phototherapy and photochemotherapy of several skin diseases. The mechanism of action for phototherapy of hyperbilirubinemia and of uremic pruritus appears to be photochemical alteration of extracellular metabolites. Psoriasis is an example of a disease benefitted by several forms of phototherapy and photochemotherapy with varying relative effectiveness and safety. Two successful forms of treatment are oral psoralen photochemotherapy and UVB plus topical adjunctive agents. New information about UVB therapy of psoriasis includes data about the therapeutic action spectrum and about the relative roles of various topical agents such as coal tar, mineral oil, ''lubricants'' and steroids. Although there are many surface similarities, phototherapy and psoralen photochemotherapy have fundamental differences which may alter longterm risks in quantitative and qualitative ways.

  12. Bodies in skin: a philosophical and theological approach to genetic skin diseases.

    PubMed

    Walser, Angelika

    2010-03-01

    This contribution evolved from my work in a European network and is dedicated to the rare genetic skin diseases. To gain a deeper knowledge about the question, what it means to suffer from a genetic skin disease, I have discussed the concepts of skin in philosophical and theological anthropology. Presuming that ancient interpretations of skin diseases (moral and cultical impurity) are still relevant today, feminist Christian theology shows the ways of deconstructing stigmatizing paradigma by using the body as a hermeneutic category. Skin becomes the "open borderline" of the human being, pointing out both the social vulnerability and the transcendent capacity of the human person.

  13. Skin diseases of the vulva: eczematous diseases and contact urticaria.

    PubMed

    Sand, Freja Lærke; Thomsen, Simon Francis

    2017-08-07

    Skin diseases in the vulvar area include a variety of disorders many of which have a chronic course with significant morbidity. It is important to be aware of the symptoms, signs and diagnostic tools in order to optimise treatment. Herein, the most common eczematous diseases of the vulvar area, i.e. lichen simplex chronicus, seborrhoeic dermatitis, atopic dermatitis, irritant contact dermatitis, and non-systemic and systemic allergic contact dermatitis are reviewed. Allergic contact urticaria is also described.

  14. Rituximab in severe skin diseases: target, disease, and dose

    PubMed Central

    Bennett, Daniel D; Ohanian, Maro; Cable, Christian T

    2010-01-01

    New clinical indications for rituximab seem to appear every day. This review will trace the use of this monoclonal antibody from lymphoid malignancy, to classic autoimmune disease, and specifically severe autoimmune skin diseases. The history leading to different dosing schema with associated pharmacokinetic data will be discussed. A case of livedoid vasculopathy (atrophie blanche) responding to rituximab will illustrate how the response to therapy can help to elucidate previously obscure pathophysiology. PMID:22291497

  15. Immunology and skin in health and disease.

    PubMed

    Richmond, Jillian M; Harris, John E

    2014-12-01

    The skin is a complex organ that, in addition to providing a strong barrier against external insults, serves as an arena for a wide variety of inflammatory processes, including immunity against infections, tumor immunity, autoimmunity, and allergy. A variety of cells collaborate to mount functional immune responses, which are initiated by resident populations and evolve through the recruitment of additional cell populations to the skin. Inflammatory responses are quite diverse, resulting in a wide range of signs and symptoms that depend on the initiating signals, characteristics of the infiltrating cell populations, and cytokines that are produced (cytokines are secreted protein that allows for cell-cell communication; usually refers to communication between immune-immune cells or stromal-immune cells). In this work, we will review the skin architecture and resident and recruited cell populations and discuss how these populations contribute to inflammation using human diseases and treatments when possible to illustrate their importance within a clinical context. Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.

  16. Skin diseases among schoolchildren in Ghana, Gabon, and Rwanda.

    PubMed

    Hogewoning, Arjan; Amoah, Abena; Bavinck, Jan Nico Bouwes; Boakye, Daniel; Yazdanbakhsh, Maria; Adegnika, Akim; De Smedt, Stefan; Fonteyne, Yannick; Willemze, Rein; Lavrijsen, Adriana

    2013-05-01

    Skin diseases, especially skin infections, among schoolchildren in Africa can be a major health problem. The objective of this study was to determine the prevalences of skin diseases among children in rural and urban schools in three different African countries and to study the influence of socioeconomic level. Cross-sectional, population-based studies were performed in Ghana, Gabon, and Rwanda. Point prevalences of skin diseases were estimated on the basis of physical examination by at least one dermatologist. A total of 4839 schoolchildren were seen. The overall prevalence of schoolchildren with any skin disease was high and amounted to 34.6% and 42.0% in two Ghanaian studies, 45.8% in Gabon, and 26.7% in Rwanda. In children with skin diseases, skin infections represented the greatest proportion of disease, accounting for 14.7% and 17.6% of skin disease in the Ghanaian studies, and 27.7% and 22.7% in Gabon and Rwanda, respectively. Diseases with the highest prevalence were tinea capitis and bacterial skin infections, especially in rural areas and in schools serving children living at lower socioeconomic levels. The prevalences of skin diseases among African schoolchildren were high. Skin infections such as tinea capitis and pyoderma predominated. © 2013 The International Society of Dermatology.

  17. Atrazine induced epigenetic transgenerational inheritance of disease, lean phenotype and sperm epimutation pathology biomarkers.

    PubMed

    McBirney, Margaux; King, Stephanie E; Pappalardo, Michelle; Houser, Elizabeth; Unkefer, Margaret; Nilsson, Eric; Sadler-Riggleman, Ingrid; Beck, Daniel; Winchester, Paul; Skinner, Michael K

    2017-01-01

    Ancestral environmental exposures to a variety of environmental toxicants and other factors have been shown to promote the epigenetic transgenerational inheritance of adult onset disease. The current study examined the potential transgenerational actions of the herbicide atrazine. Atrazine is one of the most commonly used herbicides in the agricultural industry, in particular with corn and soy crops. Outbred gestating female rats were transiently exposed to a vehicle control or atrazine. The F1 generation offspring were bred to generate the F2 generation and then the F2 generation bred to generate the F3 generation. The F1, F2 and F3 generation control and atrazine lineage rats were aged and various pathologies investigated. The male sperm were collected to investigate DNA methylation differences between the control and atrazine lineage sperm. The F1 generation offspring (directly exposed as a fetus) did not develop disease, but weighed less compared to controls. The F2 generation (grand-offspring) was found to have increased frequency of testis disease and mammary tumors in males and females, early onset puberty in males, and decreased body weight in females compared to controls. The transgenerational F3 generation rats were found to have increased frequency of testis disease, early onset puberty in females, behavioral alterations (motor hyperactivity) and a lean phenotype in males and females. The frequency of multiple diseases was significantly higher in the transgenerational F3 generation atrazine lineage males and females. The transgenerational transmission of disease requires germline (egg or sperm) epigenetic alterations. The sperm differential DNA methylation regions (DMRs), termed epimutations, induced by atrazine were identified in the F1, F2 and F3 generations. Gene associations with the DMRs were identified. For the transgenerational F3 generation sperm, unique sets of DMRs (epimutations) were found to be associated with the lean phenotype or testis

  18. Pesticide and insect repellent mixture (permethrin and DEET) induces epigenetic transgenerational inheritance of disease and sperm epimutations.

    PubMed

    Manikkam, Mohan; Tracey, Rebecca; Guerrero-Bosagna, Carlos; Skinner, Michael K

    2012-12-01

    Environmental compounds are known to promote epigenetic transgenerational inheritance of disease. The current study was designed to determine if a "pesticide mixture" (pesticide permethrin and insect repellent N,N-diethyl-meta-toluamide, DEET) promotes epigenetic transgenerational inheritance of disease and associated DNA methylation epimutations in sperm. Gestating F0 generation female rats were exposed during fetal gonadal sex determination and the incidence of disease evaluated in F1 and F3 generations. There were significant increases in the incidence of total diseases in animals from pesticide lineage F1 and F3 generation animals. Pubertal abnormalities, testis disease, and ovarian disease (primordial follicle loss and polycystic ovarian disease) were increased in F3 generation animals. Analysis of the pesticide lineage F3 generation sperm epigenome identified 363 differential DNA methylation regions (DMR) termed epimutations. Observations demonstrate that a pesticide mixture (permethrin and DEET) can promote epigenetic transgenerational inheritance of adult onset disease and potential sperm epigenetic biomarkers for ancestral environmental exposures.

  19. Occupational skin disease in Victoria, Australia.

    PubMed

    Cahill, Jennifer L; Williams, Jason D; Matheson, Melanie C; Palmer, Amanda M; Burgess, John A; Dharmage, Shyamali C; Nixon, Rosemary L

    2016-05-01

    To describe the characteristics of patients with occupational skin disease (OSD) in a tertiary referral clinic in Victoria, Australia. A retrospective review was conducted of records from patients seen at the Occupational Dermatology Clinic in Melbourne, Australia between 1 January 1993 and 31 December 2010. Of the 2894 people assessed in the clinic during the 18-year period, 44% were women and 56% were men. In all, 2177 (75%) were diagnosed with occupational skin disease (OSD). Of the patients with a work-related skin condition, 45% (n = 979) were considered to be atopic. The most common diagnosis in those with OSD was irritant contact dermatitis (ICD) (44%), followed by allergic contact dermatitis (33%) and endogenous eczema (11%). Women were significantly more likely to have soaps and detergents (P < 0.001) and water/wet work (P < 0.001) as causes of their ICD than men. Men were significantly more likely to have oils and coolants (P < 0.001) and solvent exposures (P < 0.001) as causes of their ICD. Occupational groups with the highest incidence of OSD were the hair and beauty professions (70 per 100 000), followed by machine and plant operators (38 per 100 000) and health-care workers (21 per 100 000). We confirm the importance of occupational contact dermatitis as the most common cause of OSD, with ICD being the most common diagnosis. There are differences in the causes of ICD between our group of male and female workers. For the first time in Australia, rates of OSD in certain industries have been calculated. © 2015 The Australasian College of Dermatologists.

  20. Biochemical basis for dominant inheritance, variable penetrance and maternal effects in RBP4 congenital eye disease

    PubMed Central

    Chou, Christopher M.; Nelson, Christine; Tarlè, Susan A.; Pribila, Jonathan T.; Bardakjian, Tanya; Woods, Sean; Schneider, Adele; Glaser, Tom

    2015-01-01

    SUMMARY Gestational vitamin A (retinol) deficiency poses a risk for ocular birth defects and blindness. We identified missense mutations in RBP4, encoding serum retinol binding protein (RBP), in three families with eye malformations of differing severity. The mutant phenotypes exhibit dominant inheritance but incomplete penetrance. Maternal inheritance significantly increases the probability of phenotypic expression. RBP normally delivers retinol from hepatic stores to peripheral tissues, including the placenta and fetal eye. The disease mutations greatly reduce retinol binding to RBP yet paradoxically increase RBP affinity for its cell surface receptor, STRA6. By occupying STRA6 nonproductively, the dominant-negative proteins are predicted to disrupt vitamin A delivery from wild-type proteins within the fetus but also, in the case of maternal transmission, at the placenta. These findings establish a previously uncharacterized mode of maternal inheritance, distinct from imprinting and oocyte-derived mRNA, and define a group of hereditary disorders plausibly modulated by dietary vitamin A levels. PMID:25910211

  1. Adipocytes in Skin Health and Disease

    PubMed Central

    Rivera-Gonzalez, Guillermo; Shook, Brett; Horsley, Valerie

    2014-01-01

    Adipocytes are intimately associated with the dermal compartment of the skin, existing in a specialized dermal depot and displaying dynamic changes in size during tissue homeostasis. However, the roles of adipocytes in cutaneous biology and disease are not well understood. Traditionally, adipocytes within tissues were thought to act as reservoirs of energy, as thermal, or as structural support. In this review, we discuss recent studies revealing the cellular basis of the dynamic development and regenerative capacity of dermal adipocytes associated with the hair cycle and following injury. We discuss and speculate on potential roles of dermal adipocytes in cutaneous biology with an emphasis on communication during hair follicle growth and wound healing. Finally, we explore how alterations in the dermal adipose tissue may support clinical manifestations of cutaneous diseases such as lipodystrophy, obesity, and alopecia. PMID:24591537

  2. Psoriasis: experiencing a chronic skin disease.

    PubMed

    Chrissopoulos, A; Cleaver, G

    1996-03-01

    Psoriasis is an incurable chronic skin disease that affects one in fifty people. Psychological factors play a role in the aetiology and experience of psoriasis but there is little pertaining to the psychological experience of psoriasis in research literature. In this study the phenomenological approach is used to describe the everyday experiences of a person with psoriasis. By using Giorgi's (1985) steps of data analysis a description of the lifeworld of the person with psoriasis was compiled. The description presented several essential components of the experience of psoriasis and the results emphasize the effects of the disease on the sufferer's life. Problematic interpersonal relationships, a negative selfconcept, fluctuating moods, loss of control, negativity and loneliness are a part of this experience. It is hoped that knowledge of the world of the psoriasis sufferer will assist the help professions to understanding and empathize with the suffering and limitations that psoriasis brings.

  3. Skin manifestations of chronic kidney disease.

    PubMed

    Robles-Mendez, J C; Vazquez-Martinez, O; Ocampo-Candiani, J

    2015-10-01

    Skin manifestations associated with chronic kidney disease are very common. Most of these conditions present in the end stages and may affect the patient's quality of life. Knowledge of these entities can contribute to establishing an accurate diagnosis and prognosis. Severe renal pruritus is associated with increased mortality and a poor prognosis. Nail exploration can provide clues about albumin and urea levels. Nephrogenic systemic fibrosis is a preventable disease associated with gadolinium contrast. Comorbidities, such as diabetes mellitus and secondary hyperparathyroidism, can lead to acquired perforating dermatosis and calciphylaxis, respectively. Effective and innovative treatments are available for all of these conditions. Copyright © 2015 Elsevier España, S.L.U. and AEDV. All rights reserved.

  4. A Post-Developmental Genetic Screen for Zebrafish Models of Inherited Liver Disease

    PubMed Central

    Kim, Seok-Hyung; Wu, Shu-Yu; Baek, Jeong-In; Choi, Soo Young; Su, Yanhui; Flynn, Charles R.; Gamse, Joshua T.; Ess, Kevin C.; Hardiman, Gary; Lipschutz, Joshua H.; Abumrad, Naji N.; Rockey, Don C.

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease such as simple steatosis, nonalcoholic steatohepatitis (NASH), cirrhosis and fibrosis. However, the molecular pathogenesis and genetic variations causing NAFLD are poorly understood. The high prevalence and incidence of NAFLD suggests that genetic variations on a large number of genes might be involved in NAFLD. To identify genetic variants causing inherited liver disease, we used zebrafish as a model system for a large-scale mutant screen, and adopted a whole genome sequencing approach for rapid identification of mutated genes found in our screen. Here, we report on a forward genetic screen of ENU mutagenized zebrafish. From 250 F2 lines of ENU mutagenized zebrafish during post-developmental stages (5 to 8 days post fertilization), we identified 19 unique mutant zebrafish lines displaying visual evidence of hepatomegaly and/or steatosis with no developmental defects. Histological analysis of mutants revealed several specific phenotypes, including common steatosis, micro/macrovesicular steatosis, hepatomegaly, ballooning, and acute hepatocellular necrosis. This work has identified multiple post-developmental mutants and establishes zebrafish as a novel animal model for post-developmental inherited liver disease. PMID:25950913

  5. The ethical framework for performing research with rare inherited neurometabolic disease patients.

    PubMed

    Giannuzzi, Viviana; Devlieger, Hugo; Margari, Lucia; Odlind, Viveca Lena; Ragab, Lamis; Bellettato, Cinzia Maria; D'Avanzo, Francesca; Lampe, Christina; Cassis, Linda; Cortès-Saladelafont, Elisenda; Cazorla, Ángels Garcia; Barić, Ivo; Cvitanović-Šojat, Ljerka; Fumić, Ksenija; Dali, Christine I; Bartoloni, Franco; Bonifazi, Fedele; Scarpa, Maurizio; Ceci, Adriana

    2017-03-01

    The need for performing clinical trials to develop well-studied and appropriate medicines for inherited neurometabolic disease patients faces ethical concerns mainly raising from four aspects: the diseases are rare; include young and very young patients; the neurological impairment may compromise the capability to provide 'consent'; and the genetic nature of the disease leads to further ethical implications. This work is intended to identify the ethical provisions applicable to clinical research involving these patients and to evaluate if these cover the ethical issues. Three searches have been performed on the European regulatory/legal framework, the literature and European Union-funded projects. The European legal framework offers a number of ethical provisions ruling the clinical research on paediatric, rare, inherited diseases with neurological symptoms. In the literature, relevant publications deal with informed consent, newborn genetic screenings, gene therapy and rights/interests of research participants. Additional information raised from European projects on sharing patients' data from different countries, the need to fill the gap of the regulatory framework and to improve information to stakeholders and patients/families.

  6. Consanguinity and prevalence patterns of inherited disease in the UK Pakistani community.

    PubMed

    Corry, Peter C

    2014-01-01

    The aim of this paper is to describe the current knowledge about inherited diseases in UK children of Pakistani origin, who now number over 300,000, and to investigate disease associations with parental consanguinity. Published data on the overall prevalence of inherited diseases were reviewed in conjunction with published and unpublished information from the city of Bradford where there is a large resident Pakistani community. There is significant literature on infant mortality, congenital anomalies, disabilities and many clinical conditions, often drawing attention to ethnic variations and an increased disease prevalence in UK Pakistani children. A further analysis is frequently necessary to differentiate both between genetic and non-genetic causes, and Pakistani and non-Pakistani children, who collectively have been labelled as 'Asian' or 'South Asian'. The analysis suggests that much of the increased mortality and morbidity in UK Pakistani children is due to autosomal recessive conditions. Evidence suggests that this finding is associated with the custom of consanguineous marriage, but future studies might also explore the role of community endogamy. Prevalence data from the first and second post-migration generations could additionally be useful in informing health planning in Pakistan. © 2014 S. Karger AG, Basel.

  7. A post-developmental genetic screen for zebrafish models of inherited liver disease.

    PubMed

    Kim, Seok-Hyung; Wu, Shu-Yu; Baek, Jeong-In; Choi, Soo Young; Su, Yanhui; Flynn, Charles R; Gamse, Joshua T; Ess, Kevin C; Hardiman, Gary; Lipschutz, Joshua H; Abumrad, Naji N; Rockey, Don C

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease such as simple steatosis, nonalcoholic steatohepatitis (NASH), cirrhosis and fibrosis. However, the molecular pathogenesis and genetic variations causing NAFLD are poorly understood. The high prevalence and incidence of NAFLD suggests that genetic variations on a large number of genes might be involved in NAFLD. To identify genetic variants causing inherited liver disease, we used zebrafish as a model system for a large-scale mutant screen, and adopted a whole genome sequencing approach for rapid identification of mutated genes found in our screen. Here, we report on a forward genetic screen of ENU mutagenized zebrafish. From 250 F2 lines of ENU mutagenized zebrafish during post-developmental stages (5 to 8 days post fertilization), we identified 19 unique mutant zebrafish lines displaying visual evidence of hepatomegaly and/or steatosis with no developmental defects. Histological analysis of mutants revealed several specific phenotypes, including common steatosis, micro/macrovesicular steatosis, hepatomegaly, ballooning, and acute hepatocellular necrosis. This work has identified multiple post-developmental mutants and establishes zebrafish as a novel animal model for post-developmental inherited liver disease.

  8. Plan of Action for Inherited Cardiovascular Diseases: Synthesis of Recommendations and Action Algorithms.

    PubMed

    Barriales-Villa, Roberto; Gimeno-Blanes, Juan Ramón; Zorio-Grima, Esther; Ripoll-Vera, Tomás; Evangelista-Masip, Artur; Moya-Mitjans, Angel; Serratosa-Fernández, Luis; Albert-Brotons, Dimpna C; García-Pinilla, José Manuel; García-Pavía, Pablo

    2016-03-01

    The term inherited cardiovascular disease encompasses a group of cardiovascular diseases (cardiomyopathies, channelopathies, certain aortic diseases, and other syndromes) with a number of common characteristics: they have a genetic basis, a familial presentation, a heterogeneous clinical course, and, finally, can all be associated with sudden cardiac death. The present document summarizes some important concepts related to recent advances in sequencing techniques and understanding of the genetic bases of these diseases. We propose diagnostic algorithms and clinical practice recommendations and discuss controversial aspects of current clinical interest. We highlight the role of multidisciplinary referral units in the diagnosis and treatment of these conditions. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  9. Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes Afford New Opportunities in Inherited Cardiovascular Disease Modeling

    PubMed Central

    Bayzigitov, Daniel R.; Medvedev, Sergey P.; Dementyeva, Elena V.; Bayramova, Sevda A.; Pokushalov, Evgeny A.; Karaskov, Alexander M.; Zakian, Suren M.

    2016-01-01

    Fundamental studies of molecular and cellular mechanisms of cardiovascular disease pathogenesis are required to create more effective and safer methods of their therapy. The studies can be carried out only when model systems that fully recapitulate pathological phenotype seen in patients are used. Application of laboratory animals for cardiovascular disease modeling is limited because of physiological differences with humans. Since discovery of induced pluripotency generating induced pluripotent stem cells has become a breakthrough technology in human disease modeling. In this review, we discuss a progress that has been made in modeling inherited arrhythmias and cardiomyopathies, studying molecular mechanisms of the diseases, and searching for and testing drug compounds using patient-specific induced pluripotent stem cell-derived cardiomyocytes. PMID:27110425

  10. Skin Diseases Modeling using Combined Tissue Engineering and Microfluidic Technologies.

    PubMed

    Mohammadi, Mohammad Hossein; Heidary Araghi, Behnaz; Beydaghi, Vahid; Geraili, Armin; Moradi, Farshid; Jafari, Parya; Janmaleki, Mohsen; Valente, Karolina Papera; Akbari, Mohsen; Sanati-Nezhad, Amir

    2016-10-01

    In recent years, both tissue engineering and microfluidics have significantly contributed in engineering of in vitro skin substitutes to test the penetration of chemicals or to replace damaged skins. Organ-on-chip platforms have been recently inspired by the integration of microfluidics and biomaterials in order to develop physiologically relevant disease models. However, the application of organ-on-chip on the development of skin disease models is still limited and needs to be further developed. The impact of tissue engineering, biomaterials and microfluidic platforms on the development of skin grafts and biomimetic in vitro skin models is reviewed. The integration of tissue engineering and microfluidics for the development of biomimetic skin-on-chip platforms is further discussed, not only to improve the performance of present skin models, but also for the development of novel skin disease platforms for drug screening processes. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Multiparameter MR imaging in the 6-OPRI variant of inherited prion disease.

    PubMed

    De Vita, E; Ridgway, G R; Scahill, R I; Caine, D; Rudge, P; Yousry, T A; Mead, S; Collinge, J; Jäger, H R; Thornton, J S; Hyare, H

    2013-09-01

    Inherited prion diseases represent over 15% of human prion cases and are a frequent cause of early onset dementia. The purpose of this study was to define the distribution of changes in cerebral volumetric and microstructural parenchymal tissues in a specific inherited human prion disease mutation combining VBM with VBA of cerebral MTR and MD. VBM and VBA of cerebral MTR and MD were performed in 16 healthy control participants and 9 patients with the 6-OPRI mutation. An analysis of covariance consisting of diagnostic grouping with age and total intracranial volume as covariates was performed. On VBM, there was a significant reduction in gray matter volume in patients compared with control participants in the basal ganglia, perisylvian cortex, lingual gyrus, and precuneus. Significant MTR reduction and MD increases were more anatomically extensive than volume differences on VBM in the same cortical areas, but MTR and MD changes were not seen in the basal ganglia. Gray matter and WM changes were seen in brain areas associated with motor and cognitive functions known to be impaired in patients with the 6-OPRI mutation. There were some differences in the anatomic distribution of MTR-VBA and MD-VBA changes compared with VBM, likely to reflect regional variations in the type and degree of the respective pathophysiologic substrates. Combined analysis of complementary multiparameter MR imaging data furthers our understanding of prion disease pathophysiology.

  12. Polar body genome transfer for preventing the transmission of inherited mitochondrial diseases.

    PubMed

    Wang, Tian; Sha, Hongying; Ji, Dongmei; Zhang, Helen L; Chen, Dawei; Cao, Yunxia; Zhu, Jianhong

    2014-06-19

    Inherited mtDNA diseases transmit maternally and cause severe phenotypes. Currently, there is no effective therapy or genetic screens for these diseases; however, nuclear genome transfer between patients' and healthy eggs to replace mutant mtDNAs holds promises. Considering that a polar body contains few mitochondria and shares the same genomic material as an oocyte, we perform polar body transfer to prevent the transmission of mtDNA variants. We compare the effects of different types of germline genome transfer, including spindle-chromosome transfer, pronuclear transfer, and first and second polar body transfer, in mice. Reconstructed embryos support normal fertilization and produce live offspring. Importantly, genetic analysis confirms that the F1 generation from polar body transfer possesses minimal donor mtDNA carryover compared to the F1 generation from other procedures. Moreover, the mtDNA genotype remains stable in F2 progeny after polar body transfer. Our preclinical model demonstrates polar body transfer has great potential to prevent inherited mtDNA diseases.

  13. Disease-driven detection of differential inherited SNP modules from SNP network.

    PubMed

    Li, Chuanxing; Li, Yongsheng; Xu, Juan; Lv, Junying; Ma, Ye; Shao, Tingting; Gong, Binsheng; Tan, Renjie; Xiao, Yun; Li, Xia

    2011-12-10

    Detection of the synergetic effects between variants, such as single-nucleotide polymorphisms (SNPs), is crucial for understanding the genetic characters of complex diseases. Here, we proposed a two-step approach to detect differentially inherited SNP modules (synergetic SNP units) from a SNP network. First, SNP-SNP interactions are identified based on prior biological knowledge, such as their adjacency on the chromosome or degree of relatedness between the functional relationships of their genes. These interactions form SNP networks. Second, disease-risk SNP modules (or sub-networks) are prioritised by their differentially inherited properties in IBD (Identity by Descent) profiles of affected and unaffected sibpairs. The search process is driven by the disease information and follows the structure of a SNP network. Simulation studies have indicated that this approach achieves high accuracy and a low false-positive rate in the identification of known disease-susceptible SNPs. Applying this method to an alcoholism dataset, we found that flexible patterns of susceptible SNP combinations do play a role in complex diseases, and some known genes were detected through these risk SNP modules. One example is GRM7, a known alcoholism gene successfully detected by a SNP module comprised of two SNPs, but neither of the two SNPs was significantly associated with the disease in single-locus analysis. These identified genes are also enriched in some pathways associated with alcoholism, including the calcium signalling pathway, axon guidance and neuroactive ligand-receptor interaction. The integration of network biology and genetic analysis provides putative functional bridges between genetic variants and candidate genes or pathways, thereby providing new insight into the aetiology of complex diseases. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Identifying strains that contribute to complex diseases through the study of microbial inheritance

    PubMed Central

    Faith, Jeremiah J.; Colombel, Jean-Frédéric; Gordon, Jeffrey I.

    2015-01-01

    It has been 35 y since Carl Woese reported in PNAS how sequencing ribosomal RNA genes could be used to distinguish the three domains of life on Earth. During the past decade, 16S rDNA sequencing has enabled the now frequent enumeration of bacterial communities that populate the bodies of humans representing different ages, cultural traditions, and health states. A challenge going forward is to quantify the contributions of community members to wellness, disease risk, and disease pathogenesis. Here, we explore a theoretical framework for studies of the inheritance of bacterial strains and discuss the advantages and disadvantages of various study designs for assessing the contribution of strains to complex diseases. PMID:25576328

  15. Mycobacterial disease and impaired IFN-γ immunity in humans with inherited ISG15 deficiency.

    PubMed

    Bogunovic, Dusan; Byun, Minji; Durfee, Larissa A; Abhyankar, Avinash; Sanal, Ozden; Mansouri, Davood; Salem, Sandra; Radovanovic, Irena; Grant, Audrey V; Adimi, Parisa; Mansouri, Nahal; Okada, Satoshi; Bryant, Vanessa L; Kong, Xiao-Fei; Kreins, Alexandra; Velez, Marcela Moncada; Boisson, Bertrand; Khalilzadeh, Soheila; Ozcelik, Ugur; Darazam, Ilad Alavi; Schoggins, John W; Rice, Charles M; Al-Muhsen, Saleh; Behr, Marcel; Vogt, Guillaume; Puel, Anne; Bustamante, Jacinta; Gros, Philippe; Huibregtse, Jon M; Abel, Laurent; Boisson-Dupuis, Stéphanie; Casanova, Jean-Laurent

    2012-09-28

    ISG15 is an interferon (IFN)-α/β-inducible, ubiquitin-like intracellular protein. Its conjugation to various proteins (ISGylation) contributes to antiviral immunity in mice. Here, we describe human patients with inherited ISG15 deficiency and mycobacterial, but not viral, diseases. The lack of intracellular ISG15 production and protein ISGylation was not associated with cellular susceptibility to any viruses that we tested, consistent with the lack of viral diseases in these patients. By contrast, the lack of mycobacterium-induced ISG15 secretion by leukocytes-granulocyte, in particular-reduced the production of IFN-γ by lymphocytes, including natural killer cells, probably accounting for the enhanced susceptibility to mycobacterial disease. This experiment of nature shows that human ISGylation is largely redundant for antiviral immunity, but that ISG15 plays an essential role as an IFN-γ-inducing secreted molecule for optimal antimycobacterial immunity.

  16. Mycobacterial disease and impaired IFN-γ immunity in humans with inherited ISG15 deficiency

    PubMed Central

    Bogunovic, Dusan; Byun, Minji; Durfee, Larissa A.; Abhyankar, Avinash; Sanal, Ozden; Mansouri, Davood; Salem, Sandra; Radovanovic, Irena; Grant, Audrey V.; Adimi, Parisa; Mansouri, Nahal; Okada, Satoshi; Bryant, Vanessa L.; Kong, Xiao-Fei; Kreins, Alexandra; Velez, Marcela Moncada; Boisson, Bertrand; Khalilzadeh, Soheila; Ozcelik, Ugur; Darazam, Ilad Alavi; Schoggins, John W.; Rice, Charles M.; Al-Muhsen, Saleh; Behr, Marcel; Vogt, Guillaume; Puel, Anne; Bustamante, Jacinta; Gros, Philippe; Huibregtse, Jon M.; Abel, Laurent; Boisson-Dupuis, Stéphanie; Casanova, Jean-Laurent

    2012-01-01

    ISG15 is an interferon (IFN)-α/β-inducible, ubiquitin-like intracellular protein. Its conjugation to various proteins (ISGylation) contributes to antiviral immunity in mice. We describe human patients with inherited ISG15 deficiency and mycobacterial, but not viral diseases. The lack of intracellular ISG15 production and protein ISGylation was not associated with cellular susceptibility to any viruses tested, consistent with the lack of viral diseases in these patients. By contrast, the lack of mycobacterium-induced ISG15 secretion by leukocytes — granulocytes in particular — reduced the production of IFN-γ by lymphocytes, including natural killer cells, probably accounting for the enhanced susceptibility to mycobacterial disease. This experiment of Nature shows that human ISGylation is largely redundant for antiviral immunity, but that ISG15 plays an essential role as an IFN-γ-inducing secreted molecule for optimal antimycobacterial immunity. PMID:22859821

  17. [Swinepox--skin disease with sporadic occurrence].

    PubMed

    Moorkamp, L; Beineke, A; Kaim, U; Diesterbeck, U; Urstadt, S; Czerny, C P; Rüberg, H; Grosse Beilage, E

    2008-04-01

    Swinepox virus infection results in an acute, mild or subclinical course and is characterised by typical poxvirus skin lesions in affected pigs. Additionally, sporadic vertical swinepox virus transmission leads to congenital generalised infection and subsequent abortion or stillbirth. The present report describes the occurrence of epidermal efflorescences in two piglets after intrauterine natural suipoxvirus infection. No clinical abnormalities of the gilt and littermates as well as in other pigs from this herd were present. One of the affected piglets was stillborn and submitted for necropsy, the other animal was alive at birth, but died 3 days later. Histologically, a proliferative to ulcerative dermatitis with epithelial ballooning degeneration and characteristic intracytoplasmatic inclusion bodies was observed. The pathomorphological and histopathological suspected diagnosis of a poxvirus infection was confirmed by electron microscopy. Furthermore, the agent was identified as suipoxvirus by polymerase chain reaction. As demonstrated here, obvious skin lesions in suipoxvirus infection leads to a suspected diagnosis in newborn piglets on macroscopic examination. However, further post mortem examinations, including electron microscopy as well as molecular techniques are essential for the identification of the aetiology and the exclusion of differential diagnoses. Because the disease only affected two pigs there was only a small economic loss. A valid diagnostic plays an important role in advising farmers and for herd health monitoring.

  18. Global burden of skin disease in the elderly: a grand challenge to skin health.

    PubMed

    Hay, R J; Fuller, L C

    2015-12-01

    Skin diseases, as estimated in the global burden of disease study 2010, are a significant health problem in all global regions and many of those analyzed in this study show an increasing burden over recent years, extending into old age. Some of the conditions which have the highest impact on the elderly include non-melanoma skin cancer and skin ulceration, but bacterial skin infection, fungal disease or pruritus are all significant problems. With predicted changes in demography and a higher proportion of individuals above the age of 80 in the coming years concentrating new resources on gathering better data and devising preventative, therapeutic and palliative strategies is a priority.

  19. Epidemiology of Skin Disease in an Automobile Factory*

    PubMed Central

    Newhouse, Muriel L.

    1964-01-01

    A survey was made of a random sample of workers from the machine shops, assembly lines, and stock and store departments of an automobile factory. Among the 1,223 men seen, representing 97% of the sample, the prevalence of non-infective skin diseases was 14·5%. Skin diseases were classified into four groups: `dermatitis' and `folliculitis' of occupational origin, endogenous `eczemas', and miscellaneous skin diseases. Slightly more than half of all the skin diseases seen were considered to be occupational in origin. In this population the prevalence of skin disease was more than four times that based on patients attending the factory medical department. An unsuspected cause of allergic dermatitis was found on the assembly lines, where the incidence of dermatitis was significantly higher than among the non-production workers. The prevalence of folliculitis was significantly higher among production than non-production workers. There was no significant difference in the prevalence of `eczema' or the miscellaneous skin diseases in the various occupational groups. Among European workers fair men were more prone to skin disease than darker men. In another factory, a West Indian and Asiatic group of workers had a significantly lower prevalence of skin diseases than a group of Europeans doing similar work. Folliculitis was more prevalent among the younger workers and those recently employed in the factory; there was no obvious association between age and length of service and the occurrence of other types of skin disease. PMID:14249898

  20. Skin diseases in geriatric patients: our experience from a public skin outpatient clinic in Siena.

    PubMed

    Rubegni, P; Poggiali, S; Nami, N; Rubegni, M; Fimiani, M

    2012-12-01

    With the progressive aging of the Italian population, geriatric health care has become a major issue for health authorities. However, little data is available regarding geriatric skin diseases. In order to provide rapid access to specialist help, in 2003 we created a dermatology clinic dedicated only to geriatric patients age 65 and older. To determine the characteristic pattern and the prevalence of various skin disorders among the geriatric patients seen at the clinic, we performed a retrospective and descriptive study of all skin diseases in patients seen in our office from January 2003 to December 2009. We evaluated: age, proportion and gender for all skin disease categories. A total of 2100 geriatric patients were examined. The male to female ratio was 1.4 to 1. The most common disorder was pruritus "sine materia" (18.9%) followed by benign tumors (13.5%); 9.1% of our patients presented with actinic keratoses and 13.2% with malignant tumors. As reported by others, the quality of life in patients with skin cancer was better than patients with rashes as skin cancer patients tended to wait longer before seeking specialist care. To improve the assessment of skin diseases, we often worked closely with The prevalence of skin diseases in our patients emphasized the importance of educating the elderly about sun protection, the early detection of skin cancer, the use of emollients and proper skin care in general.

  1. National Athletic Trainers' Association Position Statement: Skin Diseases

    PubMed Central

    Zinder, Steven M.; Basler, Rodney S. W.; Foley, Jack; Scarlata, Chris; Vasily, David B.

    2010-01-01

    Abstract Objective: To present recommendations for the prevention, education, and management of skin infections in athletes. Background: Trauma, environmental factors, and infectious agents act together to continually attack the integrity of the skin. Close quarters combined with general poor hygiene practices make athletes particularly vulnerable to contracting skin diseases. An understanding of basic prophylactic measures, clinical features, and swift management of common skin diseases is essential for certified athletic trainers to aid in preventing the spread of infectious agents. Recommendations: These guidelines are intended to provide relevant information on skin infections and to give specific recommendations for certified athletic trainers and others participating in athletic health care. PMID:20617918

  2. Inherited disorders of desmosomes.

    PubMed

    McGrath, John A

    2005-11-01

    Desmosomes are highly organized intercellular junctions that provide mechanical integrity to tissues by anchoring intermediate filaments to sites of strong adhesion. These cell-cell adhesion junctions are found in skin, heart, lymph nodes and meninges. Over the last 8 years, several naturally occurring human gene mutations in structural components of desmosomes have been reported. These comprise autosomal dominant or recessive mutations in plakophilin 1, plakophilin 2, desmoplakin, plakoglobin, desmoglein 1, desmoglein 4 and corneodesmosin. These discoveries have often highlighted novel or unusual phenotypes, including abnormal skin fragility and differentiation, and developmental anomalies of various ectodermal appendages, especially hair. Some desmosomal gene mutations may also result in cardiac disease, notably cardiomyopathy. This article describes the spectrum of clinical features that may be found in the inherited disorders of desmosomes and highlights the key functions of several of the desmosomal proteins in tissue adhesion and cell biology.

  3. GJB2 Gene Mutations in Syndromic Skin Diseases with Sensorineural Hearing Loss.

    PubMed Central

    Iossa, Sandra; Marciano, Elio; Franzé, Annamaria

    2011-01-01

    The GJB2 gene is located on chromosome 13q12 and it encodes the connexin 26, a transmembrane protein involved in cell-cell attachment of almost all tissues. GJB2 mutations cause autosomal recessive (DFNB1) and sometimes dominant (DFNA3) non-syndromic sensorineural hearing loss. Moreover, it has been demonstrated that connexins are involved in regulation of growth and differentiation of epidermis and, in fact, GJB2 mutations have also been identified in syndromic disorders with hearing loss associated with various skin disease phenotypes. GJB2 mutations associated with skin disease are, in general, transmitted with a dominant inheritance pattern. Nonsyndromic deafness is caused prevalently by a loss-of-function, while literature evidences suggest for syndromic deafness a mechanism based on gain-of-function. The spectrum of skin manifestations associated with some mutations seems to have a very high phenotypic variability. Why some mutations can lead to widely varying cutaneous manifestations is poorly understood and in particular, the reason why the skin disease-deafness phenotypes differ from each other thus remains unclear. This review provides an overview of recent findings concerning pathogenesis of syndromic deafness imputable to GJB2 mutations with an emphasis on relevant clinical genotype-phenotype correlations. After describing connexin 26 fundamental characteristics, the most relevant and recent information about its known mutations involved in the syndromic forms causing hearing loss and skin problems are summarized. The possible effects of the mutations on channel expression and function are discussed. PMID:22547955

  4. GJB2 Gene Mutations in Syndromic Skin Diseases with Sensorineural Hearing Loss.

    PubMed

    Iossa, Sandra; Marciano, Elio; Franzé, Annamaria

    2011-11-01

    The GJB2 gene is located on chromosome 13q12 and it encodes the connexin 26, a transmembrane protein involved in cell-cell attachment of almost all tissues. GJB2 mutations cause autosomal recessive (DFNB1) and sometimes dominant (DFNA3) non-syndromic sensorineural hearing loss. Moreover, it has been demonstrated that connexins are involved in regulation of growth and differentiation of epidermis and, in fact, GJB2 mutations have also been identified in syndromic disorders with hearing loss associated with various skin disease phenotypes. GJB2 mutations associated with skin disease are, in general, transmitted with a dominant inheritance pattern. Nonsyndromic deafness is caused prevalently by a loss-of-function, while literature evidences suggest for syndromic deafness a mechanism based on gain-of-function. The spectrum of skin manifestations associated with some mutations seems to have a very high phenotypic variability. Why some mutations can lead to widely varying cutaneous manifestations is poorly understood and in particular, the reason why the skin disease-deafness phenotypes differ from each other thus remains unclear. This review provides an overview of recent findings concerning pathogenesis of syndromic deafness imputable to GJB2 mutations with an emphasis on relevant clinical genotype-phenotype correlations. After describing connexin 26 fundamental characteristics, the most relevant and recent information about its known mutations involved in the syndromic forms causing hearing loss and skin problems are summarized. The possible effects of the mutations on channel expression and function are discussed.

  5. [Dermatology of neonatal period--skin diseases undemanding of treatment].

    PubMed

    Brzeziński, Piotr

    2009-01-01

    The skin of newborns differs from adult skin in many aspects. It is in the developing age which makes it difficult to fulfill it's correct function. There are diseases which appear in the first month of the infants life and require treatment. Mild local therapy may be administered or extensive moisturization of skin changes. Common mild and easy passing skin syndromes are: vernix caseosa, cutis marmarotta, hyperplasia sebacea, milia, acne neonatorum, erythema toxicum neonatorum, transient neonatal pustular melanosis, and neonatal dermalia pustulosis.

  6. Management of the risks for inherited disease in donor-conceived offspring.

    PubMed

    Isley, Lauren; Falk, Rena E; Shamonki, Jaime; Sims, Charles A; Callum, Pamela

    2016-11-01

    To illustrate the burden of inherited disease on donor-conceived offspring based on mode of inheritance and to provide guidance on methods of risk reduction. An 8.5-year retrospective review of outcome reports and donor management to summarize medical risks to donor-conceived offspring that presented after the sperm donors were qualified for participation in the donor program. Not applicable. None. None. Description of our experience with newly identified medical risks in donor-conceived offspring as well as how this information was ascertained and managed. More than half of the indications to restrict donor specimen distribution were due to multifactorial disorders. Approximately one third of the restrictions involved autosomal recessive disorders. The remainder of the restrictions were due to the other indications, including autosomal dominant disorders. The risks for multifactorial disorders or undiagnosed autosomal dominant disease cannot be significantly reduced or eliminated with routine donor screening procedures. Ongoing risk assessment is essential to identify new genetic risks for autosomal dominant and multifactorial disorders. These assessments require an investment of resources and genetics professionals in the long-term management of changing health information as well as collaboration among gamete facilities, recipients, donors, and their health care providers. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  7. Inherited Disease Genetics Improves the Identification of Cancer-Associated Genes

    PubMed Central

    2016-01-01

    The identification of biologically significant variants in cancer genomes is critical to therapeutic discovery, but it is limited by the statistical power needed to discern driver from passenger. Independent biological data can be used to filter cancer exomes and increase statistical power. Large genetic databases for inherited diseases are uniquely suited to this task because they contain specific amino acid alterations with known pathogenicity and molecular mechanisms. However, no rigorous method to overlay this information onto the cancer exome exists. Here, we present a computational methodology that overlays any variant database onto the somatic mutations in all cancer exomes. We validate the computation experimentally and identify novel associations in a re-analysis of 7362 cancer exomes. This analysis identified activating SOS1 mutations associated with Noonan syndrome as significantly altered in melanoma and the first kinase-activating mutations in ACVR1 associated with adult tumors. Beyond a filter, significant variants found in both rare cancers and rare inherited diseases increase the unmet medical need for therapeutics that target these variants and may bootstrap drug discovery efforts in orphan indications. PMID:27304678

  8. [Skin diseases among refugees and immigrants. Four exotic case reports].

    PubMed

    Poulsen, A G; Petersen, C S; Weismann, K

    2000-11-13

    The influx of immigrants from outside the Western world, has led to a wider spectrum of dermatological diseases seen by doctors in Denmark. We present four case histories, in which the disease was brought to Denmark from the patient's land of origin. Tropical diseases may present as a skin disease as such, or a generalised disease with skin manifestations, the commonest signs being ulcers, papules, exanthema, changes in pigmentation, and itching.

  9. Genetic correction of stem cells in the treatment of inherited diseases and focus on xeroderma pigmentosum.

    PubMed

    Rouanet, Sophie; Warrick, Emilie; Gache, Yannick; Scarzello, Sabine; Avril, Marie-Françoise; Bernerd, Françoise; Magnaldo, Thierry

    2013-10-09

    Somatic stem cells ensure tissue renewal along life and healing of injuries. Their safe isolation, genetic manipulation ex vivo and reinfusion in patients suffering from life threatening immune deficiencies (for example, severe combined immunodeficiency (SCID)) have demonstrated the efficacy of ex vivo gene therapy. Similarly, adult epidermal stem cells have the capacity to renew epidermis, the fully differentiated, protective envelope of our body. Stable skin replacement of severely burned patients have proven life saving. Xeroderma pigmentosum (XP) is a devastating disease due to severe defects in the repair of mutagenic DNA lesions introduced upon exposure to solar radiations. Most patients die from the consequences of budding hundreds of skin cancers in the absence of photoprotection. We have developed a safe procedure of genetic correction of epidermal stem cells isolated from XP patients. Preclinical and safety assessments indicate successful correction of XP epidermal stem cells in the long term and their capacity to regenerate a normal skin with full capacities of DNA repair.

  10. The skin microbiome: Associations between altered microbial communities and disease.

    PubMed

    Weyrich, Laura S; Dixit, Shreya; Farrer, Andrew G; Cooper, Alan J; Cooper, Alan J

    2015-11-01

    A single square centimetre of the human skin can contain up to one billion microorganisms. These diverse communities of bacteria, fungi, mites and viruses can provide protection against disease, but can also exacerbate skin lesions, promote disease and delay wound healing. This review addresses the current knowledge surrounding the healthy skin microbiome and examines how different alterations to the skin microbial communities can contribute to disease. Current methodologies are considered, changes in microbial diversity and colonisation by specific microorganisms are discussed in the context of atopic dermatitis, psoriasis, acne vulgaris and chronic wounds. The recent impact of modern Westernised lifestyles on the human skin microbiome is also examined, as well as the potential benefits and pitfalls of novel therapeutic strategies. Further analysis of the human skin microbiome, and its interactions with the host immune system and other commensal microorganisms, will undoubtedly elucidate molecular mechanisms for disease and reveal gateways for novel therapeutic treatment strategies.

  11. Flood-related skin diseases: a literature review.

    PubMed

    Tempark, Therdpong; Lueangarun, Saoraya; Chatproedprai, Susheera; Wananukul, Siriwan

    2013-10-01

    Flood is one of the most common natural disasters, which commonly occurs in all parts of the world. The effects of the disasters considerably become enormous problems to overall public health systems. Flood-related skin diseases are a portion of these consequences presenting with cutaneous manifestations and/or signs of systemic illnesses. We conducted a systematic literature review of research publications relating to flooding and skin diseases. The purpose of this review was to provide dermatologists as well as general practitioners with comprehensive conditions of flood-related skin diseases and suggested treatments. Moreover, we categorized these flood-related diseases into four groups comprising inflammatory skin diseases, skin infections, traumatic skin diseases, and other miscellaneous skin diseases in a bid to implement early interventions and educate, prevent, and efficaciously handle those skin diseases under such a catastrophic situation so that better treatment outcomes and prevention of further complications could be ultimately achieved and accomplished. © 2013 The International Society of Dermatology.

  12. Inherited heart rhythm disease: negotiating the minefield for the practicing cardiologist.

    PubMed

    Krahn, Andrew D; Sanatani, Shubhayan; Gardner, Martin J; Arbour, Laura

    2013-01-01

    Inherited heart rhythm disorders are uncommon conditions that have emerged as a challenge to recognize and treat for the practicing clinician. The common electrical forms are long QT and Brugada syndrome, catecholaminergic ventricular tachycardia, and early repolarization syndrome. Inherited cardiomyopathies, including hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy, and left ventricular noncompaction can also cause serious cardiac rhythm disturbances and sudden death. We review the key historic and diagnostic considerations to provide guidance for day-to-day management, and the resources accessible to health care professionals and patients including a Canadian network of expert clinics. This allows for the initiation of disease-specific treatments and enables family screening. These heterogenous conditions can be challenging to diagnose with equally difficult management decisions. However, some common measures can be applied that will assist health care providers and reduce risk for patients. Condition-specific treatment strategies that are deployed in regional clinics are discussed, including the role of the referring health care team.

  13. [The notion of occupational skin disease. Medical and legal aspects].

    PubMed

    Elsner, P; Schliemann, S

    2015-03-01

    The different definitions of skin disease in medicine and in law are frequently confusing for dermatologists. While a skin disease may be defined medically referring to the definition of health by the WHO as a pathological condition of the skin leading to a disruption of the physical, mental and social well-being of the individual, legal definitions vary depending on the field of insurance law that is referred to. In the law of private health insurance, a skin disease is defined as an anomalous condition of the skin requiring medical treatment that exists independently of the subjective judgement of the insured person and needs to be objectively confirmed by a medical evaluation. In contrast, in the law of the social health insurance, the Federal Court of Social Justice defines disease as irregular physical or mental condition, deviating from the perception of a healthy human being that requires medical treatment or leads to inability to work. Substantial bodily disfigurement may be regarded as an irregular physical condition. In the law of the statutory accident insurance, occupational skin diseases are defined under clause 5101 of the occupational disease regulation as serious or repeatedly relapsing skin diseases that have forced a person to refrain from any work activities causal for the development, the aggravation or the recurrence of the disease. The Federal Court of Social Justice interprets the term "skin disease" from the protective purpose of the law, i.e. the protection against the economic and health consequences of the exposure to harmful agents and a thereby forced change of profession. This broad interpretation of the term "skin disease" leads to the recognition of diseases of the conjunctiva of the eye or diseases of the blood vessels of the skin due to cold damage as skin diseases according to clause 5101. For the correct treatment and possibly notification of occupational skin diseases in collaboration with various insurance carriers

  14. [Glycoproteins, inherited diseases of platelets, and the role of platelets in wound healing].

    PubMed

    Nurden, Alan T; Nurden, Paquita

    2013-02-01

    Recognition that platelets have a glycocalyx rich in membrane glycoproteins prompted the discovery in France that inherited bleeding syndromes due to defects of platelet adhesion and aggregation were caused by deficiencies in major receptors at the platelet surface. Identification of the alpha IIb beta3 integrin prompted the development of powerful anti-thrombotic drugs that have gained worldwide use. Since these discoveries, the genetic causes of many other defects of platelet function and production have been elucidated, with the identification of an ADP receptor, P2 Y12, another widespread target for anti-thrombotic drugs. Discovery of the molecular basis of a rare disease of storage of biologically active proteins in platelet alpha-granules has been accompanied by the recognition of the roles of platelets in inflammation, the innate immune system and tissue repair, opening new avenues for therapeutic advances.

  15. The usual suspects in sudden cardiac death of the young: a focus on inherited arrhythmogenic diseases.

    PubMed

    Mazzanti, Andrea; O'Rourke, Sean; Ng, Kevin; Miceli, Carlotta; Borio, Gianluca; Curcio, Antonio; Esposito, Francesca; Napolitano, Carlo; Priori, Silvia G

    2014-04-01

    Up to 14,500 young individuals die suddenly every year in Europe of cardiac pathologies. The majority of these tragic events are related to a group of genetic defects that predispose the development of malignant arrhythmias (inherited arrhythmogenic diseases [IADs]). IADs include both cardiomyopathies (hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy) and channelopathies (long QT syndrome, short QT syndrome, Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia). Every time an IAD is identified in a patient, other individuals in his/her family may be at risk of cardiac events. However; if a timely diagnosis is made, simple preventative measures may be applied. Genetic studies play a pivotal role in the diagnosis of IADs and may help in the management of patients and their relatives.

  16. Genetic testing for inherited ocular disease: delivering on the promise at last?

    PubMed

    Gillespie, Rachel L; Hall, Georgina; Black, Graeme C

    2014-01-01

    Genetic testing is of increasing clinical utility for diagnosing inherited eye disease. Clarifying a clinical diagnosis is important for accurate estimation of prognosis, facilitating genetic counselling and management of families, and in the future will direct gene-specific therapeutic strategies. Often, precise diagnosis of genetic ophthalmic conditions is complicated by genetic heterogeneity, a difficulty that the so-called 'next-generation sequencing' technologies promise to overcome. Despite considerable counselling and ethical complexities, next-generation sequencing offers to revolutionize clinical practice. This will necessitate considerable adjustment to standard practice but has the power to deliver a personalized approach to genomic medicine for many more patients and enhance the potential for preventing vision loss. © 2013 Royal Australian and New Zealand College of Ophthalmologists.

  17. Inherited retinal diseases in dogs: advances in gene/mutation discovery

    PubMed Central

    Miyadera, Keiko

    2015-01-01

    1. Inherited retinal diseases (RDs) are vision-threatening conditions affecting humans as well as many domestic animals. Through many years of clinical studies of the domestic dog population, a wide array of RDs has been phenotypically characterized. Extensive effort to map the causative gene and to identify the underlying mutation followed. Through candidate gene, linkage analysis, genome-wide association studies, and more recently, by means of next-generation sequencing, as many as 31 mutations in 24 genes have been identified as the underlying cause for canine RDs. Most of these genes have been associated with human RDs providing opportunities to study their roles in the disease pathogenesis and in normal visual function. The canine model has also contributed in developing new treatments such as gene therapy which has been clinically applied to human patients. Meanwhile, with increasing knowledge of the molecular architecture of RDs in different subpopulations of dogs, the conventional understanding of RDs as a simple monogenic disease is beginning to change. Emerging evidence of modifiers that alters the disease outcome is complicating the interpretation of DNA tests. In this review, advances in the gene/mutation discovery approaches and the emerging genetic complexity of canine RDs are discussed. PMID:26120276

  18. APOE AND ALZHEIMER DISEASE: A MAJOR GENE WITH SEMI-DOMINANT INHERITANCE

    PubMed Central

    Genin, Emmanuelle; Hannequin, Didier; Wallon, David; Sleegers, Kristel; Hiltunen, Mikko; Combarros, Onofre; Bullido, Maria J; Engelborghs, Sebastiaan; De Deyn, Peter; Berr, Claudine; Pasquier, Florence; Dubois, Bruno; Tognoni, Gloria; Fiévet, Nathalie; Brouwers, Nathalie; Bettens, Karolien; Arosio, Beatrice; Coto, Eliecer; Zompo, Maria Del; Mateo, Ignacio; Epelbaum, Jacques; Frank-Garcia, Ana; Helisalmi, Seppo; Porcellini, Elisa; Pilotto, Alberto; Forti, Paola; Ferri, Raffaele; Scarpini, Elio; Siciliano, Gabriele; Solfrizzi, Vincenzo; Sorbi, Sandro; Spalletta, Gianfranco; Valdivieso, Fernando; Vepsäläinen, Saila; Alvarez, Victoria; Bosco, Paolo; Mancuso, Michelangelo; Panza, Francesco; Nacmias, Benedetta; Bossù, Paola; Hanon, Olivier; Piccardi, Paola; Annoni, Giorgio; Seripa, Davide; Galimberti, Daniela; Licastro, Federico; Soininen, Hilkka; Dartigues, Jean-François; Kamboh, M Ilyas; Van Broeckhoven, Christine; Lambert, Jean Charles; Amouyel, Philippe; Campion, Dominique

    2011-01-01

    Apolipoprotein E (APOE) dependent lifetime risks (LTRs) for Alzheimer Disease (AD) are currently not accurately known and odds ratios (ORs) alone are insufficient to assess these risks. We calculated AD lifetime risk in 7,351 cases and 10,132 controls from Caucasian ancestry using Rochester (USA) incidence data. At the age of 85 the LTR of AD without reference to APOE genotype was 11% in males and 14% in females. At the same age, this risk ranged from 51% for APOE44 male carriers to 60% for APOE44 female carriers, and from 23% for APOE34 male carriers to 30% for APOE34 female carriers, consistent with semi-dominant inheritance of a moderately penetrant gene. Using PAQUID (France) incidence data, estimates were globally similar except that at age 85 the LTRs reached 68% and 35 % for APOE 44 and APOE 34 female carriers, respectively. These risks are more similar to those of major genes in Mendelian diseases, such as BRCA1 in breast cancer, than those of low-risk common alleles identified by recent GWAS in complex diseases. In addition, stratification of our data by age- groups clearly demonstrates that APOE4 is a risk factor not only for late- onset but for early- onset AD as well. Together, these results urge a reappraisal of the impact of APOE in Alzheimer disease. PMID:21556001

  19. Antisense Mediated Splicing Modulation For Inherited Metabolic Diseases: Challenges for Delivery

    PubMed Central

    Pérez, Belen; Vilageliu, Lluisa; Grinberg, Daniel

    2014-01-01

    In the past few years, research in targeted mutation therapies has experienced significant advances, especially in the field of rare diseases. In particular, the efficacy of antisense therapy for suppression of normal, pathogenic, or cryptic splice sites has been demonstrated in cellular and animal models and has already reached the clinical trials phase for Duchenne muscular dystrophy. In different inherited metabolic diseases, splice switching oligonucleotides (SSOs) have been used with success in patients' cells to force pseudoexon skipping or to block cryptic splice sites, in both cases recovering normal transcript and protein and correcting the enzyme deficiency. However, future in vivo studies require individual approaches for delivery depending on the gene defect involved, given the different patterns of tissue and organ expression. Herein we review the state of the art of antisense therapy targeting RNA splicing in metabolic diseases, grouped according to their expression patterns—multisystemic, hepatic, or in central nervous system (CNS)—and summarize the recent progress achieved in the field of in vivo delivery of oligonucleotides to each organ or system. Successful body-wide distribution of SSOs and preferential distribution in the liver after systemic administration have been reported in murine models for different diseases, while for CNS limited data are available, although promising results with intratechal injections have been achieved. PMID:24506780

  20. Inherited retinal diseases in dogs: advances in gene/mutation discovery.

    PubMed

    Miyadera, Keiko

    1. Inherited retinal diseases (RDs) are vision-threatening conditions affecting humans as well as many domestic animals. Through many years of clinical studies of the domestic dog population, a wide array of RDs has been phenotypically characterized. Extensive effort to map the causative gene and to identify the underlying mutation followed. Through candidate gene, linkage analysis, genome-wide association studies, and more recently, by means of next-generation sequencing, as many as 31 mutations in 24 genes have been identified as the underlying cause for canine RDs. Most of these genes have been associated with human RDs providing opportunities to study their roles in the disease pathogenesis and in normal visual function. The canine model has also contributed in developing new treatments such as gene therapy which has been clinically applied to human patients. Meanwhile, with increasing knowledge of the molecular architecture of RDs in different subpopulations of dogs, the conventional understanding of RDs as a simple monogenic disease is beginning to change. Emerging evidence of modifiers that alters the disease outcome is complicating the interpretation of DNA tests. In this review, advances in the gene/mutation discovery approaches and the emerging genetic complexity of canine RDs are discussed.

  1. Inherited glaucoma in DBA/2J mice: pertinent disease features for studying the neurodegeneration.

    PubMed

    Libby, Richard T; Anderson, Michael G; Pang, Iok-Hou; Robinson, Zachary H; Savinova, Olga V; Cosma, I Mihai; Snow, Amy; Wilson, Lawriston A; Smith, Richard S; Clark, Abbot F; John, Simon W M

    2005-01-01

    The glaucomas are neurodegenerative diseases involving death of retinal ganglion cells and optic nerve head excavation. A major risk factor for this neurodegeneration is a harmfully elevated intraocular pressure (IOP). Human glaucomas are typically complex, progressive diseases that are prevalent in the elderly. Family history and genetic factors are clearly important in human glaucoma. Mouse studies have proven helpful for investigating the genetic and mechanistic basis of complex diseases. We previously reported inherited, age-related progressive glaucoma in DBA/2J mice. Here, we report our updated findings from studying the disease in a large number of DBA/2J mice. The period when mice have elevated IOP extends from 6 months to 16 months, with 8-9 months representing an important transition to high IOP for many mice. Optic nerve degeneration follows IOP elevation, with the majority of optic nerves being severely damaged by 12 months of age. This information should help with the design of experiments, and we present the data in a manner that will be useful for future studies of retinal ganglion cell degeneration and optic neuropathy.

  2. [Role of IL-22 in the pathogenesis of skin diseases].

    PubMed

    Fujita, Hideki

    2012-01-01

    IL-22 is an IL-10 family cytokine that acts mainly on epithelial cells. It is produced by immune cell subsets, including CD4⁺ T cells, natural killer cells, and natural killer T cells. In the skin, IL-22 mediates keratinocyte proliferation and epidermal hyperplasia, inhibits terminal differentiation of keratinocytes, and induces the production of antimicrobial proteins. Although IL-22 production was initially linked with IL-17 expression in Th17 cells, IL-22 production can also occur in an apparently unique subset of cells that lacks the production of IL-17 and IFN-γ (Th22). Interestingly, Th22 cells express skin homing chemokine receptors CCR4 and CCR10. Indeed, Th22 cells reside in the normal skin and are shown to be enriched in the lesional skin of inflammatory skin diseases, indicating the importance of IL-22 in skin homeostasis and pathogenesis of skin diseases. Although psoriasis is the first example of an organ-specific immune disorder for which the role of IL-22 has been comprehensively studied, a growing body of evidence indicates that this cytokine also plays a critical role in the pathogenesis of atopic dermatitis. In this review, we discuss the role of IL-22 in the pathogenesis of skin diseases, particularly focusing on psoriasis and atopic dermatitis. Targeting IL-22 may have promise as a potential therapeutic for various skin diseases.

  3. Functions of the skin microbiota in health and disease

    PubMed Central

    Sanford, James A.; Gallo, Richard L.

    2014-01-01

    The skin, the human body’s largest organ, is home to a diverse and complex variety of innate and adaptive immune functions. Despite this potent immune system present at the cutaneous barrier, the skin encourages colonization by microorganisms. Characterization these microbial communities has enhanced our knowledge of the ecology of organisms present in normal skin; furthermore, studies have begun to bring to light the intimate relationships shared between host and resident microbes. In particular, it is apparent that just as host immunological factors and behaviors shape the composition of these communities, microbes present on the skin greatly impact the functions of human immunity. Thus, today the skin immune system should be considered a collective mixture of elements from the host and microbes acting in a mutualistic relationship. In this article we will review recent findings of the interactions of skin microbial communities with host immunity, and discuss the role that dysbiosis of these communities plays in diseases of the skin. PMID:24268438

  4. Inherited mitochondrial disorders.

    PubMed

    Finsterer, Josef

    2012-01-01

    Though inherited mitochondrial disorders (MIDs) are most well known for their syndromic forms, for which widely known acronyms (MELAS, MERRF, NARP, LHON etc.) have been coined, the vast majority of inherited MIDs presents in a non-syndromic form. Since MIDs are most frequently multisystem disorders already at onset or during the disease course, a MID should be suspected if there is a combination of neurological and non-neurological abnormalities. Neurological abnormalities occurring as a part of a MID include stroke-like episodes, epilepsy, migraine-like headache, movement disorders, cerebellar ataxia, visual impairment, encephalopathy, cognitive impairment, dementia, psychosis, hypopituitarism, aneurysms, or peripheral nervous system disease, such as myopathy, neuropathy, or neuronopathy. Non-neurological manifestations concern the ears, the endocrine organs, the heart, the gastrointestinal tract, the kidneys, the bone marrow, and the skin. Whenever there is an unexplained combination of neurological and non-neurological disease in a patient or kindred, a MID should be suspected and appropriate diagnostic measures initiated. Genetic testing should be guided by the phenotype, the biopsy findings, and the biochemical results.

  5. Regional distribution of ten common skin diseases in dogs.

    PubMed

    Sischo, W M; Ihrke, P J; Franti, C E

    1989-09-15

    We investigated the regional distributions of the most commonly diagnosed skin diseases in dogs from 17 North American veterinary teaching hospitals. Between January 1983 and December 1983, 11,456 diagnoses of skin disease were made. The 10 most common diagnoses were fleabite allergic dermatitis, skin cancer, pyoderma, seborrhea, allergy, demodectic acariasis (demodicosis), sarcoptic acariasis, immune-mediated skin disease, endocrine related skin disease, and acral lick dermatitis. Regional differences in the frequency of skin diseases were apparent. The northeast region had high frequencies of fleabite allergic dermatitis, allergy, and immune-mediated disease, and a low frequency of seborrhea. The midwest had a high frequency of seborrhea, and low frequencies of demodectic acariasis and allergy. In the plains region, low frequencies of fleabite allergic dermatitis, pyoderma, seborrhea, allergy, and demodectic acariasis were detected. In the west, the frequencies of fleabite allergic dermatitis, skin cancer, pyoderma, seborrhea, and acral lick dermatitis were high, whereas few dogs had allergic disease and sarcoptic acariasis. The southwest had high frequencies of fleabite allergic dermatitis and demodectic and sarcoptic acariasis. Fleabite allergic dermatitis, pyoderma, and demodectic and sarcoptic acariasis were frequently diagnosed in the southeast, but the number of dogs with seborrhea was low.

  6. Genetically modified skin to treat disease: potential and limitations.

    PubMed

    Krueger, G G; Morgan, J R; Jorgensen, C M; Schmidt, L; Li, H L; Kwan, M K; Boyce, S T; Wiley, H S; Kaplan, J; Petersen, M J

    1994-11-01

    Molecular definition of disease at the level of the gene and advances in recombinant DNA technology suggest that many diseases are amenable to correction by genes not bearing the defective elements that result in disease. Many questions must be answered before this therapy can be used to correct chronic diseases. These questions fall into safety and efficacy categories. Experience with transplanting cellular elements of skin or skin substitutes (defined as skin that possess the cell types and a dermal structure to develop into a functioning skin) to athymic rodents is considerable and is seen as a system where these questions can be answered. This paper reviews these questions and presents our early analysis of genetically modified cells in skin substitutes in vivo and in vitro. Experimental data demonstrate that both a matrix of woven nylon, housing a fibroblast generated collage, and dead dermis can be utilized to shuttle genetically modified human fibroblasts from the laboratory to an in vivo setting. Genetically modified fibroblasts do not migrate from the shuttle to the surrounding tissue. The survival of significant numbers, approximately 70%, of genetically modified fibroblasts for at least 6 weeks in these shuttles, supports this general approach as having clinical utility. It is also concluded that skin substitute systems can be used to generate a genetically modified skin in vitro that has the capacity to develop into functional skin in vivo. Further, as genetically modified keratinocytes differentiate there is increased production by the transgene, supporting the concept that keratinocytes have true potential as shuttles for therapeutic genes. This work demonstrates that transplantation of systems containing genetically modified cells of the skin can be used to experimentally define many aspects of gene therapy using skin before this technology is taken to the clinic. Examples include determining the effect of gene transduction and expression on

  7. Dissecting the genetics of complex inheritance: linkage disequilibrium mapping provides insight into Crohn disease.

    PubMed

    Elding, Heather; Lau, Winston; Swallow, Dallas M; Maniatis, Nikolas

    2011-12-09

    Family studies for Crohn disease (CD) report extensive linkage on chromosome 16q and pinpoint NOD2 as a possible causative locus. However, linkage is also observed in families that do not bear the most frequent NOD2 causative mutations, but no other signals on 16q have been found so far in published genome-wide association studies. Our aim is to identify this missing genetic contribution. We apply a powerful genetic mapping approach to the Wellcome Trust Case-Control Consortium and the National Institute of Diabetes and Digestive and Kidney Diseases genome-wide association data on CD. This method takes into account the underlying structure of linkage disequilibrium (LD) by using genetic distances from LD maps and provides a location for the causal agent. We find genetic heterogeneity within the NOD2 locus and also show an independent and unsuspected involvement of the neighboring gene, CYLD. We find associations with the IRF8 region and the region containing CDH1 and CDH3, as well as substantial phenotypic and genetic heterogeneity for CD itself. The genes are known to be involved in inflammation and immune dysregulation. These findings provide insight into the genetics of CD and suggest promising directions for understanding disease heterogeneity. The application of this method thus paves the way for understanding complex inheritance in general, leading to the dissection of different pathways and ultimately, personalized treatment. Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  8. Dissecting the Genetics of Complex Inheritance: Linkage Disequilibrium Mapping Provides Insight into Crohn Disease

    PubMed Central

    Elding, Heather; Lau, Winston; Swallow, Dallas M.; Maniatis, Nikolas

    2011-01-01

    Family studies for Crohn disease (CD) report extensive linkage on chromosome 16q and pinpoint NOD2 as a possible causative locus. However, linkage is also observed in families that do not bear the most frequent NOD2 causative mutations, but no other signals on 16q have been found so far in published genome-wide association studies. Our aim is to identify this missing genetic contribution. We apply a powerful genetic mapping approach to the Wellcome Trust Case-Control Consortium and the National Institute of Diabetes and Digestive and Kidney Diseases genome-wide association data on CD. This method takes into account the underlying structure of linkage disequilibrium (LD) by using genetic distances from LD maps and provides a location for the causal agent. We find genetic heterogeneity within the NOD2 locus and also show an independent and unsuspected involvement of the neighboring gene, CYLD. We find associations with the IRF8 region and the region containing CDH1 and CDH3, as well as substantial phenotypic and genetic heterogeneity for CD itself. The genes are known to be involved in inflammation and immune dysregulation. These findings provide insight into the genetics of CD and suggest promising directions for understanding disease heterogeneity. The application of this method thus paves the way for understanding complex inheritance in general, leading to the dissection of different pathways and ultimately, personalized treatment. PMID:22152681

  9. Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease.

    PubMed

    Carss, Keren J; Arno, Gavin; Erwood, Marie; Stephens, Jonathan; Sanchis-Juan, Alba; Hull, Sarah; Megy, Karyn; Grozeva, Detelina; Dewhurst, Eleanor; Malka, Samantha; Plagnol, Vincent; Penkett, Christopher; Stirrups, Kathleen; Rizzo, Roberta; Wright, Genevieve; Josifova, Dragana; Bitner-Glindzicz, Maria; Scott, Richard H; Clement, Emma; Allen, Louise; Armstrong, Ruth; Brady, Angela F; Carmichael, Jenny; Chitre, Manali; Henderson, Robert H H; Hurst, Jane; MacLaren, Robert E; Murphy, Elaine; Paterson, Joan; Rosser, Elisabeth; Thompson, Dorothy A; Wakeling, Emma; Ouwehand, Willem H; Michaelides, Michel; Moore, Anthony T; Webster, Andrew R; Raymond, F Lucy

    2017-01-05

    Inherited retinal disease is a common cause of visual impairment and represents a highly heterogeneous group of conditions. Here, we present findings from a cohort of 722 individuals with inherited retinal disease, who have had whole-genome sequencing (n = 605), whole-exome sequencing (n = 72), or both (n = 45) performed, as part of the NIHR-BioResource Rare Diseases research study. We identified pathogenic variants (single-nucleotide variants, indels, or structural variants) for 404/722 (56%) individuals. Whole-genome sequencing gives unprecedented power to detect three categories of pathogenic variants in particular: structural variants, variants in GC-rich regions, which have significantly improved coverage compared to whole-exome sequencing, and variants in non-coding regulatory regions. In addition to previously reported pathogenic regulatory variants, we have identified a previously unreported pathogenic intronic variant in CHM in two males with choroideremia. We have also identified 19 genes not previously known to be associated with inherited retinal disease, which harbor biallelic predicted protein-truncating variants in unsolved cases. Whole-genome sequencing is an increasingly important comprehensive method with which to investigate the genetic causes of inherited retinal disease.

  10. Skin microbiota: overview and role in the skin diseases acne vulgaris and rosacea.

    PubMed

    Murillo, Nathalia; Raoult, Didier

    2013-02-01

    As the first barrier to environmental exposures, human skin has developed an integrated immune system to protect the inner body from chemical, physical or microbial insults. Microorganisms inhabiting superficial skin layers are known as skin microbiota and include bacteria, viruses, archaea and fungi. The microbiota composition is crucial in the instruction and support of the skin's immune system. Changes in microbiota can be due to individual, environmental or behavioral factors, such as age, climate, hygiene or antibiotic consumption, which can cause dysbiosis. The contribution of skin microbiota to disease development is known in atopic dermatitis, where there is an increase in Staphylococcus aureus. Culture-independent studies have enabled more accurate descriptions of this complex interplay. Microbial imbalance is associated with the development of various diseases. This review focuses on microbial imbalances in acne vulgaris and rosacea.

  11. Metamaterial-based sensor for skin disease diagnostics

    NASA Astrophysics Data System (ADS)

    La Spada, L.; Iovine, R.; Tarparelli, R.; Vegni, L.

    2013-05-01

    Skin absorption properties, under diseases conditions, are modified due to the structural variations of chromophores and pigments. The measurement of such different absorptions can be a useful tool for the recognition of different skin diseases. In this study the design of a multi-resonant metamaterial-based sensor operating in the optical frequency range is presented. The sensor has been designed, in order to have multiple specific resonant frequencies, tuned to the skin components spectral characteristics. A change in the frequency amplitude of the sensor response is related to the different absorption rate of skin chromophores and pigments. A new analytical model, describing the multi-resonant sensor behaviour, is developed. Good agreement among analytical and numerical results was achieved. Full-wave simulations have validated the capability of the proposed sensor to identify different skin diseases.

  12. Evaluation of a Mitochondrial DNA Mutation in Maternally Inherited and Sporadic Cases of Dupuytren Disease

    PubMed Central

    Anderson, Eric R.; Burmester, James K.; Caldwell, Michael D.

    2012-01-01

    Objective The purpose was to test the hypothesis that Dupuytren disease (DD) is associated with a previously reported mutation in mitochondrial DNA at position 2839. Methods Two hundred sixty-nine cases of DD and an equal number of matched controls were identified in Marshfield Clinic’s Personalized Medicine Research Project (PMRP). Clinical data used to describe the cohort were abstracted from the electronic medical records of the population. Genetic analysis of all the cases and controls was done using a custom synthesis TaqMan assay, while genetic analysis of sixteen of the above cases with a familial history of DD was performed by mitochondrial DNA sequencing at position C2839A. Results Cases and controls were evenly distributed with 167 (62%) men and 102 (38%) women. The majority, 264 (98%) of the cases and controls were white non-Hispanic. Of the 269 cases, 16 were found to have a familial history of DD. Two cases had a maternal history, eight a paternal history, five an affected sibling, and one a paternal grandfather. All cases and controls were found to have only the C allele at the site of the reported mitochondrial C2839A polymorphism. Conclusions The previously reported mitochondrial mutation was not present in our small, maternally inherited cohort or in the total population of 538 cases and controls. This finding does not support the reported incidence of this polymorphism in 90% of the affected population with a maternal inheritance, and calls into question the role of the C2839A mitochondrial DNA polymorphism in familial or sporadic cases of DD. PMID:22634541

  13. Dietary flax oil during pregnancy and lactation retards disease progression in rat offspring with inherited kidney disease.

    PubMed

    Sankaran, Deepa; Bankovic-Calic, Neda; Peng, Claudia Yu-Chen; Ogborn, Malcolm R; Aukema, Harold M

    2006-12-01

    Dietary flax oil (FO) retards disease progression in growing or adult animal models of kidney disease. To determine whether dietary flax oil during the perinatal period would alter renal disease progression in offspring, Han-SPRD-cy rats with inherited cystic kidney disease were given diets with either 7% FO or corn oil (CO), throughout pregnancy and lactation. At 3 wk of age, offspring were then given either the same or the alternate diet for 7 wk. Rats given FO during the maternal period had 15% less renal cyst growth compared with rats given FO only in the postweaning period. Dietary FO, compared with CO, in the maternal period also resulted in 12% lower cell proliferation and 15% less oxidant injury in diseased kidneys of offspring. Including FO in both the maternal and postweaning period resulted in 29-34% less renal interstitial fibrosis and 22-23% lower glomerular hypertrophy. Along with improved histology, these rats exhibited 13% less proteinuria and 30% lower creatinine clearance when dietary FO was given in the maternal period. The potential for dietary FO during pregnancy and lactation to positively modulate adult renal disease has significant implications for the 1 in 1000 individuals with congenital cystic kidney disease.

  14. The Diagnostic Value of Skin Disease Diagnosis Expert System.

    PubMed

    Jeddi, Fatemeh Rangraz; Arabfard, Masoud; Arabkermany, Zahra; Gilasi, Hamidreza

    2016-02-01

    Evaluation is a necessary measure to ensure the effectiveness and efficiency of all systems, including expert systems. The aim of this study was to determine the diagnostic value of expert system for diagnosis of complex skin diseases. A case-control study was conducted in 2015 to determine the diagnostic value of an expert system. The study population included patients who were referred to Razi Specialized Hospital, affiliated to Tehran University of Medical Sciences. The control group was selected from patients without the selected skin diseases. Data collection tool was a checklist of clinical signs of diseases including pemphigus vulgaris, lichen planus, basal cell carcinoma, melanoma, and scabies. The sample size formula estimated 400 patients with skin diseases selected by experts and 200 patients without the selected skin diseases. Patient selection was undertaken with randomized stratified sampling and their sign and symptoms were logged into the system. Physician's diagnosis was determined as the gold standard and was compared with the diagnosis of expert system by SPSS software version 16 and STATA. Kappa statistics, indicators of sensitivity, specificity, accuracy and confidence intervals were calculated for each disease. An accuracy of 90% was considered appropriate. Comparing the results of expert system and physician's diagnosis at the evaluation stage showed an accuracy of 97.1%, sensitivity of 97.5% and specificity of 96.5% The Kappa test indicated a high agreement of 93.6%. The expert system can diagnose complex skin diseases. Development of such systems is recommended to identify all skin diseases.

  15. Co-inheritance of mild hemophilia A and heterozygosity for type 2N von Willebrand disease: a diagnostic and therapeutic challenge.

    PubMed

    Lindsay, Holly; Bergstrom, Katie; Srivaths, Lakshmi

    2014-10-01

    Hemophilia A and von Willebrand disease are the two most common inherited bleeding disorders. Despite their frequency, however, there are very few reports of co-inheritance of the two disorders. We present the first report of a patient with mild hemophilia A and heterozygosity for type 2N von Willebrand disease (VWD). We discuss the patient's phenotype and highlight the diagnostic and therapeutic challenges caused by this co-inheritance.

  16. The Adeno-Associated Virus - A Safe and Effective Vehicle For Liver-Specific Gene Therapy of Inherited and Non-Inherited Diseases.

    PubMed

    Mak, Kai Yan; Rajapaksha, Indu G; Angus, Peter W; Herath, Chandana B

    2017-03-14

    The first human adeno-associated virus (AAV) was originally discovered in 1960s as a contaminant of adenovirus stocks preparation and thus it had not been of medical interest. Throughout last three decades AAV has gained popularity to be used in gene therapy, mainly due to its replicative defectiveness and lack of pathogenicity in human. In addition, the ability to mediate a stable and long-term expression in both non-dividing and dividing cells with specific tissue tropism makes AAV as one of the most promising candidates for therapeutic gene transfer to treat many genetic as well as non-genetic disorders. Moreover, the use of AAV is not only restricted to over-expression of recombinant transgene and protein, but also includes short hairpin RNAs and microRNAs to knock down the expression of genes in targeted tissues. This review will be organized into four parts. Firstly, we will discuss the discovery and history of AAV, followed by detailed AAV biology such as virus genome and virion structure and life cycle of AAV. In the second part of the review, molecular mechanisms of AAV tissue transduction will be discussed extensively, including receptor recognition and cell binding, endosomal and nucleus entry, virus uncoating and genome replication, capsid assembly and packaging. Advantages and limitations of using AAV as a vehicle for gene deliver will also be discussed. In the third part of the review, we will discuss the most commonly used AAV serotypes and variants isolated from human and primate origins, focusing on their diverse tissue tropisms, transduction efficiency, immunological profiles and their applications in animal studies. The final part of the review we will discuss the recent progress in in-vivo gene transfer for inherited and non-inherited diseases in both preclinical and clinical settings using AAV, with a special emphasis on its potential clinical application in the field of liver disease.

  17. Spectrum analysis of common inherited metabolic diseases in Chinese patients screened and diagnosed by tandem mass spectrometry.

    PubMed

    Han, Lianshu; Han, Feng; Ye, Jun; Qiu, Wenjuan; Zhang, Huiwen; Gao, Xiaolan; Wang, Yu; Ji, Wenjun; Gu, Xuefan

    2015-03-01

    Information concerning inherited metabolic diseases in China is scarce. We investigated the prevalence and age distributions of amino acid, organic acid, and fatty acid oxidation disorders in Chinese patients. Blood levels of amino acids and acylcarnitines (tandem mass spectrometry) were measured in 18,303 patients with suspected inherited metabolic diseases. Diagnosis was based on clinical features, blood levels of amino acids or acylcarnitines, urinary organic acid levels (gas chromatography-mass spectrometry), and (in some) gene mutation tests. Inherited metabolic diseases were confirmed in 1,135 patients (739 males, 396 females). Median age was 12 months (1 day to 59 years). There were 28 diseases: 12 amino acid disorders (580 patients, 51.1%), with hyperphenylalaninemia (HPA) being the most common; nine organic acidemias (408 patients, 35.9%), with methylmalonic acidemia (MMA) as the most common; and seven fatty acid oxidation defects (147 patients, 13.0%), with multiple acyl-coenzyme A dehydrogenase deficiency (MADD) being the most common. Onset was mainly at 1-6 months for citrin deficiency, 0-6 months for MMA, and in newborns for ornithine transcarbamylase deficiency (OTCD). HPA was common in patients aged 1-3 years, and MADD was common in patients >18 years. In China, HPA, citrin deficiency, MMA, and MADD are the most common inherited disorders, particularly in newborns/infants. © 2014 Wiley Periodicals, Inc.

  18. [Gene therapy for inherited diseases using heamatopoietic stem cells--gene therapy for patients with chronic granulomatous disease].

    PubMed

    Nunoi, H; Ishibashi, F

    1999-09-01

    The possibility of gene therapy for inherited diseases with a single gene mutation in Figure 1 had been verified by the successful treatment with bone marrow transplantation. As the gene therapy method and theory has been progressing rapidly, it is expected that gene therapy will overcome the complications of bone marrow transplantation. Of these inherited diseases, chronic granulomatous disease (CGD) is the one of the most expected disease for gene therapy. CGD is an inherited immune deficiency caused by mutations in any of the following four phox genes encoding subunits of the superoxide generating phagocyte NADPH oxidase. It consists of membranous cytochrom b558 composed of gp91 phox and p22 phox, and four cytosolic components, p47 phox, p67 phox, rac p21 and p40 phox, which translocate to the membrane upon activation. In our group study, more than 220 CGD patients has been enrolled. The incidence of CGD patients was estimated as 1 out of 250,000 births. The expected life span of the CGD patients is 25 to 30 years old by the Kaplan Meier analysis. Comparing with the ratio of CGD subtype in US and Europe, that with p47phox deficiency is lower (less than 10%/o vs. 23%) and that of gp91 phox deficiency is higher (more than 75% vs. 60%). Prophylactic administration of ST antibiotics and IFN-gamma and bone marrow transplantation have been successfully employed in our therapeutic strategy. However, it is necessary to develop the gene therapy technology for CGD patients as more promising treatment. In the current study we constructed two retrovirus vectors; MFGS-gp91/293 SPA which contains only the therapeutic gp91 phox gene, a bicistronic retrovirus pHa-MDR-IRES-gp91/PA317 which carries a multi drug resistant gene (MDR1) and the gp91phox gene connected with an internal ribosome entry site (IRES). We demonstrate high efficiency transduction of gp 91 phox to CGD EB virus established cell line with high levels of functional correction of the oxidase by MFGS-gp91 and by p

  19. Pattern of Skin Diseases in a Tertiary Institution in Kolkata

    PubMed Central

    Kar, Chinmay; Das, Sudip; Roy, Alok Kumar

    2014-01-01

    Background: There are very little elaborative studies in India about various patterns of skin diseases and various factors those influence the diseases in a tertiary institution. Aims: To find out the various patterns of skin diseases in relation to age, sex, occupation, and socio-economic status. To find out the magnitude of skin diseases and compare with other similar studies. Materials and Methods: Collection of data of all new skin cases in a specified period of one year and put on proforma for diagnosis. Few investigations were done for correct diagnosis. Results: It was found that skin OPD patients (new) were 4.16% of total new OPD patients, and male female ratio was 1.1:1. Among all patients (12910), infection was commonest (39.54%), followed by allergic skin disorder (29.20%). 25.05% patients were housewives, followed by students (23.21%). Study showed that 33.28% patients had per capita income of ` 361-720/month, and 22.35% patients were educated and/or studied up to class V. Conclusion: Pattern of skin diseases are mostly depend not only on environmental factors but also on occupation, socio-economic status, literacy, and age of the patients. PMID:24700954

  20. Molecular Diagnosis of Inherited Retinal Diseases in Indigenous African Populations by Whole-Exome Sequencing

    PubMed Central

    Roberts, Lisa; Ratnapriya, Rinki; du Plessis, Morné; Chaitankar, Vijender; Ramesar, Raj S.; Swaroop, Anand

    2016-01-01

    Purpose A majority of genes associated with inherited retinal diseases (IRDs) have been identified in patients of European origin. Indigenous African populations exhibit rich genomic diversity, and evaluation of reported genetic mutations has yielded low returns so far. Our goal was to perform whole-exome sequencing (WES) to examine variants in known IRD genes in underrepresented African cohorts. Methods Whole-exome sequencing was performed on 56 samples from 16 families with diverse IRD phenotypes that had remained undiagnosed after screening for known mutations using genotyping-based microarrays (Asper Ophthalmics). Variants in reported IRD genes were identified using WES and validated by Sanger sequencing. Custom TaqMan assays were used to screen for identified mutations in 193 unrelated indigenous Africans with IRDs. Results A total of 3494 variants were identified in 217 known IRD genes, leading to the identification of seven different mutations (including six novel) in six genes (RHO, PRPF3, PRPF31, ABCA4, CERKL, and PDE6B) in six distinct families. TaqMan screening in additional probands revealed identical homozygous CERKL and PDE6B variants in four more patients. Conclusions This is the first report of WES of patients with IRDs in indigenous African populations. Our study identified genetic defects in almost 40% of the families analyzed, significantly enhancing the molecular diagnosis of IRD in South Africa. Thus, WES of understudied cohorts seems to present an effective strategy for determining novel mutations in heterogeneous retinal diseases. PMID:27898983

  1. Multi-parameter MRI in the 6-OPRI variant of inherited prion disease

    PubMed Central

    De Vita, Enrico; Ridgway, Gerard R.; Scahill, Rachael I; Caine, Diana; Rudge, Peter; Yousry, Tarek A; Mead, Simon; Collinge, John; Jäger, H R; Thornton, John S; Hyare, Harpreet

    2013-01-01

    Background and Purpose To define the distribution of cerebral volumetric and microstructural parenchymal tissue changes in a specific mutation within inherited human prion diseases (IPD) combining voxel-based morphometry (VBM) with voxel-based analysis (VBA) of cerebral magnetization transfer ratio (MTR) and mean diffusivity (MD). Materials and Methods VBM and VBA of cerebral MTR and MD were performed in 16 healthy controls and 9 patients with the 6-octapeptide repeat insertion (6-OPRI) mutation. An ANCOVA consisting of diagnostic grouping with age and total intracranial volume as covariates was performed. Results On VBM there was significant grey matter (GM) volume reduction in patients compared with controls in the basal ganglia, perisylvian cortex, lingual gyrus and precuneus. Significant MTR reduction and MD increases were more anatomically extensive than volume differences on VBM in the same cortical areas, but MTR and MD changes were not seen in the basal ganglia. Conclusions GM and WM changes were seen in brain areas associated with motor and cognitive functions known to be impaired in patients with the 6-OPRI mutation. There were some differences in the anatomical distribution of MTR-VBA and MDVBA changes compared to VBM, likely to reflect regional variations in the type and degree of the respective pathophysiological substrates. Combined analysis of complementary multi-parameter MRI data furthers our understanding of prion disease pathophysiology. PMID:23538406

  2. New and emerging technologies for the treatment of inherited retinal diseases: a horizon scanning review

    PubMed Central

    Smith, J; Ward, D; Michaelides, M; Moore, A T; Simpson, S

    2015-01-01

    The horizon scanning review aimed to identify new and emerging technologies in development that have the potential to slow or stop disease progression and/or reverse sight loss in people with inherited retinal diseases (IRDs). Potential treatments were identified using recognized horizon scanning methods. These included a combination of online searches using predetermined search terms, suggestions from clinical experts and patient and carer focus groups, and contact with commercial developers. Twenty-nine relevant technologies were identified. These included 9 gene therapeutic approaches, 10 medical devices, 5 pharmacological agents, and 5 regenerative and cell therapies. A further 11 technologies were identified in very early phases of development (typically phase I or pre-clinical) and were included in the final report to give a complete picture of developments ‘on the horizon'. Clinical experts and patient and carer focus groups provided helpful information and insights, such as the availability of specialised services for patients, the potential impacts of individual technologies on people with IRDs and their families, and helped to identify additional relevant technologies. This engagement ensured that important areas of innovation were not missed. Most of the health technologies identified are still at an early stage of development and it is difficult to estimate when treatments might be available. Further, well designed trials that generate data on efficacy, applicability, acceptability, and costs of the technologies, as well as the long-term impacts for various conditions are required before these can be considered for adoption into routine clinical practice. PMID:26113499

  3. New and emerging technologies for the treatment of inherited retinal diseases: a horizon scanning review.

    PubMed

    Smith, J; Ward, D; Michaelides, M; Moore, A T; Simpson, S

    2015-09-01

    The horizon scanning review aimed to identify new and emerging technologies in development that have the potential to slow or stop disease progression and/or reverse sight loss in people with inherited retinal diseases (IRDs). Potential treatments were identified using recognized horizon scanning methods. These included a combination of online searches using predetermined search terms, suggestions from clinical experts and patient and carer focus groups, and contact with commercial developers. Twenty-nine relevant technologies were identified. These included 9 gene therapeutic approaches, 10 medical devices, 5 pharmacological agents, and 5 regenerative and cell therapies. A further 11 technologies were identified in very early phases of development (typically phase I or pre-clinical) and were included in the final report to give a complete picture of developments 'on the horizon'. Clinical experts and patient and carer focus groups provided helpful information and insights, such as the availability of specialised services for patients, the potential impacts of individual technologies on people with IRDs and their families, and helped to identify additional relevant technologies. This engagement ensured that important areas of innovation were not missed. Most of the health technologies identified are still at an early stage of development and it is difficult to estimate when treatments might be available. Further, well designed trials that generate data on efficacy, applicability, acceptability, and costs of the technologies, as well as the long-term impacts for various conditions are required before these can be considered for adoption into routine clinical practice.

  4. Pesticide and Insect Repellent Mixture (Permethrin and DEET) Induces Epigenetic Transgenerational Inheritance of Disease and Sperm Epimutations

    PubMed Central

    Manikkam, Mohan; Tracey, Rebecca; Guerrero-Bosagna, Carlos; Skinner, Michael K.

    2012-01-01

    Environmental compounds are known to promote epigenetic transgenerational inheritance of disease. The current study was designed to determine if a “pesticide mixture” (pesticide permethrin and insect repellent N,N-Diethyl-meta-toluamide, DEET) promotes epigenetic transgenerational inheritance of disease and associated DNA methylation epimutations in sperm. Gestating F0 generation female rats were exposed during fetal gonadal sex determination and the incidence of disease evaluated in F1 and F3 generations. There were significant increases in the incidence of total diseases in animals from pesticide lineage F1 and F3 generation animals. Pubertal abnormalities, testis disease, and ovarian disease (primordial follicle loss and polycystic ovarian disease) were increased in F3 generation animals. Analysis of the pesticide lineage F3 generation sperm epigenome identified 363 differential DNA methylation regions (DMR) termed epimutations. Observations demonstrate that a pesticide mixture (permethrin and DEET) can promote epigenetic transgenerational inheritance of adult onset disease and potential sperm epigenetic biomarkers for ancestral environmental exposures. PMID:22975477

  5. Early behavioural changes in familial Alzheimer’s disease in the Dominantly Inherited Alzheimer Network

    PubMed Central

    Liang, Li-Jung; Zhou, Yan; Vangala, Sitaram; Teng, Edmond; Kremen, Sarah; Wharton, David; Goate, Alison; Marcus, Daniel S.; Farlow, Martin; Ghetti, Bernardino; McDade, Eric; Masters, Colin L.; Mayeux, Richard P.; Rossor, Martin; Salloway, Stephen; Schofield, Peter R.; Cummings, Jeffrey L.; Buckles, Virginia; Bateman, Randall; Morris, John C.

    2015-01-01

    Prior studies indicate psychiatric symptoms such as depression, apathy and anxiety are risk factors for or prodromal symptoms of incipient Alzheimer’s disease. The study of persons at 50% risk for inheriting autosomal dominant Alzheimer’s disease mutations allows characterization of these symptoms before progressive decline in a population destined to develop illness. We sought to characterize early behavioural features in carriers of autosomal dominant Alzheimer’s disease mutations. Two hundred and sixty-one persons unaware of their mutation status enrolled in the Dominantly Inherited Alzheimer Network, a study of persons with or at-risk for autosomal dominant Alzheimer’s disease, were evaluated with the Neuropsychiatric Inventory-Questionnaire, the 15-item Geriatric Depression Scale and the Clinical Dementia Rating Scale (CDR). Ninety-seven asymptomatic (CDR = 0), 25 mildly symptomatic (CDR = 0.5), and 33 overtly affected (CDR > 0.5) autosomal dominant Alzheimer’s disease mutation carriers were compared to 106 non-carriers with regard to frequency of behavioural symptoms on the Neuropsychiatric Inventory-Questionnaire and severity of depressive symptoms on the Geriatric Depression Scale using generalized linear regression models with appropriate distributions and link functions. Results from the adjusted analyses indicated that depressive symptoms on the Neuropsychiatric Inventory-Questionnaire were less common in cognitively asymptomatic mutation carriers than in non-carriers (5% versus 17%, P = 0.014) and the odds of experiencing at least one behavioural sign in cognitively asymptomatic mutation carriers was lower than in non-carriers (odds ratio = 0.50, 95% confidence interval: 0.26–0.98, P = 0.042). Depression (56% versus 17%, P = 0.0003), apathy (40% versus 4%, P < 0.0001), disinhibition (16% versus 2%, P = 0.009), irritability (48% versus 9%, P = 0.0001), sleep changes (28% versus 7%, P = 0.003), and agitation (24% versus 6%, P = 0.008) were

  6. Early behavioural changes in familial Alzheimer's disease in the Dominantly Inherited Alzheimer Network.

    PubMed

    Ringman, John M; Liang, Li-Jung; Zhou, Yan; Vangala, Sitaram; Teng, Edmond; Kremen, Sarah; Wharton, David; Goate, Alison; Marcus, Daniel S; Farlow, Martin; Ghetti, Bernardino; McDade, Eric; Masters, Colin L; Mayeux, Richard P; Rossor, Martin; Salloway, Stephen; Schofield, Peter R; Cummings, Jeffrey L; Buckles, Virginia; Bateman, Randall; Morris, John C

    2015-04-01

    Prior studies indicate psychiatric symptoms such as depression, apathy and anxiety are risk factors for or prodromal symptoms of incipient Alzheimer's disease. The study of persons at 50% risk for inheriting autosomal dominant Alzheimer's disease mutations allows characterization of these symptoms before progressive decline in a population destined to develop illness. We sought to characterize early behavioural features in carriers of autosomal dominant Alzheimer's disease mutations. Two hundred and sixty-one persons unaware of their mutation status enrolled in the Dominantly Inherited Alzheimer Network, a study of persons with or at-risk for autosomal dominant Alzheimer's disease, were evaluated with the Neuropsychiatric Inventory-Questionnaire, the 15-item Geriatric Depression Scale and the Clinical Dementia Rating Scale (CDR). Ninety-seven asymptomatic (CDR = 0), 25 mildly symptomatic (CDR = 0.5), and 33 overtly affected (CDR > 0.5) autosomal dominant Alzheimer's disease mutation carriers were compared to 106 non-carriers with regard to frequency of behavioural symptoms on the Neuropsychiatric Inventory-Questionnaire and severity of depressive symptoms on the Geriatric Depression Scale using generalized linear regression models with appropriate distributions and link functions. Results from the adjusted analyses indicated that depressive symptoms on the Neuropsychiatric Inventory-Questionnaire were less common in cognitively asymptomatic mutation carriers than in non-carriers (5% versus 17%, P = 0.014) and the odds of experiencing at least one behavioural sign in cognitively asymptomatic mutation carriers was lower than in non-carriers (odds ratio = 0.50, 95% confidence interval: 0.26-0.98, P = 0.042). Depression (56% versus 17%, P = 0.0003), apathy (40% versus 4%, P < 0.0001), disinhibition (16% versus 2%, P = 0.009), irritability (48% versus 9%, P = 0.0001), sleep changes (28% versus 7%, P = 0.003), and agitation (24% versus 6%, P = 0.008) were more common and

  7. Non-infectious skin disease in Indigenous Australians.

    PubMed

    Heyes, Christopher; Tait, Clare; Toholka, Ryan; Gebauer, Kurt

    2014-08-01

    The burden of non-infectious skin disease in the Indigenous Australian population has not been previously examined. This study considers the published data on the epidemiology and clinical features of a number of non-infectious skin diseases in Indigenous Australians. It also outlines hypotheses for the possible differences in the prevalence of such diseases in this group compared with the general Australian population. There is a paucity of literature on the topic but, from the material available, Indigenous Australians appear to have a reduced prevalence of psoriasis, type 1 hypersensitivity reactions and skin cancer but increased rates of lupus erythematosus, kava dermopathy and vitamin D deficiency when compared to the non-Indigenous Australian population. This article profiles the prevalence and presentation of non-infectious skin diseases in the Indigenous Australian population to synthesise our limited knowledge and highlight deficiencies in our understanding. © 2013 The Australasian College of Dermatologists.

  8. Skin Diseases Take Big Slice Out of America's Health, Economy

    MedlinePlus

    ... gov/news/fullstory_163888.html Skin Diseases Take Big Slice Out of America's Health, Economy The sometimes ... each, the researchers found. Costs are also a big concern. In 2013, the United States spent $75 ...

  9. Skin Diseases: Questions for Your Health Care Provider

    MedlinePlus

    ... Issue Past Issues Skin Diseases Questions for Your Health Care Provider Past Issues / Fall 2008 Table of Contents ... Sun—Not a good mix / Questions for Your Health Care Provider Fall 2008 Issue: Volume 3 Number 4 ...

  10. Complex Inheritance of ABCA4 Disease: Four Mutations in a Family with Multiple Macular Phenotypes

    PubMed Central

    Lee, Winston; Xie, Yajing (Angela); Zernant, Jana; Yuan, Bo; Bearelly, Srilaxmi; Tsang, Stephen H.; Lupski, James R.; Allikmets, Rando

    2015-01-01

    Over 800 mutations in the ABCA4 gene cause autosomal recessive Stargardt disease. Due to extensive genetic heterogeneity, observed variant-associated phenotypes can manifest tremendous variability of expression. Furthermore, the high carrier frequency of pathogenic ABCA4 alleles in the general population (~1:20) often results in pseudo-dominant inheritance patterns further complicating the diagnosis and characterization of affected individuals. This study describes a genotype/phenotype analysis of an unusual family with multiple macular disease phenotypes spanning across two generations and segregating four distinct ABCA4 mutant alleles. Complete sequencing of ABCA4 discovered two known missense mutations, p.C54Y and p.G1961E. Array comparative genomic hybridization revealed a large novel deletion combined with a small insertion, c.6148-698_c.6670del/insTGTGCACCTCCCTAG, and complete sequencing of the entire ABCA4 genomic locus uncovered a new deep intronic variant, c.302+68C>T. Patients with the p.G1961E mutation had the mildest, confined maculopathy phenotype with peripheral flecks while those with all other mutant allele combinations exhibited a more advanced stage of generalized retinal and choriocapillaris atrophy. This family epitomizes the clinical and genetic complexity of ABCA4-associated diseases. It contained variants from all classes of mutations, in the coding region, deep intronic, both single nucleotide variants (SNV) and copy number variants (CNV) that accounted for varying phenotypes segregating in an apparent dominant fashion. Unequivocally defining disease-associated alleles in the ABCA4 locus requires a multifaceted approach that includes advanced mutation detection methods and a thorough analysis of clinical phenotypes. PMID:26527198

  11. Mitochondrial dysfunction: a neglected component of skin diseases.

    PubMed

    Feichtinger, René G; Sperl, Wolfgang; Bauer, Johann W; Kofler, Barbara

    2014-09-01

    Aberrant mitochondrial structure and function influence tissue homeostasis and thereby contribute to multiple human disorders and ageing. Ten per cent of patients with primary mitochondrial disorders present skin manifestations that can be categorized into hair abnormalities, rashes, pigmentation abnormalities and acrocyanosis. Less attention has been paid to the fact that several disorders of the skin are linked to alterations of mitochondrial energy metabolism. This review article summarizes the contribution of mitochondrial pathology to both common and rare skin diseases. We explore the intriguing observation that a wide array of skin disorders presents with primary or secondary mitochondrial pathology and that a variety of molecular defects can cause dysfunctional mitochondria. Among them are mutations in mitochondrial- and nuclear DNA-encoded subunits and assembly factors of oxidative phosphorylation (OXPHOS) complexes; mutations in intermediate filament proteins involved in linking, moving and shaping of mitochondria; and disorders of mitochondrial DNA metabolism, fatty acid metabolism and heme synthesis. Thus, we assume that mitochondrial involvement is the rule rather than the exception in skin diseases. We conclude the article by discussing how improving mitochondrial function can be beneficial for aged skin and can be used as an adjunct therapy for certain skin disorders. Consideration of mitochondrial energy metabolism in the skin creates a new perspective for both dermatologists and experts in metabolic disease. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. The role of antimicrobial peptides in chronic inflammatory skin diseases

    PubMed Central

    Majewski, Sławomir

    2016-01-01

    Antimicrobial peptides (AMPs) are effector molecules of the innate immune system of the skin. They present an activity against a broad spectrum of Gram-positive and Gram-negative bacteria as well as some fungi, parasites and enveloped viruses. Several inflammatory skin diseases including psoriasis, atopic dermatitis, acne vulgaris and rosacea are characterized by a dysregulated expression of AMPs. Antimicrobial peptides are excessively produced in lesional psoriatic scales or rosacea in contrast to the atopic skin that shows lower AMP levels when compared with psoriasis. The importance of the AMPs contribution to host immunity is indisputable as alterations in the antimicrobial peptide expression have been associated with various pathologic processes. This review discusses the biology and clinical relevance of antimicrobial peptides expressed in the skin and their role in the pathogenesis of inflammatory skin diseases. PMID:26985172

  13. [Co-inheritance of autosomal dominant polycystic kidney disease and sickle cell trait in African Americans].

    PubMed

    Peces, R; Peces, C; Cuesta-López, E; Vega-Cabrera, C; Azorín, S; Pérez-Dueñas, V; Selgas, R

    2011-01-01

    Macroscopic haematuria secondary to renal cyst rupture is a frequent complication in autosomal dominant polycystic kidney disease (ADPKD). Sickle-cell disease is an autosomal recessive haemoglobinopathy that involves a qualitative anomaly of haemoglobin due to substitution of valine for the glutamic acid in the sixth position of 3-globin gene on the short arm of chromosome 11. For the full disease to be manifested, this mutation must be present on both inherited alleles. The severity of the disease is proportional to the quantity of haemoglobin S (Hb S) in the red cells; sickle-cell trait (Hb S <50%) and homozygous sickle-cell disease (Hb S >75%). In sickle-cell disease, the abnormal Hb S loses its rheological characteristics and is responsible of the various systemic manifestations including those of the kidney, such as macroscopic haematuria secondary to papilar necrosis. Despite the generally benign nature of the sickle-cell trait, several potentially serious complications have been described. Metabolic or environmental changes such as hypoxia, acidosis, dehydration, hyperosmolality or hyperthermia may transform silent sickle-cell trait into a syndrome resembling sickle-cell disease with vaso-occlusive crisis due to an accumulation of low deformable red blood cells in the microcirculation originating haematuria from papilar necrosis. On the other hand, it has been demonstrated an earlier onset of end-stage renal disease (ESRD), in blacks with ADPKD and sickle-cell trait when compared with blacks with ADPKD without the trait. We studied 2 african-american families (4 patients) which presented with both ADPKD and sickle-cell trait (Hb S <50%). The diagnosis of sickle-cell trait was confirmed by haemoglobin electrophoresis. The renal volume was measured by magnetic resonance imaging (MRI). The proband subject in family 1 presented frequent haematuria episodes, associated to increase of renal volume, developed very early ESRD and was dialyzed at the age of 39 years

  14. Mortality from nonneoplastic skin disease in the United States.

    PubMed

    Lott, Jason P; Gross, Cary P

    2014-01-01

    The mortality burden from nonneoplastic skin disease in the United States is unknown. We sought to estimate mortality from nonneoplastic skin disease as underlying and contributing causes of death. Population-based death certificate data detailing mortality from nonneoplastic skin disease for years 1999 to 2009 were used to calculate absolute numbers of death and age-adjusted mortality by year, patient demographics, and 10 most commonly reported diagnoses. Nonneoplastic skin diseases were reported as underlying and contributing causes of mortality for approximately 3948 and 19,542 patients per year, respectively. Age-adjusted underlying cause mortality (per 100,000 persons) were significantly greater (P < .0001) for patients who were black/African American (3.4), women (1.4), and residing in the South (1.6). Most deaths occurred in patients ages 65 years and older (34,248 total deaths). Common underlying causes of death included chronic ulcers (1789 deaths/y) and cellulitis (1348 deaths/y). Errors in death certificate data and inability to adjust for patient-level confounders may limit the accuracy and generalizability of our results. Mortality from nonneoplastic skin disease is uncommon yet potentially preventable. The elderly bear the greatest burden of mortality from nonneoplastic skin disease. Chronic ulcers and cellulitis constitute frequent causes of death. Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  15. The Moroccan Genetic Disease Database (MGDD): a database for DNA variations related to inherited disorders and disease susceptibility

    PubMed Central

    Charoute, Hicham; Nahili, Halima; Abidi, Omar; Gabi, Khalid; Rouba, Hassan; Fakiri, Malika; Barakat, Abdelhamid

    2014-01-01

    National and ethnic mutation databases provide comprehensive information about genetic variations reported in a population or an ethnic group. In this paper, we present the Moroccan Genetic Disease Database (MGDD), a catalogue of genetic data related to diseases identified in the Moroccan population. We used the PubMed, Web of Science and Google Scholar databases to identify available articles published until April 2013. The Database is designed and implemented on a three-tier model using Mysql relational database and the PHP programming language. To date, the database contains 425 mutations and 208 polymorphisms found in 301 genes and 259 diseases. Most Mendelian diseases in the Moroccan population follow autosomal recessive mode of inheritance (74.17%) and affect endocrine, nutritional and metabolic physiology. The MGDD database provides reference information for researchers, clinicians and health professionals through a user-friendly Web interface. Its content should be useful to improve researches in human molecular genetics, disease diagnoses and design of association studies. MGDD can be publicly accessed at http://mgdd.pasteur.ma. PMID:23860041

  16. Treating skin disease: self-management behaviors of Latino farmworkers.

    PubMed

    Arcury, Thomas A; Vallejos, Quirina M; Feldman, Steven R; Quandt, Sara A

    2006-01-01

    Latino migrant and seasonal farmworkers experience high rates of skin disease that result from their working and living conditions. Knowledge of the ways farmworkers treat skin disease symptoms will provide a foundation for developing culturally appropriate health education, improving the delivery of health services, and improving occupational health policy for agricultural workers. The purpose of this paper is to describe skin disease self-management practices among Latino migrant and seasonal farmworkers in North Carolina. This analysis uses a qualitative design based on in-depth interviews with 30 Latino farmworkers (six females, 24 males). Computer assisted, systematic procedures are used to analyze the verbatim transcripts of these interviews. Participants shared a consistent set of health self-management actions in treating skin disease. These actions were within the domains of self-care and medical care. A model of skin disease self-management among Latino farmworkers includes the self-care actions of hygiene, use of home remedies and use of over-the-counter remedies, with farmworkers often combining different domains of self-care. While farmworkers acknowledge the benefits of medical care, they are also mindful of barriers to its use, including cost, transportation and language. The large percentage of farmworkers who experience skin problems indicates that health outreach workers who serve this population need to provide education on preventing and treating skin problems, and they need to recommend to farmworkers appropriate over-the-counter medicines for the treatment of these skin problems. Appropriate medical care for treating skin problems that are dangerous and reduce farmworkers' quality-of-life needs to be made available to this population.

  17. The hidden Niemann-Pick type C patient: clinical niches for a rare inherited metabolic disease.

    PubMed

    Hendriksz, Christian J; Anheim, Mathieu; Bauer, Peter; Bonnot, Olivier; Chakrapani, Anupam; Corvol, Jean-Christophe; de Koning, Tom J; Degtyareva, Anna; Dionisi-Vici, Carlo; Doss, Sarah; Duning, Thomas; Giunti, Paola; Iodice, Rosa; Johnston, Tracy; Kelly, Dierdre; Klünemann, Hans-Hermann; Lorenzl, Stefan; Padovani, Alessandro; Pocovi, Miguel; Synofzik, Matthis; Terblanche, Alta; Then Bergh, Florian; Topçu, Meral; Tranchant, Christine; Walterfang, Mark; Velten, Christian; Kolb, Stefan A

    2017-05-01

    Niemann-Pick disease type C (NP-C) is a rare, inherited neurodegenerative disease of impaired intracellular lipid trafficking. Clinical symptoms are highly heterogeneous, including neurological, visceral, or psychiatric manifestations. The incidence of NP-C is under-estimated due to under-recognition or misdiagnosis across a wide range of medical fields. New screening and diagnostic methods provide an opportunity to improve detection of unrecognized cases in clinical sub-populations associated with a higher risk of NP-C. Patients in these at-risk groups ("clinical niches") have symptoms that are potentially related to NP-C, but go unrecognized due to other, more prevalent clinical features, and lack of awareness regarding underlying metabolic causes. Twelve potential clinical niches identified by clinical experts were evaluated based on a comprehensive, non-systematic review of literature published to date. Relevant publications were identified by targeted literature searches of EMBASE and PubMed using key search terms specific to each niche. Articles published in English or other European languages up to 2016 were included. Several niches were found to be relevant based on available data: movement disorders (early-onset ataxia and dystonia), organic psychosis, early-onset cholestasis/(hepato)splenomegaly, cases with relevant antenatal findings or fetal abnormalities, and patients affected by family history, consanguinity, and endogamy. Potentially relevant niches requiring further supportive data included: early-onset cognitive decline, frontotemporal dementia, parkinsonism, and chronic inflammatory CNS disease. There was relatively weak evidence to suggest amyotrophic lateral sclerosis or progressive supranuclear gaze palsy as potential niches. Several clinical niches have been identified that harbor patients at increased risk of NP-C.

  18. Inherited deficiency of the second component of complement. Rheumatic disease associations.

    PubMed Central

    Glass, D; Raum, D; Gibson, D; Stillman, J S; Schur, P H

    1976-01-01

    The prevalence of homozygous and heterozygous deficiency of the second component of complement (C2) was determined in patients with rheumatic disease including 137 with systemic lupus erythematosus (SLE), 274 with juvenile rheumatoid arthritis, and 134 with rheumatoid arthritis. 1 C2 homozygous deficient and 19 possible heterozygous deficient individuals were identified by using both immunochemical and functional assays to determine C2 levels. Of the 20, 8 had SLE (5.9%), 10 had juvenile rheumatoid arthritis (3.7%), and 2 had rheumatoid arthritis (1.4%), the homozygous deficient individual having SLE. The prevalence of C2 deficiency in the SLE and juvenile rheumatoid arthritis patients was significantly increased (P = 0.0009 and P = 0.02, respectively) when compared with controls, 6 (1.2%) of 509 blood donors having C2 levels consistent with heterozygous deficiency. 15 of the 20 C2 deficient patients were HLA typed and found to have antigens A10(Aw25), B18, or both. The patients with C2 deficiency and SLE had earlier age of onset of disease and less antinuclear antibody when compared with the C2 normal SLE patients. 11 families of the propositi were studied and found to have one or more C2 heterozygous deficient individuals. The family members had an equal distribution of rheumatic disease and antinuclear antibody in the C2 deficient and C2 normal groups. C2 deficient individuals were found to have significantly lower levels of properdin Factor B (242 mug/ml+/-54) when compared with the non-C2 deficient family members (282 mug/ml+/-73). These data support the concept that inherited deficiency of C2 is significantly associated with both SLE and juvenile rheumatoid arthritis. PMID:965492

  19. Interlocus gene conversion events introduce deleterious mutations into at least 1% of human genes associated with inherited disease.

    PubMed

    Casola, Claudio; Zekonyte, Ugne; Phillips, Andrew D; Cooper, David N; Hahn, Matthew W

    2012-03-01

    Establishing the molecular basis of DNA mutations that cause inherited disease is of fundamental importance to understanding the origin, nature, and clinical sequelae of genetic disorders in humans. The majority of disease-associated mutations constitute single-base substitutions and short deletions and/or insertions resulting from DNA replication errors and the repair of damaged bases. However, pathological mutations can also be introduced by nonreciprocal recombination events between paralogous sequences, a phenomenon known as interlocus gene conversion (IGC). IGC events have thus far been linked to pathology in more than 20 human genes. However, the large number of duplicated gene sequences in the human genome implies that many more disease-associated mutations could originate via IGC. Here, we have used a genome-wide computational approach to identify disease-associated mutations derived from IGC events. Our approach revealed hundreds of known pathological mutations that could have been caused by IGC. Further, we identified several dozen high-confidence cases of inherited disease mutations resulting from IGC in ∼1% of all genes analyzed. About half of the donor sequences associated with such mutations are functional paralogous genes, suggesting that epistatic interactions or differential expression patterns will determine the impact upon fitness of specific substitutions between duplicated genes. In addition, we identified thousands of hitherto undescribed and potentially deleterious mutations that could arise via IGC. Our findings reveal the extent of the impact of interlocus gene conversion upon the spectrum of human inherited disease.

  20. Diseases of the tooth: the genetic and molecular basis of inherited anomalies affecting the dentition.

    PubMed

    Cobourne, Martyn T; Sharpe, Paul T

    2013-01-01

    In humans, inherited variation in the number, size, and shape of teeth within the dentitions are relatively common, while rarer defects of hard tissue formation, including amelogenesis and dentinogenesis imperfecta, and problems associated with tooth eruption are also seen. In many cases, these anomalies occur in isolation, but they can also present as a feature of numerous well-characterized developmental syndromes. Complex reiterative signaling between the epithelium and mesenchyme is a feature of normal tooth development in the embryo, occurring from early patterning through morphogenesis, hard tissue formation and during root development. Significant events also occur during postnatal development of the dentition, including hard tissue maturation and tooth eruption. In the last decade, advances in human and mouse genetics have meant that in many cases candidate genes have been identified for these anomalies. These genes have provided a useful platform for developmental biologists, allowing them to begin elucidating how these signals interact to generate a functional dentition and understand the mechanisms underlying many of the anomalies that are seen in human populations. In this article, we review current concepts relating to the developmental biology of tooth number, size, and shape, formation of the dental hard tissues and eruption of the tooth into the oral cavity. We will focus on the molecular mechanisms underlying these processes in both health and disease.

  1. The clinical implications of molecular monitoring and analyses of inherited retinal diseases.

    PubMed

    Chacón-Camacho, Oscar F; García-Montaño, Leopoldo A; Zenteno, Juan C

    2017-11-01

    Retinal dystrophies (RDs) are the most common cause of inherited blindness and one of the most genetically heterogeneous human diseases. RDs arise from mutations in genes involved in development and function of photoreceptors or other retinal cells. Identification of the genetic defect causing RD allows accurate diagnosis, prognosis, and counseling in affected patients. Molecular diagnosis is a tremendous challenge in RDs due to their locus and phenotypic heterogeneity. As conventional DNA sequencing approaches are impractical in such situation, Next Generation Sequencing (NGS)-based protocols are needed to identify RD-causing mutations. This is being accomplished by sequencing RD gene panels or by whole exome or whole genome sequencing approaches. Areas covered: This review discusses the current strategies for molecular diagnosis in RDs including their advantages and limitations, as well as their utility in diagnosis of non-syndromic versus syndromic RDs. Results of ongoing gene therapy protocols in RDs are also presented. Expert commentary: Molecular diagnosis in RD improves the medical management of patients. Importantly, demand for molecular screening for RDs is greatly expanding not only as a result of increasing development and availability of NGS technologies, but also of the growing number of gene-based clinical trials offering a potential treatment to patients.

  2. The Jeremiah Metzger Lecture: Gene Therapy for Inherited Disorders: From Christmas Disease to Leber's Amaurosis

    PubMed Central

    High, Katherine A.

    2009-01-01

    This paper will focus on recent developments in the field of gene therapy for inherited disorders. From a historical perspective, this Metzger lecture is a follow-on to one presented by Dr. William Kelley in 1987, entitled “Current Status of Human Gene Therapy” (Transactions Am Clin. Climatol. Assoc. 99:152–169) (1). In 1987, gene transfer studies in human subjects were yet to be undertaken; the first clinical studies, infusion of genetically modified autologous T cells into two young girls with ADA-SCID, would not take place until 1990 (2). Today's lecture will summarize progress since that time in one area, that of in vivo gene transfer for genetic disease. I will describe progress in two areas, gene therapy for the bleeding disorder hemophilia B, and for a subset of retinal degenerative disorders termed Leber's congenital amaurosis, due to mutations in the gene encoding retinal pigment epithelium-specific 65 kilodalton protein (RPE65). This lecture will demonstrate the interconnected nature of progress in these two areas, as careful delineation of the obstacles in hemophilia led to the realization that success could be achieved in Leber's. PMID:19768188

  3. The Jeremiah Metzger Lecture: gene therapy for inherited disorders: from Christmas disease to Leber's amaurosis.

    PubMed

    High, Katherine A

    2009-01-01

    This paper will focus on recent developments in the field of gene therapy for inherited disorders. From a historical perspective, this Metzger lecture is a follow-on to one presented by Dr. William Kelley in 1987, entitled "Current Status of Human Gene Therapy" (Transactions Am Clin. Climatol. Assoc. 99:152-169) (1). In 1987, gene transfer studies in human subjects were yet to be undertaken; the first clinical studies, infusion of genetically modified autologous T cells into two young girls with ADA-SCID, would not take place until 1990 (2). Today's lecture will summarize progress since that time in one area, that of in vivo gene transfer for genetic disease. I will describe progress in two areas, gene therapy for the bleeding disorder hemophilia B, and for a subset of retinal degenerative disorders termed Leber's congenital amaurosis, due to mutations in the gene encoding retinal pigment epithelium-specific 65 kilodalton protein (RPE65). This lecture will demonstrate the interconnected nature of progress in these two areas, as careful delineation of the obstacles in hemophilia led to the realization that success could be achieved in Leber's.

  4. Dupuytren Disease Infiltrating a Full-Thickness Skin Graft.

    PubMed

    Wade, Ryckie George; Igali, Laszlo; Figus, Andrea

    2016-08-01

    Although the role of the skin in the development and propagation of Dupuytren disease remains unclear, dermofasciectomy and full-thickness skin grafting (FTSG) appears to delay recurrence. In 2011, a 71-year-old, left-handed man presented with recurrent Dupuytren disease in the dominant hand. In 1991, he originally underwent a primary dermofasciectomy and FTSG for Dupuytren disease involving the palmar skin. Twenty years later, the left middle finger was drawn into flexion by a recurrent cord, and the old graft and adjacent palmar skin were clinically involved by fibromatosis. We performed a revision dermofasciectomy and FTSG. Microscopic analysis of the excised graft demonstrated dense infiltration of the entire skin graft by Dupuytren disease, with areas of active and burnt-out fibromatosis distinct from hypertrophic scarring. This report of Dupuytren fibromatosis infiltrating a skin graft raises questions about the pathophysiology of Dupuytren disease. Copyright © 2016 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

  5. A pseudo-outbreak of skin disease in British troops.

    PubMed Central

    Croft, A; Smith, H; Creamer, I

    1996-01-01

    When a newspaper report claimed that a serious outbreak of skin disease had occurred in British Army troops stationed at the Bocac Dam, in western Bosnia, all troops at the Bocac Dam location (n = 96), followed by a matched control group of troops (n = 91) at a nearby location, were examined by two investigators. 14% of the study population and 21% of the control group were found to have skin disorders. Most were complaints that are commonly encountered in general medical practice. There was a striking absence of skin infestations. The historical consultation rate for skin disorders had not increased. It was concluded that an outbreak of skin disease had not occurred in British troops guarding the dam. This epidemiological study shows that, even under conditions of modern field hygiene, up to one in five soldiers will have skin disease. Skin infestations, however, have become progressively less common during military campaigns this century, probably because of better personal hygiene, good preventive medicine practices and better access to effective health care. PMID:8976888

  6. The global burden of skin disease in 2010: an analysis of the prevalence and impact of skin conditions.

    PubMed

    Hay, Roderick J; Johns, Nicole E; Williams, Hywel C; Bolliger, Ian W; Dellavalle, Robert P; Margolis, David J; Marks, Robin; Naldi, Luigi; Weinstock, Martin A; Wulf, Sarah K; Michaud, Catherine; J L Murray, Christopher; Naghavi, Mohsen

    2014-06-01

    The Global Burden of Disease (GBD) Study 2010 estimated the GBD attributable to 15 categories of skin disease from 1990 to 2010 for 187 countries. For each of the following diseases, we performed systematic literature reviews and analyzed resulting data: eczema, psoriasis, acne vulgaris, pruritus, alopecia areata, decubitus ulcer, urticaria, scabies, fungal skin diseases, impetigo, abscess, and other bacterial skin diseases, cellulitis, viral warts, molluscum contagiosum, and non-melanoma skin cancer. We used disability estimates to determine nonfatal burden. Three skin conditions, fungal skin diseases, other skin and subcutaneous diseases, and acne were in the top 10 most prevalent diseases worldwide in 2010, and eight fell into the top 50; these additional five skin problems were pruritus, eczema, impetigo, scabies, and molluscum contagiosum. Collectively, skin conditions ranged from the 2nd to 11th leading cause of years lived with disability at the country level. At the global level, skin conditions were the fourth leading cause of nonfatal disease burden. Using more data than has been used previously, the burden due to these diseases is enormous in both high- and low-income countries. These results argue strongly to include skin disease prevention and treatment in future global health strategies as a matter of urgency.

  7. Disease-Phenotype Deconvolution in Genetic Eye Diseases Using Online Mendelian Inheritance in Man.

    PubMed

    Pandey, Priyanka; Acharya, Moulinath

    2016-05-01

    Capturing organ-specific phenomes in genetic diseases is an uphill task for the eye as it comprises tissue types derived from all three germinal layers. We attempted to deconstruct genetic eye diseases (GEDs) into primary phenotypic features, to understand the complex genome-phenome relationship in GEDs. Using phenotype, molecular basis, and gene description features in OMIM as a primary resource, we analyzed gene-phenotype information. All ocular and systemic phenotypes were categorized and ranked based on occurrence. Clustering was performed on shared ocular features to identify genetic interactions and the largest cluster of each phenotype was used for functional analyses. We collected 527 GEDs associated with 440 unique protein-coding genes. We indexed 787 ocular and 3094 systemic features, for an average of 2.17 ocular and 8.14 systemic features, respectively, per disease unit. The most common ocular features included nystagmus, hypertelorism, and myopia, while neurological and skeletal are the most common systemic groups associated with GEDs. Functional analyses revealed pathways relevant to GEDs (e.g., extracellular matrix organization in ONH3 [glaucoma]) and protein metabolism in EOM35 (nystagmus) phenotype clusters. Our work imparts a structure in dissecting GEDs into unique phenotypes to study the relationship between genes and diseases involving the eye.

  8. Electrochemical Skin Conductance in Diabetic Kidney Disease.

    PubMed

    Freedman, Barry I; Smith, Susan Carrie; Bagwell, Benjamin M; Xu, Jianzhao; Bowden, Donald W; Divers, Jasmin

    2015-01-01

    There is a need to identify patients with diabetic kidney disease (DKD) using noninvasive, cost-effective screening tests. Sudoscan®, a device using electrochemical skin conductance (ESC) to measure sweat gland dysfunction, is valuable for detecting peripheral neuropathy. ESC was tested for association with DKD (estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2)) in 383 type 2 diabetes mellitus (T2D)-affected patients; diagnostic thresholds were determined in 540 patients. Relationships between ESC with eGFR and urine albumin:creatinine ratio (UACR) were assessed in 202 European Americans and 181 African Americans with T2D. In 92 European American DKD cases and 110 T2D non-nephropathy controls, respectively, mean (SD) ages were 69 (9.7) and 61 (10.8) years, hemoglobin A1c (HbA1c) 7.4 (1.2) and 7.4 (1.3)%, eGFR 29.6 (12.2) and 87.8 (14.2) ml/min/1.73 m(2), and UACR 1,214 (1,705) and 7.5 (5.8) mg/g. In 57 African American cases and 124 controls, respectively, mean (SD) ages were 64.0 (11.9) and 59.5 (9.7) years, HbA1c 7.4 (1.3) and 7.5 (1.7)%, eGFR 29.6 (13.3) and 90.2 (16.2) ml/min/1.73 m(2), and UACR 1,172 (1,564) and 7.8 (7.1) mg/g. Mean (SD) ESC (μS) was lower in cases than controls (European Americans: case/control hands 49.5 (18.5)/62.3 (16.2); feet 62.1 (17.9)/73.6 (13.8), both p < 1.3 × 10(-6); African Americans: case/control hands 39.8 (19.0)/48.5 (17.1); feet 53.2 (21.3)/63.5 (19.4), both p ≤ 0.01). Adjusting for age, sex, body mass index and HbA1c, hands and feet ESC associated with eGFR <60 ml/min/1.73 m(2) (p ≤ 7.2 × 10(-3)), UACR >30 mg/g (p ≤ 7.0 × 10(-3)), UACR >300 mg/g (p ≤ 8.1 × 10(-3)), and continuous traits eGFR and UACR (both p ≤ 5.0 × 10(-9)). HbA1c values were not useful for risk stratification. ESC measured using Sudoscan® is strongly associated with DKD in African Americans and European Americans. ESC is a useful screening test to identify DKD in patients with T2D.

  9. Electrochemical skin conductance in diabetic kidney disease

    PubMed Central

    Freedman, Barry I.; Smith, S. Carrie; Bagwell, Benjamin M.; Xu, Jianzhao; Bowden, Donald W.; Divers, Jasmin

    2015-01-01

    Background There is a need to identify patients with diabetic kidney disease (DKD) using non-invasive, cost-effective screening tests. Sudoscan®, a device using electrochemical skin conductance (ESC) to measure sweat gland dysfunction, is valuable for detecting peripheral neuropathy. ESC was tested for association with DKD (estimated glomerular filtration rate [eGFR] <60 ml/min/1.73m2) in 383 type 2 diabetes mellitus (T2D)-affected patients; diagnostic thresholds were determined in 540 patients. Methods Relationships between ESC with eGFR and urine albumin:creatinine ratio (UACR) were assessed in 202 European Americans (EA) and 181 African Americans (AA) with T2D. Results In 92 EA DKD cases and 110 T2D non-nephropathy controls, respectively, mean(SD) ages were 68.9(9.8) and 61.1(10.8) years, HbA1c 7.4(1.2) and 7.4(1.3)%, eGFR 29.5(12.2) and 87.7(14.1) ml/min/1.73m2, and UACR 1227(1710) and 7.6(5.9) mg/g. In 57 AA cases and 124 controls, respectively, mean (SD) ages were 64.0(12.0) and 59.5(9.7) years, HbA1c 7.4(1.3) and 7.6 (1.7)%, eGFR 29.7(13.3) and 90.2(16.2) ml/min/1.73m2, and UACR 1172(1564) and 7.8(7.1) mg/g. Mean(SD) ESC (μS) was lower in cases than controls (EA: case/control hands 49.3(18.5)/62.4(16.2); feet 62.2(18.0)/73.4(13.9), both p<5.8×10−7; AA: case/control hands 39.8(19.0)/48.5(17.1); feet 53.2(21.3)/63.5(19.4), both p≤0.01). Adjusting for age, sex, BMI and HbA1c, hands and feet ESC associated with eGFR <60 ml/min/1.73m2 (p≤7.2×10−3), UACR >30 mg/g (p≤7.0×10−3), UACR >300 mg/g (p≤8.1×10−3), and continuous traits eGFR and UACR (both p≤5.0×10−9). HbA1c values were not useful for risk stratification. Conclusions ESC measured using Sudoscan® is strongly associated with DKD in AA and EA. ESC is a useful screening test to identify DKD in patients with T2D. PMID:26228248

  10. A novel mutation in LRSAM1 causes axonal Charcot-Marie-Tooth disease with dominant inheritance

    PubMed Central

    2014-01-01

    Background Charcot-Marie-Tooth disease (CMT) refers to a heterogeneous group of genetic motor and sensory neuropathies. According to the primary site of damage, a distinction is made between demyelinating and axonal forms (CMT1 and 2, respectively, when inherited as an autosomal dominant trait). Leucine-rich repeat and sterile alpha motif-containing protein 1 (LRSAM1) is a ubiquitin-protein ligase with a role in sorting internalised cell-surface receptor proteins. So far, mutations in the LRSAM1 gene have been shown to cause axonal CMT in three different families and can confer either dominant or recessive transmission of the disease. Case presentation We have identified a novel mutation in LRSAM1 in a small family with dominant axonal CMT. Electrophysiological studies show evidence of a sensory axonal neuropathy and are interesting in so far as giant motor unit action potentials (MUAPs) are present on needle electromyography (EMG), while motor nerve conduction studies including compound motor action potential (CMAP) amplitudes are completely normal. The underlying mutation c.2046+1G >T results in the loss of a splice donor site and the inclusion of 63 additional base pairs of intronic DNA into the aberrantly spliced transcript. This disrupts the catalytically active RING (Really Interesting New Gene) domain of LRSAM1. Conclusions Our findings suggest that, beyond the typical length-dependent degeneration of motor axons, damage of cell bodies in the anterior horn might play a role in LRSAM1-associated neuropathies. Moreover, in conjunction with other data in the literature, our results support a model, by which disruption of the C-terminal RING domain confers dominant negative properties to LRSAM1. PMID:24894446

  11. The role of the inherited disorders of hemoglobin, the first "molecular diseases," in the future of human genetics.

    PubMed

    Weatherall, David J

    2013-01-01

    Although the inherited hemoglobin disorders were the first genetic diseases to be explored at the molecular level, they still have important messages for the future of medical genetics. In particular, they can offer a better understanding of the evolutionary and population biology of genetic disease, the mechanisms that underlie the phenotypic diversity of monogenic disease, and how, by developing appropriate partnerships, richer countries can help low-income countries to evolve programs for the control and management of these diseases where, in many cases, they are particularly common.

  12. Zebrafish as a model system to study heritable skin diseases.

    PubMed

    Li, Qiaoli; Uitto, Jouni

    2013-01-01

    Heritable skin diseases represent a broad spectrum of clinical manifestations due to mutations in ∼500 different genes. A number of model systems have been developed to advance our understanding of the pathomechanisms of genodermatoses. Zebrafish (Danio rerio), a freshwater vertebrate, has a well-characterized genome, the expression of which can be easily manipulated. The larvae develop rapidly, with all major organs having largely developed by 5-6 days post-fertilization, including the skin which consists at that stage of the epidermis comprising two cell layers and separated from the dermal collagenous matrix by a basement membrane zone. Here, we describe the use of morpholino-based antisense oligonucleotides to knockdown the expression of specific genes in zebrafish and to examine the consequent knockdown efficiency and skin phenotypes. Zebrafish can provide a useful model system to study heritable skin diseases.

  13. Identification of Malassezia pachydermatis from healthy and diseased human skin.

    PubMed

    Prohic, Asja; Kasumagic-Halilovic, Emina

    2009-01-01

    Malassezia pachydermatis is the only species in the genus Malassezia that is classically considered to be zoophilic. This yeast is only occasionally isolated from human skin, although it has been found to cause septic epidemics, especially in neonates. The aim of our study was to investigate the prevalence of M. pachydermatis on the skin of patients with Malassezia-associated diseases and of healthy subjects. One hundred and sixty skin scrapings from patients with pityriasis versicolor (PV), seborrhoeic dermatitis (SD), psoriasis (PS) and healthy individuals, forty each, were inoculated into Sabouraud dextrose agar and into modified Dixon agar. The yeasts isolated were identified according to their macroscopic and microscopic features and physiological properties. M. globosa was the most commonly isolated species in lesional skin of PV (65%) and PS (55%), M. restricta in lesional skin of SD (27.5%), while M. sympodialis was the predominant species recovered from healthy skin, representing 30% of the isolates. Zoophilic species, M. pachydermatis was identified in only one case, from the lesional skin of SD. The results of our study confirm that M. pachydermatis is not a member of the normal human flora and its presence on human skin is rare and indicates transmission from an external source.

  14. Epilepsy-related sudden unexpected death: targeted molecular analysis of inherited heart disease genes using next-generation DNA sequencing.

    PubMed

    Hata, Yukiko; Yoshida, Koji; Kinoshita, Koshi; Nishida, Naoki

    2017-05-01

    Inherited heart disease causing electric instability in the heart has been suggested to be a risk factor for sudden unexpected death in epilepsy (SUDEP). The purpose of this study was to reveal the correlation between epilepsy-related sudden unexpected death (SUD) and inherited heart disease. Twelve epilepsy-related SUD cases (seven males and five females, aged 11-78 years) were examined. Nine cases fulfilled the criteria of SUDEP, and three cases died by drowning. In addition to examining three major epilepsy-related genes, we used next-generation sequencing (NGS) to examine 73 inherited heart disease-related genes. We detected both known pathogenic variants and rare variants with minor allele frequencies of <0.5%. The pathogenicity of these variants was evaluated and graded by eight in silico predictive algorithms. Six known and six potential rare variants were detected. Among these, three known variants of LDB3, DSC2 and KCNE1 and three potential rare variants of MYH6, DSP and DSG2 were predicted by in silico analysis as possibly highly pathogenic in three of the nine SUDEP cases. Two of three cases with desmosome-related variants showed mild but possible significant right ventricular dysplasia-like pathology. A case with LDB3 and MYH6 variants showed hypertrabeculation of the left ventricle and severe fibrosis of the cardiac conduction system. In the three drowning death cases, one case with mild prolonged QT interval had two variants in ANK2. This study shows that inherited heart disease may be a significant risk factor for SUD in some epilepsy cases, even if pathological findings of the heart had not progressed to an advanced stage of the disease. A combination of detailed pathological examination of the heart and gene analysis using NGS may be useful for evaluating arrhythmogenic potential of epilepsy-related SUD. © 2016 International Society of Neuropathology.

  15. The Diagnostic Value of Skin Disease Diagnosis Expert System

    PubMed Central

    Jeddi, Fatemeh Rangraz; Arabfard, Masoud; Arabkermany, Zahra; Gilasi, Hamidreza

    2016-01-01

    Background: Evaluation is a necessary measure to ensure the effectiveness and efficiency of all systems, including expert systems. The aim of this study was to determine the diagnostic value of expert system for diagnosis of complex skin diseases. Methods: A case-control study was conducted in 2015 to determine the diagnostic value of an expert system. The study population included patients who were referred to Razi Specialized Hospital, affiliated to Tehran University of Medical Sciences. The control group was selected from patients without the selected skin diseases. Data collection tool was a checklist of clinical signs of diseases including pemphigus vulgaris, lichen planus, basal cell carcinoma, melanoma, and scabies. The sample size formula estimated 400 patients with skin diseases selected by experts and 200 patients without the selected skin diseases. Patient selection was undertaken with randomized stratified sampling and their sign and symptoms were logged into the system. Physician’s diagnosis was determined as the gold standard and was compared with the diagnosis of expert system by SPSS software version 16 and STATA. Kappa statistics, indicators of sensitivity, specificity, accuracy and confidence intervals were calculated for each disease. An accuracy of 90% was considered appropriate. Results: Comparing the results of expert system and physician’s diagnosis at the evaluation stage showed an accuracy of 97.1%, sensitivity of 97.5% and specificity of 96.5% The Kappa test indicated a high agreement of 93.6%. Conclusion: The expert system can diagnose complex skin diseases. Development of such systems is recommended to identify all skin diseases. PMID:27046943

  16. The canine and feline skin microbiome in health and disease.

    PubMed

    Weese, J Scott

    2013-02-01

    The skin harbours a diverse and abundant, yet inadequately investigated, microbial population. The population is believed to play an important role in both the pathophysiology and the prevention of disease, through a variety of poorly explored mechanisms. Early studies of the skin microbiota in dogs and cats reported a minimally diverse microbial composition of low overall abundance, most probably as a reflection of the limitations of testing methodology. Despite these limitations, it was clear that the bacterial population of the skin plays an important role in disease and in changes in response to both infectious and noninfectious diseases. Recent advances in technology are challenging some previous assumptions about the canine and feline skin microbiota and, with preliminary application of next-generation sequenced-based methods, it is apparent that the diversity and complexity of the canine skin microbiome has been greatly underestimated. A better understanding of this complex microbial population is critical for elucidation of the pathophysiology of various dermatological (and perhaps systemic) diseases and to develop novel ways to manipulate this microbial population to prevent or treat disease.

  17. Disturbed skin barrier in children with chronic kidney disease.

    PubMed

    Wojtowicz-Prus, Elzbieta; Kilis-Pstrusinska, Katarzyna; Reich, Adam; Zachwieja, Katarzyna; Miklaszewska, Monika; Szczepanska, Maria; Szepietowski, Jacek C

    2015-02-01

    There are limited data on skin lesions in children with end-stage renal failure. The aim of the study was an evaluation of the skin barrier in children with different stages of chronic kidney disease (CKD). The prevalence of xerosis, its severity, as well as its link selected demographic factors, were examined. The study included 103 children: 72 with CKD stages 3-5 (38 on conservative treatment and 34 on dialysis) and 31 patients with primary monosymptomatic nocturnal enuresis as a control group. Initially, the study subjects described the localisation and severity of dry skin by themselves. Next, clinical evaluation of xerosis, non-invasive corneometric assessment of epidermis moisturising and the measurement of transepidermal water loss were performed. Most CKD children reported dry skin. The problem of xerosis was identified more frequently in patients on dialysis (67.6 %) than on conservative treatment (42.1 %) (p = 0.01). CKD patients divided according to skin dryness did not differ with regards to age, sex, initial kidney disease and CKD duration. Disturbed skin barrier is an important concern of children with CKD, intensifying as the disease progresses. This symptom occurs on early stages of CKD and it should be taken into consideration in the CKD management.

  18. Letter to Editor: Chemokine Network Involved in Inflammatory Skin Diseases.

    PubMed

    Shaik-Dasthagirisaheb, Y B; Conti, P

    2015-01-01

    Chemokines are low-molecular-weight chemotactic proteins that regulate the trafficking of leukocytes to inflammatory sites and may recruit inflammatory cells to the epidermis. Chemokines are produced by many immune cells such as macrophages, mast cells, T lymphocytes and others, in response to pro-inflammatory stimuli including IL-1, TNF and LPS. Immune cells which participate in inflammatory skin disorders, upon activation express several adhesive and immune receptors such as P-selectin, CD40 ligand, and Toll-like receptors on their surface, and generate cytokines/chemokines. Chemokines have crucial functions in inflammation, and cell dysregulations and they are recognized as potentially important in diverse skin pathologies associated with the severity of disease. Injection of chemokines in the rat skin provoke the recruitment of inflammatory cells, release of cytokines, and activation of transcription of histidine decarboxylase (HDC), the enzyme responsible for the generation of histamine from histidine, which may cause fatal anaphylactic shock. Therefore, the use of anti-chemokines for inflammatory skin diseases remains a promising therapeutic approach. However, the complete role of chemokines in inflammatory skin diseases remains to be further studied. Here we report the relationship between chemokines and skin inflammation. © 2015 by the Association of Clinical Scientists, Inc.

  19. Plastics derived endocrine disruptors (BPA, DEHP and DBP) induce epigenetic transgenerational inheritance of obesity, reproductive disease and sperm epimutations.

    PubMed

    Manikkam, Mohan; Tracey, Rebecca; Guerrero-Bosagna, Carlos; Skinner, Michael K

    2013-01-01

    Environmental compounds are known to promote epigenetic transgenerational inheritance of adult onset disease in subsequent generations (F1-F3) following ancestral exposure during fetal gonadal sex determination. The current study was designed to determine if a mixture of plastic derived endocrine disruptor compounds bisphenol-A (BPA), bis(2-ethylhexyl)phthalate (DEHP) and dibutyl phthalate (DBP) at two different doses promoted epigenetic transgenerational inheritance of adult onset disease and associated DNA methylation epimutations in sperm. Gestating F0 generation females were exposed to either the "plastics" or "lower dose plastics" mixture during embryonic days 8 to 14 of gonadal sex determination and the incidence of adult onset disease was evaluated in F1 and F3 generation rats. There were significant increases in the incidence of total disease/abnormalities in F1 and F3 generation male and female animals from plastics lineages. Pubertal abnormalities, testis disease, obesity, and ovarian disease (primary ovarian insufficiency and polycystic ovaries) were increased in the F3 generation animals. Kidney and prostate disease were only observed in the direct fetally exposed F1 generation plastic lineage animals. Analysis of the plastics lineage F3 generation sperm epigenome previously identified 197 differential DNA methylation regions (DMR) in gene promoters, termed epimutations. A number of these transgenerational DMR form a unique direct connection gene network and have previously been shown to correlate with the pathologies identified. Observations demonstrate that a mixture of plastic derived compounds, BPA and phthalates, can promote epigenetic transgenerational inheritance of adult onset disease. The sperm DMR provide potential epigenetic biomarkers for transgenerational disease and/or ancestral environmental exposures.

  20. Plastics Derived Endocrine Disruptors (BPA, DEHP and DBP) Induce Epigenetic Transgenerational Inheritance of Obesity, Reproductive Disease and Sperm Epimutations

    PubMed Central

    Manikkam, Mohan; Tracey, Rebecca; Guerrero-Bosagna, Carlos; Skinner, Michael K.

    2013-01-01

    Environmental compounds are known to promote epigenetic transgenerational inheritance of adult onset disease in subsequent generations (F1–F3) following ancestral exposure during fetal gonadal sex determination. The current study was designed to determine if a mixture of plastic derived endocrine disruptor compounds bisphenol-A (BPA), bis(2-ethylhexyl)phthalate (DEHP) and dibutyl phthalate (DBP) at two different doses promoted epigenetic transgenerational inheritance of adult onset disease and associated DNA methylation epimutations in sperm. Gestating F0 generation females were exposed to either the “plastics” or “lower dose plastics” mixture during embryonic days 8 to 14 of gonadal sex determination and the incidence of adult onset disease was evaluated in F1 and F3 generation rats. There were significant increases in the incidence of total disease/abnormalities in F1 and F3 generation male and female animals from plastics lineages. Pubertal abnormalities, testis disease, obesity, and ovarian disease (primary ovarian insufficiency and polycystic ovaries) were increased in the F3 generation animals. Kidney and prostate disease were only observed in the direct fetally exposed F1 generation plastic lineage animals. Analysis of the plastics lineage F3 generation sperm epigenome previously identified 197 differential DNA methylation regions (DMR) in gene promoters, termed epimutations. A number of these transgenerational DMR form a unique direct connection gene network and have previously been shown to correlate with the pathologies identified. Observations demonstrate that a mixture of plastic derived compounds, BPA and phthalates, can promote epigenetic transgenerational inheritance of adult onset disease. The sperm DMR provide potential epigenetic biomarkers for transgenerational disease and/or ancestral environmental exposures. PMID:23359474

  1. Old diseases and contemporary crisis. Inherited blood disorders in the Sultanate of Oman.

    PubMed

    Beaudevin, Claire

    2013-01-01

    This contribution draws on ethnographic research conducted in Oman on inherited blood disorders (IBD). By interpreting results from population genomics studies that trace mutation processes over centuries of human activities, lay-representations of IBD often consider them historical evidence. The perceived spread of IBD in Oman may thus provide unusual historical depth in a country where past conflicts have been erased from historiography and representations of time are politically prescribed. Through the notions of crisis and diversification, this contribution shows how IBD's chronicity challenges the healthcare system and became a national issue, politically labelled as urgent. The paper casts light on several aspects of contemporary Omani society: it first addresses the dynamics of disease taxonomies - although biomedically described in the early twentieth century, IBD were not individualized within local nosologies until the 1970s. Secondly, it shows how biomedical knowledge about IBD led to diversification within the healthcare system, through the introduction of clinical genetics, genomics, and community genetics. Thirdly, it attempts to broach modalities of the biopower exerted by the Omani regime over its citizens: IBD are targeted by various public health measures that jeopardize patients' autonomy by aiming to control their bodies through their matrimonial behaviour. In addition, two aspects of the intersections between Omani social hierarchy and IBD are noteworthy: the creation of a patients' association that constitutes a potential disturbance of the social order; and the way IBD mutations traced by genomics are considered direct historical documents that challenge representations of the recently crafted 'Omanity' in a context of regional concern regarding national identities' durability.

  2. A Population-Based Genomic Study of Inherited Metabolic Diseases Detected Through Newborn Screening.

    PubMed

    Park, Kyoung Jin; Park, Seungman; Lee, Eunhee; Park, Jong Ho; Park, June Hee; Park, Hyung Doo; Lee, Soo Youn; Kim, Jong Won

    2016-11-01

    A newborn screening (NBS) program has been utilized to detect asymptomatic newborns with inherited metabolic diseases (IMDs). There have been some bottlenecks such as false-positives and imprecision in the current NBS tests. To overcome these issues, we developed a multigene panel for IMD testing and investigated the utility of our integrated screening model in a routine NBS environment. We also evaluated the genetic epidemiologic characteristics of IMDs in a Korean population. In total, 269 dried blood spots with positive results from current NBS tests were collected from 120,700 consecutive newborns. We screened 97 genes related to NBS in Korea and detected IMDs, using an integrated screening model based on biochemical tests and next-generation sequencing (NGS) called NewbornSeq. Haplotype analysis was conducted to detect founder effects. The overall positive rate of IMDs was 20%. We identified 10 additional newborns with preventable IMDs that would not have been detected prior to the implementation of our NGS-based platform NewbornSeq. The incidence of IMDs was approximately 1 in 2,235 births. Haplotype analysis demonstrated founder effects in p.Y138X in DUOXA2, p.R885Q in DUOX2, p.Y439C in PCCB, p.R285Pfs*2 in SLC25A13, and p.R224Q in GALT. Through a population-based study in the NBS environment, we highlight the screening and epidemiological implications of NGS. The integrated screening model will effectively contribute to public health by enabling faster and more accurate IMD detection through NBS. This study suggested founder mutations as an explanation for recurrent IMD-causing mutations in the Korean population.

  3. A Population-Based Genomic Study of Inherited Metabolic Diseases Detected Through Newborn Screening

    PubMed Central

    Park, Kyoung-Jin; Park, Seungman; Lee, Eunhee; Park, Jong-Ho; Park, June-Hee; Park, Hyung-Doo; Lee, Soo-Youn

    2016-01-01

    Background A newborn screening (NBS) program has been utilized to detect asymptomatic newborns with inherited metabolic diseases (IMDs). There have been some bottlenecks such as false-positives and imprecision in the current NBS tests. To overcome these issues, we developed a multigene panel for IMD testing and investigated the utility of our integrated screening model in a routine NBS environment. We also evaluated the genetic epidemiologic characteristics of IMDs in a Korean population. Methods In total, 269 dried blood spots with positive results from current NBS tests were collected from 120,700 consecutive newborns. We screened 97 genes related to NBS in Korea and detected IMDs, using an integrated screening model based on biochemical tests and next-generation sequencing (NGS) called NewbornSeq. Haplotype analysis was conducted to detect founder effects. Results The overall positive rate of IMDs was 20%. We identified 10 additional newborns with preventable IMDs that would not have been detected prior to the implementation of our NGS-based platform NewbornSeq. The incidence of IMDs was approximately 1 in 2,235 births. Haplotype analysis demonstrated founder effects in p.Y138X in DUOXA2, p.R885Q in DUOX2, p.Y439C in PCCB, p.R285Pfs*2 in SLC25A13, and p.R224Q in GALT. Conclusions Through a population-based study in the NBS environment, we highlight the screening and epidemiological implications of NGS. The integrated screening model will effectively contribute to public health by enabling faster and more accurate IMD detection through NBS. This study suggested founder mutations as an explanation for recurrent IMD-causing mutations in the Korean population. PMID:27578510

  4. The skin in autoimmune diseases-Unmet needs.

    PubMed

    Kuhn, A; Landmann, A; Bonsmann, G

    2016-10-01

    Treatment of skin manifestations in systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and dermatomyositis (DM) is based on the results of only few randomized controlled trials. The first-line treatment for disfiguring and widespread cutaneous involvement in SLE is antimalarials, but some patients are therapy resistant. Recently, the monoclonal antibody belimumab was approved for SLE as an adjunct therapy for patients with autoantibody-positive disease who despite standard therapy show high disease activity, intolerance of other treatments, or an unacceptably high need for corticosteroids. However, a validated skin score has not been used to confirm the efficacy of belimumab on mucocutaneous manifestations. In SSc, another multi-systemic progressive disease, involvement of the lung, kidney, and the heart is frequently treated with corticosteroids and immunosuppressives, but therapeutic modalities for cutaneous lesions, such as skin sclerosis and digital ulcers, are limited. In the past years, treatment with the endothelin-receptor antagonist bosentan has been proven to reduce the occurrence of new digital ulcers in SSc patients but has no or limited effect on healing of digital ulcers. DM is an idiopathic autoimmune disease characterized by inflammation of the muscles and skin, which is treated with immunosuppressives. Corticosteroids are the first-line treatment for muscle involvement in DM, but skin lesions often flare by reduction or discontinuation. In summary, there is a high unmet need for new therapeutic strategies focusing on skin involvement in systemic autoimmune diseases. Therefore, innovative designs of randomized controlled trials with validated skin scores are warranted to develop new therapeutic strategies for patients with cutaneous manifestations. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Loss of corneodesmosin leads to severe skin barrier defect, pruritus, and atopy: unraveling the peeling skin disease.

    PubMed

    Oji, Vinzenz; Eckl, Katja-Martina; Aufenvenne, Karin; Nätebus, Marc; Tarinski, Tatjana; Ackermann, Katharina; Seller, Natalia; Metze, Dieter; Nürnberg, Gudrun; Fölster-Holst, Regina; Schäfer-Korting, Monika; Hausser, Ingrid; Traupe, Heiko; Hennies, Hans Christian

    2010-08-13

    Generalized peeling skin disease is an autosomal-recessive ichthyosiform erythroderma characterized by lifelong patchy peeling of the skin. After genome-wide linkage analysis, we have identified a homozygous nonsense mutation in CDSN in a large consanguineous family with generalized peeling skin, pruritus, and food allergies, which leads to a complete loss of corneodesmosin. In contrast to hypotrichosis simplex, which can be associated with specific dominant CDSN mutations, peeling skin disease is characterized by a complete loss of CDSN expression. The skin phenotype is consistent with a recent murine Cdsn knockout model. Using three-dimensional human skin models, we demonstrate that lack of corneodesmosin causes an epidermal barrier defect supposed to account for the predisposition to atopic diseases, and we confirm the role of corneodesmosin as a decisive epidermal adhesion molecule. Therefore, peeling skin disease will represent a new model disorder for atopic diseases, similarly to Netherton syndrome and ichthyosis vulgaris in the recent past.

  6. UCB Transplant of Inherited Metabolic Diseases With Administration of Intrathecal UCB Derived Oligodendrocyte-Like Cells

    ClinicalTrials.gov

    2017-04-03

    Adrenoleukodystrophy; Batten Disease; Mucopolysaccharidosis II; Leukodystrophy, Globoid Cell; Leukodystrophy, Metachromatic; Neimann Pick Disease; Pelizaeus-Merzbacher Disease; Sandhoff Disease; Tay-Sachs Disease; Brain Diseases, Metabolic, Inborn

  7. Skin-specific drug delivery: a rapid solution to skin diseases?

    PubMed

    Sadik, Christian D; Zillikens, Detlef

    2013-09-01

    In this issue of The Journal of Investigative Dermatology, Kouno et al. achieve skin-specific drug delivery using an antibody to deliver substances in a highly specific manner to nontransformed cells. They make use of a nonpathogenic anti-desmoglein 3 autoantibody that had been derived from a patient with pemphigus vulgaris to deliver drugs to the surface of keratinocytes. This approach may turn out to be a new "magic bullet", thereby revolutionizing the therapy of skin disease. The authors then used a conjugate of this antibody with a new drug entity, TNF-related apoptosis-inducing ligand, to demonstrate, as a proof-of-principle, that their approach has the potential to facilitate the treatment of both cancerous and inflammatory skin diseases.

  8. Genetic skin diseases related to desmosomes and corneodesmosomes.

    PubMed

    Ishida-Yamamoto, Akemi; Igawa, Satomi

    2014-05-01

    The integrity of the epidermis depends on the cohesion between keratinocytes, and desmosomes are the main adhesion structures. When cells become cornified, desmosomes are modified and transformed into corneodesmosomes. Mutations in the genes encoding desmosomal components underlie several skin diseases including palmoplantar keratoderma and forms of epidermolysis bullosa, indicating the importance of desmosomes as mechanical stress-bearing structures. Other types of genetic defects in a desmosome component (desmoglein 1), a corneodesmosome component (corneodesmosin), and an inhibitor for proteases involved in corneodesmosome degradation (LEKTI) result in three clinically overlapping conditions: SAM syndrome, an inflammatory type of peeling skin disease, and Netherton syndrome. All three result in allergies to multiple allergens due to severe barrier impairment. Conversely, impaired corneodesmosomal degradation due to matriptase mutations could lead to ichthyosis. By discovering the diverse clinical phenotypes of these diseases, we can enrich our understanding of the multifunctional roles of desmosomes and corneodesmosomes in skin biology.

  9. MicroRNAs in Human Diseases: From Autoimmune Diseases to Skin, Psychiatric and Neurodegenerative Diseases

    PubMed Central

    2011-01-01

    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. PMID:22194706

  10. MicroRNAs in Human Diseases: From Autoimmune Diseases to Skin, Psychiatric and Neurodegenerative Diseases.

    PubMed

    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.

  11. Numerical identity: the creation of tri-parental embryos to correct inherited mitochondrial disease.

    PubMed

    Legge, Michael; Fitzgerald, Ruth

    2013-11-01

    Inherited mitochondrial disorders affect between 1 in 5000 to 1 in 8000 people. These are a heterogeneous group of maternally-inherited disorders, with an array of outcomes such as heart and liver failure, defects in energy metabolism, blindness, deafness, loss of motor skills and premature death. Recently the Human Fertilisation and Embryology Authority provided advice to the UK Government to permit the use of enucleated donated oocytes with normal (wild-type) mitochondria (a currently prohibited IVF technique) to be used as recipients of nuclear DNA from intending mothers to overcome transmission of mitochondrial disorders. In this short communication we present the basis for this radical new IVF technology, and discuss the implications for its use both in the context of treating a group of inherited disorders and the current New Zealand IVF legislation.

  12. Functions of the skin microbiota in health and disease.

    PubMed

    Sanford, James A; Gallo, Richard L

    2013-11-30

    The skin, the human body's largest organ, is home to a diverse and complex variety of innate and adaptive immune functions. Despite this potent immune system present at the cutaneous barrier, the skin encourages colonization by microorganisms. Characterization these microbial communities has enhanced our knowledge of the ecology of organisms present in normal skin; furthermore, studies have begun to bring to light the intimate relationships shared between host and resident microbes. In particular, it is apparent that just as host immunological factors and behaviors shape the composition of these communities, microbes present on the skin greatly impact the functions of human immunity. Thus, today the skin immune system should be considered a collective mixture of elements from the host and microbes acting in a mutualistic relationship. In this article we will review recent findings of the interactions of skin microbial communities with host immunity, and discuss the role that dysbiosis of these communities plays in diseases of the skin. Copyright © 2013. Published by Elsevier Ltd.

  13. Signaling by reactive oxygen and nitrogen species in skin diseases.

    PubMed

    Afanas'ev, Igor B

    2010-06-01

    For many years the formation of reactive oxygen and nitrogen species (ROS) and (RNS) in living organisms has been considered to be dangerous phenomenon due to their damaging action on biomolecules. However, present studies demonstrated another important activity of ROS and RNS: their signaling functions in physiological and pathological processes. In this work we discuss the new data concerning a role of ROS and RNS in many enzymatic/gene cascades causing damaging changes during the development of skin diseases and pathological disorders (skin cancer, the toxic effects of irradiation on the skin, and skin wounding). It has been suggested that the enhancement of ROS formation in tumor cells through the inactivation of mitochondrial MnSOD or the activation of NADPH oxidase leads to apoptosis and might be applied for developing a new cancer therapy. On the other hand ROS overproduction might stimulate malignant transformation of melanoma. Role of ROS signaling is also considered in the damaging action of UVA, UVB, and IRA irradiation on the skin and the processes of wound healing. In the last part of review the possibility of the right choice of antioxidants and free radical scavengers for the treatment of skin disease is discussed.

  14. Over-the-counter topical skin products--a common component of skin disease management.

    PubMed

    Vogel, Curt A; Balkrishnan, Rajesh; Fleischer, Alan B; Cayce, Kimberly A; Feldman, Steven R

    2004-07-01

    Over-the-counter (OTC) products are widely recommended by physicians and utilized by the public for the treatment and prevention of disease. The use of OTC drugs has been studied extensively, but the patterns of physician recommendations for OTC topical skin products and the characteristics associated with patients receiving such recommendations remain unclear. We aimed to look at patterns of OTC topical skin product recommendations by physician specialty, patient demographics, geographical region, diagnosis, and metropolitan status to determine whether there are differences in the utilization of these products in the treatment of dermatologic conditions. We analyzed office-based physician visits for OTC topical skin product recommendations recorded in the 1995 to 2000 National Ambulatory Medical Care Survey (NAMCS). From 1995 to 2000, there were an estimated 36 million physician recommendations for OTC topical skin products. Although dermatologists were responsible for 53.8% of recommendations, pediatricians had the largest proportion of recommendations per prescription recommendation (OTC/Rx=0.58). Women patients, white patients, patients younger than 20 years, urban residents, and those living in the Southern United States received greater numbers of OTC topical skin product recommendations. Of the leading products recommended, hydrocortisone (27.6%), anti-infectives (23.4%), and moisturizers (13.4%) were the most common. OTC topical skin product recommendations by US physicians are substantial, particularly among dermatologists and primary care physicians. Physician specialty, gender, race, and age appear to be factors associated with those recommendations.

  15. Sjögren-Larsson syndrome: a rare disease of the skin and central nervous system.

    PubMed

    Roy, Ujjawal; Das, Urmila; Pandit, Alak; Debnath, Anjan

    2016-04-19

    Sjögren-Larsson syndrome is a recessively inherited disease caused by a deficiency of fatty aldehyde dehydrogenase with presenting features of congenital ichthyosis, spastic diplegia or tetraplegia, and mental retardation. The basic pathogenic mechanism is deficiency of fatty aldehyde dehydrogenase, which may lead to an accumulation of long-chain fatty alcohols hampering cell membrane integrity, which further disrupts the barrier function of skin and white matter of the brain. MRI of the brain shows diffuse symmetrical white matter hyperintensities on T2-weighted sequences. Although there is no definitive cure for Sjögren-Larsson syndrome, most patients survive until adulthood and management involves therapies directed towards controlling specific problems. We present a case of Sjögren-Larsson syndrome with classical clinical and MRI features, including a few distinctly atypical characteristics in various attributes. 2016 BMJ Publishing Group Ltd.

  16. Inherited epidermolysis bullosa

    PubMed Central

    2010-01-01

    Inherited epidermolysis bullosa (EB) encompasses a number of disorders characterized by recurrent blister formation as the result of structural fragility within the skin and selected other tissues. All types and subtypes of EB are rare; the overall incidence and prevalence of the disease within the United States is approximately 19 per one million live births and 8 per one million population, respectively. Clinical manifestations range widely, from localized blistering of the hands and feet to generalized blistering of the skin and oral cavity, and injury to many internal organs. Each EB subtype is known to arise from mutations within the genes encoding for several different proteins, each of which is intimately involved in the maintenance of keratinocyte structural stability or adhesion of the keratinocyte to the underlying dermis. EB is best diagnosed and subclassified by the collective findings obtained via detailed personal and family history, in concert with the results of immunofluorescence antigenic mapping, transmission electron microscopy, and in some cases, by DNA analysis. Optimal patient management requires a multidisciplinary approach, and revolves around the protection of susceptible tissues against trauma, use of sophisticated wound care dressings, aggressive nutritional support, and early medical or surgical interventions to correct whenever possible the extracutaneous complications. Prognosis varies considerably and is based on both EB subtype and the overall health of the patient. PMID:20507631

  17. Animal models of skin disease for drug discovery

    PubMed Central

    Avci, Pinar; Sadasivam, Magesh; Gupta, Asheesh; De Melo, Wanessa CMA; Huang, Ying-Ying; Yin, Rui; Rakkiyappan, Chandran; Kumar, Raj; Otufowora, Ayodeji; Nyame, Theodore; Hamblin, Michael R

    2013-01-01

    Introduction Discovery of novel drugs, treatments, and testing of consumer products in the field of dermatology is a multi-billion dollar business. Due to the distressing nature of many dermatological diseases, and the enormous consumer demand for products to reverse the effects of skin photodamage, aging, and hair loss, this is a very active field. Areas covered In this paper, we will cover the use of animal models that have been reported to recapitulate to a greater or lesser extent the features of human dermatological disease. There has been a remarkable increase in the number and variety of transgenic mouse models in recent years, and the basic strategy for constructing them is outlined. Expert opinion Inflammatory and autoimmune skin diseases are all represented by a range of mouse models both transgenic and normal. Skin cancer is mainly studied in mice and fish. Wound healing is studied in a wider range of animal species, and skin infections such as acne and leprosy also have been studied in animal models. Moving to the more consumer-oriented area of dermatology, there are models for studying the harmful effect of sunlight on the skin, and testing of sunscreens, and several different animal models of hair loss or alopecia. PMID:23293893

  18. Animal models of skin disease for drug discovery.

    PubMed

    Avci, Pinar; Sadasivam, Magesh; Gupta, Asheesh; De Melo, Wanessa Cma; Huang, Ying-Ying; Yin, Rui; Chandran, Rakkiyappan; Kumar, Raj; Otufowora, Ayodeji; Nyame, Theodore; Hamblin, Michael R

    2013-03-01

    Discovery of novel drugs, treatments, and testing of consumer products in the field of dermatology is a multi-billion dollar business. Due to the distressing nature of many dermatological diseases, and the enormous consumer demand for products to reverse the effects of skin photodamage, aging, and hair loss, this is a very active field. In this paper, we will cover the use of animal models that have been reported to recapitulate to a greater or lesser extent the features of human dermatological disease. There has been a remarkable increase in the number and variety of transgenic mouse models in recent years, and the basic strategy for constructing them is outlined. Inflammatory and autoimmune skin diseases are all represented by a range of mouse models both transgenic and normal. Skin cancer is mainly studied in mice and fish. Wound healing is studied in a wider range of animal species, and skin infections such as acne and leprosy also have been studied in animal models. Moving to the more consumer-oriented area of dermatology, there are models for studying the harmful effect of sunlight on the skin, and testing of sunscreens, and several different animal models of hair loss or alopecia.

  19. The New Human Genetics: A Cell Bank Helps Researchers Fight Inherited Disease.

    ERIC Educational Resources Information Center

    Pines, Maya

    Research in human genetics is now expanding rapidly, leading to increasingly precise ways of preventing or treating some of the 2,000 or more inherited disorders that afflict human beings. At the same time, it has produced a wealth of new ideas and techniques which are laying the groundwork for new medical science for the 21st century. Recent work…

  20. Scabies: a ubiquitous neglected skin disease.

    PubMed

    Hengge, Ulrich R; Currie, Bart J; Jäger, Gerold; Lupi, Omar; Schwartz, Robert A

    2006-12-01

    Scabies has been a scourge among human beings for thousands of years. Its worldwide occurrence with epidemics during war, famine, and overcrowding is responsible for an estimated 300 million people currently infested. Scabies refers to the various skin lesions produced by female mites, and their eggs and scybala that are deposited in the epidermis, leading to delayed-type hypersensitivity reaction. Recent immunological findings such as cross-reactivity with house dust mite allergens and an altered T-helper-1/T-helper-2 pattern contribute to a better understanding of the pathomechanism. Furthermore, progress in molecular biology and cloning of relevant antigens could enable the development of a diagnostic ELISA system and candidate vaccines in the near future. Typical and atypical clinical presentations with pruritus as a hallmark of scabies occur in young, pregnant, immunocompromised, and elderly patients and include bullous and crusted (Norwegian) manifestations as well as those masked by steroid use (scabies incognito). This article reviews scabies management strategies in developed countries and resource-poor communities as well as typical complications, including the emergence of resistance and drug-related adverse events. Other problems such as post-scabies eczema and reinfestation, and newer treatments such as ivermectin are also discussed.

  1. Zoonotic skin diseases of dogs and cats.

    PubMed

    Moriello, Karen A

    2003-12-01

    Although there are over 250 zoonotic diseases, only 30-40 of them involve dogs and cats. Transmission of zoonotic infections occurs via bites, scratches or touch; exposure to saliva, urine or feces; inhalation of particles or infectious aerosols; contact with a transport or intermediate host (e.g. ticks, fleas); or exposure to contaminated water, soil or vegetation. This paper summarizes the most important common zoonotic dermatological diseases of dogs and cats. The most common dermatological zoonoses are flea and tick infestations and the diseases they transmit; dermatophytosis; and mite infestations (Sarcoptes and Cheyletiella). Prevention of zoonotic infestations or infections can be accomplished easily by the use of routine flea and tick control, screening of new pets for dermatophytosis, and routine hand-washing.

  2. Psychological factors in skin diseases: stress and skin: facts and controversies.

    PubMed

    Orion, Edith; Wolf, Ronni

    2013-01-01

    Psychological stress (PS) has long been related to many common skin diseases and conditions, thought to be the cause of their onset or aggravation. Although clinical experience is often in concordance with this notion, apparently scientific proof can sometimes be challenging rather than straight forward. Although many data have been published, it appears that not enough good statistical evidence exists to support them. The difficulty in validating beyond a doubt the stress-skin interactions has rendered some skepticism among physicians. The gap between clinical expertise and problematic clinical research data has led scientists to bypass the need to tackle the question directly by searching the evidence in basic science.

  3. Something Old, Something New: Using Family History and Genetic Testing to Diagnose and Manage Athletes with Inherited Cardiovascular Disease.

    PubMed

    Thomas, Matthew J; Battle, Robert W

    2015-07-01

    A primary objective of the preparticipation physical examination is to identify athletes at increased risk for sudden cardiac arrest (SCA). Review of an athlete's family history may identify those at risk for SCA. Genetic testing for inherited cardiovascular disease has emerged as a valuable addition to the repertoire of cardiologists facing the decision of clearing athletes with concerning clinical signs and/or family histories. Genetic testing may lead to various outcomes for an athlete including: reassurance, diagnosis in those with borderline clinical features, finding disease predisposition prior to the onset of clinical signs (ie, genotype-positive/phenotype-negative), or continued uncertainty. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. [Incidence of skin manifestations of Lyme disease in Croatia].

    PubMed

    Kansky, A; Balić-Winter, A; Bolanca-Bumber, S; Skerlev, M

    1992-01-01

    In the study, the most relevant historical data concerning Lyme-borreliosis are shortly reviewed. The most frequent skin manifestations, i.e. erythema cronicum migrans (ECM), lymphocytoma cutis (LCC) and acrodermatitis chronica atrophicans (ACA) are described. The clinical course of Lyme disease and the chronologic review of the most significant data on the disease are given. The frequency of skin manifestations of Lyme-borreliosis in various areas of Croatia from 1988 to 1989 based on the reports of dermatologists throughout Croatia is presented. According to our results, it can be concluded that skin manifestations of Lyme-borreliosis are much more frequent in the central and western parts of Croatia than elsewhere. The authors hope that the use of a fluorescent method for detecting antibodies to Borrelia burgdorferi since 1989 in the Serologic Laboratory of the Department of Dermatology, Salata, Zagreb will lead to more precise results about this disorder in the future.

  5. Various applications of microRNAs in skin diseases.

    PubMed

    Jinnin, Masatoshi

    2014-04-01

    microRNA (miRNA) is a family of non-coding RNAs, which consists of 19-25 nucleotides and regulates the expression of approximately 30% of human protein-coding mRNAs. miRNAs can bind to complementary sequences of the three prime untranslated regions of target mRNAs, leading to the modulation of gene expression. By altering target expression, miRNAs can affect various cellular activities including cell proliferation and cell development in vitro or carcinogenesis and immune response in vivo. A lot of researches have paid attention to the possibility that miRNAs play a role in the pathogenesis of various human disorders including skin diseases. For example, miR-29a down-regulation is thought to mediate the posttranscriptional up-regulation of collagens, which contributes to the tissue fibrosis in scleroderma. In addition, recent studies indicate that extracellular miRNA levels may be useful for the diagnosis and/or the estimation of disease activity of skin diseases. miR-150 levels were significantly decreased in sera of scleroderma patients, and were inversely correlated with the prevalence of pitting scars/ulcers and the incidence of anti-topoisomerase I antibody. Currently, the therapeutic value of miRNAs for the treatment of human diseases is under evaluation in animal models. let-7a can be overexpressed in the mouse skin by intermittent intraperitoneal miRNA injection, and skin fibrosis induced by bleomycin in mice can be improved by the supplementation of let-7a. This paper discusses the possible applications of miRNAs in the clarification of pathogenesis, diagnosis, evaluation of disease activity and treatment of skin diseases. Copyright © 2014 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  6. Children with Rare Chronic Skin Diseases: Hemangiomas and Epidermolysis Bullosa.

    ERIC Educational Resources Information Center

    Jones, Sheila Dove; Miller, Cynthia Dieterich

    The paper reports on studies involving children having the rare chronic skin diseases of hemangiomas and epidermolysis bullosa (characterized by easy blistering). One study compared the self-concept and psychosocial development of young (mean age 46 months) children (N=19) with hemangiomas with 19 children without hemangiomas. Findings indicated…

  7. The nature and consequence of Karl Marx's skin disease.

    PubMed

    Shuster, S

    2008-01-01

    From an analysis of the original correspondence, it has been possible to establish that Karl Marx's incapacitating skin disease was hidradenitis suppurativa, not 'boils' as was universally assumed at the time and since; the psychological effect of this illness on the man and his work appears to have been considerable.

  8. Children with Rare Chronic Skin Diseases: Hemangiomas and Epidermolysis Bullosa.

    ERIC Educational Resources Information Center

    Jones, Sheila Dove; Miller, Cynthia Dieterich

    The paper reports on studies involving children having the rare chronic skin diseases of hemangiomas and epidermolysis bullosa (characterized by easy blistering). One study compared the self-concept and psychosocial development of young (mean age 46 months) children (N=19) with hemangiomas with 19 children without hemangiomas. Findings indicated…

  9. Multidimensional two-photon imaging of diseased skin

    NASA Astrophysics Data System (ADS)

    Cicchi, R.; Sestini, S.; De Giorgi, V.; Massi, D.; Lotti, T.; Pavone, F. S.

    2008-02-01

    We used combined two photon intrinsic fluorescence (TPE), second harmonic generation microscopy (SHG), fluorescence lifetime imaging microscopy (FLIM), and multispectral two photon emission detection (MTPE) to investigate different kinds of human cutaneous ex-vivo skin lesions. Morphological and spectroscopic analyses allowed to characterize both healthy and pathological skin samples, including tumors, as well as to discriminate between healthy and diseased tissue, in a good agreement with common routine histology. In particular, we examined tissue samples from normal and pathological scar tissue (keloid), and skin tumors, including basal cell carcinoma (BCC) and malignant melanoma (MM). By using combined TPE-SHG microscopy we investigated morphological features of different skin regions, as BCC, tumor-stroma interface, healthy dermis, fibroblastic proliferation, and keloids. The SHG to autofluorescence aging index of dermis (SAAID) score was used to characterize each region, finding differences between BCC, healthy skin, tumor-stroma interface, keloids, and fibroblastic proliferation. Further comparative analysis of healthy skin and neoplastic samples was performed using FLIM. In particular, BCC showed a blue-shifted fluorescence emission, a higher absorption at 800 nm excitation wavelength, and a slightly longer mean fluorescence lifetime. MM showed a lifetime distribution similar to the corresponding melanocytic nevus (MN) lifetime distribution for the slow lifetime component, and different for the fast lifetime component.

  10. Three-parent in vitro fertilization: gene replacement for the prevention of inherited mitochondrial diseases.

    PubMed

    Amato, Paula; Tachibana, Masahito; Sparman, Michelle; Mitalipov, Shoukhrat

    2014-01-01

    The exchange of nuclear genetic material between oocytes and embryos offers a novel reproductive option for the prevention of inherited mitochondrial diseases. Mitochondrial dysfunction has been recognized as a significant cause of a number of serious multiorgan diseases. Tissues with a high metabolic demand, such as brain, heart, muscle, and central nervous system, are often affected. Mitochondrial disease can be due to mutations in mitochondrial DNA or in nuclear genes involved in mitochondrial function. There is no curative treatment for patients with mitochondrial disease. Given the lack of treatments and the limitations of prenatal and preimplantation diagnosis, attention has focused on prevention of transmission of mitochondrial disease through germline gene replacement therapy. Because mitochondrial DNA is strictly maternally inherited, two approaches have been proposed. In the first, the nuclear genome from the pronuclear stage zygote of an affected woman is transferred to an enucleated donor zygote. A second technique involves transfer of the metaphase II spindle from the unfertilized oocyte of an affected woman to an enucleated donor oocyte. Our group recently reported successful spindle transfer between human oocytes, resulting in blastocyst development and embryonic stem cell derivation, with very low levels of heteroplasmy. In this review we summarize these novel assisted reproductive techniques and their use to prevent transmission of mitochondrial disorders. The promises and challenges are discussed, focusing on their potential clinical application.

  11. Tropical Skin Diseases in Children: A Review- Part I.

    PubMed

    García-Romero, Maria Teresa; Lara-Corrales, Irene; Kovarik, Carrie L; Pope, Elena; Arenas, Roberto

    2016-05-01

    Because of travel and migration patterns, tropical skin diseases are now seen all around the world, not just in tropical or developing countries. Nutrition, housing, and environmental factors play an important role in these infectious diseases, so when they appear out of their normal environments, their classic presentation may vary. Tropical diseases can also present differently in childhood, making their recognition, diagnosis, and management a clinical challenge. Health care providers in developed countries need to be familiar with tropical skin diseases and be able to diagnose them in returning travelers or immigrants in order to optimize care. This article aims to review the epidemiologic, clinical, diagnostic, and therapeutic aspects of some of the most common tropical dermatologic conditions in children.

  12. Toll-like receptors in skin infections and inflammatory diseases.

    PubMed

    Lai, Yuping; Gallo, Richard L

    2008-09-01

    The skin is the ultimate example of the function of innate immunity, it alerts the host of danger by many systems including sensing pathogen-associated molecule patterns (PAMPs) through Toll-like receptors and other pattern recognition receptors (PRRs), yet normally provides defense without inflammation. The skin responds rapidly to invading microbes by producing antimicrobial peptides or other antimicrobial intermediates before cytokine release results in inflammation. To achieve maximal immune responses for clearing invading microbes, the activation of select PRRs in skin then initiates and shapes adaptive immune responses through the activation of dendritic cells and recruitment of T cell subsets. Importantly, cross-talk between TLRs can influence this system in several ways including augmenting or suppressing the immune response. As a consequence of their pivotal role, TLR responses need to be tightly controlled by associated negative regulators or negative feedback loops to prevent detrimental effects from TLRs overactivation. This review focuses on describing the involvement of TLRs in the development of skin infections and inflammatory diseases, and highlights the potential application of TLR agonists or antagonists in these skin diseases.

  13. Autoimmune and infectious skin diseases that target desmogleins

    PubMed Central

    AMAGAI, Masayuki

    2010-01-01

    Desmosomes are intercellular adhesive junctions of epithelial cells that contain two major transmembrane components, the desmogleins (Dsg) and desmocollins (Dsc), which are cadherin-type cell–cell adhesion molecules and are anchored to intermediate filaments of keratin through interactions with plakoglobin and desmoplakin. Desmosomes play an important role in maintaining the proper structure and barrier function of the epidermis and mucous epithelia. Four Dsg isoforms have been identified to date, Dsg1–Dsg4, and are involved in several skin and heart diseases. Dsg1 and Dsg3 are the two major Dsg isoforms in the skin and mucous membranes, and are targeted by IgG autoantibodies in pemphigus, an autoimmune disease of the skin and mucous membranes. Dsg1 is also targeted by exfoliative toxin (ET) released by Staphylococcus aureus in the infectious skin diseases bullous impetigo and staphylococcal scalded skin syndrome (SSSS). ET is a unique serine protease that shows lock and key specificity to Dsg1. Dsg2 is expressed in all tissues possessing desmosomes, including simple epithelia and myocardia, and mutations in this gene are responsible for arrhythmogenic right ventricular cardiomyopathy/dysplasia. Dsg4 plays an important adhesive role mainly in hair follicles, and Dsg4 mutations cause abnormal hair development. Recently, an active disease model for pemphigus was generated by a unique approach using autoantigen-deficient mice that do not acquire tolerance against the defective autoantigen. Adoptive transfer of Dsg3−/− lymphocytes into mice expressing Dsg3 induces stable anti-Dsg3 IgG production with development of the pemphigus phenotype. This mouse model is a valuable tool with which to investigate immunological mechanisms of harmful IgG autoantibody production in pemphigus. Further investigation of desmoglein molecules will continue to provide insight into the unsolved pathophysiological mechanisms of diseases and aid in the development of novel therapeutic

  14. Classification of papulo-squamous skin diseases using image analysis.

    PubMed

    Mashaly, H M; Masood, N A; Mohamed, Abdalla S A

    2012-02-01

    Papulo-squamous skin diseases are variable but are very close in their clinical features. They present with the same lesions, erythematous scaly lesions. Clinical evaluation of skin lesions is based on common sense and experience of the dermatologist to differentiate features of each disease. To evaluate a computer-based image analysis system as a helping tool for classification of commonly encountered diseases. The study included 50 selected images from each of psoriasis, lichen planus, atopic dermatitis, seborrheic dermatitis, pityrasis rosea, and pitryasis rubra pilaris with a total of 300 images. The study comprised three main processes peformed on the 300 included images: segmentation, feature extraction followed by classification. Rough sets recorded the highest percentage of accuracy and sensitivity of segmentation for the six groups of diseases compared with the other three used techniques (topological derivative, K-means clustering, and watershed). Rule-based classifier using the concept of rough sets recorded the best percentage of classification (96.7%) for the six groups of diseases compared with the other six techniques of classification used: K-means clustering, fuzzy c-means clustering, classification and regression tree, rule-based classifier with discretization, and K-nearest neighbor technique. Rough sets approach proves its superiority for both the segmentation and the classification processes of papulo-squamous skin diseases compared with the other used segmentation and classification techniques. © 2011 John Wiley & Sons A/S.

  15. Incidence of skin and respiratory diseases among Danish hairdressing apprentices.

    PubMed

    Foss-Skiftesvik, Majken H; Winther, Lone; Johnsen, Claus R; Zachariae, Claus; Johansen, Jeanne D

    2017-03-01

    Hairdressing is one of the professions with the highest risk of occupational skin and respiratory diseases. The incidence of these diseases in hairdressing apprentices has been studied only sparsely. To determine the incidence of skin and respiratory diseases in hairdressing apprentices, and to explore whether hairdressing apprentices leave the trade during training because of these diseases. A 3-year follow-up questionnaire study was conducted among 248 hairdressing apprentices and a control group comprising 816 young adults from the general population. The incidence rate ratios (IRRs) for contact urticaria (IRR 4.7, 95%CI: 2.6-8.6), hand eczema (IRR 1.7, 95%CI: 1.1-2.6) and rhinitis symptoms (IRR 1.6, 95%CI: 1.2-2.2) were significantly increased in the hairdressing apprentices, whereas wheezing was similar between groups. During the follow-up period, 21.8% of the hairdressing apprentices had left the trade, and 70.3% of these had left because of health complaints. The most frequently reported reasons for leaving were musculoskeletal pain (47.4%) and skin diseases (47.4%), followed by respiratory symptoms (23.7%). Hairdressing apprentices are at increased risk for contact urticaria, hand eczema and rhinitis symptoms compared with the general population, and a substantial proportion leave the trade because of these diseases, causing a 'healthy worker survivor effect.' © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Clinicopathologic analysis of IgG4-related skin disease.

    PubMed

    Sato, Yasuharu; Takeuchi, Mai; Takata, Katsuyoshi; Ohno, Kyotaro; Iwaki, Noriko; Orita, Yorihisa; Goto, Naoe; Hida, Akira I; Iwamoto, Toshiyuki; Asano, Naoko; Ito, Toshihiro; Hanakawa, Hiroyuki; Yanai, Hiroyuki; Yoshino, Tadashi

    2013-04-01

    IgG4-related disease is a recently recognized systemic syndrome characterized by mass-forming lesions with lymphoplasmacytic infiltration, increase in the number of IgG4(+) cells in affected tissues and elevation of serum IgG4 levels. In 2009, we were the first to report skin lesions in patients with IgG4-related disease, but no large case series has been reported and clinicopathological findings remain unclear. To clarify these features, we herein report 10 patients (9 men and 1 woman; median age, 64 years; age range, 46-81 years) with IgG4-related skin disease. All patients had erythematous and itchy plaques or subcutaneous nodules on the skin of the head and neck, particularly in the periauricular, cheek, and mandible regions, except for one patient, whose forearm and waist skin were affected. In addition, eight patients had extracutaneous lesions: these were found on the lymph nodes in six patients, the lacrimal glands in three patients, the parotid glands in three patients, and the kidney in one patient. Histologically examined extracutaneous lesions were consistent with IgG4-related disease; five of six lymph node lesions showed progressively transformed germinal centers-type IgG4-related lymphadenopathy. Cases of IgG4-related skin disease were classified into two histological patterns: those exhibiting a nodular dermatitis pattern and those with a subcutaneous nodule pattern. The infiltrate was rich in plasma cells, small lymphocytes, and eosinophils; the majority of the plasma cells were IgG4(+). The IgG4(+) cell count was 49-396 per high-power field (mean±s.d., 172±129), with an IgG4(+)/IgG(+) cell ratio ranging from 62 to 92%. Serum IgG4 levels were elevated in all examined patients. In conclusion, patients with IgG4-related skin disease had uniform clinicopathology. Lesions were frequently present on the skin of the periauricular, cheek, and mandible regions, and were frequently accompanied by IgG4-related lymphadenopathy.

  17. Trends in mortality from skin diseases in the United States: skin infectious diseases are claiming more lives.

    PubMed

    Fleischer, Alan B

    2016-07-15

    BackgroundAlthough there has been some excellent work published on the mortality from non-neoplastic skin disease In the United States, further analysis of trends is limited.MethodsData from the Centers for Disease Control and Prevention (CDC) for mortality abstracted from Death Certificates was obtained from the WONDER (wide-ranging online data for epidemiologic research) system from 1999 to 2014. Categorical variables were analyzed with Excel 2013 data analysis software using Chi-squared tests whereas regression was performed for trends.ResultsCrude death rates were highest in the South, especially in Mississippi and Louisiana. This work also confirmed that Blacks or African Americans had higher risk of death from skin disease, whereas Hispanic or Latinos had lower risk. Overall mortality from non-neoplastic diseases is increasing over time and significant increases in mortality from infectious and papulosquamous diseases were observed, whereas there appears to be decreasing mortality from dermatitis and miscellaneous skin disorders (ICD-10-CM L80-90).ConclusionsMortality is increasing from non-neoplastic diseases, especially infectious and papulosquamous diseases. Demographic factors such age race and Hispanic or Latino ethnicity also confer differential risk.

  18. Skin diseases in Nigeria: the Calabar experience.

    PubMed

    Henshaw, Eshan B; Olasode, Olayinka A

    2015-03-01

    This paper reports on a 6-year study (April 2006 to April 2012) and a follow-up of a 9-month baseline survey of the pattern of dermatoses in Calabar, the capital of Cross River State in southern Nigeria. Prior to the time of this study, this region had not benefited from the services of a resident dermatologist for over a century. Data on the age, gender, and diagnoses of 1307 consecutive new patients attending the relatively new dermatology clinic at the University of Calabar Teaching Hospital during the study period were obtained and analyzed. Most diagnoses were based on clinical findings but were supported by relevant laboratory investigations and histopathologic examinations when necessary. The male : female ratio of patients was 1 : 1.5. The mean ± standard deviation age of the patients was 27.7 ± 17.2 years (range: 4 weeks to 84 years). A total of 1459 diagnoses were recorded; 143 patients had more than one dermatosis. Diagnoses were broadly divided into 10 groups. Allergic/hypersensitivity diseases represented the most common group (30.4%), followed by infections/infestations (28.9%). A comparison of this study with others from various geopolitical zones of Nigeria revealed some similarities. Dermatophytosis and acne were consistent reasons for visits to dermatologists in all zones. Despite the wide spectrum of dermatoses observed, a small number of diseases account for a sizeable percentage of diagnoses. The pattern of dermatoses in Calabar is similar to that in other parts of the country. Climate and socioeconomic factors are synergistic in causing dermatoses that remain a major cause of morbidity in all age groups and both genders across Nigeria. © 2014 The International Society of Dermatology.

  19. 77 FR 28397 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-14

    ... Skin Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act... Musculoskeletal and Skin Diseases Special Emphasis Panel, P30 Rheumatic Diseases Core Center Review. Date: June 13... Skin Diseases, National Institutes of Health, 6701 Democracy Blvd., Suite 800, Bethesda, MD...

  20. Next-generation sequencing-based molecular diagnosis of 12 inherited retinal disease probands of Uyghur ethnicity.

    PubMed

    Tajiguli, Abulikemu; Xu, Mingchu; Fu, Qing; Yiming, Rouzimaimaiti; Wang, Keqing; Li, Yumei; Eblimit, Aiden; Sui, Ruifang; Chen, Rui; Aisa, Haji Akber

    2016-02-09

    Inherited retinal disease (IRD) is a category of genetic disorders affecting retina. Understanding the molecular basis of IRD is vital for clinical and genetic classification of patients. Uyghur people is an isolated ethnic group mainly residing in northwestern China with genetic admixture from Europeans and East Asians. The genetic etiology of IRD in this specific population still remains unknown. Here, by next-generation sequencing (NGS), we screened mutations in over 200 known retinal disease genes in a cohort of 12 unrelated Uyghur IRD probands. Out of the 12 probands, six are solved with high confidence, two with low confidence, while the remaining four are unsolved. We identified known disease-causing alleles in this cohort that suggest ancient Uyghur migration and also discovered eight novel disease-associated variants. Our results showed NGS-based mutation screening as a reliable approach for molecular diagnosis. In addition, this approach can also be applied to reveal the genetic history of a specific ethnic group.

  1. INHERITED CARDIOMYOPATHIES

    PubMed Central

    Towbin, Jeffrey A.

    2015-01-01

    Cardiomyopathies, diseases of the heart muscle, are major causes of morbidity and mortality. A significant percentage of patients with cardiomyopathies have genetic-based, inheritable disease and, over the past two decades the genetic causes of these disorders have been increasingly discovered. The genes causing these disorders when they are mutated appear to encode proteins that frame a “final common pathway” for that specific disorder but the specifics of the phenotype, including age of onset, severity, and outcome is variable for reasons not yet understood. The “final common pathways” for the classified forms of cardiomyopathy include the sarcomere in the primarily diastolic dysfunction disorders hypertrophic cardiomyopathy (HCM) and restrictive cardiomyopathy (RCM), the linkage of the sarcomere and sarcolemma in the systolic dysfunction disorder dilated cardiomyopathy (DCM), and the desmosome in arrhythmogenic cardiomyopathy (AVC). Left ventricular noncompaction cardiomyopathy (LVNC) is an overlap disorder and appears that any of these “final common pathways” can be involved depending on the specific form of LVNC. The genetics and mechanisms responsible for these clinical phenotypes will be described. PMID:25186923

  2. Treatment of early diffuse systemic sclerosis skin disease.

    PubMed

    Frech, Tracy M; Shanmugam, Victoria K; Shah, Ami A; Assassi, Shervin; Gordon, Jessica K; Hant, Faye N; Hinchcliff, Monique E; Steen, Virginia; Khanna, Dinesh; Kayser, Cristiane; Domsic, Robyn T

    2013-01-01

    Diffuse systemic sclerosis carries a high morbidity and mortality. The Prospective Registry of Early Systemic Sclerosis (PRESS), a multicentre incident cohort study of patients with early diffuse cutaneous systemic sclerosis, has the goal of advancing the understanding of disease pathogenesis and identifying novel biomarkers. In this review, PRESS investigators discuss the evidence pertaining to the more commonly used treatments for early diffuse SSc skin disease including methotrexate, mycophenolate, cyclophosphamide, azathioprine, and intravenous immunoglobulin. This review highlights the unmet need for effective treatment in early diffuse SSc as well as its more rigorous study. Nonetheless, the PRESS investigators aim to decrease intra- and inter-institutional variability in prescribing in order to improve the understanding of the clinical course of early diffuse SSc skin disease.

  3. Management of "refractory" skin disease in patients with lupus erythematosus.

    PubMed

    Callen, Jeffrey P

    2005-10-01

    Skin disease in patients with lupus erythematosus can be subdivided into two broad categories-those lesions that, when biopsied, demonstrate an interface dermatitis and those that do not demonstrate an interface dermatitis. The skin lesions that are represented by the interface dermatitis include discoid lupus erythematosus (DLE), subacute cutaneous lupus erythematosus (SCLE), and acute cutaneous lupus erythematosus. Many patients with these cutaneous lesions can be managed with "standard" therapies, including sunscreens, protective clothing and behavioral alteration, and topical corticosteroids with or without an oral antimalarial agent. These standard therapies are often not used appropriately, resulting in a situation in which the patient is felt to have refractory disease. This chapter discusses these therapies and defines what is meant by refractory disease and how the author approaches these patients.

  4. Skin diseases among elderly inhabitants of Bialystok, Poland

    PubMed Central

    Cybulski, Mateusz; Krajewska-Kulak, Elzbieta

    2015-01-01

    Purpose The aim of the study was to assess the most frequent skin diseases in people over 60 years old among residents of a public nursing home and students of the University of the Third Age in Bialystok. Subjects and methods The study was carried out from April to June 2015 in Bialystok, in two groups: 100 residents of a public nursing home and 100 participants of the University of the Third Age, aged over 60 years, using a method of diagnostic survey with the authors’ anonymous questionnaire. Results A total of 30.5% of respondents (n=61) had been treated due to skin diseases, most frequently for 6–10 years (26.2%). Fungal infection, psoriasis, and atopic dermatitis were the most frequent dermatological diseases among the study elderly. The sites affected most frequently with these diseases were upper and lower extremities and the face. A majority of the examined (63.9%) visited a dermatologist, but only when it was necessary. Conclusion Skin diseases constitute a significant health problem among seniors. The elderly should be educated about healthy lifestyle, preventing the development of fungal infections. It is necessary to encourage seniors to visit dermatologists, seeking professional advice. PMID:26677319

  5. Occupational skin diseases in hairdressing apprentices - has anything changed?

    PubMed

    Hougaard, Majken G; Winther, Lone; Søsted, Heidi; Zachariae, Claus; Johansen, Jeanne D

    2015-01-01

    Hairdressers are at risk for occupational skin diseases. Since 2008, an educational programme has been conducted in Danish hairdressing schools to prevent occupational skin diseases. Its effect is unknown. To examine the current frequency of self-reported hand eczema and contact urticaria in Danish hairdressing apprentices as compared with controls, and to determine the occurrence of hand eczema and contact urticaria in hairdressing apprentices with different durations of exposure to the trade. This was a cross-sectional, web-based questionnaire study conducted among 504 hairdressing apprentices and a control group of 1400 adolescents from the general population. Hand eczema was significantly more prevalent in the hairdressing apprentices than in controls (34.5% versus 18.8%, p < 0.001). The incidence rate of hand eczema among hairdressing apprentices was 98 cases/1000 person-years. Contact urticaria was also more prevalent in the hairdressing apprentices (7.3% versus 4.2%, p = 0.006). Both diseases increased with increasing duration of exposure to the trade. Despite educational efforts to prevent occupational skin diseases in the hairdressing schools, Danish apprentices are still at increased risk for hand eczema and contact urticaria. Both diseases develop after only a few years of work in hairdressing. Further preventive strategies are warranted. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Skin diseases among elderly inhabitants of Bialystok, Poland.

    PubMed

    Cybulski, Mateusz; Krajewska-Kulak, Elzbieta

    2015-01-01

    The aim of the study was to assess the most frequent skin diseases in people over 60 years old among residents of a public nursing home and students of the University of the Third Age in Bialystok. The study was carried out from April to June 2015 in Bialystok, in two groups: 100 residents of a public nursing home and 100 participants of the University of the Third Age, aged over 60 years, using a method of diagnostic survey with the authors' anonymous questionnaire. A total of 30.5% of respondents (n=61) had been treated due to skin diseases, most frequently for 6-10 years (26.2%). Fungal infection, psoriasis, and atopic dermatitis were the most frequent dermatological diseases among the study elderly. The sites affected most frequently with these diseases were upper and lower extremities and the face. A majority of the examined (63.9%) visited a dermatologist, but only when it was necessary. Skin diseases constitute a significant health problem among seniors. The elderly should be educated about healthy lifestyle, preventing the development of fungal infections. It is necessary to encourage seniors to visit dermatologists, seeking professional advice.

  7. Skin microbiota: a source of disease or defence?

    PubMed Central

    Cogen, A. L.; Nizet, V.; Gallo, R. L.

    2009-01-01

    Summary Microbes found on the skin are usually regarded as pathogens, potential pathogens or innocuous symbiotic organisms. Advances in microbiology and immunology are revising our understanding of the molecular mechanisms of microbial virulence and the specific events involved in the host–microbe interaction. Current data contradict some historical classifications of cutaneous microbiota and suggest that these organisms may protect the host, defining them not as simple symbiotic microbes but rather as mutualistic. This review will summarize current information on bacterial skin flora including Staphylococcus, Corynebacterium, Propioni-bacterium, Streptococcus and Pseudomonas. Specifically, the review will discuss our current understanding of the cutaneous microbiota as well as shifting paradigms in the interpretation of the roles microbes play in skin health and disease. PMID:18275522

  8. A short history of phototherapy, vitamin D and skin disease.

    PubMed

    Jarrett, Paul; Scragg, Robert

    2017-03-16

    The earliest record between sun exposure and skin disease goes back five millennia to the ancient Egyptians. The modern scientific era of medical light therapy and skin diseases started in 1877 when Downs and Blunt reported that exposure to light inhibited fungal growth in test tubes. Continuing research generated a growing medical interest in the potential the effects of light to treat and cure skin diseases considered as parasitic. This culminated in the awarding of the 1903 Nobel Prize in Medicine to Niels Finsen for his pioneering work showing that light could successfully treat cutaneous mycobacterium tuberculosis (lupus vulgaris), a disfiguring disorder common at the time. Cod liver oil was used as a folk remedy to treat rickets prior to 1789 in Manchester, UK and sunlight was published as the cure for this disease in 1921. The work by Hess and Weinstock in 1925 showed that food irradiated with ultraviolet (UV) light prevented rickets in rats, which paved the way for the discovery of vitamin D. The range of skin diseases treated by light therapy increased in the following years, to the point where a 1932 review by the American Medical Association on the use of UV therapy in dermatology listed 34 skin conditions for which UV radiation may be useful. This period coincided with the development of sanatoria in Europe and North America which used heliotherapy for the treatment of tuberculosis. UV therapy and vitamin D continued to be used successfully for the treatment of tuberculosis up to the 1950s when it was superseded by more effective antibiotics. Modern phototherapy developed in the 1980s with the discovery of the action spectrum for psoriasis leading to the development of narrow band UVB. Subsequently a biological mechanism by which UV light and vitamin D treated tuberculosis was identified in 2006. This involves activation of human macrophages via toll-like receptors to upregulate the vitamin D receptor gene resulting in induction of the antimicrobial

  9. Work-related skin disease in the plastics industry.

    PubMed

    Socie, E M; Gromen, K D; Migliozzi, A A; Geidenberger, C A

    1997-05-01

    In a survey of a representative sample of workers taken at each of four different plastics manufacturers, 122 completed self-administered questionnaires were obtained. Twenty-six respondents (21.3%) met the case definition for having a work-related skin disorder during the preceding year. Sixteen (61.5%) cases indicated that their skin problems were present for 11 or more days, and 50% reported that their normal daily activities were at least somewhat affected. Risk of disease was elevated for workers who reported skin contact with formaldehyde (OR = 3.30; 95% CI = 1.02-10.69) or with polyvinyl-chlorides (PVCs) or their precursors (OR = 4.08; CI = 1.19-14.06), used barrier creams (OR = 4.51; CI = 1.22-16.68), were female (OR = 5.42; CI = 0.97-30.22), were 35 or younger (OR = 4.65; CI = 1.53-14.19), and for each use of hand cleaner at work (OR = 1.22; CI = 1.05-1.41). These findings should be considered when designing programs to reduce the incidence of skin disease among workers in the plastics industry.

  10. Characterization of inflammatory cell infiltration in feline allergic skin disease.

    PubMed

    Taglinger, K; Day, M J; Foster, A P

    2007-11-01

    Sixteen cats with allergic dermatitis and six control cats with no skin disease were examined. Lymphoid and histiocytic cells in skin sections were examined immunohistochemically and mast cells were identified by toluidine blue staining. The 16 allergic cats showed one or more of several features (alopecia, eosinophilic plaques or granulomas, papulocrusting lesions), and histopathological findings were diverse. In control cats there were no cells that expressed IgM or MAC387, a few that were immunolabelled for IgG, IgA or CD3, and moderate numbers of mast cells. In allergic cats, positively labelled inflammatory cells were generally more numerous in lesional than in non-lesional skin sections, and were particularly associated with the superficial dermis and perifollicular areas. There were low numbers of plasma cells expressing cytoplasmic immunoglobulin; moderate numbers of MHC II-, MAC387- and CD3-positive cells; and moderate to numerous mast cells. MHC class II expression was associated with inflammatory cells morphologically consistent with dermal dendritic cells and macrophages, and epidermal Langerhans cells. Dendritic cells expressing MHC class II were usually associated with an infiltrate of CD3 lymphocytes, suggesting that these cells participate in maintenance of the local immune response by presenting antigen to T lymphocytes. These findings confirm that feline allergic skin disease is characterized by infiltration of activated antigen-presenting cells and T lymphocytes in addition to increased numbers of dermal mast cells. This pattern mimics the dermal inflammation that occurs in the chronic phase of both canine and human atopic dermatitis.

  11. Skin diseases associated with Agent Orange and other organochlorine exposures.

    PubMed

    Patterson, Andrew T; Kaffenberger, Benjamin H; Keller, Richard A; Elston, Dirk M

    2016-01-01

    Organochlorine exposure is an important cause of cutaneous and systemic toxicity. Exposure has been associated with industrial accidents, intentional poisoning, and the use of defoliants, such as Agent Orange in the Vietnam War. Although long-term health effects are systematically reviewed by the Institute of Medicine, skin diseases are not comprehensively assessed. This represents an important practice gap as patients can present with cutaneous findings. This article provides a systematic review of the cutaneous manifestations of known mass organochlorine exposures in military and industrial settings with the goal of providing clinically useful recommendations for dermatologists seeing patients inquiring about organochlorine effects. Patients with a new diagnosis of chloracne, porphyria cutanea tarda, cutaneous lymphomas (non-Hodgkin lymphoma), and soft-tissue sarcomas including dermatofibrosarcoma protuberans and leiomyosarcomas should be screened for a history of Vietnam service or industrial exposure. Inconclusive evidence exists for an increased risk of other skin diseases in Vietnam veterans exposed to Agent Orange including benign fatty tumors, melanomas, nonmelanoma skin cancers, milia, eczema, dyschromias, disturbance of skin sensation, and rashes not otherwise specified. Affected veterans should be informed of the uncertain data in those cases. Referral to Department of Veterans Affairs for disability assessment is indicated for conditions with established associations. Copyright © 2015 American Academy of Dermatology, Inc. All rights reserved.

  12. Benign skin disease with pustules in the newborn*

    PubMed Central

    Reginatto, Flávia Pereira; Villa, Damie De; Cestari, Tania Ferreira

    2016-01-01

    The neonatal period comprises the first four weeks of life. It is a period of adaptation where the skin often presents several changes: transient lesions, resulting from a physiological response, others as a consequence of transient diseases and some as markers of severe disorders. The presence of pustules in the skin of the newborn is always a reason for the family and for the assisting doctor to be worried, since the newborn is especially vulnerable to bacterial, viral or fungal infection. However, the majority of neonatal skin pustules is not infectious, comprising the benign neonatal pustulosis. Benign neonatal pustuloses are a group of clinical disease characterized by pustular eruptions in which a contagious agent is not responsible for its etiology. The most common ones are erythema toxicum neonatorum, the transient neonatal pustular melanosis and the benign cephalic pustulosis. These dermatoses are usually benign, asymptomatic and self-limited. It is important that the dermatologist and the neonatologist can identify benign and transient lesions, those caused by genodermatoses, and especially differentiate between neonates with systemic involvement from those with benign skin lesions, avoiding unnecessary diagnostic tests and worries. PMID:27192509

  13. Searching Online Mendelian Inheritance in Man (OMIM) for information on genetic loci involved in human disease.

    PubMed

    Borate, Bhavesh; Baxevanis, Andreas D

    2009-09-01

    Online Mendelian Inheritance in Man (OMIM) is a comprehensive compendium of information on human genes and genetic disorders, with a particular emphasis on the interplay between observed phenotypes and underlying genotypes. This unit focuses on the basic methodology for formulating OMIM searches and illustrates the types of information that can be retrieved from OMIM, including descriptions of clinical manifestations resulting from genetic abnormalities. This unit also provides information on additional relevant medical and molecular biology databases. A basic knowledge of OMIM should be part of the armamentarium of physicians and scientists with an interest in research on and clinical aspects of genetic disorders.

  14. Searching Online Mendelian Inheritance in Man (OMIM) for information on genetic loci involved in human disease.

    PubMed

    Baxevanis, Andreas D

    2012-04-01

    Online Mendelian Inheritance in Man (OMIM) is a comprehensive compendium of information on human genes and genetic disorders, with a particular emphasis on the interplay between observed phenotypes and underlying genotypes. This unit focuses on the basic methodology for formulating OMIM searches and illustrates the types of information that can be retrieved from OMIM, including descriptions of clinical manifestations resulting from genetic abnormalities. This unit also provides information on additional relevant medical and molecular biology databases. A basic knowledge of OMIM should be part of the armamentarium of physicians and scientists with an interest in research on the clinical aspects of genetic disorders.

  15. 78 FR 32261 - National Institute of Arthritis And Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-29

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis And Musculoskeletal and... unwarranted invasion of personal privacy. Name of Committee: Arthritis and Musculoskeletal and Skin Diseases Initial Review Group, Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee...

  16. 78 FR 8549 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-06

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and... unwarranted invasion of personal privacy. Name of Committee: Arthritis and Musculoskeletal and Skin Diseases Initial Review Group; Arthritis and Musculoskeletal and Skin Diseases Clinical Trials Review Committee...

  17. 78 FR 64509 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-29

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and... unwarranted invasion of personal privacy. Name of Committee: Arthritis and Musculoskeletal and Skin Diseases Initial Review Group; Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee...

  18. 76 FR 6807 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-08

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and... unwarranted invasion of personal privacy. Name of Committee: Arthritis and Musculoskeletal and Skin Diseases..., National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, 6701...

  19. 77 FR 35988 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-15

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and... unwarranted invasion of personal privacy. Name of Committee: Arthritis and Musculoskeletal and Skin Diseases Initial Review Group; Arthritis and Musculoskeletal and Skin Diseases Clinical Trials Review Committee...

  20. 78 FR 40486 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-05

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and... unwarranted invasion of personal privacy. Name of Committee: National Institute of Arthritis and Musculoskeletal and Skin Diseases Special Emphasis Panel; Arthritis and Musculoskeletal and Skin Diseases Clinical...

  1. 77 FR 60447 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-03

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and... unwarranted invasion of personal privacy. Name of Committee: Arthritis and Musculoskeletal and Skin Diseases Initial Review Group; Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee...

  2. 78 FR 58320 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-23

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and... unwarranted invasion of personal privacy. Name of Committee: Arthritis and Musculoskeletal and Skin Diseases Initial Review Group; Arthritis and Musculoskeletal and Skin Diseases Clinical Trials Review Committee...

  3. 76 FR 55399 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-07

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and... unwarranted invasion of personal privacy. Name of Committee: Arthritis and Musculoskeletal and Skin Diseases Initial Review Group, Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee...

  4. 77 FR 4048 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-26

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and... unwarranted invasion of personal privacy. Name of Committee: Arthritis and Musculoskeletal and Skin Diseases Initial Review Group, Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee...

  5. 77 FR 61011 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-05

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and... unwarranted invasion of personal privacy. Name of Committee: Arthritis and Musculoskeletal and Skin Diseases Initial Review Group; Arthritis and Musculoskeletal and Skin Diseases Clinical Trials Review Committee...

  6. 77 FR 14407 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Amended Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-09

    ... Skin Diseases; Amended Notice of Meeting Notice is hereby given of a change in the meeting of the National Institute of Arthritis and Musculoskeletal and Skin Diseases Special Emphasis Panel, March...

  7. 78 FR 64223 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Amended Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-28

    ... Skin Diseases; Amended Notice of Meeting Notice is hereby given of a change in the meeting of the National Institute of Arthritis and Musculoskeletal and Skin Diseases Special Emphasis Panel, October...

  8. 75 FR 63492 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-15

    ... Skin Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the Federal Advisory Committee... Musculoskeletal and Skin Diseases Special Emphasis Panel, Career Development, Research Training & Pathways to... Review Officer, Scientific Review Branch, National Institute of Arthritis, Musculoskeletal and...

  9. Internet resources cataloguing inherited disorders in dogs.

    PubMed

    Nicholas, Frank W; Crook, Alice; Sargan, David R

    2011-08-01

    Up-to-date annotated catalogues of known inherited disorders in dogs are freely available on the Internet, providing vital information to existing and prospective dog owners, dog breeders, veterinarians, geneticists and others interested in the occurrence and control of inherited disorders. These resources are the Canine Inherited Disorders Database (CIDD), Inherited Diseases in Dogs (IDID) and Online Mendelian Inheritance in Animals (OMIA) the latter associated with Listing of Inherited Disorders in Animals (LIDA). The history and features of these resources are summarised.

  10. An Excess of Risk-Increasing Low-Frequency Variants Can Be a Signal of Polygenic Inheritance in Complex Diseases

    PubMed Central

    Chan, Yingleong; Lim, Elaine T.; Sandholm, Niina; Wang, Sophie R.; McKnight, Amy Jayne; Ripke, Stephan; Daly, Mark J.; Neale, Benjamin M.; Salem, Rany M.; Hirschhorn, Joel N.

    2014-01-01

    In most complex diseases, much of the heritability remains unaccounted for by common variants. It has been postulated that lower-frequency variants contribute to the remaining heritability. Here, we describe a method to test for polygenic inheritance from lower-frequency variants by using GWAS summary association statistics. We explored scenarios with many causal low-frequency variants and showed that there is more power to detect risk variants than to detect protective variants, resulting in an increase in the ratio of detected risk to protective variants (R/P ratio). Such an excess can also occur if risk variants are present and kept at lower frequencies because of negative selection. The R/P ratio can be falsely elevated because of reasons unrelated to polygenic inheritance, such as uneven sample sizes or asymmetric population stratification, so precautions to correct for these confounders are essential. We tested our method on published GWAS results and observed a strong signal in some diseases (schizophrenia and type 2 diabetes) but not others. We also explored the shared genetic component in overlapping phenotypes related to inflammatory bowel disease (Crohn disease [CD] and ulcerative colitis [UC]) and diabetic nephropathy (macroalbuminuria and end-stage renal disease [ESRD]). Although the signal was still present when both CD and UC were jointly analyzed, the signal was lost when macroalbuminuria and ESRD were jointly analyzed, suggesting that these phenotypes should best be studied separately. Thus, our method may also help guide the design of future genetic studies of various traits and diseases. PMID:24607388

  11. Body image satisfaction and anxiety of a Turkish sample of university students with skin diseases.

    PubMed

    Kaymak, Yeşim; Ulutaş, Ilkay; Taner, Ender; Bakir, Bilal; Simşek, Isil

    2007-04-01

    The aim of this study was to evaluate perception of body image and anxiety of 221 university students presenting to the dermatology outpatient clinic with a skin disease and 205 students without skin disease. Analysis of anxiety and body image scores yielded differences by sex and age in both groups. The group with skin disease had lower scores on body image. Acne vulgaris seems to be the most disturbing among the skin diseases, and this was more prominent in younger patients.

  12. Measurement of the area of involvement in skin disease

    NASA Astrophysics Data System (ADS)

    Roening, Juha; Kontinen, Jukka

    1996-10-01

    The ability to assess the severity of dermatoses by measuring the area of involvement is important in both clinical practice and research, but it has been shown that physicians, nurses and other groups are unable to do this accurately. A common practice in current use is the 'rule of nine' method, but wide variations have been found between observers' estimates. The purpose of this work was to test and demonstrate the feasibility of a computer vision technique for measuring the area of involvement in skin diseases by developing a system for psoriasis area assessment form slides, which can be operated in an image processing environment. The exact percentage of the slide area involved varied from 1 percent to 59 percent, thus providing realistic material for the system. The system proved sufficiently accurate, and the techniques evidently have a potential for inclusion as parts of a more accurate and rapid method for area measurement in the case of skin diseases.

  13. Preventing Occupational Skin Disease: A Review of Training Programs.

    PubMed

    Zack, Bethany; Arrandale, Victoria H; Holness, D Linn

    Occupational contact dermatitis (OCD) is a common occupational disease that impacts a variety of worker groups. Skin protection and disease prevention training programs have shown promise for improving prevention practices and reducing the incidence of OCD. This review details the features of training programs for primary prevention of OCD and identifies gaps in the literature. Twelve studies were identified for in-depth review: many studies included wet workers employed in health care, hairdressing, cleaning, and food preparation; 1 program featured manufacturing workers. Few programs provided content on allergic contact dermatitis, and only 1 was evaluated for long-term effectiveness. Effective programs were similar in content, delivery method, and timing and were characterized by industry specificity, multimodal learning, participatory elements, skin care resource provision, repeated sessions, and management engagement. Long-term effectiveness, generalizability beyond OCD, workplace health and safety culture impact, and translation of programs in the North American context represent areas for future research.

  14. Neutralising antibodies to lumpy skin disease virus in African wildlife.

    PubMed

    Hedger, R S; Hamblin, C

    1983-01-01

    A total of 3445 sera from 44 different wild species collected between 1963 and 1982 in 11 African countries south of the Sahara, were examined for neutralising antibodies to Lumpy Skin Diseases (LSD) Virus (prototype Neethling). Antibodies were demonstrated in six species but were of low prevalence. It was concluded from the generally negative results, that wildlife in Africa probably does not play a very important part in he perpetuation and spread of LSD Virus.

  15. Skin disease and thyroid autoimmunity in atopic South Italian children

    PubMed Central

    Pedullà, Marcella; Fierro, Vincenzo; Marzuillo, Pierluigi; Capuano, Francesco; Miraglia del Giudice, Emanuele; Ruocco, Eleonora

    2016-01-01

    AIM To verify the prevalence of thyroid autoimmunity (TA) and the possible association between atopy and TA in children affected by skin disease. METHODS Three hundred and twenty-four children consecutively referred due to skin disease symptoms to our Pediatric Department were enrolled. One hundred and eighty-seven were diagnosed with atopic dermatitis (AD), 95 with acute urticaria, 40 with chronic urticaria (CU), and 2 with alopecia areata (AA). According to the work-up for atopy, the children were divided into two groups: Atopics and non-atopics. TA was diagnosed by serum thyroid peroxidase autoantibodies and/or thyroglobulin autoantibodies levels more than twice normal values over a period of two months by immunoassay. RESULTS In all children with skin disease, a significant prevalence of TA in atopics compared with non-atopics (13.67% vs 2.67%, P = 0.0016) and a significant association between TA and atopy (OR = 5.76, 95%CI: 1.71-19.35) were observed. These findings were confirmed as significant in children with AD: TA in atopics was 11.5%, while TA in non-atopics was 2.7% (P = 0.03, OR = 4.68, 95%CI: 1.02-21.38). In addition, atopics with CU showed a significantly higher prevalence of TA (26.9%), but none of the non-atopics showed CU (P = 0.0326). On the other hand, atopics with AA showed a 100% (2 out of 2) prevalence of TA, compared with none of the non-atopics. CONCLUSION In children with skin disease, atopy seems to be associated with an increased risk of TA. PMID:27610344

  16. An unusual case of granulomatous slack skin disease with necrobiosis.

    PubMed

    Benton, Emma Clare; Morris, Stephen L; Robson, Alistair; Whittaker, Sean J

    2008-10-01

    Granulomatous slack skin disease (GSS) is a very rare form of T-cell lymphoma, with only 52 cases reported in the literature. In the recent World Health Organization-European Organization for Research and Treatment of Cancer consensus classification GSS is considered to be a variant of mycosis fungoides. We describe a patient with GSS and histologic evidence of necrobiosis, which has not been previously reported.

  17. Skin symptoms as diagnostic clue for autoinflammatory diseases*

    PubMed Central

    Moreira, Alvaro; Torres, Barbara; Peruzzo, Juliano; Mota, Alberto; Eyerich, Kilian; Ring, Johannes

    2017-01-01

    Autoinflammatory disorders are immune-mediated diseases with increased production of inflammatory cytokines and absence of detectable autoantibodies. They course with recurrent episodes of systemic inflammation and fever is the most common symptom. Cutaneous manifestations are prevalent and important to diagnosis and early treatment of the syndromes. The purpose of this review is to emphasize to dermatologists the skin symptoms present in these syndromes in order to provide their early diagnosis. PMID:28225960

  18. 77 FR 39714 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-05

    ... Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting Pursuant to section... Institute of Arthritis and Musculoskeletal and Skin Diseases, Special Emphasis Panel, Clinical Trials... of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, 6701 Democracy Blvd...

  19. 76 FR 77544 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-13

    ... Skin Diseases; Notice of Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act, as... and Skin Diseases Advisory Council. The meeting will be open to the public as indicated below, with... Committee: National Arthritis and Musculoskeletal and Skin Diseases Advisory Council. Date: January 31,...

  20. 78 FR 66021 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-04

    ... Skin Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act... Musculoskeletal and Skin Diseases Special Emphasis Panel; Mentored Career Development, Institutional Research... Musculoskeletal and Skin Diseases, NIH, 6701 Democracy Boulevard, Suite 800, Bethesda, MD 20892. Contact...

  1. 77 FR 59937 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-01

    ... Skin Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the Federal Advisory Committee... Musculoskeletal and Skin Diseases Special Emphasis Panel; NIAMS Small Grant Program for New Investigators (R03..., National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health,...

  2. 76 FR 61722 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-05

    ... Skin Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act... Musculoskeletal and Skin Diseases Special Emphasis Panel, Career Development, Research Training & Pathways to..., Scientific Review Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases,...

  3. 77 FR 32651 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-01

    ... Skin Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the Federal Advisory Committee... Musculoskeletal and Skin Diseases Special Emphasis Panel; Program Project Grant Review. Date: June 13, 2012. Time... Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, 6701...

  4. 78 FR 17679 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-22

    ... Skin Diseases; Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act, as... Musculoskeletal and Skin Diseases Special Emphasis Panel; NIAMS Clinical Trial Outcome Development. Date: March 29... Skin Diseases, NIH, 6701 Democracy Boulevard, Suite 800, Bethesda, MD 20892, 301-594-4953,...

  5. 75 FR 70679 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-18

    ... Skin Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the Federal Advisory Committee... Musculoskeletal and Skin Diseases Special Emphasis Panel, Clinical Trials Review. Date: December 2, 2010. Time: 8..., Scientific Review Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases,...

  6. 77 FR 12605 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-01

    ... Skin Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act... invasion of personal privacy. Name of Committee: Arthritis and Musculoskeletal and Skin Diseases Initial Review Group, Arthritis and Musculoskeletal and Skin Diseases Clinical Trials Review Committee....

  7. 78 FR 29144 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-17

    ... Skin Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act... Musculoskeletal and Skin Diseases Special Emphasis Panel; Ancillary Studies to Large Clinical Projects Grant... Institute of Arthritis, Musculoskeletal and Skin Diseases, NIH, 6701 Democracy Boulevard, Suite...

  8. 78 FR 64223 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-28

    ... Skin Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the Federal Advisory Committee... Musculoskeletal and Skin Diseases Special Emphasis Panel, NIAMS Small Grant Program for New Investigators (R03... applications. Place: National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, 6701...

  9. 77 FR 16246 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-20

    ... Skin Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act... Musculoskeletal and Skin Diseases, including consideration of personnel qualifications and performance, and the...., Scientific Director, National Institute of Arthritis & Musculoskeletal and Skin Diseases, Building 10,...

  10. 75 FR 14173 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-24

    ... Skin Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the Federal Advisory Committee... Musculoskeletal and Skin Diseases Special Emphasis Panel; Small Business Research Funding Opportunities. Date... Arthritis, Musculoskeletal and Skin Diseases, 6701 Democracy Blvd, Suite 800, Bethesda, MD 20892,...

  11. 75 FR 34752 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-18

    ... Skin Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the Federal Advisory Committee... Musculoskeletal and Skin Diseases Special Emphasis Panel, Program Project Grant Review. Date: July 2, 2010. Time... Institute of Arthritis and Musculoskeletal and Skin Diseases Special Emphasis Panel, Clinical...

  12. 76 FR 31968 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-02

    ... Skin Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act... Musculoskeletal and Skin Diseases Special Emphasis Panel; Ancillary Studies to Large Ongoing Clinical Projects..., Musculoskeletal and Skin Diseases, National Institutes of Health, 6701 Democracy Blvd., Suite 800, Bethesda,...

  13. 78 FR 38065 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-25

    ... Skin Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act... unwarranted invasion of personal privacy. Name of Committee: Arthritis and Musculoskeletal and Skin Diseases Initial Review Group; Arthritis and Musculoskeletal and Skin Diseases Clinical Trials Review...

  14. 77 FR 26301 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-03

    ... Skin Diseases; Notice of Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act, as... and Skin Diseases Advisory Council. The meeting will be open to the public as indicated below, with... Committee: National Arthritis and Musculoskeletal and Skin Diseases Advisory Council. Date: June 5,...

  15. 76 FR 13649 - National Institute of Arthritis and Musculoskeletal And Skin Diseases; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-14

    ... Skin Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the Federal Advisory Committee... Musculoskeletal and Skin Diseases Special Emphasis Panel; Program Project Grant Review. Date: March 24, 2011. Time... Skin Diseases, National Institutes of Health, 6701 Democracy Blvd., Suite 800, MSC 4872, Bethesda,...

  16. 78 FR 7790 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-04

    ... Skin Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act... unwarranted invasion of personal privacy. Name of Committee: Arthritis and Musculoskeletal and Skin Diseases Initial Review Group; Arthritis and Musculoskeletal and Skin Diseases Special Grants Review...

  17. 77 FR 20646 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-05

    ... Skin Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act... Musculoskeletal and Skin Diseases Special Emphasis Panel, Program Project Grant Review. Date: April 25, 2012. Time..., National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health,...

  18. 78 FR 70312 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-25

    ... Skin Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act... Musculoskeletal and Skin Diseases Special Emphasis Panel; Small Business Innovation Research on Rare Musculoskeletal, Rheumatic and Skin Diseases. Date: December 16, 2013. Time: 9:00 a.m. to 4:00 p.m. Agenda:...

  19. 75 FR 6676 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-10

    ... Skin Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act... unwarranted invasion of personal privacy. Name of Committee: Arthritis and Musculoskeletal and Skin Diseases... Federal Domestic Assistance Program Nos. 93.846, Arthritis, Musculoskeletal and Skin Diseases...

  20. 77 FR 38847 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-29

    ... Skin Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act... Musculoskeletal and Skin Diseases, Special Emphasis Panel, Small Grant Research Review (R03). Date: July 18, 2012...,Musculoskeletal and Skin Diseases, National Institutes of Health, 6701 Democracy Blvd., Room 824, MSC...

  1. 75 FR 63496 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-15

    ... Skin Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act... unwarranted invasion of personal privacy. Name of Committee: Arthritis and Musculoskeletal and Skin Diseases..., Musculoskeletal and Skin Diseases Research, National Institutes of Health, HHS) Dated: October 8, 2010. Jennifer...

  2. 75 FR 26762 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-12

    ... Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting Pursuant to section... Institute of Arthritis and Musculoskeletal and Skin Diseases Special Emphasis Panel, Ancillary Clinical... Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, 6701...

  3. 78 FR 59945 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-30

    ... Skin Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the Federal Advisory Committee... Musculoskeletal and Skin Diseases Special Emphasis Panel; NIAMS Building Interdisciplinary Research Team Review... applications. Place: National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, 6701...

  4. 76 FR 28440 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-17

    ... Skin Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act... unwarranted invasion of personal privacy. Name of Committee: Arthritis and Musculoskeletal and Skin Diseases Initial Review Group, Arthritis and Musculoskeletal and Skin Diseases Special Grants Review...

  5. 76 FR 51044 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-17

    ... Skin Diseases; Notice of Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act, as... and Skin Diseases Advisory Council. The meeting will be open to the public as indicated below, with... Committee: National Arthritis and Musculoskeletal and Skin Diseases Advisory Council. Date: September...

  6. 77 FR 27470 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-10

    ... Skin Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act... unwarranted invasion of personal privacy. Name of Committee: Arthritis and Musculoskeletal and Skin Diseases Initial Review Group;Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee....

  7. Localized scleroderma in childhood is not just a skin disease.

    PubMed

    Zulian, Francesco; Vallongo, Cristina; Woo, Patricia; Russo, Ricardo; Ruperto, Nicolino; Harper, John; Espada, Graciela; Corona, Fabrizia; Mukamel, Masha; Vesely, Richard; Musiej-Nowakowska, Elzbieta; Chaitow, Jeff; Ros, Joan; Apaz, Maria T; Gerloni, Valeria; Mazur-Zielinska, Henryka; Nielsen, Susan; Ullman, Susanne; Horneff, Gerd; Wouters, Carine; Martini, Giorgia; Cimaz, Rolando; Laxer, Ronald; Athreya, Balu H

    2005-09-01

    Juvenile localized scleroderma is usually considered a disease that is confined to the skin and subcutaneous tissue. We studied the prevalence and clinical features of extracutaneous manifestations in a large cohort of children with juvenile localized scleroderma. Data from a multinational study on juvenile scleroderma was used for this in-depth study. Clinical features of patients with extracutaneous manifestations were compared with those of patients who had exclusively skin involvement. Seven hundred fifty patients entered the study. One hundred sixty-eight patients (22.4%) presented with a total of 193 extracutaneous manifestations, as follows: articular (47.2%), neurologic (17.1%), vascular (9.3%), ocular (8.3%), gastrointestinal (6.2%), respiratory (2.6%), cardiac (1%), and renal (1%). Other autoimmune conditions were present in 7.3% of patients. Neurologic involvement consisted of epilepsy, central nervous system vasculitis, peripheral neuropathy, vascular malformations, headache, and neuroimaging abnormalities. Ocular manifestations were episcleritis, uveitis, xerophthalmia, glaucoma, and papilledema. In more than one-fourth of these children, articular, neurologic, and ocular involvements were unrelated to the site of skin lesions. Raynaud's phenomenon was reported in 16 patients. Respiratory involvement consisted essentially of restrictive lung disease. Gastrointestinal involvement was reported in 12 patients and consisted exclusively of gastroesophageal reflux. Thirty patients (4%) had multiple extracutaneous features, but systemic sclerosis (SSc) developed in only 1 patient. In patients with extracutaneous involvement, the prevalence of antinuclear antibodies and rheumatoid factor was significantly higher than that among patients with only skin involvement. However, Scl-70 and anticentromere, markers of SSc, were not significantly increased. Extracutaneous manifestations of juvenile localized scleroderma developed in almost one-fourth of the children in

  8. Skin diseases and tattoos: a five-year experience.

    PubMed

    Napolitano, Maddalena; Megna, Matteo; Cappello, Milena; Mazzella, Caterina; Patruno, Cataldo

    2017-05-16

    Decorative tattooing as a body art form underwent an exponential increase during the last two decades, particularly among teenagers and young adults. Consequently, the number of reported adverse reactions after tattooing has increased. The most frequent reported skin reactions to tattoo include infectious (bacterial, viral, fungal) or inflammatory (allergic contact dermatitis and granulomatous reaction) diseases. Moreover, tattoos can also induce the development of typical skin lesions of pre-existing dermatoses, a phenomenon known as isomorphism reactive or Koëbner phenomenon, which commonly occurs in patients with psoriasis, vitiligo, or lichen planus. A retrospective study analyzing records data of patients attending the Department of Dermatology, University of Naples "Federico II" during 2011-2015 was performed. All cases of tattoorelated or closely located dermatitis were selected. We observed 19 patients (mean age: 26.4 year-old) showing cutaneous conditions related to the practice of tattooing. Allergic contact dermatitis was reported as the most common cutaneous disease linked to tattooing (31.6%), followed by granulomatous reactions (26.3%). These data are consistent with those already reported in literature. Our results highlight the need to develop detailed regulations regarding tattoos practice, used materials, as well as execution procedures in order to limit the outbreak of tattooing related skin diseases.

  9. Serum Biochemistry of Lumpy Skin Disease Virus-Infected Cattle

    PubMed Central

    Avci, Oğuzhan; Doğan, Müge; İnce, Ömer Barış

    2016-01-01

    Lumpy skin disease is an economically important poxvirus disease of cattle. Vaccination is the main method of control but sporadic outbreaks have been reported in Turkey. This study was carried out to determine the changes in serum biochemical values of cattle naturally infected with lumpy skin disease virus (LSDV). For this study, blood samples in EDTA, serum samples, and nodular skin lesions were obtained from clinically infected animals (n = 15) whereas blood samples in EDTA and serum samples were collected from healthy animals (n = 15). A quantitative real-time PCR method was used to detect Capripoxvirus (CaPV) DNA in clinical samples. A real-time PCR high-resolution melt assay was performed to genotype CaPVs. Serum cardiac, hepatic, and renal damage markers and lipid metabolism products were measured by autoanalyzer. LSDV nucleic acid was detected in all samples which were obtained from clinically infected cattle. The results of serum biochemical analysis showed that aspartate aminotransferase, alkaline phosphatase, total protein, and creatinine concentrations were markedly increased in serum from infected animals. However, there were no significant differences in the other biochemical parameters evaluated. The results of the current study suggest that liver and kidney failures occur during LSDV infection. These findings may help in developing effective treatment strategies in LSDV infection. PMID:27294125

  10. Diet and skin disease in dogs and cats.

    PubMed

    Watson, T D

    1998-12-01

    Dietary factors have a major role in the maintenance of healthy coat and skin, and are significant in the etiology and therapy of certain skin diseases. Nutritional deficiencies are now uncommon as a result of the widespread feeding of complete and balanced pet foods. Deficiencies of (n-6) polyunsaturated fatty acids, zinc and vitamins, however, do arise in certain animal- or product-related instances. Supraphysiologic doses of vitamin A have been used in the management of vitamin A-responsive dermatosis in Cocker spaniels; other keratinization defects and seborrheic conditions may respond to retinoid therapy. Much interest has been paid to the therapeutic value of polyunsaturated fatty acid supplements in the management of dermatologic conditions associated with hypersensitivity reactions or keratinization defects. These studies have generally yielded disappointing results, which may reflect shortcomings in the design of some trials. Nevertheless, a placebo-controlled, double-blind, cross-over study has demonstrated a clear benefit of high dose (n-3) fatty acids in the management of pruritic skin disease. There is also preliminary experimental evidence that specific dietary (n-6):(n-3) fatty ratios are useful in the dietary management of inflammatory diseases. Although results of controlled clinical trials are awaited, the argument exists that it is the absolute amount of (n-3) fatty acid intake rather than ratio that is responsible for potential health benefits.

  11. Serum Biochemistry of Lumpy Skin Disease Virus-Infected Cattle.

    PubMed

    Şevik, Murat; Avci, Oğuzhan; Doğan, Müge; İnce, Ömer Barış

    2016-01-01

    Lumpy skin disease is an economically important poxvirus disease of cattle. Vaccination is the main method of control but sporadic outbreaks have been reported in Turkey. This study was carried out to determine the changes in serum biochemical values of cattle naturally infected with lumpy skin disease virus (LSDV). For this study, blood samples in EDTA, serum samples, and nodular skin lesions were obtained from clinically infected animals (n = 15) whereas blood samples in EDTA and serum samples were collected from healthy animals (n = 15). A quantitative real-time PCR method was used to detect Capripoxvirus (CaPV) DNA in clinical samples. A real-time PCR high-resolution melt assay was performed to genotype CaPVs. Serum cardiac, hepatic, and renal damage markers and lipid metabolism products were measured by autoanalyzer. LSDV nucleic acid was detected in all samples which were obtained from clinically infected cattle. The results of serum biochemical analysis showed that aspartate aminotransferase, alkaline phosphatase, total protein, and creatinine concentrations were markedly increased in serum from infected animals. However, there were no significant differences in the other biochemical parameters evaluated. The results of the current study suggest that liver and kidney failures occur during LSDV infection. These findings may help in developing effective treatment strategies in LSDV infection.

  12. Surveillance of occupational skin disease using the Supplementary Data System.

    PubMed

    O'Malley, M; Thun, M; Morrison, J; Mathias, C G; Halperin, W E

    1988-01-01

    The utility of the Supplementary Data System (SDS) compiled by the Bureau of Labor Statistics (BLS) in conducting surveillance of occupational skin disease was evaluated by examining 14,703 workers' compensation cases reported to the SDS for the year 1981. Combined with state employment denominators obtained from the BLS Employment and Earnings Program, rates of illness (cases of dermatitis/10,000 employed) calculated for eight major industrial divisions varied significantly according to the criteria used for reporting cases. Despite quantitative variations in the rate of skin disease that depended on specific reporting criteria, the relative ranking of the major industrial divisions remained unchanged, with highest rates of skin disease consistently found in three major industry divisions: agriculture, manufacturing, and construction. This ranking of major industry divisions by rate of dermatitis corresponded extremely well with rankings generated from the 1981 Annual Survey (Spearman rank correlation = .98, p less than .01). At the two-digit level of the Standard Industrial Classification, the rankings based on the SDS had a 77% rank correlation with those from the Annual Survey. Two-digit SIC codes identified from the top 10 in both sets of rankings included crop and livestock production from the agricultural division and leather products, food products, rubber and plastic products from the manufacturing division.

  13. Skin gangrene as an extraintestinal manifestation of inflammatory bowel disease*

    PubMed Central

    Komatsu, Yumi Cristina; Capareli, Gabriela Cunha; Boin, Maria Fernanda Feitosa de Camargo; Lellis, Rute; de Freitas, Thaís Helena Proença; Simone, Karine

    2014-01-01

    Inflammatory bowel diseases can commonly present many cutaneous lesions which can contribute to the diagnosis of the disease or its activity. The most frequent cutaneous or mucocutaneous manifestations suggesting ulcerative rectocolitis activity are erythema nodosum (3-10%), pyoderma gangrenosum (5-12%) and aphthous stomatitis (4%). Other reactive skin manifestations related to immunological mechanisms associated with the inflammatory bowel disease are: Sweet's syndrome, arthritis-dermatitis syndrome associated with inflammatory bowel disease and leukocytoclastic vasculitis. We describe the case of a young man with diagnosis of ulcerative rectocolitis, which presented an extensive cutaneous gangrene secondary to microvascular thrombosis. The case represents a dermatologic rarity and should be recognized as a cutaneous manifestation related to the hypercoagulability state observed in the disease's activity. PMID:25387503

  14. Skin gangrene as an extraintestinal manifestation of inflammatory bowel disease.

    PubMed

    Komatsu, Yumi Cristina; Capareli, Gabriela Cunha; Boin, Maria Fernanda Feitosa de Camargo; Lellis, Rute; Freitas, Thaís Helena Proença de; Simone, Karine

    2014-01-01

    Inflammatory bowel diseases can commonly present many cutaneous lesions which can contribute to the diagnosis of the disease or its activity. The most frequent cutaneous or mucocutaneous manifestations suggesting ulcerative rectocolitis activity are erythema nodosum (3-10%), pyoderma gangrenosum (5-12%) and aphthous stomatitis (4%). Other reactive skin manifestations related to immunological mechanisms associated with the inflammatory bowel disease are: Sweet's syndrome, arthritis-dermatitis syndrome associated with inflammatory bowel disease and leukocytoclastic vasculitis. We describe the case of a young man with diagnosis of ulcerative rectocolitis, which presented an extensive cutaneous gangrene secondary to microvascular thrombosis. The case represents a dermatologic rarity and should be recognized as a cutaneous manifestation related to the hypercoagulability state observed in the disease's activity.

  15. Evaluation of skin thickness lesions in patients with Lyme disease measured by modified Rodnan total skin score.

    PubMed

    Moniuszko, A; Gińdzieńska-Sieśkiewicz, E; Pancewicz, S A; Czupryna, P; Zajkowska, J; Sierakowski, S

    2012-10-01

    Recently, a possible etiological connection between infection with Borrelia burgdorferi and various skin lesions, including morphea and systemic sclerosis (SSc), has been discussed. The aim of our study was the evaluation of frequency of skin thickening typical of SSc or morphea in the group of patients with Lyme disease (LD) with frequent exposition to tick bites. The group consisted of 110 patients with LD frequently exposed to tick bites form the northeastern Poland, which is an endemic area for this disease. To measure the skin lesions, the modified Rodnan total skin score (RTSS) was used. In the analyzed group, no skin changes typical of morphea or skin thickening were found. According to RTSS, all patients scored 0 points. Raynaud's phenomenon in all patients was not found. The relationship between scleroderma or morphea and LD is still a matter of controversy. Described by some authors, cases with LD and scleroderma may be associated with co-existence of B. burgdorferi infection with autoimmune process.

  16. Tropical Skin Diseases in Children: A Review-Part II.

    PubMed

    García-Romero, Maria Teresa; Lara-Corrales, Irene; Kovarik, Carrie L; Pope, Elena; Arenas, Roberto

    2016-05-01

    Tropical skin diseases are infectious conditions influenced by factors such as nutrition, housing, and the environment. Migration patterns have caused these conditions to be seen all around the world, not only in developing countries. Many of these diseases have a different presentation in childhood, which changes the diagnostic approach and management options. In this article, we review some of the most common tropical mycobacterial, protozoan, parasitic, and viral dermatologic conditions in children, including their epidemiologic, clinical, diagnostic, and therapeutic aspects. © 2016 Wiley Periodicals, Inc.

  17. Parkinson disease and progressive supranuclear palsy: protein expression in skin.

    PubMed

    Rodríguez-Leyva, Ildefonso; Chi-Ahumada, Erika G; Carrizales, Juan; Rodríguez-Violante, Mayela; Velázquez-Osuna, Salvador; Medina-Mier, Verónica; Martel-Gallegos, María G; Zarazúa, Sergio; Enríquez-Macías, Lourdes; Castro, Adriana; Calderón-Garcidueñas, Ana Laura; Jiménez-Capdeville, María E

    2016-03-01

    This study characterizes the expression of tau (p-tau) and α-synuclein (α-syn) by immunohistochemistry in the skin of three different populations: healthy control (HC), Parkinson disease (PD), and progressive supranuclear paralysis (PSP) subjects, with the purpose of finding a biomarker that could differentiate between subjects with PD and PSP. We evaluated the presence of p-tau and α-syn in a pilot study in the skin of three distinct groups of patients: 17 healthy subjects, 17 patients with PD, and 10 patients with PSP. Four millimeters punch biopsies were obtained from the occipital area and analyzed by immunohistochemistry using antibodies against α-syn and phosphorylated species of tau. PHF (paired helical filaments) antibody identifies p-tau in both normal and pathological conditions and AT8 recognizes p-tau characteristic of pathological conditions. Differences between the three groups were assessed by quantification of immunopositive areas in the epidermis. The immunopositivity pattern of p-tau and α-syn was significantly different among the three groups. Healthy subjects showed minimal staining using AT8 and α-syn. The PD group showed significantly higher α-syn and AT8 immunopositivity, while the PSP group only expressed higher AT8 immunopositivity than HCs. These data suggest that the skin reflects brain pathology. Therefore, immunohistochemical analysis of p-tau and α-syn in the skin can be useful for further characterization of PD and PSP.

  18. Arsenic-related Bowen's disease, palmar keratosis, and skin cancer.

    PubMed Central

    Cöl, M; Cöl, C; Soran, A; Sayli, B S; Oztürk, S

    1999-01-01

    Chronic arsenical intoxication can still be found in environmental and industrial settings. Symptoms of chronic arsenic intoxication include general pigmentation or focal "raindrop" pigmentation of the skin and the appearance of hyperkeratosis of the palms of the hands and soles of the feet. In addition to arsenic-related skin diseases including keratosis, Bowen's disease, basal-cell-carcinoma, and squamous-cell carcinoma, there is also an increased risk of some internal malignancies. Arsenic-related diseases are common in areas of the world where the drinking water has a high arsenic content. In this paper, we describe a 35-year-old male patient who had arsenic-related keratosis, squamous-cell carcinoma in the palmar area of his left hand, and Bowen's disease on his left thigh. The patient worked in a borax mine for 15 years, so he was exposed to arsenic in drinking water, airborne arsenic in his workplace, and had direct contact. The patient was treated for 11 months for arsenic-related keratosis until an axillary lymph node metastasis occurred; the lesion was excised and diagnosed to be malignant. Bowen's disease was detected when the patient was being treated for cancer. No other malignancy was found. The patient is still receiving regular follow-up care. Images Figure 1 Figure 2 PMID:10417369

  19. Is there a need for repetition of skin test in childhood allergic diseases? Repetition of skin test and allergic diseases.

    PubMed

    Dogru, Mahmut; Bostanci, Ilknur; Ozmen, Serap; Ginis, Tayfur; Duman, Handan

    2014-06-01

    Skin prick tests are widely used to determine sensitivity in allergic diseases. There is limited information about the natural history of skin sensitization tests and factors that affect them. It was aimed to determine the changes in skin test results and the factors affecting the reactivity of skin tests after a period of approximately four years in children with allergic disease. SPT of 170 patients among 2485 children with asthma and/or allergic rhinitis and/or atopic dermatitis, who underwent SPT between 2005 and 2007, were repeated after an interval of at least 3 years. The mean age was 10.7 ± 3.1 (5-18) years and 70% of the patients were male. In total 66 (39.0% of the study population) had a different skin tests result in follow-up. Alterations: loss of sensitivity in 18 (11%) patients, the formation of a new sensitivity in 37 (22%) patients, and 11 (6%) both gained and lost sensitization. The presence of atopy in the family, the presence of allergic rhinitis and IgE elevation significantly predicted the incidence of new sensitization. The presence of sensitization to multiple allergens significantly predicted the incidence of loss of sensitization. It is found that there was an alteration of sensitization in 4/10 children at the end of the average 4-year period. The presence of family atopy, the presence of allergic rhinitis and serum total IgE elevation were risk factors for the development of new sensitization. On the other hand sensitization to multiple allergens was risk factors for the loss of sensitization.

  20. Prevalences of skin diseases among primary schoolchildren in Damietta, Egypt.

    PubMed

    El-Khateeb, Ekramy A; Lotfi, Ranya A; Abd Elaziz, Khaled M; Abdel-Aziz, Khaled M; El-Shiekh, Suzan E

    2014-05-01

    Information on prevalences of pediatric dermatoses in Egypt is scanty. This study aimed to supplement existing data. A cross-sectional study was conducted in Damietta, Egypt between October 2011 and March 2012. It involved 6162 pupils randomly selected from 30 primary schools. The sample was equally divided (3081 pupils/15 schools) between urban and rural areas. Each participant was interviewed for age, gender, residence and complaint. Hygiene status was evaluated and a clinical examination was carried out for skin diseases. Data were coded and analyzed. Although most children revealed more than one dermatosis, the majority (76.2%) had not complained of disease. The most common disease group included benign neoplasms (87.0%), followed by pigmentary disorders (68.3%), infections (50.9%), adnexal disorders (14.1%), hypersensitivity diseases (14.0%), genodermatoses (0.3%) and papulosquamous diseases (0.2%). The most common subgroup of diseases comprised parasitic infections (47.5%), among which pediculosis prevailed (47.5%), followed by dermatitis (10.0%) in which pityriasis alba dominated (6.0%), followed by hair disorders (9.3%), bacterial infections (5.9%), urticaria (4.4%), sebaceous gland disorders (2.7%), sweat gland disorders (2.3%), viral infections (1.6%) and fungal infections (0.7%). The most commonly found diseases included, in descending order, acquired melanocytic nevus, post-inflammatory hyperpigmentation, pediculosis, leukoderma, café au lait spots, atrophic scar, cicatricial alopecia, hypertrophic scar, pityriasis alba, papular urticaria, xerosis and impetigo. The high prevalence of skin diseases, especially of trauma-related disorders and infections, may be mainly attributable to a lack of appropriate health awareness and care, which has created a tendency within the population to adapt without complaining or seeking medical help. Such circumstances, unfortunately, have resulted in a growing community of silent patients. © 2013 The International

  1. Evidence of intrauterine transmission of lumpy skin disease virus.

    PubMed

    Rouby, Sherin; Aboulsoud, Emad

    2016-03-01

    The current study describes the clinical, histopathological, molecular and serological diagnosis of lumpy skin disease (LSD) in a premature 1-day old calf that has been delivered from a cow that exhibited signs of LSD during the seventh month of pregnancy. The calf showed generalized skin lesions accompanied with signs of immaturity and died 36 h after birth. Postmortem and histopathological examinations revealed the involvement of multiple tissues. The presence of Neethling virus DNA in tissues was confirmed by polymerase chain reaction (PCR) and gene sequencing. Results of ELISA and serum neutralization test (SNT) confirmed that the calf had developed precolostral serum antibodies to LSD virus indicating in utero virus transmission. All tested sera collected from animals located in the same area were serologically positive, indicating exposure to LSD virus.

  2. Direct immunofluorescence for immunobullous and other skin diseases.

    PubMed

    Ghanadan, Alireza; Saghazadeh, Amene; Daneshpazhooh, Maryam; Rezaei, Nima

    2015-05-01

    A swift glance at ample evidence currently available about the assay clearly illustrates that the development of direct immunofluorescence (DIF), in which direct fluorescent antibodies are utilized to identify the target antigen, has been of immense importance. The immunoreactant deposits have been delineated by the DIF assay in three main locations, including throughout the epidermis, at the dermoepidermal junction (also known as the basement membrane zone) and in and/or around blood vessel walls. DIF testing can be conducted on several specimen sources, which are categorized according to feasibility of collection into invasive (e.g., skin) and non-invasive (e.g., hair). This review was intended to indicate that inspection of immunoreactant deposits via DIF is highly instrumental in diagnosing and monitoring the immunobullous and other diseases of the skin.

  3. [Skin diseases in hemodialysis and kidney transplant patients].

    PubMed

    Gerhardt, Clarissa Morais Busatto; Gussão, Bruna Calvi; de Matos, Jorge Paulo Strogoff; Lugon, Jocemir Ronaldo; Pinto, Jane Marcy Neffá

    2011-01-01

    Recently, the world is facing an escalate in the incidence of chronic kidney disease (CKD). Databases containing information about patients in end stage renal disease (ESRD), especially in the United States, were the sources of initial information about it. Brazil has the third largest population on dialysis in the world, and there are about 680 dialysis centers, spread across all units of the federation in the present, providing treatment to an estimated population of almost 90,000 patients. Cutaneous involvement in the chronic renal failure is characterized by a number of manifestations, which may be related to three processes: the primary renal disease, the uremic state, or the therapeutic measures used in their handling. The skin changes in these two classes of patients, dialysis and transplant recipients, have been the subject of several studies. n recent years, however, great progress has been achieved in these two therapeutic modalities, which may have changed not only the type of the dermatologic disorders associated with these two conditions, but also their intensity or frequency. This article aims to yield an update as to the topic skin diseases in hemodialysis and kidney transplant patients.

  4. Evidence for major gene inheritance of Alzheimer disease in families of patients with and without Apolipoprotein E {epsilon}4

    SciTech Connect

    Rao, V.S.; Auerbach, S.A.; Farrer, L.A.

    1996-09-01

    Apolipoprotein E (APOE) genotype is the single most important determinant to the common form of Alzheimer disease (AD) yet identified. Several studies show that family history of AD is not entirely accounted for by APOE genotype. Also, there is evidence for an interaction between APOE genotype and gender. We carried out a complex segregation analysis in 636 nuclear families of consecutively ascertained and rigorously diagnosed probands in the Multi-Institutional Research in Alzheimer Genetic Epidemiology study in order to derive models of disease transmission which account for the influences of APOE genotype of the proband and gender. In the total group of families, models postulating sporadic occurrence, no major gene effect, random environmental transmission, and Mendelian inheritance were rejected. Transmission of AD in families of probands with at least one {epsilon}4 allele best fit a dominant model. Moreover, single gene inheritance best explained clustering of the disorder in families of probands lacking E4, but a more complex genetic model or multiple genetic models may ultimately account for risk in this group of families. Our results also suggest that susceptibility to AD differs between men and women regardless of the proband`s APOE status. Assuming a dominant model, AD appears to be completely penetrant in women, whereas only 62%-65% of men with predisposing genotypes develop AD. However, parameter estimates from the arbitrary major gene model suggests that AD is expressed dominantly in women and additively in men. These observations, taken together with epidemiologic data, are consistent with the hypothesis of an interaction between genes and other biological factors affecting disease susceptibility. 76 refs., 4 tabs.

  5. Evidence of major genes for resistance to bacterial cold-water disease in rainbow trout using mixed inheritance multiple-threshold models and Bayesian segregation analysis

    USDA-ARS?s Scientific Manuscript database

    PURPOSE: Bacterial cold water disease (BCWD) causes significant economic loss in salmonid aquaculture, and in 2005, a rainbow trout breeding program was initiated at the NCCCWA to select for increased disease survival. The main objectives of this study were to determine the mode of inheritance of di...

  6. Inheritance of rainbow trout Oncorhynchus mykiss spleen size and correlation with bacterial cold water disease resistance

    USDA-ARS?s Scientific Manuscript database

    Infectious disease causes substantial loss in aquaculture and selective breeding for increased innate resistance offers an attractive strategy for controlling disease. In 2005, the NCCCWA implemented a selective breeding program to increase rainbow trout survival following challenge with Flavobacte...

  7. 77 FR 51544 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-24

    ... Skin Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act... Musculoskeletal and Skin Diseases Special Emphasis Panel: Tissue Engineering and Regenerative Medicine. Date... of Federal Domestic Assistance Program Nos. 93.846, Arthritis, Musculoskeletal and Skin...

  8. 77 FR 1702 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-11

    ... Skin Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act... Musculoskeletal and Skin Diseases, including consideration of personnel qualifications and performance, and the... Inflammation Branch and the Laboratory of Skin Biology. Place: National Institutes of Health, Building 31,...

  9. 75 FR 29770 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-27

    ... Skin Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act... Musculoskeletal and Skin Diseases Special Emphasis Panel; Career Development, Research Training & Pathways to... . (Catalogue of Federal Domestic Assistance Program Nos. 93.846, Arthritis, Musculoskeletal and Skin...

  10. 77 FR 66853 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-07

    ... Skin Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act... Musculoskeletal and Skin Diseases Special Emphasis Panel; Multidisciplinary Clinical Research Centers. Date... . (Catalogue of Federal Domestic Assistance Program Nos. 93.846, Arthritis, Musculoskeletal and Skin...

  11. Inherited determinants of Crohn's disease and ulcerative colitis phenotypes: a genetic association study.

    PubMed

    Cleynen, Isabelle; Boucher, Gabrielle; Jostins, Luke; Schumm, L Philip; Zeissig, Sebastian; Ahmad, Tariq; Andersen, Vibeke; Andrews, Jane M; Annese, Vito; Brand, Stephan; Brant, Steven R; Cho, Judy H; Daly, Mark J; Dubinsky, Marla; Duerr, Richard H; Ferguson, Lynnette R; Franke, Andre; Gearry, Richard B; Goyette, Philippe; Hakonarson, Hakon; Halfvarson, Jonas; Hov, Johannes R; Huang, Hailang; Kennedy, Nicholas A; Kupcinskas, Limas; Lawrance, Ian C; Lee, James C; Satsangi, Jack; Schreiber, Stephan; Théâtre, Emilie; van der Meulen-de Jong, Andrea E; Weersma, Rinse K; Wilson, David C; Parkes, Miles; Vermeire, Severine; Rioux, John D; Mansfield, John; Silverberg, Mark S; Radford-Smith, Graham; McGovern, Dermot P B; Barrett, Jeffrey C; Lees, Charlie W

    2016-01-09

    Crohn's disease and ulcerative colitis are the two major forms of inflammatory bowel disease; treatment strategies have historically been determined by this binary categorisation. Genetic studies have identified 163 susceptibility loci for inflammatory bowel disease, mostly shared between Crohn's disease and ulcerative colitis. We undertook the largest genotype association study, to date, in widely used clinical subphenotypes of inflammatory bowel disease with the goal of further understanding the biological relations between diseases. This study included patients from 49 centres in 16 countries in Europe, North America, and Australasia. We applied the Montreal classification system of inflammatory bowel disease subphenotypes to 34,819 patients (19,713 with Crohn's disease, 14,683 with ulcerative colitis) genotyped on the Immunochip array. We tested for genotype-phenotype associations across 156,154 genetic variants. We generated genetic risk scores by combining information from all known inflammatory bowel disease associations to summarise the total load of genetic risk for a particular phenotype. We used these risk scores to test the hypothesis that colonic Crohn's disease, ileal Crohn's disease, and ulcerative colitis are all genetically distinct from each other, and to attempt to identify patients with a mismatch between clinical diagnosis and genetic risk profile. After quality control, the primary analysis included 29,838 patients (16,902 with Crohn's disease, 12,597 with ulcerative colitis). Three loci (NOD2, MHC, and MST1 3p21) were associated with subphenotypes of inflammatory bowel disease, mainly disease location (essentially fixed over time; median follow-up of 10·5 years). Little or no genetic association with disease behaviour (which changed dramatically over time) remained after conditioning on disease location and age at onset. The genetic risk score representing all known risk alleles for inflammatory bowel disease showed strong association with

  12. Inherited determinants of Crohn's disease and ulcerative colitis phenotypes: a genetic association study

    PubMed Central

    Cleynen, Isabelle; Boucher, Gabrielle; Jostins, Luke; Schumm, L Philip; Zeissig, Sebastian; Ahmad, Tariq; Andersen, Vibeke; Andrews, Jane M; Annese, Vito; Brand, Stephan; Brant, Steven R; Cho, Judy H; Daly, Mark J; Dubinsky, Marla; Duerr, Richard H; Ferguson, Lynnette R; Franke, Andre; Gearry, Richard B; Goyette, Philippe; Hakonarson, Hakon; Halfvarson, Jonas; Hov, Johannes R; Huang, Hailang; Kennedy, Nicholas A; Kupcinskas, Limas; Lawrance, Ian C; Lee, James C; Satsangi, Jack; Schreiber, Stephan; Théâtre, Emilie; van der Meulen-de Jong, Andrea E; Weersma, Rinse K; Wilson, David C; Parkes, Miles; Vermeire, Severine; Rioux, John D; Mansfield, John; Silverberg, Mark S; Radford-Smith, Graham; McGovern, Dermot P B; Barrett, Jeffrey C; Lees, Charlie W

    2016-01-01

    Summary Background Crohn's disease and ulcerative colitis are the two major forms of inflammatory bowel disease; treatment strategies have historically been determined by this binary categorisation. Genetic studies have identified 163 susceptibility loci for inflammatory bowel disease, mostly shared between Crohn's disease and ulcerative colitis. We undertook the largest genotype association study, to date, in widely used clinical subphenotypes of inflammatory bowel disease with the goal of further understanding the biological relations between diseases. Methods This study included patients from 49 centres in 16 countries in Europe, North America, and Australasia. We applied the Montreal classification system of inflammatory bowel disease subphenotypes to 34 819 patients (19 713 with Crohn's disease, 14 683 with ulcerative colitis) genotyped on the Immunochip array. We tested for genotype–phenotype associations across 156 154 genetic variants. We generated genetic risk scores by combining information from all known inflammatory bowel disease associations to summarise the total load of genetic risk for a particular phenotype. We used these risk scores to test the hypothesis that colonic Crohn's disease, ileal Crohn's disease, and ulcerative colitis are all genetically distinct from each other, and to attempt to identify patients with a mismatch between clinical diagnosis and genetic risk profile. Findings After quality control, the primary analysis included 29 838 patients (16 902 with Crohn's disease, 12 597 with ulcerative colitis). Three loci (NOD2, MHC, and MST1 3p21) were associated with subphenotypes of inflammatory bowel disease, mainly disease location (essentially fixed over time; median follow-up of 10·5 years). Little or no genetic association with disease behaviour (which changed dramatically over time) remained after conditioning on disease location and age at onset. The genetic risk score representing all known risk alleles for

  13. Autoimmune bullous skin diseases. Part 1: Clinical manifestations.

    PubMed

    Kneisel, Andrea; Hertl, Michael

    2011-10-01

    Autoimmune bullous skin diseases are characterized by autoantibodies against adhesion molecules of the skin. Pemphigus is a disorder with an intraepidermal loss of adhesion and is characterized by fragile blisters and erosions. Pemphigus vulgaris often shows extensive lesions of the oral mucosa, while pemphigus foliaceus is commonly restricted to cutaneous involvement with puff pastry-like scale formation. Paraneoplastic pemphigus is obligatorily associated with malignancies and often presents as hemorrhagic stomatitis with multiforme-like exanthems. IgA pemphigus typically presents with pustules and annular plaques but not with mucosal involvement. The clinical spectrum of the pemphigoids includes tense blisters, urticarial plaques, and prurigo- like eczematous lesions. Pemphigoid gestationis mostly occurs during the last trimester of pregnancy and mucous membrane pemphigoid primarily involves the oral mucosa and conjunctivae and leads to scarring. Linear IgA bullous dermatosis manifests with tense blisters in a "cluster of jewels"-like pattern in childhood and is more heterogeneous in adulthood. Classical epidermolysis bullosa acquisita shows extensive skin fragility. Dermatitis herpetiformis is associated with gluten-sensitive enteropathy and manifests clinically with severe itching and papulovesicles on the extensor surfaces of the extremities and the lumbosacral area. The intention of the review is to demonstrate the heterogeneous clinical spectrum of autoimmune bullous disorders.

  14. The Malassezia Genus in Skin and Systemic Diseases

    PubMed Central

    Magiatis, Prokopios; Hantschke, Markus; Bassukas, Ioannis D.; Velegraki, Aristea

    2012-01-01

    Summary: In the last 15 years, the genus Malassezia has been a topic of intense basic research on taxonomy, physiology, biochemistry, ecology, immunology, and metabolomics. Currently, the genus encompasses 14 species. The 1996 revision of the genus resulted in seven accepted taxa: M. furfur, M. pachydermatis, M. sympodialis, M. globosa, M. obtusa, M. restricta, and M. slooffiae. In the last decade, seven new taxa isolated from healthy and lesional human and animal skin have been accepted: M. dermatis, M. japonica, M. yamatoensis, M. nana, M. caprae, M. equina, and M. cuniculi. However, forthcoming multidisciplinary research is expected to show the etiopathological relationships between these new species and skin diseases. Hitherto, basic and clinical research has established etiological links between Malassezia yeasts, pityriasis versicolor, and sepsis of neonates and immunocompromised individuals. Their role in aggravating seborrheic dermatitis, dandruff, folliculitis, and onychomycosis, though often supported by histopathological evidence and favorable antifungal therapeutic outcomes, remains under investigation. A close association between skin and Malassezia IgE binding allergens in atopic eczema has been shown, while laboratory data support a role in psoriasis exacerbations. Finally, metabolomic research resulted in the proposal of a hypothesis on the contribution of Malassezia-synthesized aryl hydrocarbon receptor (AhR) ligands to basal cell carcinoma through UV radiation-induced carcinogenesis. PMID:22232373

  15. The Malassezia genus in skin and systemic diseases.

    PubMed

    Gaitanis, Georgios; Magiatis, Prokopios; Hantschke, Markus; Bassukas, Ioannis D; Velegraki, Aristea

    2012-01-01

    In the last 15 years, the genus Malassezia has been a topic of intense basic research on taxonomy, physiology, biochemistry, ecology, immunology, and metabolomics. Currently, the genus encompasses 14 species. The 1996 revision of the genus resulted in seven accepted taxa: M. furfur, M. pachydermatis, M. sympodialis, M. globosa, M. obtusa, M. restricta, and M. slooffiae. In the last decade, seven new taxa isolated from healthy and lesional human and animal skin have been accepted: M. dermatis, M. japonica, M. yamatoensis, M. nana, M. caprae, M. equina, and M. cuniculi. However, forthcoming multidisciplinary research is expected to show the etiopathological relationships between these new species and skin diseases. Hitherto, basic and clinical research has established etiological links between Malassezia yeasts, pityriasis versicolor, and sepsis of neonates and immunocompromised individuals. Their role in aggravating seborrheic dermatitis, dandruff, folliculitis, and onychomycosis, though often supported by histopathological evidence and favorable antifungal therapeutic outcomes, remains under investigation. A close association between skin and Malassezia IgE binding allergens in atopic eczema has been shown, while laboratory data support a role in psoriasis exacerbations. Finally, metabolomic research resulted in the proposal of a hypothesis on the contribution of Malassezia-synthesized aryl hydrocarbon receptor (AhR) ligands to basal cell carcinoma through UV radiation-induced carcinogenesis.

  16. An integrated systems genetics screen reveals the transcriptional structure of inherited predisposition to metastatic disease.

    PubMed

    Faraji, Farhoud; Hu, Ying; Wu, Gang; Goldberger, Natalie E; Walker, Renard C; Zhang, Jinghui; Hunter, Kent W

    2014-02-01

    Metastasis is the result of stochastic genomic and epigenetic events leading to gene expression profiles that drive tumor dissemination. Here we exploit the principle that metastatic propensity is modified by the genetic background to generate prognostic gene expression signatures that illuminate regulators of metastasis. We also identify multiple microRNAs whose germline variation is causally linked to tumor progression and metastasis. We employ network analysis of global gene expression profiles in tumors derived from a panel of recombinant inbred mice to identify a network of co-expressed genes centered on Cnot2 that predicts metastasis-free survival. Modulating Cnot2 expression changes tumor cell metastatic potential in vivo, supporting a functional role for Cnot2 in metastasis. Small RNA sequencing of the same tumor set revealed a negative correlation between expression of the Mir216/217 cluster and tumor progression. Expression quantitative trait locus analysis (eQTL) identified cis-eQTLs at the Mir216/217 locus, indicating that differences in expression may be inherited. Ectopic expression of Mir216/217 in tumor cells suppressed metastasis in vivo. Finally, small RNA sequencing and mRNA expression profiling data were integrated to reveal that miR-3470a/b target a high proportion of network transcripts. In vivo analysis of Mir3470a/b demonstrated that both promote metastasis. Moreover, Mir3470b is a likely regulator of the Cnot2 network as its overexpression down-regulated expression of network hub genes and enhanced metastasis in vivo, phenocopying Cnot2 knockdown. The resulting data from this strategy identify Cnot2 as a novel regulator of metastasis and demonstrate the power of our systems-level approach in identifying modifiers of metastasis.

  17. An integrated systems genetics screen reveals the transcriptional structure of inherited predisposition to metastatic disease

    PubMed Central

    Faraji, Farhoud; Hu, Ying; Wu, Gang; Goldberger, Natalie E.; Walker, Renard C.; Zhang, Jinghui; Hunter, Kent W.

    2014-01-01

    Metastasis is the result of stochastic genomic and epigenetic events leading to gene expression profiles that drive tumor dissemination. Here we exploit the principle that metastatic propensity is modified by the genetic background to generate prognostic gene expression signatures that illuminate regulators of metastasis. We also identify multiple microRNAs whose germline variation is causally linked to tumor progression and metastasis. We employ network analysis of global gene expression profiles in tumors derived from a panel of recombinant inbred mice to identify a network of co-expressed genes centered on Cnot2 that predicts metastasis-free survival. Modulating Cnot2 expression changes tumor cell metastatic potential in vivo, supporting a functional role for Cnot2 in metastasis. Small RNA sequencing of the same tumor set revealed a negative correlation between expression of the Mir216/217 cluster and tumor progression. Expression quantitative trait locus analysis (eQTL) identified cis-eQTLs at the Mir216/217 locus, indicating that differences in expression may be inherited. Ectopic expression of Mir216/217 in tumor cells suppressed metastasis in vivo. Finally, small RNA sequencing and mRNA expression profiling data were integrated to reveal that miR-3470a/b target a high proportion of network transcripts. In vivo analysis of Mir3470a/b demonstrated that both promote metastasis. Moreover, Mir3470b is a likely regulator of the Cnot2 network as its overexpression down-regulated expression of network hub genes and enhanced metastasis in vivo, phenocopying Cnot2 knockdown. The resulting data from this strategy identify Cnot2 as a novel regulator of metastasis and demonstrate the power of our systems-level approach in identifying modifiers of metastasis. PMID:24322557

  18. Inherited peripheral neuropathies.

    PubMed

    Saporta, Mario A; Shy, Michael E

    2013-05-01

    Charcot-Marie-Tooth (CMT) disease is a heterogeneous group of inherited peripheral neuropathies in which the neuropathy is the sole or primary component of the disorder, as opposed to diseases in which the neuropathy is part of a more generalized neurologic or multisystem syndrome. Because of the great genetic heterogeneity of this condition, it can be challenging for the general neurologist to diagnose patients with specific types of CMT. This article reviews the biology of the inherited peripheral neuropathies, delineates major phenotypic features of the CMT subtypes, and suggest strategies for focusing genetic testing. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Inherited Peripheral Neuropathies

    PubMed Central

    Saporta, Mario A.; Shy, Michael E.

    2013-01-01

    SYNOPSIS Charcot Marie Tooth disease (CMT) is a heterogeneous group of inherited peripheral neuropathies in which the neuropathy is the sole or primary component of the disorder, as opposed to diseases in which the neuropathy is part of a more generalized neurological or multisystem syndrome. Due to the great genetic heterogeneity of this condition, it can be challenging for the general neurologist to diagnose patients with specific types of CMT. Here, we review the biology of the inherited peripheral neuropathies, delineate major phenotypic features of the CMT subtypes and suggest strategies for focusing genetic testing. PMID:23642725

  20. Concise Review: Patient-Specific Stem Cells to Interrogate Inherited Eye Disease

    PubMed Central

    Giacalone, Joseph C.; Wiley, Luke A.; Burnight, Erin R.; Songstad, Allison E.; Mullins, Robert F.; Stone, Edwin M.

    2016-01-01

    Whether we are driving to work or spending time with loved ones, we depend on our sense of vision to interact with the world around us. Therefore, it is understandable why blindness for many is feared above death itself. Heritable diseases of the retina, such as glaucoma, age-related macular degeneration, and retinitis pigmentosa, are major causes of blindness worldwide. The recent success of gene augmentation trials for the treatment of RPE65-associated Leber congenital amaurosis has underscored the need for model systems that accurately recapitulate disease. With the advent of patient-specific induced pluripotent stem cells (iPSCs), researchers are now able to obtain disease-specific cell types that would otherwise be unavailable for molecular analysis. In the present review, we discuss how the iPSC technology is being used to confirm the pathogenesis of novel genetic variants, interrogate the pathophysiology of disease, and accelerate the development of patient-centered treatments. Significance Stem cell technology has created the opportunity to advance treatments for multiple forms of blindness. Researchers are now able to use a person’s cells to generate tissues found in the eye. This technology can be used to elucidate the genetic causes of disease and develop treatment strategies. In the present review, how stem cell technology is being used to interrogate the pathophysiology of eye disease and accelerate the development of patient-centered treatments is discussed. PMID:26683869

  1. Biology and therapy of inherited retinal degenerative disease: insights from mouse models.

    PubMed

    Veleri, Shobi; Lazar, Csilla H; Chang, Bo; Sieving, Paul A; Banin, Eyal; Swaroop, Anand

    2015-02-01

    Retinal neurodegeneration associated with the dysfunction or death of photoreceptors is a major cause of incurable vision loss. Tremendous progress has been made over the last two decades in discovering genes and genetic defects that lead to retinal diseases. The primary focus has now shifted to uncovering disease mechanisms and designing treatment strategies, especially inspired by the successful application of gene therapy in some forms of congenital blindness in humans. Both spontaneous and laboratory-generated mouse mutants have been valuable for providing fundamental insights into normal retinal development and for deciphering disease pathology. Here, we provide a review of mouse models of human retinal degeneration, with a primary focus on diseases affecting photoreceptor function. We also describe models associated with retinal pigment epithelium dysfunction or synaptic abnormalities. Furthermore, we highlight the crucial role of mouse models in elucidating retinal and photoreceptor biology in health and disease, and in the assessment of novel therapeutic modalities, including gene- and stem-cell-based therapies, for retinal degenerative diseases.

  2. Concise Review: Patient-Specific Stem Cells to Interrogate Inherited Eye Disease.

    PubMed

    Giacalone, Joseph C; Wiley, Luke A; Burnight, Erin R; Songstad, Allison E; Mullins, Robert F; Stone, Edwin M; Tucker, Budd A

    2016-02-01

    Whether we are driving to work or spending time with loved ones, we depend on our sense of vision to interact with the world around us. Therefore, it is understandable why blindness for many is feared above death itself. Heritable diseases of the retina, such as glaucoma, age-related macular degeneration, and retinitis pigmentosa, are major causes of blindness worldwide. The recent success of gene augmentation trials for the treatment of RPE65-associated Leber congenital amaurosis has underscored the need for model systems that accurately recapitulate disease. With the advent of patient-specific induced pluripotent stem cells (iPSCs), researchers are now able to obtain disease-specific cell types that would otherwise be unavailable for molecular analysis. In the present review, we discuss how the iPSC technology is being used to confirm the pathogenesis of novel genetic variants, interrogate the pathophysiology of disease, and accelerate the development of patient-centered treatments. Significance: Stem cell technology has created the opportunity to advance treatments for multiple forms of blindness. Researchers are now able to use a person's cells to generate tissues found in the eye. This technology can be used to elucidate the genetic causes of disease and develop treatment strategies. In the present review, how stem cell technology is being used to interrogate the pathophysiology of eye disease and accelerate the development of patient-centered treatments is discussed.

  3. Biology and therapy of inherited retinal degenerative disease: insights from mouse models

    PubMed Central

    Veleri, Shobi; Lazar, Csilla H.; Chang, Bo; Sieving, Paul A.; Banin, Eyal; Swaroop, Anand

    2015-01-01

    Retinal neurodegeneration associated with the dysfunction or death of photoreceptors is a major cause of incurable vision loss. Tremendous progress has been made over the last two decades in discovering genes and genetic defects that lead to retinal diseases. The primary focus has now shifted to uncovering disease mechanisms and designing treatment strategies, especially inspired by the successful application of gene therapy in some forms of congenital blindness in humans. Both spontaneous and laboratory-generated mouse mutants have been valuable for providing fundamental insights into normal retinal development and for deciphering disease pathology. Here, we provide a review of mouse models of human retinal degeneration, with a primary focus on diseases affecting photoreceptor function. We also describe models associated with retinal pigment epithelium dysfunction or synaptic abnormalities. Furthermore, we highlight the crucial role of mouse models in elucidating retinal and photoreceptor biology in health and disease, and in the assessment of novel therapeutic modalities, including gene- and stem-cell-based therapies, for retinal degenerative diseases. PMID:25650393

  4. Occupational skin diseases and prevention among sanitation workers in China.

    PubMed

    Yan, Yuehua; Wang, Xinggang; Wu, Jianbo; Xu, Li

    2015-09-01

    Little research has been focused on the health status or the occupational protection awareness of sanitation workers. The policy recommendations on the occupational safety and health of sanitation workers based on the scientific research are also insufficient in developing countries like China. To study the incidence of dermatoses and the relevance with occupational exposure, protection awareness and protective measures among sanitation workers for better management and protection of the sanitation workers. 273 sanitation workers and 113 administrative staff from 11 streets of Wuhan were recruited. Dermatological problems were evaluated and recorded by physical examination. Occupational exposure, protection awareness, the use of protective equipments and personal history of skin disease were assessed by questionnaires. Compared with administrative staff, sanitation workers had much more occupational dermatological problems and had a much higher rate of harmful ultraviolet ray exposure. Young sanitation workers were more aware of occupational self-protection and a relatively higher rate of them using protective equipments compared with old ones. Exposure to multiple health hazards and the poor use of protective equipments are related to skin diseases in sanitation workers. Prejob training of self-protection and the use of protective equipments are recommended.

  5. Spread of lumpy skin disease in Israeli dairy herds.

    PubMed

    Yeruham, I; Nir, O; Braverman, Y; Davidson, M; Grinstein, H; Haymovitch, M; Zamir, O

    1995-07-22

    Fourteen of the 17 dairy herds in Peduyim, an Israeli village, became infected with lumpy skin disease during a period of 37 days in August and September 1989. One cow in one neighbouring village and four cows in another neighbouring village also became infected, probably through being treated by a veterinarian who treated cows in Peduyim. Circumstantial evidence suggests that the original infection was brought to Peduyim and spread by stable flies (Stomoxys calcitrans) carried by the wind from foci of the disease at El Arish in northern Sinai, or at Ismailiya and the Nile delta in Egypt. All the cattle and the small flocks of sheep and goats in the village were slaughtered.

  6. Dissecting disease inheritance modes in a three-dimensional protein network challenges the "guilt-by-association" principle.

    PubMed

    Guo, Yu; Wei, Xiaomu; Das, Jishnu; Grimson, Andrew; Lipkin, Steven M; Clark, Andrew G; Yu, Haiyuan

    2013-07-11

    To better understand different molecular mechanisms by which mutations lead to various human diseases, we classified 82,833 disease-associated mutations according to their inheritance modes (recessive versus dominant) and molecular types (in-frame [missense point mutations and in-frame indels] versus truncating [nonsense mutations and frameshift indels]) and systematically examined the effects of different classes of disease mutations in a three-dimensional protein interactome network with the atomic-resolution interface resolved for each interaction. We found that although recessive mutations affecting the interaction interface of two interacting proteins tend to cause the same disease, this widely accepted "guilt-by-association" principle does not apply to dominant mutations. Furthermore, recessive truncating mutations in regions encoding the same interface are much more likely to cause the same disease, even for interfaces close to the N terminus of the protein. Conversely, dominant truncating mutations tend to be enriched in regions encoding areas between interfaces. These results suggest that a significant fraction of truncating mutations can generate functional protein products. For example, TRIM27, a known cancer-associated protein, interacts with three proteins (MID2, TRIM42, and SIRPA) through two different interfaces. A dominant truncating mutation (c.1024delT [p.Tyr342Thrfs*30]) associated with ovarian carcinoma is located between the regions encoding the two interfaces; the altered protein retains its interaction with MID2 and TRIM42 through the first interface but loses its interaction with SIRPA through the second interface. Our findings will help clarify the molecular mechanisms of thousands of disease-associated genes and their tens of thousands of mutations, especially for those carrying truncating mutations, often erroneously considered "knockout" alleles. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All

  7. Skin disease in United Nations peacekeepers in Lebanon.

    PubMed

    Zhou, Zhou; Liu, T; Zhang, Z

    2017-02-01

    Skin disease is one of the major components of health problems for soldiers either during war or peacetime. Despite increased numbers and scale of military missions, dermatological survey is limited. The aim of this study was to outline the dermatological profile in international peacekeepers in Lebanon and to explore the features of disease pattern. The dermatological records of peacekeepers visiting a Chinese Level 2 hospital during a 7-year period were retrospectively assessed. Comparisons with previous reports of skin disease in military personnel were performed. A total of 1658 patients (91% men, with a mean age of 32 years) were included. More than half of them were Asian (62%). Dermatitis and eczema (27%) was the leading category. Tinea pedis (13%), lichen simplex chronicus (9%), unspecified dermatitis (8%), verruca vulgaris (7%) and alopecia areata (5%) were the top five complaints. Dermatitis and eczematous eruptions appeared to be the most common condition in troops deployed in the Middle East, whereas fungal infection was highly prevalent in tropical regions. Additionally, a remarkably high rate of alopecia areata was noted in two studies including ours. Environment, group living, occupational activities and work-related stress act as initiating and/or aggravating factors in the development and/or spread of some conditions. The knowledge of disease profile empowers doctors to enforce preventive measures and prepare for treatment modalities. In particular, the underlying psychological component in lichen simplex chronicus and alopecia areata should be addressed appropriately. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  8. Feasibility and outcomes of ajmaline provocation testing for Brugada syndrome in children in a specialist paediatric inherited cardiovascular diseases centre

    PubMed Central

    McMillan, Merlin Ranald; Day, Thomas George; Bartsota, Margarita; Mead-Regan, Sarah; Bryant, Rory; Mangat, Jasveer; Abrams, Dominic; Lowe, Martin; Kaski, Juan Pablo

    2014-01-01

    Objectives Brugada syndrome (BrS) is an inherited arrhythmia syndrome that causes sudden cardiac death in the young. The class Ia antiarrhythmic ajmaline can be used to provoke the diagnostic ECG pattern. Its use has been established in adults, but little data exist on the ajmaline provocation test in children. This study aims to determine the safety and feasibility of ajmaline provocation testing in a large paediatric cohort in a specialist paediatric inherited cardiac diseases centre. Methods 98 consecutive ajmaline tests were performed in 95 children between September 2004 and July 2012 for family history of BrS (n=46 (48%)); family history of unexplained sudden cardiac death (n=39 (41%); symptoms with suspicious ECG abnormalities (n=9 (10%)). Three patients were retested with age, due to the possibility of age-related penetrance. ECG parameters were measured at baseline and during maximal ajmaline effect. Results The mean patient age was 12.55 years, 43% were female. Nineteen patients (20%) had a positive ajmaline test. There were no arrhythmias or adverse events during testing. Ajmaline provoked significant prolongation of the PR, QRS and QTc in all patients. Mean follow-up was 3.62 years with no adverse outcomes reported in any patients with BrS. There were no predictors of a positive ajmaline provocation test on multivariable analysis. One patient who tested negative at 12 years of age, subsequently tested positive at 15 years of age. Conclusions Ajmaline testing appears safe and feasible in children when performed in an appropriate setting by an experienced team. Test positivity may change with age in individuals, suggesting that the test should be repeated in the late teenage years or early adulthood. PMID:25332787

  9. Highlighting Kathleen Green and Mario Delmar, guest editors of special issue (part 2): junctional targets of skin and heart disease.

    PubMed

    Cowin, Pamela

    2014-06-01

    Cell Communication and Adhesion has been fortunate to enlist two pioneers of epidermal and cardiac cell junctions, Kathleen Green and Mario Delmar, as Guest Editors of a two part series on junctional targets of skin and heart disease. Part 2 of this series begins with an overview from Dipal Patel and Kathy Green comparing epidermal desmosomes to cardiac area composita junctions, and surveying the pathogenic mechanisms resulting from mutations in their components in heart disease. This is followed by a review from David Kelsell on the role of desmosomal mutation in inherited syndromes involving skin fragility. Agnieszka Kobeliak discusses how structural deficits in the epidermal barrier intersect with the NFkB signaling pathway to induce inflammatory diseases such as psoriasis and atopic dermatitis. Farah Sheikh reviews the specialized junctional components in cardiomyocytes of the cardiac conduction system and Robert Gourdie discusses how molecular complexes between sodium channels and gap junction proteins within the perijunctional microdomains within the intercalated disc facilitate conduction. Glenn Radice evaluates the role of N-cadherin in heart. Andre Kleber and Chris Chen explore new approaches to study junctional mechanotransduction in vitro with a focus on the effects of connexin ablation and the role of cadherins, respectively. To complement this series of reviews, we have interviewed Werner Franke, whose systematic documentation the tissue-specific complexity of desmosome composition and pioneering discovery of the cardiac area composita junction greatly facilitated elucidation of the role of desmosomal components in the pathophysiology of human heart disease.

  10. Functional imaging of inherited retinal disease with a commercial optical coherence tomography device

    NASA Astrophysics Data System (ADS)

    Theelen, T.; Hoyng, C. B.; Klevering, B. J.; Cense, B.

    2011-06-01

    Retinal dystrophies (RD) are blinding diseases affecting visual acuity mostly at young age. Intrinsic optical signals (IOS) on optical coherence tomography (OCT) may give topographical information on injure of retinal function in these patients. We demonstrate light response of the healthy and diseased human retina by IOS on a commercially available spectral-domain OCT. Significant IOS could be measured in the healthy retina and in unchanged retinal sectors of the RD patients. Main responses were located in the outer retina (photoreceptors) and the nerve fiber layer. In affected areas of RD eyes IOS were significantly reduced or even absent. Functional OCT imaging was able to give information about retinal function in RD patients on a micrometer scale. These results could be of value for refined disease analysis and control of upcoming gene therapy studies.

  11. Biomedical genetics of the inherited metabolic diseases: the GM2-gangliosidoses.

    PubMed

    Kolodny, E H

    1984-03-01

    Many of the known gene defects result in inborn errors of metabolism that produce irreversible damage to the central nervous system. A variety of new clinical, morphologic, biochemical, and genetic techniques are being used to characterize these disorders more precisely. At the Shriver Center, the different genotypes of GM2-gangliosidosis are distinguished according to the ability of cells in culture to metabolize radioactively-labeled GM2-ganglioside. Large-scale screening for carriers of the trait for Tay-Sachs disease, the most common of the GM2-gangliosidoses, has dramatically reduced the incidence of this disease. Current efforts to isolate the genes for the alpha and beta chains of hexosaminidase A will lay the groundwork for better understanding of the molecular defects in these diseases and offers hope for a possible treatment.

  12. Chemokines and cytokines network in the pathogenesis of the inflammatory skin diseases: atopic dermatitis, psoriasis and skin mastocytosis.

    PubMed

    Nedoszytko, Bogusław; Sokołowska-Wojdyło, Małgorzata; Ruckemann-Dziurdzińska, Katarzyna; Roszkiewicz, Jadwiga; Nowicki, Roman J

    2014-05-01

    Chemokines are signaling peptides which regulate cell trafficking and provide control of the tissue-specific cell homing. In the skin, chemokines are secreted both by the resident cells such as keratinocytes, melanocytes, fibroblasts, dendritic cells and mast cells, as well as by infiltrated cells - lymphocytes, eosinophils, and monocytes. Chemokines, together with cytokines, participate in induction and maintenance of inflammation in the skin and regulate the composition of the cellular infiltrates. Inflammation within the skin is a feature shared by atopic dermatitis and psoriasis, two of the most common dermatoses. Accumulation of activated mast cells in the affected skin is seen both in atopic dermatitis and in psoriasis. This paper presents a concise overview of the current knowledge on the role chemokines have in pathogenesis of atopic dermatitis, psoriasis, and mastocytosis, a disease caused directly by the accumulation and activation of mast cells in the skin.

  13. Evaluation of allele frequencies of inherited disease genes in subgroups of American Quarter Horses.

    PubMed

    Tryon, Robert C; Penedo, M Cecilia T; McCue, Molly E; Valberg, Stephanie J; Mickelson, James R; Famula, Thomas R; Wagner, Michelle L; Jackson, Mark; Hamilton, Michael J; Nooteboom, Sabine; Bannasch, Danika L

    2009-01-01

    To estimate allele frequencies of the hyperkalaemic periodic paralysis (HYPP), lethal white foal syndrome (LWFS), glycogen branching enzyme deficiency (GBED), hereditary equine regional dermal asthenia (HERDA), and type 1 polysaccharide storage myopathy (PSSM) genes in elite performance subgroups of American Quarter Horses (AQHs). Prospective genetic survey. 651 elite performance AQHs, 200 control AQHs, and 180 control American Paint Horses (APHs). Elite performance AQHs successful in 7 competitive disciplines (barrel racing, cutting, halter, racing, reining, western pleasure, and working cow horse) were geno- typed for 5 disease-causing alleles. Age-matched control AQHs and APHs were used to establish comparative whole-breed estimates of allele frequencies. Highest allele frequencies among control AQHs were for type 1 PSSM (0.055) and GBED (0.054), whereas HERDA (0.021) and HYPP (0.008) were less prevalent. Control APHs uniquely harbored LWFS (0.107) and had high prevalence of HYPP (0.025), relative to AQHs. Halter horse subgroups had significantly greater allele frequencies for HYPP (0.299) and PSSM (0.155). Glycogen branching enzyme deficiency, HERDA, and PSSM were found broadly throughout subgroups; cutting subgroups were distinct for HERDA (0.142), and western pleasure subgroups were distinct for GBED (0.132). Racing and barrel racing subgroups had the lowest frequencies of the 5 disease genes. Accurate estimates of disease-causing alleles in AQHs and APHs may guide use of diagnostic genetic testing, aid management of genetic diseases, and help minimize production of affected foals.

  14. Changes in Bacteria Induce Inflammatory Skin Diseases | Center for Cancer Research

    Cancer.gov

    Atopic dermatitis (AD) is a chronic inflammatory skin disease that manifests as dry skin with a relentless itch and eczema. AD is considered an allergic disease in which the skin inflammation manifests in response to chronic exposure to contact allergens. However, identification of a responsible allergen is uncommon. Meanwhile, analyses have demonstrated that the surface of the human body is colonized by large numbers of diverse bacteria. This observation has led researchers to examine the roles these bacteria play in healthy and diseased skin. In a variety of genetic and chronic inflammatory skin diseases, including in patients with AD or with cancer who receive epidermal growth factor receptor (EGFR) inhibitors, Staphylococcus aureus and Corynebacterium species are the predominant bacteria isolated from the skin. However, the cause-and-effect relationship between this microbial imbalance and skin inflammation has not been determined.

  15. Radiation therapy for Bowen's disease of the skin

    SciTech Connect

    Lukas VanderSpek, Lauren A. . E-mail: lauren.vanderspek@lrcc.on.ca; Pond, Gregory R.; Wells, Woodrow; Tsang, Richard W.

    2005-10-01

    Purpose: To assess the clinical outcome in the radiation therapy (RT) of squamous carcinoma in situ of the skin (Bowen's disease). We focused on the local control rate and the toxicity according to the biologically effective dose (BED). Methods and Materials: A retrospective review was performed on 44 patients with Bowen's disease treated at Princess Margaret Hospital from April 1985 to November 2000. RT was the primary treatment for 32 patients, whereas 12 received RT for residual disease after local ablative therapy. Lesions were located as follows: scalp, 9 patients (20%); face, 12 (27%); trunk, 6 (14%), extremity, 12 (27%), perianal, 3 (7%), and penis, 2 (5%). Orthovoltage X-rays were used in the majority (39 of 44, 89%). There was no standard fractionation regimen: some physicians prescribed high doses, as for invasive skin cancer, whereas others prescribed lower doses because of the noninvasive nature of the disease, a sensitive anatomic location (e.g., extremity), or large treatment area. Because of the variations in fractionation regimens, BED was used as a common metric for biologic effect in the comparison of different regimens and analyzed for correlation with recurrence and toxicity. Local control was defined as the lack of persistent or recurrent disease at the treated site for the follow-up period. Grade 4 toxicity was defined as necrosis (cartilage/bone damage) and/or ulceration for a duration of >3 months. Results: The mean patient age was 67.7 years, and the male/female ratio was 29:15. The median pretreatment lesion size was 2.65 cm{sup 2} (range, 0.07-34.56 cm{sup 2}). Complete remission was achieved in 42 patients, with follow-up unavailable for the remaining 2 patients. Subsequently, 3 patients experienced recurrences at 0.2, 1.1, and 1-1.5 years after complete remission. One recurrence was Bowen's disease (local); the others were squamous cell carcinoma (one local, one marginal). Four patients experienced a new squamous lesion at a distant

  16. Whole Exome Sequencing Reveals Mutations in Known Retinal Disease Genes in 33 out of 68 Israeli Families with Inherited Retinopathies

    PubMed Central

    Beryozkin, Avigail; Shevah, Elia; Kimchi, Adva; Mizrahi-Meissonnier, Liliana; Khateb, Samer; Ratnapriya, Rinki; Lazar, Csilla H.; Blumenfeld, Anat; Ben-Yosef, Tamar; Hemo, Yitzhak; Pe’er, Jacob; Averbuch, Eduard; Sagi, Michal; Boleda, Alexis; Gieser, Linn; Zlotogorski, Abraham; Falik-Zaccai, Tzipora; Alimi-Kasem, Ola; Jacobson, Samuel G.; Chowers, Itay; Swaroop, Anand; Banin, Eyal; Sharon, Dror

    2015-01-01

    Whole exome sequencing (WES) is a powerful technique for identifying sequence changes in the human genome. The goal of this study was to delineate the genetic defects in patients with inherited retinal diseases (IRDs) using WES. WES was performed on 90 patient DNA samples from 68 families and 226 known genes for IRDs were analyzed. Sanger sequencing was used to validate potential pathogenic variants that were also subjected to segregation analysis in families. Thirty-three causative mutations (19 novel and 14 known) in 25 genes were identified in 33 of the 68 families. The vast majority of mutations (30 out of 33) have not been reported in the Israeli and the Palestinian populations. Nine out of the 33 mutations were detected in additional families from the same ethnic population, suggesting a founder effect. In two families, identified phenotypes were different from the previously reported clinical findings associated with the causative gene. This is the largest genetic analysis of IRDs in the Israeli and Palestinian populations to date. We also demonstrate that WES is a powerful tool for rapid analysis of known disease genes in large patient cohorts. PMID:26306921

  17. Molecular and Bioenergetic Differences between Cells with African versus European Inherited Mitochondrial DNA Haplogroups: Implications for Population Susceptibility to Diseases

    PubMed Central

    Kenney, M. Cristina; Chwa, Marilyn; Atilano, Shari R.; Falatoonzadeh, Payam; Ramirez, Claudio; Malik, Deepika; Tarek, Mohamed; Cáceres del Carpio, Javier; Nesburn, Anthony B.; Boyer, David S.; Kuppermann, Baruch D.; Vawter, Marquis P.; Jazwinski, S. Michal; Miceli, Michael V.; Wallace, Douglas C.; Udar, Nitin

    2015-01-01

    The geographic origins of populations can be identified by their maternally inherited mitochondrial DNA (mtDNA) haplogroups. This study compared human cybrids (cytoplasmic hybrids), which are cell lines with identical nuclei but mitochondria from different individuals with mtDNA from either the H haplogroup or L haplogroup backgrounds. The most common European haplogroup is H while individuals of maternal African origin are of the L haplogroup. Despite lower mtDNA copy numbers, L cybrids had higher expression levels for nine mtDNA-encoded respiratory complex genes, decreased ATP turnover rates and lower levels of ROS production, parameters which are consistent with more efficient oxidative phosphorylation. Surprisingly, GeneChip arrays showed that the L and H cybrids had major differences in expression of genes of the canonical complement system (5 genes), dermatan/chondroitin sulfate biosynthesis (5 genes) and CCR3 signaling (9 genes). Quantitative nuclear gene expression studies confirmed that L cybrids had (a) lower expression levels of complement pathway and innate immunity genes and (b) increased levels of inflammation-related signaling genes, which are critical in human diseases. Our data support the hypothesis that mtDNA haplogroups representing populations from different geographic origins may play a role in differential susceptibilities to diseases. PMID:24200652

  18. Inherited variability of tumor necrosis factor production and susceptibility to infectious disease.

    PubMed

    Knight, J C; Kwiatkowski, D

    1999-01-01

    Tumor necrosis factor (TNF) is a critical mediator of host defense against infection but may cause severe pathology when produced in excess. Individuals vary in the amount of TNF produced when their peripheral blood mononuclear cells are stimulated in vitro, and family studies indicate that much of this variability is genetically determined. Since the TNF response to infection is partly regulated at the transcriptional level, TNF promoter polymorphisms have been the subject of intense interest as potential determinants of disease susceptibility. A single nucleotide polymorphism at nucleotide -308 relative to the transcriptional start site has been associated with susceptibility to severe malaria, leishmaniasis, scarring trachoma, and lepromatous leprosy. Some experimental data indicate that this polymorphism acts to upregulate TNF transcription, but this remains controversial. Detailed analysis of multiple genetic markers at this locus and more sophisticated investigations of TNF transcriptional regulation, in different cell types and with a wide range of stimuli, are required to understand the molecular basis of these disease associations.

  19. [Inheritance and disease in the pig: possibilities of use for breeding].

    PubMed

    Vögeli; Bertschinger; Bürgi; Neuenschwander

    2014-06-01

    Single-locus disorders in domesticated animals were among the first Mendelian traits to be documented, and to be included in early linkage maps. The use of linkage maps and comparative genomics has been essential to the identification of the causative genes for disorders. A DNA marker for selection of resistance to F18+ E. coli in the pig is available since several years. The use of this marker decreases mortality due to post-weaning diarrhoea and/or oedema disease. For more than 100 disorders the molecular lesion has been identified and hence for which a DNA test is available. However, for most diseases such as Porcine Reproductive and Respiratory Syndrome (PRRS) and Porcine Circovirus Associated Diseases (PCVAD), resistance is a complex and polygenic trait. Novel technologies such as gene microarrays and advanced bioinformatics are being used to analyse health data. Lagging behind, however, is availability of large DNA data sets from pedigreed populations with accurately measured health phenotypes that are needed to identify associations between markers and health traits. As the pig genome is sequenced to a great extent and ten thousands of markers can be analysed at a reasonable price, genomic selection for health traits is possible.

  20. Emotional reactions to predictive testing in Alzheimer's disease and other inherited dementias.

    PubMed

    Molinuevo, José L; Pintor, Luis; Peri, Josep M; Lleó, Alberto; Oliva, Rafael; Marcos, Teodor; Blesa, Rafael

    2005-01-01

    This work describes the reasons and emotional responses of healthy descendants after counseling for presenilin mutations in early-onset familial Alzheimer's disease (EOFAD), tau mutations in familial frontotemporal dementia (FTD), and prion mutations in fatal familial insomnia (FFI). A multidisciplinary protocol following Huntington's disease counseling guidelines and a post-test follow-up program were developed to counsel healthy descendants of affected families. The psychological consequences, anxiety levels, and depression status were assessed through validated scales before and after disclosing the information. Nine people from three different families, one with EOFAD, another with FTD, and the other with FFI came for counseling. Their main reason for testing was to initiate early treatment in the future. Disclosing the information decreased anxiety in two carriers, increased it temporarily in one, and had no effect in another. All noncarriers felt relieved. Overall, after a mean of 30 months of follow-up, no negative psychological reactions were observed. All participants positively valued the program. Although preliminary, our observations suggest that predictive testing in EOFAD, FTD, and FFI is safe and may be of benefit when performed with a delicate approach under strict pretest counseling protocols and post-test follow-up programs. The emotional reactions were similar, although the diseases, their phenotype, and mutation characteristics were different.

  1. Occupational skin diseases: options for multidisciplinary networking in preventive medicine

    PubMed Central

    John, Swen Malte

    2008-01-01

    Occupational dermatoses (OD) have topped the list of occupational diseases in Germany for years. Presently, approximately 16,000 new OD cases are officially reported to public statutory employers’ liability insurance bodies, each year. The disease burden is high not only for individuals but also for society as a whole. Estimated annual economic costs in Germany due to sick-leave and lack of productivity due to OD are more than 1.5 billion euros. Thus, in recent years, various pilot initiatives aiming to improve prevention of occupational skin diseases (of various degrees of severity) have been developed and recently evaluated in Osnabrück. These activities have been funded by statutory employers’ liability insurance schemes. Concepts underpinning these initiatives include multidisciplinary skin protection teaching programs for various high-risk professions, which turned out to be pivotal for the success of these projects. A corollary of this work is a nationwide multi-step intervention approach currently implemented by the public statutory insurance system. This approach offers quick preventive help for all levels of severity of OD. These nation-wide activities are accompanied by a national Prevention Campaign: Skin 2007/2008 (Figure 1 (Fig. 1)), which focuses mainly on primary prevention. Despite the high prevalence of OD and its poor prognosis, little is known about the molecular mechanisms underlying individual susceptibility to develop chronic irritant dermatitis. Skin irritation tests are thus far of only limited value. Presently, our institution, in collaboration with Amsterdam universities, focuses on immunogenetic risk factors potentially involved in individual susceptibility to OD in order to improve pre-employment counseling and predictive skin testing. For early secondary prevention, the so-called dermatologist’s procedure was recently up-dated in order to provide more rapid dermatological consultation. Additionally, combined outpatient

  2. Localization of the defect in skin diseases analyzed in the human skin graft-nude mouse model.

    PubMed

    Briggaman, R A

    1980-01-01

    Human skin can be grown away from its donor for prolonged periods as grafts on congenitally athymic "nude" mice. This system has been used to analyze the defect in several skin diseases, specifically to localize the site of the defect to the skin itself or to the epidermal or dermal components of the skin. In order to validate the use of the nude mouse human skin graft system in the analysis of skin defects, we have demonstrated that a systemic metabolic defect which involves the skin, namely essential fatty acid deficiency, can be differentiated from a defect residing primarily in the skin itself. Skin-marker systems have been developed for use with the nude mouse-human skin graft model to document the identity of human skin grafts and epidermal and dermal components of the grafts after prolonged periods of growth on the nude athymic mice. Y-body, a small fluorescent segment of the Y-chromosome seen in interphase cells, is used as a sex marker and serves to distinguish sex differences between the graft and the mouse recipient or between skin components of the graft. The ABH "blood-group" antigens are present on differentiated epidermal cell surfaces and identify the grafted epidermis according to the blood groups of the donor. In previous studies, lamellar ichthyosis was shown to be well maintained after prolonged periods of growth on nude athymic mice, indicating that the defect in this disease resides in the skin itself. Recombinant grafts composed of normal and lamellar ichthyosis epidermis and dermis further localize the defect to lamellar ichthyosis epidermis. Psoriasis is well maintained on the nude mouse-skin graft model. The epidermal hyperplasia and hyperproliferative epidermal cell kinetics of psoriasis are manifested in the grafts of active psoriasis maintained for prolonged periods on the nude mice, but the inflammatory component of psoriasis is absent. Recombinant graft studies utilizing normal and psoriatic epidermis and dermis demonstrate psoriasis

  3. Inheritance of coronary artery disease in men: an analysis of the role of the Y chromosome

    PubMed Central

    Charchar, Fadi J; Bloomer, Lisa DS; Barnes, Timothy A; Cowley, Mark J; Nelson, Christopher P; Wang, Yanzhong; Denniff, Matthew; Debiec, Radoslaw; Christofidou, Paraskevi; Nankervis, Scott; Dominiczak, Anna F; Bani-Mustafa, Ahmed; Balmforth, Anthony J; Hall, Alistair S; Erdmann, Jeanette; Cambien, Francois; Deloukas, Panos; Hengstenberg, Christian; Packard, Chris; Schunkert, Heribert; Ouwehand, Willem H; Ford, Ian; Goodall, Alison H; Jobling, Mark A; Samani, Nilesh J; Tomaszewski, Maciej

    2012-01-01

    Summary Background A sexual dimorphism exists in the incidence and prevalence of coronary artery disease—men are more commonly affected than are age-matched women. We explored the role of the Y chromosome in coronary artery disease in the context of this sexual inequity. Methods We genotyped 11 markers of the male-specific region of the Y chromosome in 3233 biologically unrelated British men from three cohorts: the British Heart Foundation Family Heart Study (BHF-FHS), West of Scotland Coronary Prevention Study (WOSCOPS), and Cardiogenics Study. On the basis of this information, each Y chromosome was tracked back into one of 13 ancient lineages defined as haplogroups. We then examined associations between common Y chromosome haplogroups and the risk of coronary artery disease in cross-sectional BHF-FHS and prospective WOSCOPS. Finally, we undertook functional analysis of Y chromosome effects on monocyte and macrophage transcriptome in British men from the Cardiogenics Study. Findings Of nine haplogroups identified, two (R1b1b2 and I) accounted for roughly 90% of the Y chromosome variants among British men. Carriers of haplogroup I had about a 50% higher age-adjusted risk of coronary artery disease than did men with other Y chromosome lineages in BHF-FHS (odds ratio 1·75, 95% CI 1·20–2·54, p=0·004), WOSCOPS (1·45, 1·08–1·95, p=0·012), and joint analysis of both populations (1·56, 1·24–1·97, p=0·0002). The association between haplogroup I and increased risk of coronary artery disease was independent of traditional cardiovascular and socioeconomic risk factors. Analysis of macrophage transcriptome in the Cardiogenics Study revealed that 19 molecular pathways showing strong differential expression between men with haplogroup I and other lineages of the Y chromosome were interconnected by common genes related to inflammation and immunity, and that some of them have a strong relevance to atherosclerosis. Interpretation The human Y chromosome is

  4. iPS cell modeling of Best disease: insights into the pathophysiology of an inherited macular degeneration.

    PubMed

    Singh, Ruchira; Shen, Wei; Kuai, David; Martin, Jessica M; Guo, Xiangrong; Smith, Molly A; Perez, Enio T; Phillips, M Joseph; Simonett, Joseph M; Wallace, Kyle A; Verhoeven, Amelia D; Capowski, Elizabeth E; Zhang, Xiaoqing; Yin, Yingnan; Halbach, Patrick J; Fishman, Gerald A; Wright, Lynda S; Pattnaik, Bikash R; Gamm, David M

    2013-02-01

    Best disease (BD) is an inherited degenerative disease of the human macula that results in progressive and irreversible central vision loss. It is caused by mutations in the retinal pigment epithelium (RPE) gene BESTROPHIN1 (BEST1), which, through mechanism(s) that remain unclear, lead to the accumulation of subretinal fluid and autofluorescent waste products from shed photoreceptor outer segments (POSs). We employed human iPS cell (hiPSC) technology to generate RPE from BD patients and unaffected siblings in order to examine the cellular and molecular processes underlying this disease. Consistent with the clinical phenotype of BD, RPE from mutant hiPSCs displayed disrupted fluid flux and increased accrual of autofluorescent material after long-term POS feeding when compared with hiPSC-RPE from unaffected siblings. On a molecular level, RHODOPSIN degradation after POS feeding was delayed in BD hiPSC-RPE relative to unaffected sibling hiPSC-RPE, directly implicating impaired POS handling in the pathophysiology of the disease. In addition, stimulated calcium responses differed between BD and normal sibling hiPSC-RPE, as did oxidative stress levels after chronic POS feeding. Subcellular localization, fractionation and co-immunoprecipitation experiments in hiPSC-RPE and human prenatal RPE further linked BEST1 to the regulation and release of endoplasmic reticulum calcium stores. Since calcium signaling and oxidative stress are critical regulators of fluid flow and protein degradation, these findings likely contribute to the clinical picture of BD. In a larger context, this report demonstrates the potential to use patient-specific hiPSCs to model and study maculopathies, an important class of blinding disorders in humans.

  5. Contribution of health care factors to the burden of skin disease in the United States.

    PubMed

    Lim, Henry W; Collins, Scott A B; Resneck, Jack S; Bolognia, Jean L; Hodge, Julie A; Rohrer, Thomas A; Van Beek, Marta J; Margolis, David J; Sober, Arthur J; Weinstock, Martin A; Nerenz, David R; Smith Begolka, Wendy; Moyano, Jose V

    2017-06-01

    The American Academy of Dermatology has developed an up-to-date national Burden of Skin Disease Report on the impact of skin disease on patients and on the US population. In this second of 3 manuscripts, data are presented on specific health care dimensions that contribute to the overall burden of skin disease. Through the use of data derived from medical claims in 2013 for 24 skin disease categories, these results indicate that skin disease health care is delivered most frequently to the aging US population, who are afflicted with more skin diseases than other age groups. Furthermore, the overall cost of skin disease is highest within the commercially insured population, and skin disease treatment primarily occurs in the outpatient setting. Dermatologists provided approximately 30% of office visit care and performed nearly 50% of cutaneous surgeries. These findings serve as a critical foundation for future discussions on the clinical importance of skin disease and the value of dermatologic care across the population. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  6. MND2: A new mouse model of inherited motor neuron disease

    SciTech Connect

    Jones, J.M.; Albin, R.L.; Feldman, E.L.; Simin, K.; Schuster, T.G.; Dunnick, W.A.; Collins, J.T.; Chrisp, C.E.; Meisler, M.H. ); Taylor, B.A. )

    1993-06-01

    The autosomal recessive mutation mnd2 results in early onset motor neuron disease with rapidly progressive paralysis, severe muscle wasting, regression of thymus and spleen, and death before 40 days of age. mnd2 has been mapped to mouse chromosome 6 with the gene order: centromere-Tcrb-Ly-2-Sftp-3-D6Mit4-mnd2-D6Mit6, D6Mit9-D6Rck132-Raf-1, D6Mit11-D6Mit12-D6Mit14. mnd2 is located within a conserved linkage group with homologs on human chromosome 2p12-p13. Spinal motor neurons of homozygous affected animals are swollen and stain weakly, and electromyography revealed spontaneous activity characteristic of muscle denervation. Myelin staining was normal throughout the neuraxis. The clinical observations are consistent with a primary abnormality of lower motor neuron function. This new animal model will be of value for identification of a genetic defect responsible for motor neuron disease and for evaluation of new therapies. 36 refs., 7 figs., 2 tabs.

  7. Inherited peripheral neuropathies.

    PubMed

    Shy, Michael E

    2011-04-01

    Mutations in genes expressed in Schwann cells and the axons they ensheathe cause the hereditary motor and sensory neuropathies, also known as Charcot-Marie-Tooth disease (CMT). More than 40 different genes have been shown to cause inherited neuropathies; chromosomal localizations of many other distinct inherited neuropathies have been mapped, and new genetic causes for inherited neuropathies continue to be discovered. How to keep track of all of these disorders, when to pursue genetic testing, and what tests to order for specific patients are difficult challenges for any neurologist. This review addresses these issues and provides illustrative cases to help in dealing with them. CMT serves as a living system to identify molecules necessary for normal peripheral nervous system (PNS) function. Understanding how these various molecules interact will provide a better understanding of the pathogenesis of peripheral neuropathies in general as well as other neurodegenerative disorders involving the PNS.

  8. Observations on the epidemiology of lumpy skin disease in Kenya.

    PubMed

    Davies, F G

    1982-02-01

    Lumpy skin disease virus strains isolated in Kenya over a period of some 20 years have proved to be serologically identical. They were indistinguishable by indirect fluorescent antibody and serum neutralization test from the South African Neethling and West African serotypes. These two serological methods proved of value in studying the antibody responses to infection. While epizootic spread of LSD has occurred in Kenya, most cases are of a sporadic nature and are thought to be the result of accidental contacts with a maintenance cycle. There is evidence of antibody to LSD in the African buffalo (Syncerus caffer) in those areas where LSD is considered to be enzootic in Kenya, and also in small numbers of domestic cattle. No buffalo or bovine sera contained antibody to cowpox virus. An area enzootic for LSD is proposed and it is suggested that the maintenance cycle involves the buffalo. No antibody was found in the other wild ruminant species examined.

  9. Skin diseases of rodents and small exotic mammals.

    PubMed

    Ellis, C; Mori, M

    2001-05-01

    Small exotic mammals and rodents are becoming popular pets in the United States. Like most other exotics, the popularity of these animals has vastly preceded the accumulation of practical husbandry and veterinary information available about them. Several dermatologic conditions have been described in most rodents and small exotic mammals; however, the practitioner can assume that more exist that have not yet been diagnosed or documented. It is not unreasonable to assume that rodents and small exotic mammals could be affected by many of the same dermatologic conditions well described in other animals. Veterinarians are encouraged always to apply the same diagnostic protocols used to work up skin problems in dogs and cats when presented with an exotic pet with a dermatologic disease.

  10. Soil Correlates and Mortality from Giraffe Skin Disease in Tanzania.

    PubMed

    Bond, Monica L; Strauss, Megan K L; Lee, Derek E

    2016-10-01

    Giraffe skin disease (GSD) is a disorder of undetermined etiology that causes lesions on the forelimbs of Masai giraffe ( Giraffa camelopardalis tippelskirchi) in Tanzania, East Africa. We examined soil correlates of prevalence of GSD from 951 giraffe in 14 sites in Tanzania, and estimated mortality using 3 yr of longitudinal mark-recapture data from 382 giraffe with and without GSD lesions, in Tarangire National Park (TNP). Spatial variation in GSD prevalence was best explained by soil fertility, measured as cation exchange capacity. We found no mortality effect of GSD on adult giraffe in TNP. Based on our findings, GSD is unlikely to warrant immediate veterinary intervention, but continued monitoring is recommended to ensure early detection if GSD-afflicted animals begin to show signs of increased mortality or other adverse effects.

  11. A survey of self-reported skin disease in the elderly African-American population.

    PubMed

    Caretti, Katherine L; Mehregan, Darius R; Mehregan, David A

    2015-09-01

    In the USA, the geriatric population, almost 12% of which will be comprised of African-Americans, is expected to exceed 88 million by 2050. Data on dermatologic conditions in elderly African-Americans are deficient. This study aimed to identify prevalences of self-reported skin disease and skin-related concerns in elderly African-Americans, and to assess participants' perceptions of skin disease and awareness of skin cancer. Elderly African-Americans were recruited into a cross-sectional study and asked to complete a 17-item questionnaire. A total of 101 participants aged 60-91 years (median age: 71 years) completed the questionnaire. The majority (75.2%) of the subjects were female. The most common self-reported skin diseases were eczema/dermatitis (28.7%), fungal skin infections (16.8%), alopecia (6.9%), viral skin infections (4.9%), and urticaria (4.9%). The most common skin concerns were dry skin/pruritus (40.6%), moles (27.7%), hair loss (25.7%), skin discoloration (20.8%), and wrinkles (15.8%). Overall, 40.6% of participants reported concern about skin cancer, and 75.2% reported examining their skin regularly. However, 34.7% did not believe that people with darker skin types should be concerned about skin cancer. This study provides an important overview of the most common self-reported skin conditions in elderly African-Americans. Substantial age-related differences in the frequencies of skin disorders were apparent. It is important to include the elderly population within campaigns to educate minority group members on skin cancer. © 2014 The International Society of Dermatology.

  12. [Clinical effects of olopatadine hydrochloride on pruritus in skin diseases].

    PubMed

    Niide, Mariko; Okubo, Yukari; Irisawa, Ryokichi; Tsuboi, Ryoji

    2006-10-01

    The clinical effects of second generation antihistamines on pruritus caused by various skin diseases were examined by keeping a daily record of their effects. Five mg of olopatadine hydrochloride (Allerock) was administered to the subjects twice daily. The severity of the pruritus and the scratch scars were scored before, and then 2 weeks and 4 weeks after, commencement of treatment. The severity of the pruritus during the day and night was measured by using a visual analogue scale (VAS), and a daily 'itch score' was recorded in an 'itch diary.' The itch scores for both day and night, as well as the scratching scores, the VAS values and the 'itch score,' significantly decreased after administration of olopatadine. The VAS value was significantly correlated with the itch scores and patient responses in the medical interview. Statistical analysis showed that there was a prompt alleviation of the pruritus in urticaria a day after administration, followed by asteatotic dermatitis and atopic dermatitis, in the order of improvement, within the next several days. The VAS value for pruritus was highly correlated with the itch score, showing that the VAS value was suitable for evaluating daily changes in the severity of pruritus. These results suggest that second generation antihistamines like olopatadine hydrochloride, which showed a prompt response to histamine, are effective against pruritus in urticaria, and that continuous use of these antihistamines is effective against pruritus in other forms of skin disease, such as asteatotic dermatitis and atopic dermatitis in which other chemical mediators besides histamine may be the triggers for pruritus.

  13. Intergenerational epigenetic inheritance in models of developmental programming of adult disease.

    PubMed

    Fernandez-Twinn, Denise S; Constância, Miguel; Ozanne, Susan E

    2015-07-01

    It is now well established that the environment to which we are exposed during fetal and neonatal life can have a long-term impact on our health. This has been termed the developmental origins of health and disease. Factors known to have such programming effects include intrauterine nutrient availability (determined by maternal nutrition and placental function), endocrine disruptors, toxins and infectious agents. Epigenetic processes have emerged as a key mechanism by which the early environment can permanently influence cell function and metabolism after multiple rounds of cell division. More recently it has been suggested that programmed effects can be observed beyond the first generation and that therefore epigenetic mechanisms could form the basis of transmission of phenotype from parent to child to grandchild and beyond. Here we review the evidence for such processes. Copyright © 2015. Published by Elsevier Ltd.

  14. Inherited Variation in Vitamin D Genes Is Associated With Predisposition to Autoimmune Disease Type 1 Diabetes

    PubMed Central

    Cooper, Jason D.; Smyth, Deborah J.; Walker, Neil M.; Stevens, Helen; Burren, Oliver S.; Wallace, Chris; Greissl, Christopher; Ramos-Lopez, Elizabeth; Hyppönen, Elina; Dunger, David B.; Spector, Timothy D.; Ouwehand, Willem H.; Wang, Thomas J.; Badenhoop, Klaus; Todd, John A.

    2011-01-01

    OBJECTIVE Vitamin D deficiency (25-hydroxyvitamin D [25(OH)D] <50 nmol/L) is commonly reported in both children and adults worldwide, and growing evidence indicates that vitamin D deficiency is associated with many extraskeletal chronic disorders, including the autoimmune diseases type 1 diabetes and multiple sclerosis. RESEARCH DESIGN AND METHODS We measured 25(OH)D concentrations in 720 case and 2,610 control plasma samples and genotyped single nucleotide polymorphisms from seven vitamin D metabolism genes in 8,517 case, 10,438 control, and 1,933 family samples. We tested genetic variants influencing 25(OH)D metabolism for an association with both circulating 25(OH)D concentrations and disease status. RESULTS Type 1 diabetic patients have lower circulating levels of 25(OH)D than similarly aged subjects from the British population. Only 4.3 and 18.6% of type 1 diabetic patients reached optimal levels (≥75 nmol/L) of 25(OH)D for bone health in the winter and summer, respectively. We replicated the associations of four vitamin D metabolism genes (GC, DHCR7, CYP2R1, and CYP24A1) with 25(OH)D in control subjects. In addition to the previously reported association between type 1 diabetes and CYP27B1 (P = 1.4 × 10−4), we obtained consistent evidence of type 1 diabetes being associated with DHCR7 (P = 1.2 × 10−3) and CYP2R1 (P = 3.0 × 10−3). CONCLUSIONS Circulating levels of 25(OH)D in children and adolescents with type 1 diabetes vary seasonally and are under the same genetic control as in the general population but are much lower. Three key 25(OH)D metabolism genes show consistent evidence of association with type 1 diabetes risk, indicating a genetic etiological role for vitamin D deficiency in type 1 diabetes. PMID:21441443

  15. Potential of mesenchymal stem cells in gene therapy approaches for inherited and acquired diseases

    PubMed Central

    Reiser, Jakob; Zhang, Xian-Yang; Hemenway, Charles S; Mondal, Debasis; Pradhan, Leena; La Russa, Vincent F

    2005-01-01

    The intriguing biology of stem cells and their vast clinical potential is emerging rapidly for gene therapy. Bone marrow stem cells, including the pluripotent haematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs) and possibly the multipotent adherent progenitor cells (MAPCs), are being considered as potential targets for cell and gene therapy-based approaches against a variety of different diseases. The MSCs from bone marrow are a promising target population as they are capable of differentiating along multiple lineagesn and, at least in vitro, have significant expansion capability. The apparently high self-renewal potential makes them strong candidates for delivering genes and restoring organ systems function. However, the high proliferative potential of MSCs, now presumed to be self-renewal, may be more apparent than real. Although expanded MSCs have great proliferation and differentiation potential in vitro, there are limitations with the biology of these cells in vivo. So far, expanded MSCs have failed to induce durable therapeutic effects expected from a true self-renewing stem cell population. The loss of in vivo self-renewal may be due to the extensive expansion of MSCs in existing in vitro expansion systems, suggesting that the original stem cell population and/or properties may no longer exist. Rather, the expanded population may indeed be heterogeneous and represents several generations of different types of mesenchymal cell progeny that have retained a limited proliferation potential and responsiveness for terminal differentiation and maturation along mesenchymal and non-mesenchymal lineages. Novel technology that allows MSCs to maintain their stem cell function in vivo is critical for distinguishing the elusive stem cell from its progenitor cell populations. The ultimate dream is to use MSCs in various forms of cellular therapies, as well as genetic tools that can be used to better understand the mechanisms leading to repair and regeneration

  16. Late-onset onchocercal skin disease among Ethiopian immigrants.

    PubMed

    Baum, S; Greenberger, S; Pavlotsky, F; Solomon, M; Enk, C D; Schwartz, E; Barzilai, A

    2014-11-01

    Onchocerciasis is an infectious disease caused by the filaria Onchocerca volvulus. Very little is known regarding onchocerciasis imported from endemic to nonendemic areas. To evaluate pruritic dermatitis simulating atopic dermatitis in Ethiopian immigrants in Israel. A retrospective study of 27 Ethiopian immigrants to Israel was conducted. Demographics and clinical and laboratory data were collected. Of the group of 27 patients, 10 (37%) were men and 17 (63%) were women. The average age at referral was 29 years. All of the patients emigrated from Kuwara, Ethiopia. Diagnosis was done by either positive skin snip test or immunoglobulin (Ig) G4 serology of onchocerciasis in 14 patients. The most common presentation was a combination of lichenified onchodermatitis with atrophy and depigmentation (36%). Eosinophilia and elevated IgE levels were common. Seventeen patients were treated with a single administration of oral ivermectin 200 μg mg(-1). Thirteen patients responded to the treatment. Immigrants from endemic regions to developed countries presenting with pruritic diseases, especially those with a clinical picture suggestive of atopic dermatitis, should be evaluated for possible onchocerciasis infection. Ivermectin, a relatively safe and low-cost treatment, should be considered even in the absence of a proven disease. Physicians should have a high index of suspicion in patients with the corresponding residential history. © 2014 British Association of Dermatologists.

  17. Health Care Utilization among Migrant Latino Farmworkers: The Case of Skin Disease

    PubMed Central

    Feldman, Steven R.; Vallejos, Quirina M.; Quandt, Sara A.; Fleischer, Alan B.; Schulz, Mark R.; Verma, Amit; Arcury, Thomas A.

    2009-01-01

    Context Skin diseases are common occupational illnesses for migrant farmworkers. Farmworkers face many barriers in accessing healthcare resources. Purpose Framed by the Health Behavior Model, the purpose of this study was to assess health care utilization for skin disease by migrant Latino farmworkers. Methods 304 migrant and seasonal Latino farmworkers in North Carolina were enrolled in a longitudinal study of skin disease and healthcare utilization over a single agricultural season. Self-reported and dermatologist-diagnosed skin condition data were collected at baseline and at up to four follow-up assessments. Medical visit rates were compared to national norms. Findings Self-reported skin problems and diagnosed skin disease were common among farmworkers. However, only 34 health care visits were reported across the entire agricultural season, and none of the visits were for skin diseases. Nevertheless, self-treatment for skin conditions was common, including use of non-prescription preparations (63%), prescription products (9%), and home remedies (6%). General medical office visits were reported in 3.2% of the assessments, corresponding to 1.6 office visits per person year. Conclusions The migrant farmworker population consists largely of young men who make little use of clinic services. Skin conditions are very common among these workers, but use of medical services for these conditions is not common. Instead, farmworkers rely primarily on self-treatment. Clinic-based studies of farmworker skin conditions will not account for most injury or disease in this population and have the potential for biased estimates. PMID:19166568

  18. White matter hyperintensities are a core feature of Alzheimer's disease: Evidence from the dominantly inherited Alzheimer network.

    PubMed

    Lee, Seonjoo; Viqar, Fawad; Zimmerman, Molly E; Narkhede, Atul; Tosto, Giuseppe; Benzinger, Tammie L S; Marcus, Daniel S; Fagan, Anne M; Goate, Alison; Fox, Nick C; Cairns, Nigel J; Holtzman, David M; Buckles, Virginia; Ghetti, Bernardino; McDade, Eric; Martins, Ralph N; Saykin, Andrew J; Masters, Colin L; Ringman, John M; Ryan, Natalie S; Förster, Stefan; Laske, Christoph; Schofield, Peter R; Sperling, Reisa A; Salloway, Stephen; Correia, Stephen; Jack, Clifford; Weiner, Michael; Bateman, Randall J; Morris, John C; Mayeux, Richard; Brickman, Adam M

    2016-06-01

    White matter hyperintensities (WMHs) are areas of increased signal on T2-weighted magnetic resonance imaging (MRI) scans that most commonly reflect small vessel cerebrovascular disease. Increased WMH volume is associated with risk and progression of Alzheimer's disease (AD). These observations are typically interpreted as evidence that vascular abnormalities play an additive, independent role contributing to symptom presentation, but not core features of AD. We examined the severity and distribution of WMH in presymptomatic PSEN1, PSEN2, and APP mutation carriers to determine the extent to which WMH manifest in individuals genetically determined to develop AD. The study comprised participants (n = 299; age = 39.03 ± 10.13) from the Dominantly Inherited Alzheimer Network, including 184 (61.5%) with a mutation that results in AD and 115 (38.5%) first-degree relatives who were noncarrier controls. We calculated the estimated years from expected symptom onset (EYO) by subtracting the affected parent's symptom onset age from the participant's age. Baseline MRI data were analyzed for total and regional WMH. Mixed-effects piece-wise linear regression was used to examine WMH differences between carriers and noncarriers with respect to EYO. Mutation carriers had greater total WMH volumes, which appeared to increase approximately 6 years before expected symptom onset. Effects were most prominent for the parietal and occipital lobe, which showed divergent effects as early as 22 years before estimated onset. Autosomal-dominant AD is associated with increased WMH well before expected symptom onset. The findings suggest the possibility that WMHs are a core feature of AD, a potential therapeutic target, and a factor that should be integrated into pathogenic models of the disease. Ann Neurol 2016;79:929-939. © 2016 American Neurological Association.

  19. White matter hyperintensities are a core feature of Alzheimer’s disease: Evidence from the Dominantly Inherited Alzheimer Network

    PubMed Central

    Lee, Seonjoo; Viqar, Fawad; Zimmerman, Molly E.; Narkhede, Atul; Tosto, Giuseppe; Benzinger, Tammie L.S.; Marcus, Daniel S.; Fagan, Anne M.; Goate, Alison; Fox, Nick C.; Cairns, Nigel J.; Holtzman, David M.; Buckles, Virginia; Ghetti, Bernardino; McDade, Eric; Martins, Ralph N.; Saykin, Andrew J.; Masters, Colin L.; Ringman, John M.; Ryan, Natalie S.; Förster, Stefan; Laske, Christoph; Schofield, Peter R.; Sperling, Reisa A.; Salloway, Stephen; Correia, Stephen; Jack, Clifford; Weiner, Michael; Bateman, Randall J.; Morris, John C.; Mayeux, Richard; Brickman, Adam M.

    2016-01-01

    Objective White matter hyperintensities(WMH) are areas of increased signal on magnetic resonance imaging(MRI) scans that most commonly reflect small vessel cerebrovascular disease. Increased WMH volume is associated with risk and progression of Alzheimer’s disease(AD). These observations are typically interpreted as evidence that vascular abnormalities play an additive, independent role contributing to symptom presentation, but not core features of AD. We examined the severity and distribution of WMH in presymptomatic PSEN1, PSEN2, and APP mutation carriers to determine the extent to which WMH manifest in individuals genetically-determined to develop AD. Methods The study comprised participants(n=299, age=39.03±10.13) from the Dominantly Inherited Alzheimer Network, including 184(61.5%) with a mutation that results in AD and 115(38.5%) first-degree relatives who were non-carrier controls. We calculated the estimated years from expected symptom onset(EYO) by subtracting the affected parent’s symptom onset age from the participant’s age. Baseline MRI data were analyzed for total and regional WMH. Mixed effects piecewise linear regression was used to examine WMH differences between carriers and non-carriers with respect to EYO. Results Mutation carriers had greater total WMH volumes, which appeared to increase approximately 6 years prior to expected symptom onset. The effects were most prominent for the parietal and occipital lobe, which showed divergent effects as early as 22 years prior to estimated onset. Interpretation Autosomal dominant AD is associated with increased WMH well before expected symptom onset. The findings suggest the possibility that WMH are a core feature of AD, a potential therapeutic target, and a factor that should be integrated into pathogenic models of the disease. PMID:27016429

  20. Epigenetic transgenerational inheritance

    PubMed Central

    Skinner, Michael K.

    2017-01-01

    Endocrine disruptors are critical environmental exposures that influence health and can promote epigenetic transgenerational inheritance of disease and abnormal physiology. Advances in 2015 included analyses of the effects of endocrine disruptors on human disease, further examples of endocrine disruptors promoting transgenerational behavioural effects, insights into effects of endocrine disruptors on epigenetic programming of primordial germ cells and the finding that endocrine disruptors can transgenerationally promote genetic mutations. PMID:26585656

  1. Conveying a probabilistic genetic test result to families with an inherited heart disease.

    PubMed

    Ingles, Jodie; Semsarian, Christopher

    2014-06-01

    The evolution of genetic testing in the past few years has been astounding. In a matter of only a few years, we now have comprehensive gene tests comprising vast panels of "cardiac" genes, whole exome sequencing (the entire coding region) and even whole genome sequencing (the entire genome). Making the call as to whether a DNA variant is causative or benign is difficult and the focus of intense research efforts. In most cases, the final answer will not be a simple yes/no outcome but rather a graded continuum of pathogenicity. This allows classification of variants in a more probabilistic way. How we convey this to a patient is the challenge, and certainly shines a spotlight on the important skills of the cardiac genetic counselor. This is an exciting step forward, but the overwhelming complexity of the information generated from these tests means our current practices of conveying genetic information to the family must be carefully considered. Despite the challenges, a genetic diagnosis in a family has great benefit both in reassuring unaffected family members and removing the need for lifetime clinical surveillance. The multidisciplinary specialized clinic model, incorporating genetic counselors, cardiologists and geneticists, provides the ideal framework for ensuring the best possible care for genetic heart disease families.

  2. Inheritance of black sigatoka disease resistance in plantain-banana (Musa spp.) hybrids.

    PubMed

    Ortiz, R; Vuylsteke, D

    1994-10-01

    Black sigatoka (Mycosphaerella fijiensis Morelet), an airborne fungal leaf-spot disease, is a major constraint to plantain and banana (Musa spp.) production world-wide. Gaining further knowledge of the genetics of host-plant resistance will enhance the development of resistant cultivars, which is considered to be the most appropriate means to achieve stable production. Genetic analysis was conducted on 101 euploid (2x, 3x and 4x) progenies, obtained from crossing two susceptible triploid plantain cultivars with the resistant wild diploid banana 'Calcutta 4'. Segregating progenies, and a susceptible reference plantain cultivar, were evaluated over 2 consecutive years. Three distinct levels of host response to black sigatoka were defined as follows: susceptible (< 8 leaves without spots), less susceptible (8-10) and partially resistant (> 10). Segregation ratios for resistance at the 2x level fitted a genetic model having one major recessive resistance allele (bs 1) and two independent alleles with additive effects (bsr 2 and bsr 3). A similar model explains the results at the 4x level assuming that the favourable resistance alleles have a dosage effect when four copies of them are present in their respective loci (bs i (4) ). The proposed model was further validated by segregation data of S 1 progenies. Mechanisms of black sigatoka resistance are discussed in relation to the genetic model.

  3. Dysfunctions of the diffusional membrane pathways mediated by hemichannels in inherited and acquired human diseases.

    PubMed

    Schalper, Kurt A; Orellana, Juan A; Berthoud, Viviana M; Sáez, Juan C

    2009-10-01

    Connexins and pannexins comprise 2 families of transmembrane proteins ubiquitously distributed in vertebrates. Most cell types express more than 1 connexin or pannexin. Members of the same protein family form homo- or hetero-hexamers termed hemichannels. Hemichannels are pathways for the transmembrane diffusional exchange of ions and small molecules. Several human genetic diseases are associated with connexin mutants that may form hemichannels with increased or reduced activity. Pro-inflammatory conditions of different duration and/or intensity can lead to acute or chronic increase in hemichannel activity. Non-lethal stimuli can lead to transient increases in hemichannel activity (required for normal autocrine and/or paracrine cell signaling that might lead to preconditioning responses) whereas lethal stimuli induce long lasting hemichannel-mediated membrane permeabilization that accelerate cell death. Thus, in addition to transporters that mediate active and facilitated transport, the plasma membrane of most cells contains diffusional transporters (hemichannels) that are essential for normal cell functioning; their malfunctioning can cause or worsen a pathological condition.

  4. Anticipation in Huntington's disease is inherited through the male line but may originate in the female.

    PubMed Central

    Ridley, R M; Frith, C D; Crow, T J; Conneally, P M

    1988-01-01

    Data from the US National Huntington's Disease Roster have been analysed in terms of the difference in age of onset (AO) between affected parents and affected offspring, that is, in terms of 'anticipation'. While mean AO in offspring of affected mothers did not differ greatly from AO in their mothers, the distribution of AO in the offspring of affected fathers falls into two groups, the larger group showing an AO only slightly younger than their affected fathers and a small group whose AO was, on average, 24 years younger than their affected fathers. Analysis of the grandparental origin of the Huntington allele suggests that while propensity to anticipation is heritable for a number of generations through the male line, it originates at the time of differentiation of the germ line of a male who acquires the Huntington allele from his mother. It is suggested that major anticipation indicates an epigenetic change in methylation of the nucleic acid of the genome, which is imposed in the course of the 'genomic imprinting', that is, in the mechanism by which the parental origin of alleles is indicated. PMID:2972838

  5. Inherited diseases involving g proteins and g protein-coupled receptors.

    PubMed

    Spiegel, Allen M; Weinstein, Lee S

    2004-01-01

    Heterotrimeric G proteins couple seven-transmembrane receptors for diverse extracellular signals to effectors that generate intracellular signals altering cell function. Mutations in the gene encoding the alpha subunit of the G protein-coupling receptors to stimulation of adenylyl cyclase cause developmental abnormalities of bone, as well as hormone resistance (pseudohypoparathyroidism caused by loss-of-function mutations) and hormone hypersecretion (McCune-Albright syndrome caused by gain-of-function mutations). Loss- and gain-of-function mutations in genes encoding G protein-coupled receptors (GPCRs) have been identified as the cause of an increasing number of retinal, endocrine, metabolic, and developmental disorders. GPCRs comprise an evolutionarily conserved gene superfamily ( 1 ). By coupling to heterotrimeric G proteins, GPCRs transduce a wide variety of extracellular signals including monoamine, amino acid, and nucleoside neurotransmitters, as well as photons, chemical odorants, divalent cations, hormones, lipids, peptides and proteins. Following a brief overview of G protein-coupled signal transduction, we review the growing body of evidence that mutations in genes encoding GPCRs and G proteins are an important cause of human disease.

  6. Activated Immune Response in an Inherited Leukodystrophy Disease Caused by the Loss of Oligodendrocyte Gap Junctions

    PubMed Central

    Wasseff, Sameh K.; Scherer, Steven S.

    2015-01-01

    Oligodendrocyte:oligodendrocyte (O:O) gap junction (GJ) coupling is a widespread and essential feature of the CNS, and is mediated by connexin47 (Cx47) and Cx32. Loss of function mutations affecting Cx47 results in a severe leukodystrophy, Pelizeus-Merzbacher-like disease (also known as Hypomyelinating Leukodystrophy 2), which can be reproduced in mice lacking both Cx47 and Cx32. Here we report the gene expression profile of the cerebellum – an affected brain region – in mice lacking both Cx47 and Cx32. Of the 43,174 mRNA probes examined, we find decreased expression of 23 probes (corresponding to 23 genes) and increased expression of 545 probes (corresponding to 348 genes). Many of the genes with reduced expression map to oligodendrocytes, and two of them (Fa2h and Ugt8a) are involved in the synthesis of myelin lipids. Many of the genes with increased expression map to microglia and lymphocytes, and to leukotriene/prostaglandin synthesis and chemokine/cytokine pathways. In accord, immunostaining showed activated microglia and astrocytes, as well as T- and B-cells in the cerebella of mutant mice. Thus, in addition to the loss of GJ coupling, there is a prominent immune response in mice lacking both Cx47 and Cx32. PMID:26051537

  7. Beyond spaghetti and meatballs: skin diseases associated with the Malassezia yeasts.

    PubMed

    Levin, Nikki A

    2009-01-01

    Malassezia are common lipid-dependent fungi that grow on the sebaceous areas of human skin, including the face, scalp, and upper trunk. Although Malassezia are a part of the normal human skin flora, they may also cause or exacerbate several skin diseases, including tinea versicolor, Pityrosporum folliculitis, and seborrheic dermatitis. Topical antifungals are the mainstay of treating Malassezia-related diseases. Chronic prophylaxis is often required to prevent recurrences.

  8. Peroxisome proliferator-activated receptors (PPARs) and the human skin: importance of PPARs in skin physiology and dermatologic diseases.

    PubMed

    Sertznig, Pit; Seifert, Markus; Tilgen, Wolfgang; Reichrath, Jörg

    2008-01-01

    Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor superfamily that regulate lipid, glucose, and amino acid metabolism. More recently, PPARs and corresponding ligands have been shown in skin and other organs to regulate important cellular functions, including cell proliferation and differentiation, as well as inflammatory responses. These new functions identify PPARs and corresponding ligands as potential targets for the treatment of various skin diseases and other disorders. It has been shown that in inflammatory skin disorders, including hyperproliferative psoriatic epidermis and the skin of patients with atopic dermatitis, the expression of both PPARalpha and PPARgamma is decreased. This observation suggests the possibility that PPARalpha and PPARgamma activators, or compounds that positively regulate PPAR gene expression, may represent novel NSAIDs for the topical or systemic treatment of common inflammatory skin diseases such as atopic dermatitis, psoriasis, and allergic contact dermatitis. Moreover, recent findings indicate that PPAR-signaling pathways may act as a promising therapeutic target for the treatment of hyperproliferative skin diseases including skin malignancies. Studies in non-diabetic patients suggest that oral thiazolidinediones, which are synthetic ligands of PPARgamma, not only exert an antidiabetic effect but also may be beneficial for moderate chronic plaque psoriasis by suppressing proliferation and inducing differentiation of keratinocytes; furthermore, they may even induce cell growth arrest, apoptosis, and terminal differentiation in various human malignant tumors. It has been reported that PPARalpha immunoreactivity is reduced in human keratinocytes of squamous cell carcinoma (SCC) and actinic keratosis (AK), while PPARdelta appears to be upregulated. Additionally, the microvessel density is significantly higher in AK and SCC that express high levels of PPARdelta. PPARdelta has been demonstrated to

  9. Antibody-dependent cellular cytotoxicity and skin disease

    SciTech Connect

    Norris, D.A.; Lee, L.A.

    1985-07-01

    Antibody dependent cellular cytotoxicity (ADCC) is a recently described mechanism of immunologic lysis in which cellular targets sensitized by specific antibodies are efficiently and selectively lysed by Fc receptor (FcR) bearing nonspecific effectors. Immunoglobulins of various classes (IgG, IgM, IgA, IgE) and various cellular effectors (large granular lymphocytes, monocyte/macrophages, T lymphocytes, neutrophils, and eosinophils) can induce ADCC in vitro, and the importance of ADCC in vivo is being tested experimentally in resistance to viral, bacterial, and parasitic infection, in tumor surveillance, in allograft rejection, and in inflammatory diseases. There is much indirect evidence that ADCC may be the mechanism of damage of different cellular targets in skin diseases, but the best direct evidence concerns immunologic keratinocyte damage, especially in cutaneous lupus erythematosus (LE). The authors have shown that keratinocytes of several species are highly susceptible to lymphocyte and monocyte-mediated ADCC, but not to neutrophil or eosinophil ADCC in vitro using two different cytotoxicity assays. In contrast, complement was a relatively ineffective mediator of lysis of metabolically intact keratinocyte targets. Patients with certain cutaneous lupus syndromes have serum antibodies capable of inducing monocyte and lymphocyte ADCC of targets coated with extractable nuclear antigens. The authors have shown that these antigens apparently move to the cell membrane of keratinocytes in vitro following ultraviolet irradiation. In an animal model, they have shown that antibodies to SSA/Ro bind to human keratinocytes in vivo, especially after ultraviolet irradiation.

  10. Awareness of occupational skin disease in the service sector.

    PubMed

    Holness, D L; Kudla, I; Brown, J; Miller, S

    2017-06-01

    Occupational skin disease (OSD) is a common occupational disease. Although primary prevention strategies are known, OSDs remain prevalent in a variety of work environments including the service sector (restaurant/food services, retail/wholesale, tourism/hospitality and vehicle sales and service). To obtain information about awareness and prevention of OSD in the service sector. Focus groups and a survey were conducted with two groups. The first consisted of staff of the provincial health and safety association for the service sector and the second group comprised representatives from sector employers. Focus groups highlighted key issues to inform the survey that obtained information about perceptions of awareness and prevention of OSD and barriers to awareness and prevention. Both provincial health and safety association staff and sector employer representatives highlighted low awareness and a low level of knowledge of OSD in the sector. Barriers to awareness and prevention included a low reported incidence of OSD, low priority, lack of training materials, lack of time and cost of training, lack of management support and workplace culture. A starting point for improving prevention of OSD in the service sector is increased awareness. Identification of the barriers to awareness and prevention will help to shape an awareness campaign and prevention strategies. Building on existing experience in Europe will be important.

  11. Neutrophilic Skin Lesions in Autoimmune Connective Tissue Diseases

    PubMed Central

    Hau, Estelle; Vignon Pennamen, Marie-Dominique; Battistella, Maxime; Saussine, Anne; Bergis, Maud; Cavelier-Balloy, Benedicte; Janier, Michel; Cordoliani, Florence; Bagot, Martine; Rybojad, Michel; Bouaziz, Jean-David

    2014-01-01

    Abstract The pathophysiology of neutrophilic dermatoses (NDs) and autoimmune connective tissue diseases (AICTDs) is incompletely understood. The association between NDs and AICTDs is rare; recently, however, a distinctive subset of cutaneous lupus erythematosus (LE, the prototypical AICTD) with neutrophilic histological features has been proposed to be included in the spectrum of lupus. The aim of our study was to test the validity of such a classification. We conducted a monocentric retrospective study of 7028 AICTDs patients. Among these 7028 patients, a skin biopsy was performed in 932 cases with mainly neutrophilic infiltrate on histology in 9 cases. Combining our 9 cases and an exhaustive literature review, pyoderma gangrenosum, Sweet syndrome (n = 49), Sweet-like ND (n = 13), neutrophilic urticarial dermatosis (n = 6), palisaded neutrophilic granulomatous dermatitis (n = 12), and histiocytoid neutrophilic dermatitis (n = 2) were likely to occur both in AICTDs and autoinflammatory diseases. Other NDs were specifically encountered in AICTDs: bullous LE (n = 71), amicrobial pustulosis of the folds (n = 28), autoimmunity-related ND (n = 24), ND resembling erythema gyratum repens (n = 1), and neutrophilic annular erythema (n = 1). The improvement of AICTDS neutrophilic lesions under neutrophil targeting therapy suggests possible common physiopathological pathways between NDs and AICTDs. PMID:25546688

  12. Epithelial sodium channel (ENaC) family: Phylogeny, structure-function, tissue distribution, and associated inherited diseases.

    PubMed

    Hanukoglu, Israel; Hanukoglu, Aaron

    2016-04-01

    The epithelial sodium channel (ENaC) is composed of three homologous subunits and allows the flow of Na(+) ions across high resistance epithelia, maintaining body salt and water homeostasis. ENaC dependent reabsorption of Na(+) in the kidney tubules regulates extracellular fluid (ECF) volume and blood pressure by modulating osmolarity. In multi-ciliated cells, ENaC is located in cilia and plays an essential role in the regulation of epithelial surface liquid volume necessary for cilial transport of mucus and gametes in the respiratory and reproductive tracts respectively. The subunits that form ENaC (named as alpha, beta, gamma and delta, encoded by genes SCNN1A, SCNN1B, SCNN1G, and SCNN1D) are members of the ENaC/Degenerin superfamily. The earliest appearance of ENaC orthologs is in the genomes of the most ancient vertebrate taxon, Cyclostomata (jawless vertebrates) including lampreys, followed by earliest representatives of Gnathostomata (jawed vertebrates) including cartilaginous sharks. Among Euteleostomi (bony vertebrates), Actinopterygii (ray finned-fishes) branch has lost ENaC genes. Yet, most animals in the Sarcopterygii (lobe-finned fish) branch including Tetrapoda, amphibians and amniotes (lizards, crocodiles, birds, and mammals), have four ENaC paralogs. We compared the sequences of ENaC orthologs from 20 species and established criteria for the identification of ENaC orthologs and paralogs, and their distinction from other members of the ENaC/Degenerin superfamily, especially ASIC family. Differences between ENaCs and ASICs are summarized in view of their physiological functions and tissue distributions. Structural motifs that are conserved throughout vertebrate ENaCs are highlighted. We also present a comparative overview of the genotype-phenotype relationships in inherited diseases associated with ENaC mutations, including multisystem pseudohypoaldosteronism (PHA1B), Liddle syndrome, cystic fibrosis-like disease and essential hypertension. Copyright

  13. Epithelial sodium channel (ENaC) family: Phylogeny, structure-function, tissue distribution, and associated inherited diseases

    PubMed Central

    Hanukoglu, Israel; Hanukoglu, Aaron

    2016-01-01

    The epithelial sodium channel (ENaC) is composed of three homologous subunits and allows the flow of Na+ ions across high resistance epithelia, maintaining body salt and water homeostasis. ENaC dependent reabsorption of Na+ in the kidney tubules regulates extracellular fluid (ECF) volume and blood pressure by modulating osmolarity. In multi-ciliated cells, ENaC is located in cilia and plays an essential role in the regulation of epithelial surface liquid volume necessary for cilial transport of mucus and gametes in the respiratory and reproductive tracts respectively. The subunits that form ENaC (named as alpha, beta, gamma and delta, encoded by genes SCNN1A, SCNN1B, SCNN1G, and SCNN1D) are members of the ENaC/Degenerin superfamily. The earliest appearance of ENaC orthologs is in the genomes of the most ancient vertebrate taxon, Cyclostomata (jawless vertebrates) including lampreys, followed by earliest representatives of Gnathostomata (jawed vertebrates) including cartilaginous sharks. Among Euteleostomi (bony vertebrates), Actinopterygii (ray finned-fishes) branch has lost ENaC genes. Yet, most animals in the Sarcopterygii (lobe-finned fish) branch including Tetrapoda, amphibians and amniotes (lizards, crocodiles, birds, and mammals), have four ENaC paralogs. We compared the sequences of ENaC orthologs from 20 species and established criteria for the identification of ENaC orthologs and paralogs, and their distinction from other members of the ENaC/Degenerin superfamily, especially ASIC family. Differences between ENaCs and ASICs are summarized in view of their physiological functions and tissue distributions. Structural motifs that are conserved throughout vertebrate ENaCs are highlighted. We also present a comparative overview of the genotype-phenotype relationships in inherited diseases associated with ENaC mutations, including multisystem pseudohypoaldosteronism (PHA1B), Liddle syndrome, cystic fibrosis-like disease and essential hypertension. PMID:26772908

  14. 75 FR 67989 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-04

    ... Health National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting... Committee: National Institute of Arthritis and Musculoskeletal and Skin Diseases Special Emphasis Panel...@mail.nih.gov . (Catalogue of Federal Domestic Assistance Program Nos. 93.846, Arthritis...

  15. 75 FR 27352 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-14

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and... unwarranted invasion of personal privacy. Name of Committee: Arthritis and Musculoskeletal and Skin Diseases... Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, 6701 Democracy Blvd., Suite...

  16. Fitness to work with skin disease and the Americans with Disabilities Act of 1990.

    PubMed

    Nethercott, J R

    1994-01-01

    The Americans with Disabilities Act seeks to prevent applicants from being denied work of which they are capable. This chapter discusses the act and its advantages for persons with disabilities. The author also describes skin diseases that constitute a basis for excluding a prospective employee and skin diseases that can become aggravated in the workplace.

  17. 76 FR 40385 - National Institute of Arthritis and Musculoskeletal and Skin Diseases Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-08

    ... Skin Diseases Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act... Musculoskeletal and Skin Diseases, Special Emphasis Panel, Ancillary Studies to Large Ongoing Clinical Projects... Review Officer, Scientific Review Branch, National Institute of Arthritis, Musculoskeletal and...

  18. Health Care Utilization among Migrant Latino Farmworkers: The Case of Skin Disease

    ERIC Educational Resources Information Center

    Feldman, Steven R.; Vallejos, Quirina M.; Quandt, Sara A.; Fleischer, Alan B., Jr.; Schulz, Mark R.; Verma, Amit; Arcury, Thomas A.

    2009-01-01

    Context: Skin diseases are common occupational illnesses for migrant farmworkers. Farmworkers face many barriers in accessing health care resources. Purpose: Framed by the Health Behavior Model, the purpose of this study was to assess health care utilization for skin disease by migrant Latino farmworkers. Methods: Three hundred and four migrant…

  19. 76 FR 35225 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-16

    ... Skin Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act... Musculoskeletal and Skin Diseases, Special Emphasis Panel. Clinical Trials Planning Pilot and Research. Date: July...D, Chief, Scientific Review Branch, National Institute of Arthritis, Musculoskeletal and...

  20. Health Care Utilization among Migrant Latino Farmworkers: The Case of Skin Disease

    ERIC Educational Resources Information Center

    Feldman, Steven R.; Vallejos, Quirina M.; Quandt, Sara A.; Fleischer, Alan B., Jr.; Schulz, Mark R.; Verma, Amit; Arcury, Thomas A.

    2009-01-01

    Context: Skin diseases are common occupational illnesses for migrant farmworkers. Farmworkers face many barriers in accessing health care resources. Purpose: Framed by the Health Behavior Model, the purpose of this study was to assess health care utilization for skin disease by migrant Latino farmworkers. Methods: Three hundred and four migrant…