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Sample records for inherited skin diseases

  1. [Inherited skin diseases - a review of selected genodermatoses].

    PubMed

    Wertheim-Tysarowska, Katarzyna; Gos, Monika; Niepokój, Katarzyna; Kowalewski, Cezary

    2012-01-01

    Inherited distubances in skin structure and its function are the main cause of diseases classified as genodermatoses. The following clinical entities are classified as genodermatoses: epidermolysis bullosa, keratotic disorders, disorders of skin color, ectodermal genodermatoses, genodermatoses associated with connective tissue, vascular genodermatoses and genodermatoses with skin manifestation and elevated cancer risk. One of the most clinically heterogenous group of genodermatoses, is epidermolysis bullosa. Four main subtypes were described: simplex, dystrophic, junctional and Kindler syndrome. These diseases are caused by mutations in the genes encoding proteins forming junctions between the dermis and epidermis (eg. COL7A1, COL17A1, KRT14, KRT5 or genes coding for 332 laminin). They are inherited in an autosomal recessive or dominant manner. The disease that is inherited as a dominant, sex dependent trait, is incontinenia pigmenti (Bloch-Sulzberger syndrome) characterized by the presence of extensive pigmentation changes already in the neonatal period. In patients with incontinenia pigmenti, mutations in the NEMO gene are found. The protein encoded by NEMO is involved in the negative regulation of activity of the NFκB transcription factor that is responsible for apoptosis and cell proliferation control. In the regulation of cell proliferation, the neurofibromin (NF1) - the suppressor of RAS/MAPK signaling pathway activity, is also involved. The mutations in the NF1 gene are identified in neurofibromatosis type I - a genodermatosis with higher risk of cancer development and tumor formation. Herein, a review of selected genodermatoses in the context of their molecular pathology is presented.

  2. "...Rewritten in the skin": clues to skin biology and aging from inherited disease.

    PubMed

    Monnat, Raymond J

    2015-06-01

    The growing diversity of heritable skin diseases, a practical challenge to clinicians and dermato-nosologists 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.

  3. Skin Diseases: Skin Health and Skin Diseases

    MedlinePlus

    Skip Navigation Bar Home Current Issue Past Issues Skin Diseases Skin Health and Skin Diseases Past Issues / Fall 2008 Table of Contents ... acne to wrinkles Did you know that your skin is the largest organ of your body? It ...

  4. 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.

  5. 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

  6. 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

  7. 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.

  8. 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

  9. Transgenerational epigenetic inheritance in health and disease.

    PubMed

    Whitelaw, Nadia C; Whitelaw, Emma

    2008-06-01

    Over the past century, patterns of phenotypic inheritance have been observed that are not easily rationalised by Mendel's rules of inheritance. Now that we have begun to understand more about non-DNA based, or 'epigenetic', control of phenotype at the molecular level, the idea that the transgenerational inheritance of these epigenetic states could explain non-Mendelian patterns of inheritance has become attractive. There is a growing body of evidence that abnormal epigenetic states, termed epimutations, are associated with disease in humans. For example, in several cases of colorectal cancer, epimutations have been identified that silence the human mismatch repair genes, MLH1 and MSH2. But strong evidence that the abnormal epigenetic states are primary events that occur in the absence of genetic change and are inherited across generations is still absent.

  10. 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.

  11. 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. PMID:26612372

  12. 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

  13. Prenatal diagnosis of inherited metabolic diseases.

    PubMed Central

    Diukman, R; Goldberg, J D

    1993-01-01

    Advances in the prenatal diagnosis of inherited metabolic disease have provided new reproductive options to at-risk couples. These advances have occurred in both sampling techniques and methods of analysis. In this review we present an overview of the currently available prenatal diagnostic approaches for the diagnosis of metabolic disease in a fetus. Images PMID:8236980

  14. 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 ...

  15. [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.

  16. 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

  17. The genetics of human skin disease.

    PubMed

    DeStefano, Gina M; Christiano, Angela M

    2014-10-01

    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

  18. Neuromuscular imaging in inherited muscle diseases

    PubMed Central

    Kley, Rudolf A.; Fischer, Dirk

    2010-01-01

    Driven by increasing numbers of newly identified genetic defects and new insights into the field of inherited muscle diseases, neuromuscular imaging in general and magnetic resonance imaging (MRI) in particular are increasingly being used to characterise the severity and pattern of muscle involvement. Although muscle biopsy is still the gold standard for the establishment of the definitive diagnosis, muscular imaging is an important diagnostic tool for the detection and quantification of dystrophic changes during the clinical workup of patients with hereditary muscle diseases. MRI is frequently used to describe muscle involvement patterns, which aids in narrowing of the differential diagnosis and distinguishing between dystrophic and non-dystrophic diseases. Recent work has demonstrated the usefulness of muscle imaging for the detection of specific congenital myopathies, mainly for the identification of the underlying genetic defect in core and centronuclear myopathies. Muscle imaging demonstrates characteristic patterns, which can be helpful for the differentiation of individual limb girdle muscular dystrophies. The aim of this review is to give a comprehensive overview of current methods and applications as well as future perspectives in the field of neuromuscular imaging in inherited muscle diseases. We also provide diagnostic algorithms that might guide us through the differential diagnosis in hereditary myopathies. PMID:20422195

  19. 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.

  20. Inherited metabolic diseases affecting the carrier.

    PubMed

    Endres, W

    1997-03-01

    The objective of this review is to draw attention to those inherited metabolic traits which are potentially harmful also for the carrier, and to outline preventive measures, at least for obligate heterozygotes, i.e. parents of homozygous children. Concerning carriers of food-dependent abnormalities, early vascular disease in homocystinuria, hyperammonaemic episodes in ornithine transcarbamylase deficiency, presenile cataracts in galactosaemia as well as galactokinase deficiency, spastic paraparesis in X-linked adrenoleukodystrophy, and HELLP syndrome in mothers of babies with long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency have to be mentioned. In the group of food-independent disorders, clinical features in carriers may be paraesthesias and corneal dystrophy in Fabry disease, lens clouding in Lowe syndrome, lung and/or liver diseases in alpha 1-antitrypsin deficiency, and renal stones in cystinuria type II and III. Finally, two monogenic carrier states are known which in pregnant individuals could possibly afflict the developing fetus, i.e. heterozygosity for galactosaemia and for phenylketonuria. Elevated levels of galactose-1-phosphate have been found in red blood cells of infants heterozygous for galactosaemia born to heterozygous mothers. Aspartame in very high doses is reported to increase blood phenylalanine levels in heterozygotes for phenylketonuria, thus being a risk for the fetus of a heterozygous mother. For some of these carrier states preventive measures can be recommended, e.g. restriction of lactose in parents and heterozygous grandparents of children with galactosaemia and galactokinase deficiency as well as transiently in infants heterozygous for galactosaemia, dietary supplementation with monounsaturated fatty acids in symptomatic carriers for X-linked adrenoleukodystrophy, avoidance of smoking and alcohol in heterozygotes for alpha 1-antitrypsin deficiency, avoidance of episodes of dehydration in heterozygotes for cystinuria, and

  1. 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.

  2. 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.

  3. Endocrine Disruptor Induction of Epigenetic Transgenerational Inheritance of Disease

    PubMed Central

    Skinner, Michael K.

    2014-01-01

    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. PMID:25088466

  4. 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. PMID:25088466

  5. [Travel and skin diseases].

    PubMed

    Stüttgen, G

    1992-02-20

    The problem "travelling and dermatological diseases" is presented as a temporary change of place with associated changes in ecological conditions. Latent dermatoses may be provoked--but full-blown dermatoses may also improve with no specific treatment (climatic therapy of neurodermatitis). Physiological changes at the surface of the skin brought about by, for example, temperature or the effects of solar radiation, may allow fungal, bacterial or viral infections to develop. Direct contact with the living environment on land or in the water, in particular in the tropics, can lead to the development of diseases. Some dermatoses have a lengthy latency and develop only later at home. Recommendations for general and specific prophylaxis and treatment are made.

  6. 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. PMID:27256036

  7. 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.

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

    PubMed Central

    Martos, Suzanne N.; Tang, Wan-yee; Wang, Zhibin

    2016-01-01

    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. PMID:25792089

  9. 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.

  10. Inherited Structural Heart Diseases With Potential Atrial Fibrillation Occurrence.

    PubMed

    Manuguerra, Roberta; Callegari, Sergio; Corradi, Domenico

    2016-02-01

    Inherited cardiac diseases inducing structural remodeling of the myocardium sometimes develop arrhythmias of various kinds. Among these rhythm disturbances, atrial fibrillation is well known to frequently worsen the prognosis of the primary disorder by increasing morbidity and mortality, especially because of a higher rate of heart failure. In this manuscript, we have reviewed the literature on the most important inherited structural cardiac diseases in whose clinical history atrial fibrillation may occur fairly often.

  11. 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

  12. 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.

  13. Environmentally Induced Epigenetic Transgenerational Inheritance of Disease Susceptibility

    PubMed Central

    Nilsson, Eric E.; Skinner, Michael K.

    2014-01-01

    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 in regards to disease etiology. PMID:24657180

  14. 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

  15. 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

  16. Hepatocyte transplantation for inherited metabolic diseases of the liver.

    PubMed

    Jorns, C; Ellis, E C; Nowak, G; Fischler, B; Nemeth, A; Strom, S C; Ericzon, B G

    2012-09-01

    Inherited metabolic diseases of the liver are characterized by deficiency of a hepatic enzyme or protein often resulting in life-threatening disease. The remaining liver function is usually normal. For most patients, treatment consists of supportive therapy, and the only curative option is liver transplantation. Hepatocyte transplantation is a promising therapy for patients with inherited metabolic liver diseases, which offers a less invasive and fully reversible approach. Procedure-related complications are rare. Here, we review the experience of hepatocyte transplantation for metabolic liver diseases and discuss the major obstacles that need to be overcome to establish hepatocyte transplantation as a reliable treatment option in the clinic.

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

    PubMed Central

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

    2014-01-01

    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. PMID:24856029

  18. 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…

  19. 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.

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

    MedlinePlus

    ... Current Issue Past Issues Skin Diseases Skin and Sun —Not a good mix Past Issues / Fall 2008 ... turn Javascript on. Good skin care begins with sun safety. Whether it is something as simple as ...

  1. 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.

  2. 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)

  3. 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 ...

  4. [Skin and chronic kidney disease].

    PubMed

    Rizzo, Raffaella; Mancini, Elena; Santoro, Antonio

    2014-01-01

    Kidneys and skin are seldom considered associated, but their relationship is more closer than generally believed. In some immunological diseases (SLE...) and genetic syndromes (tuberous sclerosis, Fabrys disease...) the cutaneous manifestations are integral parts of the clinical picture. In advanced uremia, besides the well-known itching skin lesions, calciphylaxis may appear, a typical example of cutaneous involvement secondary to the metabolic complications (calcium-phosphate imbalance) of the renal disease. Nephrogenic systemic fibrosis appears only in patients with renal failure and it has a very severe prognosis due to the systemic organ involvement. Moreover, there is a heterogeneous group of metabolic diseases, with renal involvement, that may be accompanied by skin lesions, either related to the disease itself or to its complications (diabetes mellitus, porphyrias). In systemic amyloidosis, fibrils may deposit even in dermis leading to different skin lesions. In some heroin abusers, in the presence of suppurative lesions in the sites of needle insertion, renal amyloidosis should be suspected, secondary to the chronic inflammation. Atheroembolic disease is nowadays frequently observed, as a consequence of the increasing number of invasive intravascular manoeuvres. Skin manifestations like livedo reticularis or the blue toe syndrome are the most typical signs, but often renal dysfunction is also present. In all these conditions, the skin lesion may be a first sign, a warning, that should arouse the suspicion of a more complex pathology, even with renal involvement. Being aware of this relationship is fundamental to accelerate the diagnostic process. PMID:25315722

  5. Inherited eye disease: cause and late effect.

    PubMed

    Manson, Forbes D C; Trump, Dorothy; Read, Andrew P; Black, Graeme C M

    2005-10-01

    Molecular genetics has provided relatively few insights into late-onset eye disorders, but epidemiological data indicate that genetic factors are important in some late-onset eye disorders that cause major health burdens. Much clinical genetic research is based on the belief that developmental and late-onset disorders are not necessarily the result of defects in different genes, but are often caused by different mutations in the same collection of genes. Thus, mutations that either abolish or radically change gene function might cause early-onset disorders, whereas more-subtle changes in gene expression might underlie late-onset diseases. We present arguments and examples that indicate that this principle might be a fruitful guide to investigating the causes of late-onset eye disorders. PMID:16153893

  6. 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

  7. Skin disease in pregnancy.

    PubMed

    Soutou, Boutros; Aractingi, Sélim

    2015-07-01

    Skin manifestations during pregnancy are common and diversified. This review will focus on the most important entities to be recognized by obstetricians. These are, on the one hand, physiological changes, where unnecessary investigations should be avoided, and on the other, the specific dermatoses of pregnancy. These develop electively in pregnancy, and they are currently grouped into three disorders: polymorphic eruption of pregnancy, atopic eczema of pregnancy, and pemphigoid gestationis. Arguments for recognition of these are presented including detection of anti-BP180 antibodies. Follow-up and treatment depend on the precise diagnosis. Risks in fetal prognosis may occur in rare pemphigoid gestationis cases. PMID:25862358

  8. Malassezia skin diseases in humans.

    PubMed

    Difonzo, E M; Faggi, E; Bassi, A; Campisi, E; Arunachalam, M; Pini, G; Scarfì, F; Galeone, M

    2013-12-01

    Although Malassezia yeasts are a part of the normal microflora, under certain conditions they can cause superficial skin infection, such as pityriasis versicolor (PV) and Malassezia folliculitis. Moreover the yeasts of the genus Malassezia have been associated with seborrheic dermatitis and dandruff, atopic dermatitis, psoriasis, and, less commonly, with confluent and reticulated papillomatosis, onychomycosis, and transient acantholytic dermatosis. The study of the clinical role of Malassezia species has been surrounded by controversy due to the relative difficulty in isolation, cultivation, and identification. This review focuses on the clinical, mycologic, and immunologic aspects of the various skin diseases associated with Malassezia. Moreover, since there exists little information about the epidemiology and ecology of Malassezia species in the Italian population and the clinical significance of these species is not fully distinguished, we will report data about a study we carried out. The aim of our study was the isolation and the identification of Malassezia species in PV-affected skin and non-affected skin in patients with PV and in clinically healthy individuals without any Malassezia associated skin disease. PMID:24442041

  9. Imported skin diseases in dermatology.

    PubMed

    James, W D

    2001-11-01

    Millions of afflicted people suffer from conditions which Japanese dermatologists may rarely encounter. Many of our patients travel extensively either as part of work-related business trips or during vacationing. From three to ten percent of travelers experience skin, hair or nail disorders. With worldwide travel heightening exposure to the causative agents, there is an increasing likelihood that a patient with leishmaniasis, Boutonneuse fever, onchocerciasis, loaiasis, dengue fever, cutaneous larva migrans or other recently acquired skin conditions from a far away land will visit your office for diagnosis and treatment. The clinical characteristics, diagnostic tests and therapeutic options for such imported tropical diseases will be discussed.

  10. Inherited antithrombin deficiency and end stage renal disease.

    PubMed

    Hara, Tomohiko; Naito, Katsusuke

    2005-11-01

    Antithrombin is a potent inhibitor of the coagulant effect of thrombin. In the latter half of 20th century, many families have been described in which an autosomaly dominant inherited antithrombin deficiency has caused severe venous thromboembolic disease in successive generations. The important complication is severe venoocclusive disease by deep venous thrombus. Some inherited antithrombin deficient patients developed renal failure because of fibrin deposition in the kidney glomeruli or renal vein thrombus, and therefore the need for replacement therapy for end stage renal disease (ESRD). Although an inherited antithrombin deficiency with renal failure is rare, prevention against renal failure in such patients, and their renal replacement therapy for ESRD are important. Proteinuria decreases plasma antithrombin level leading to more severe hyper-coagulation state. Therefore early in renal disease, it may be prudent for adaptation of anti-coagulation therapy even if recurrent thrombosis has not occurred. All replacement therapy (hemodialysis, transplantation or peritoneal dialysis) for ESRD are available for such thrombophilic disorders. Anticoagulation agents working without aggravation of antithrombin effects (Argatroban, Nafamostat mesilate etc.) are useful for hemodialysis. The renal allograft recipients with thrombophilia seem to be at risk of developing an acute rejection or other vascular event. Peritoneal dialysis is potentially a good adaptation for such thrombophilic disorders. However which therapy has the best mortality and morbidity outcomes is not clear. Physicians and Surgeons must pay attention to the coagulation state and thrombophilia in ESRD patients, give strong consideration for adequate anti-coagulation therapy and review the best renal replacement modality for each patient.

  11. Inheritance of equine sarcoid disease in Franches-Montagnes horses.

    PubMed

    Christen, Garance; Gerber, Vinzenz; Dolf, Gaudenz; Burger, Dominique; Koch, Christoph

    2014-01-01

    The mode of inheritance for susceptibility to equine sarcoid disease (ES) remains unknown. The objectives of this study were to analyse a large sample of the Franches-Montagnes (FM) horse population and investigate the heritability and mode of inheritance for susceptibility to ES. Horses were clinically examined for the presence of sarcoid tumours. A standardized examination protocol and client questionnaire were used and a pedigree- and subsequent segregation-analysis for the ES trait performed. To investigate the mode of inheritance, five models were evaluated and compared in a hierarchical way. The analyses reveal that variation in susceptibility to ES is best explained by a model incorporating polygenic variation. The possible effect of a major gene, such as specific equine leukocyte antigen alleles, is unlikely, but cannot be ruled-out entirely. The heritability of the phenotype on the observation scale for the trait 'affected with ES' was estimated to be 8%. A corrected value for the heritability on a liability scale was estimated at 21% and it is therefore possible to estimate breeding values for ES. The arguments against the practical implementation of an estimated breeding value in a multifactorial condition like ES are discussed.

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

    PubMed

    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

    2012-12-01

    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.

  13. [Occupational skin diseases in medical personnel].

    PubMed

    2011-01-01

    Occupational skin diseases develop mostly in certain occupational groups at risk. The authors studied features of occupational skin diseases in medical personnel examined over 2003-2007. During this time, occupational skin disease was diagnosed in 118 individuals out of which 24 (20.3%) were medical staffers. All 24 examinees suffered from occupational allergic skin conditions. Most common causes of these were medicines, latex, desinfectants. Nurses are most prone to skin conditions (91.67%). Special risk group covers surgeons, psychiatrists and dentists. As medical staffers are occupational risk group for occupational skin conditions, diagnosed allergic dermatoses in them should be considered as having possible occupational occupational origin.

  14. 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

  15. Skin diseases following a Christmas tree pattern.

    PubMed

    Wollenberg, Andreas; Eames, Tatiana

    2011-01-01

    Pattern analysis of skin lesions is an art and a key competence of every dermatologist. Three major line patterns cover the human body-the dermatomes or Head zones, the nevoid lines of Blaschko, and the relaxed skin tension lines, or Langer lines. Head zones represent skin areas innervated from the same sensory neuronal segment or spinal nerve zone. Blaschko lines are borderlines of epidermal aberration caused by genetic mosaicism occurring in the early stages of embryogenesis. Langer lines show the direction of the lowest naturally occurring skin tension, and its thoracodorsal manifestation is the Christmas tree pattern. Here we review clinical aspects of pityriasis rosea, mycosis fungoides, stage 2 syphilis, exanthematic Kaposi sarcoma, exanthematic psoriasis, Leser-Trelat syndrome, and other primary skin diseases with a Christmas tree pattern. Secondary skin diseases, such as herpes zoster or indeterminate cell histiocytosis, may follow this pattern if they are linked to a primary skin disease by the Wolf isotopic response.

  16. 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

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

    PubMed

    Hampel, Harald; Lista, Simone

    2012-11-01

    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.

  18. 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

  19. 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. PMID:25291137

  20. 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.

  1. 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

  2. Inflammatory and glandular skin disease in pregnancy.

    PubMed

    Yang, Catherine S; Teeple, Mary; Muglia, Jennie; Robinson-Bostom, Leslie

    2016-01-01

    A switch from cell-mediated to humoral immunity (helper T 1 [Th1] to helper T 2 [Th2] shift) during gestation plays a key role in placental immune tolerance. As a result, skin diseases that are Th2 mediated often worsen, whereas skin diseases that are Th1 mediated often improve during gestation. Also, due to fluctuations in glandular activity, skin diseases involving sebaceous and eccrine glands may flare, whereas those involving apocrine glands may improve during pregnancy. Despite these trends, inflammatory and glandular skin diseases do not always follow the predicted pattern, and courses are often diverse. We review the gestational course of inflammatory skin diseases, such as atopic dermatitis (atopic eruption of pregnancy), psoriasis, impetigo herpetiformis, urticaria, erythema annulare centrifugum, pityriasis rosea, sarcoidosis, Sweet syndrome, and erythema nodosum, as well as glandular skin diseases, including acne vulgaris, acne rosacea, perioral dermatitis, hidradenitis suppurativa, Fox-Fordyce disease, hyperhidrosis, and miliaria. For each of these diseases, we discuss the pathogenesis, clinical presentation, and management with special consideration for maternal and fetal safety. PMID:27265071

  3. Loss of exon identity is a common mechanism of human inherited disease

    PubMed Central

    Sterne-Weiler, Timothy; Howard, Jonathan; Mort, Matthew; Cooper, David N.; Sanford, Jeremy R.

    2011-01-01

    It is widely accepted that at least 10% of all mutations causing human inherited disease disrupt splice-site consensus sequences. In contrast to splice-site mutations, the role of auxiliary cis-acting elements such as exonic splicing enhancers (ESE) and exonic splicing silencers (ESS) in human inherited disease is still poorly understood. Here we use a top-down approach to determine rates of loss or gain of known human exonic splicing regulatory (ESR) sequences associated with either disease-causing mutations or putatively neutral single nucleotide polymorphisms (SNPs). We observe significant enrichment toward loss of ESEs and gain of ESSs among inherited disease-causing variants relative to neutral polymorphisms, indicating that exon skipping may play a prominent role in aberrant gene regulation. Both computational and biochemical approaches underscore the relevance of exonic splicing enhancer loss and silencer gain in inherited disease. Additionally, we provide direct evidence that both SRp20 (SRSF3) and possibly PTB (PTBP1) are involved in the function of a splicing silencer that is created de novo by a total of 83 different inherited disease mutations in 67 different disease genes. Taken together, we find that ∼25% (7154/27,681) of known mis-sense and nonsense disease-causing mutations alter functional splicing signals within exons, suggesting a much more widespread role for aberrant mRNA processing in causing human inherited disease than has hitherto been appreciated. PMID:21750108

  4. Periostin in skin tissue and skin-related diseases.

    PubMed

    Yamaguchi, Yukie

    2014-06-01

    Extracellular matrix (ECM) is not only involved in the maintenance of normal physiological tissue but also in interactions with other ECM components, tissue remodeling, and modulating immune responses. The skin provides a distinctive environment characterized by rich fibroblasts producing various ECM proteins, epithelial-mesenchymal interactions, and immune responses induced by external stimuli. Recently, periostin-a matricellular protein-has been highlighted for its pivotal functions in the skin. Analysis of periostin null mice has revealed that periostin contributes to collagen fibrillogenesis, collagen cross-linking, and the formation of ECM meshwork via interactions with other ECM components. Periostin expression is enhanced by mechanical stress or skin injury; this is indicative of the physiologically protective functions of periostin, which promotes wound repair by acting on keratinocytes and fibroblasts. Along with its physiological functions, periostin plays pathogenic roles in skin fibrosis and chronic allergic inflammation. In systemic sclerosis (SSc) patients, periostin levels reflect the severity of skin fibrosis. Periostin null mice have shown reduced skin fibrosis in a bleomycin-induced SSc mouse model, indicating a key role of periostin in fibrosis. Moreover, in atopic dermatitis (AD), attenuated AD phenotype has been observed in periostin null mice in a house dust mite extract-induced AD mouse model. Th2 cytokine-induced periostin acts on keratinocytes to produce inflammatory cytokines that further enhance the Th2 response, thereby sustaining and amplifying chronic allergic inflammation. Thus, periostin is deeply involved in the pathogenesis of AD and other inflammation-related disorders affecting the skin. Understanding the dynamic actions of periostin would be key to dissecting pathogenesis of skin-related diseases and to developing novel therapeutic strategies.

  5. 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. PMID:26996333

  6. 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.

  7. Immune-competent human skin disease models.

    PubMed

    Bergers, Lambert I J C; Reijnders, Christianne M A; van den Broek, Lenie J; Spiekstra, Sander W; de Gruijl, Tanja D; Weijers, Ester M; Gibbs, Susan

    2016-09-01

    All skin diseases have an underlying immune component. Owing to differences in animal and human immunology, the majority of drugs fail in the preclinical or clinical testing phases. Therefore animal alternative methods that incorporate human immunology into in vitro skin disease models are required to move the field forward. This review summarizes the progress, using examples from fibrosis, autoimmune diseases, psoriasis, cancer and contact allergy. The emphasis is on co-cultures and 3D organotypic models. Our conclusion is that current models are inadequate and future developments with immune-competent skin-on-chip models based on induced pluripotent stem cells could provide a next generation of skin models for drug discovery and testing.

  8. 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. PMID:27436771

  9. Skin cleansing in health and disease.

    PubMed

    Raab, W

    1990-01-01

    Skin cleansing has to be considered as an important component of daily hygiene in normal skin and as an important part of therapy in diseased skin. The crucial point is the choice of the cleansing agent to be recommended as skin tolerance of detergents is sometimes low. The evaluation of cleansing products depends upon their cleansing action (detergent or adsorptive), on the general and specifically epidermal toxicity of the components, on the rinsability of the product, and on the amount and nature of the additives, e. g. perfume oils. The knowledge of all the above-mentioned points will help the cosmetic adviser as well as the dermatologist to make the right choice depending upon the actual condition of the skin.

  10. Skin biopsy: Biopsy issues in specific diseases.

    PubMed

    Elston, Dirk M; Stratman, Erik J; Miller, Stanley J

    2016-01-01

    Misdiagnosis may result from biopsy site selection, technique, or choice of transport media. Important potential sources of error include false-negative direct immunofluorescence results based on poor site selection, uninformative biopsy specimens based on both site selection and technique, and spurious interpretations of pigmented lesions and nonmelanoma skin cancer based on biopsy technique. Part I of this 2-part continuing medical education article addresses common pitfalls involving site selection and biopsy technique in the diagnosis of bullous diseases, vasculitis, panniculitis, connective tissue diseases, drug eruptions, graft-versus-host disease, staphylococcal scalded skin syndrome, hair disorders, and neoplastic disorders. Understanding these potential pitfalls can result in improved diagnostic yield and patient outcomes.

  11. Helicobacter pylori and skin autoimmune diseases

    PubMed Central

    Magen, Eli; Delgado, Jorge-Shmuel

    2014-01-01

    Autoimmune skin diseases are characterized by dysregulation of the immune system resulting in a loss of tolerance to skin self-antigen(s). The prolonged interaction between the bacterium and host immune mechanisms makes Helicobacter pylori (H. pylori) a plausible infectious agent for triggering autoimmunity. Epidemiological and experimental data now point to a strong relation of H. pylori infection on the development of many extragastric diseases, including several allergic and autoimmune diseases. H. pylori antigens activate cross-reactive T cells and induce autoantibodies production. Microbial heat shock proteins (HSP) play an important role of in the pathogenesis of autoimmune diseases because of the high level of sequence homology with human HSP. Eradication of H. pylori infection has been shown to be effective in some patients with chronic autoimmune urticaria, psoriasis, alopecia areata and Schoenlein-Henoch purpura. There is conflicting and controversial data regarding the association of H. pylori infection with Behçet’s disease, scleroderma and autoimmune bullous diseases. No data are available evaluating the association of H. pylori infection with other skin autoimmune diseases, such as vitiligo, cutaneous lupus erythematosus and dermatomyositis. The epidemiological and experimental evidence for a possible role of H. pylori infection in skin autoimmune diseases are the subject of this review. PMID:24587626

  12. 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.

  13. Hydrocarbons (Jet Fuel JP-8) Induce Epigenetic Transgenerational Inheritance of Obesity, Reproductive Disease and Sperm Epimutations

    PubMed Central

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

    2012-01-01

    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. PMID:23453003

  14. The latest fashions in skin disease.

    PubMed Central

    Carroll, J. M.; Goldsmith, L. A.

    1995-01-01

    The complex nature of epidermal tissue homeostasis is borne out by the range of diseases affecting this tissue. Indeed, mutations in proteins involved in intracellular integrity and cell-cell or cell-matrix adhesion can cause disease in an appropriate epidermal compartment. The most important realization in epidermal disease in the last two years has been that point mutations in key structural genes can result in filaments collapsing, cell cytolysis, or cell adhesion defects; and that these defects can result in severe human skin disease. Now that these associations have been made, the important next step will be to alleviate the suffering of these patients. Animal models will be an important part of these investigations; many molecules including growth factors, oncogenes, and cell adhesion molecules have been targeted to the epidermis of transgenic mice to investigate their role in disease. Such animal models should also elucidate the causes of diseases like psoriasis, a very common skin disease, the molecular basis of which remains elusive. Gene therapy involving the replacement of defective genes or local delivery of therapeutic molecules will be one of the main goals in alleviating these known epidermal diseases. Such protocols in the epidermis are aided by the relative accessibility of the skin and the presence of the "stem cells" in relatively accessible compartments. Indeed, as the last few years have shed much light on the genetic causes of epidermal disease, it is hoped that the next several years will prove as illuminating in the alleviation of these diseases. PMID:8529091

  15. Naturally occurring plant polyphenols as potential therapies for inherited neuromuscular diseases.

    PubMed

    Fuller, Heidi R; Humphrey, Emma L; Morris, Glenn E

    2013-11-01

    There are several lines of laboratory-based evidence emerging to suggest that purified polyphenol compounds such as resveratrol, found naturally in red grapes, epigallocatechin galate from green tea and curcumin from turmeric, might be useful for the treatment of various inherited neuromuscular diseases, including spinal muscular atrophy, Duchenne muscular dystrophy and Charcot-Marie-Tooth disease. Here, we critically examine the scientific evidence related to the known molecular effects that these polyphenols have on different models of inherited neuromuscular disease, with particular attention to problems with the validity of in vitro evidence. We also present proteomic evidence that polyphenols have in vitro effects on cells related to metal ion chelation in cell-culture media. Although their precise mechanisms of action remain somewhat elusive, polyphenols could be an attractive approach to therapy for inherited neuromuscular disease, especially since they may be safer to use on young children, compared with some of the other drug candidates.

  16. Naturally occurring plant polyphenols as potential therapies for inherited neuromuscular diseases.

    PubMed

    Fuller, Heidi R; Humphrey, Emma L; Morris, Glenn E

    2013-11-01

    There are several lines of laboratory-based evidence emerging to suggest that purified polyphenol compounds such as resveratrol, found naturally in red grapes, epigallocatechin galate from green tea and curcumin from turmeric, might be useful for the treatment of various inherited neuromuscular diseases, including spinal muscular atrophy, Duchenne muscular dystrophy and Charcot-Marie-Tooth disease. Here, we critically examine the scientific evidence related to the known molecular effects that these polyphenols have on different models of inherited neuromuscular disease, with particular attention to problems with the validity of in vitro evidence. We also present proteomic evidence that polyphenols have in vitro effects on cells related to metal ion chelation in cell-culture media. Although their precise mechanisms of action remain somewhat elusive, polyphenols could be an attractive approach to therapy for inherited neuromuscular disease, especially since they may be safer to use on young children, compared with some of the other drug candidates. PMID:24215348

  17. 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. PMID:22654483

  18. 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

  19. 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.

  20. Malassezia species and their associated skin diseases.

    PubMed

    Harada, Kazutoshi; Saito, Mami; Sugita, Takashi; Tsuboi, Ryoji

    2015-03-01

    Malassezia spp. are lipophilic fungi that occur on all skin surfaces of humans and animals as commensal and pathogenic organisms. In the 2000s, several new species were added to the Malassezia genus by Japanese researchers. The genus Malassezia now includes 14 species of basidiomycetous yeast. Culture-independent molecular analysis clearly demonstrated that the DNA of Malassezia spp. was predominantly detected in core body and arm sites, suggesting that they are the dominant fungal flora of the human body. Malassezia spp. have been implicated in skin diseases including pityriasis versicolor (PV), Malassezia folliculitis (MF), seborrheic dermatitis (SD) and atopic dermatitis (AD). While Malassezia spp. are directly responsible for the infectious diseases, PV and MF, they act as an exacerbating factor in AD and SD. The fatty acids generated by Malassezia lipase can induce inflammation of the skin, resulting in development of SD. Patch and serum immunoglobulin E tests revealed that AD patients were hypersensitive to Malassezia. However, these findings only partially elucidated the mechanism by which Malassezia spp. induce inflammation in the skin; understanding of the pathogenetic role of Malassezia spp. in SD or AD remains incomplete. In this article, the latest findings of Malassezia research are reviewed with special attention to skin diseases. PMID:25736318

  1. 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. PMID:24404995

  2. Drug-induced skin disease.

    PubMed

    Kaplan, A P

    1984-10-01

    Drug-induced cutaneous reactions encompass a wide variety of rashes that depend in part on route of administration (e.g., contact versus systemic) as well as type of cutaneous response and molecular mechanism underlying the reaction. One such reaction is a type IV immunologic reaction (delayed hypersensitivity) manifest as contact dermatitis and commonly elicited by drugs such as antihistamines, antibiotic ointments, local anesthetics, and paraben esters in cosmetic creams and lotions. A generalized eruption of this sort will occasionally occur with systemic administration of a drug to someone previously sensitized by topical application. Systemic administration of agents can cause nonspecific pruritus or maculopapular eruptions that resemble visual exanthemas. The pathogenesis is unclear and no immune mechanism has been demonstrated. If the drug is continued, exfoliative dermatitis can result. Other types of reactions are urticarial in nature and include acute urticaria/angioedema, erythema multiforme (bullous and nonbullous), Stevens-Johnson syndrome, urticaria in association with serum sickness-like reactions, and urticaria associated with anaphylactoid reactions. In many of these, an allergic reaction in which there is an immunoglobulin (Ig) E-dependent release of mediators in the skin causes hives or swelling. In others, circulating immune complexes may be present, often involving IgG antibody complexed with drug and complement fixation; hives may then be caused by anaphylatoxin release or a concomitant IgE-mediated reaction. In some instances, a cellular reaction may augment the aforementioned inflammatory reactions, perhaps as part of a late-phase reaction or a true delayed hypersensitivity component.

  3. 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

  4. 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

  5. Dandruff: the most commercially exploited skin disease.

    PubMed

    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

  6. Environmental and occupational skin diseases in Taiwan.

    PubMed

    Yu, H S; Lee, C H; Jee, S H; Ho, C K; Guo, Y L

    2001-11-01

    This presentation focuses on the four most important skin diseases in Taiwan thought to be of environmental and/or occupational origin. The majority of work-related dermatoses are contact dermatitis patients. Among occupational contact dermatitis patients, 58.5% involved irritant and 41.5%, allergic dermatitis. Electronics, hairdressing, medical practice, and construction were the most important occupations causing contact dermatitis. An endemic occurrence of chronic arsenism causing hyperpigmentation, keratosis, and cancer has been reported in Taiwan. Arsenical skin cancers present as multiple lesions at different disease stages. The skin cancers are usually found in non-sun-exposed areas. UVB exerts an inhibitory effect on the proliferation of arsenical cancers; this may explain its non-sun-exposed nature. An outbreak of premalignant and malignant skin lesions was reported among paraquat manufacturers in 1985. The skin lesions were mainly distributed over the sun-exposed areas. Photodamage and photocarcinogenesis revealed a strong association with exposure to bipyridines among paraquat manufacturers. In 1979, a mass poisoning occurred in Taiwan from cooking oil contaminated by polychlorinated biphenyls (PCBs). Over 60% of patients were in grades O-II by the Japanese classification. The blood PCB levels of the Taiwanese patients were found to be higher than those of the Yusho subjects.

  7. 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.

  8. 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. PMID:27018067

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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. PMID:26333554

  15. The role of mitochondria in inherited neurodegenerative diseases.

    PubMed

    Kwong, Jennifer Q; Beal, M Flint; Manfredi, Giovanni

    2006-06-01

    In the past decade, the genetic causes underlying familial forms of many neurodegenerative disorders, such as Huntington's disease, Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, Friedreich ataxia, hereditary spastic paraplegia, dominant optic atrophy, Charcot-Marie-Tooth type 2A, neuropathy ataxia and retinitis pigmentosa, and Leber's hereditary optic atrophy have been elucidated. However, the common pathogenic mechanisms of neuronal death are still largely unknown. Recently, mitochondrial dysfunction has emerged as a potential 'lowest common denominator' linking these disorders. In this review, we discuss the body of evidence supporting the role of mitochondria in the pathogenesis of hereditary neurodegenerative diseases. We summarize the principal features of genetic diseases caused by abnormalities of mitochondrial proteins encoded by the mitochondrial or the nuclear genomes. We then address genetic diseases where mutant proteins are localized in multiple cell compartments, including mitochondria and where mitochondrial defects are likely to be directly caused by the mutant proteins. Finally, we describe examples of neurodegenerative disorders where mitochondrial dysfunction may be 'secondary' and probably concomitant with degenerative events in other cell organelles, but may still play an important role in the neuronal decay. Understanding the contribution of mitochondrial dysfunction to neurodegeneration and its pathophysiological basis will significantly impact our ability to develop more effective therapies for neurodegenerative diseases. PMID:16805775

  16. [Inherited thrombophilia].

    PubMed

    Franchini, Massimo; Veneri, Dino

    2005-02-01

    Inherited thrombophilia can be defined as a genetically determined predisposition to develop thromboembolic complications. Inherited prothrombotic risk factors include antithrombin deficiency, protein C and protein S deficiencies, activated protein C resistance due to Leiden factor V mutation, inherited hyperhomocysteinemia, prothrombin G20210A variant, dysfibrinogenemia and elevated factor VIII levels. In this review we briefly analyze, from an epidemiologic, clinic and diagnostic point of view, the main inherited prothrombotic risk factors. Finally, we discuss the synergism between genetic and acquired prothrombotic risk factors in some conditions such as pregnancy and cardiovascular diseases.

  17. 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…

  18. Gene suppression strategies for dominantly inherited neurodegenerative diseases: lessons from Huntington's disease and spinocerebellar ataxia.

    PubMed

    Keiser, Megan S; Kordasiewicz, Holly B; McBride, Jodi L

    2016-04-15

    RNA-targeting approaches are emerging as viable therapeutics that offer an alternative method to modulate traditionally 'undrugable' targets. In the case of dominantly inherited neurodegenerative diseases, gene suppression strategies can target the underlying cause of these intractable disorders. Polyglutamine diseases are caused by CAG expansions in discrete genes, making them ideal candidates for gene suppression therapies. Here, we discuss the current state of gene suppression approaches for Huntington's disease and the spinocerebellar ataxias, including the use of antisense oligonucleotides, short-interfering RNAs, as well as viral vector-mediated delivery of short hairpin RNAs and artificial microRNAs. We focus on lessons learned from preclinical studies investigating gene suppression therapies for these disorders, particularly in rodent models of disease and in non-human primates. In animal models, recent advances in gene suppression technologies have not only prevented disease progression in a number of cases, but have also reversed existing disease, providing evidence that reducing the expression of disease-causing genes may be of benefit in symptomatic patients. Both allele- and non-allele-specific approaches to gene suppression have made great strides over the past decade, showing efficacy and safety in both small and large animal models. Advances in delivery techniques allow for broad and durable suppression of target genes, have been validated in non-human primates and in some cases, are currently being evaluated in human patients. Finally, we discuss the challenges of developing and delivering gene suppression constructs into the CNS and recent advances of potential therapeutics into the clinic.

  19. Translating Mendelian and complex inheritance of Alzheimer's disease genes for predicting unique personal genome variants

    PubMed Central

    Regan, Kelly; Wang, Kanix; Doughty, Emily; Li, Haiquan; Li, Jianrong; Lee, Younghee; Kann, Maricel G

    2012-01-01

    Objective Although trait-associated genes identified as complex versus single-gene inheritance differ substantially in odds ratio, the authors nonetheless posit that their mechanistic concordance can reveal fundamental properties of the genetic architecture, allowing the automated interpretation of unique polymorphisms within a personal genome. Materials and methods An analytical method, SPADE-gen, spanning three biological scales was developed to demonstrate the mechanistic concordance between Mendelian and complex inheritance of Alzheimer's disease (AD) genes: biological functions (BP), protein interaction modeling, and protein domain implicated in the disease-associated polymorphism. Results Among Gene Ontology (GO) biological processes (BP) enriched at a false detection rate <5% in 15 AD genes of Mendelian inheritance (Online Mendelian Inheritance in Man) and independently in those of complex inheritance (25 host genes of intragenic AD single-nucleotide polymorphisms confirmed in genome-wide association studies), 16 overlapped (empirical p=0.007) and 45 were similar (empirical p<0.009; information theory). SPAN network modeling extended the canonical pathway of AD (KEGG) with 26 new protein interactions (empirical p<0.0001). Discussion The study prioritized new AD-associated biological mechanisms and focused the analysis on previously unreported interactions associated with the biological processes of polymorphisms that affect specific protein domains within characterized AD genes and their direct interactors using (1) concordant GO-BP and (2) domain interactions within STRING protein–protein interactions corresponding to the genomic location of the AD polymorphism (eg, EPHA1, APOE, and CD2AP). Conclusion These results are in line with unique-event polymorphism theory, indicating how disease-associated polymorphisms of Mendelian or complex inheritance relate genetically to those observed as ‘unique personal variants’. They also provide insight for

  20. 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

  1. 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

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

    PubMed

    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.

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

    PubMed

    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

  4. 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. PMID:25194296

  5. Dioxin Induction of Transgenerational Inheritance of Disease in Zebrafish

    PubMed Central

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

    2014-01-01

    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. PMID:25194296

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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. PMID:26856793

  11. 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.

  12. Pesticide Methoxychlor Promotes the Epigenetic Transgenerational Inheritance of Adult-Onset Disease through the Female Germline

    PubMed Central

    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. PMID:25057798

  13. Electron microscopy analysis of skin biopsies in CADASIL disease.

    PubMed

    Cotrutz, Carmen Elena; Indrei, Anca; Bădescu, L; Dacălu, Cristina; Neamţu, Monica; Dumitrescu, Gabriela Florenţa; Stefanache, Felicia; Petreuş, T

    2010-01-01

    Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is an inherited vascular disorder, non-amyloid and non-atherosclerotic, affecting predominantly the central nervous system. We examined samples of skin biopsies from six patients (men, 43-52-year-old), admitted for treatment in the Neurology Clinic regarding the presence of partial motor impairment on upper and lower right limbs, facial asymmetry and phrasing impairment (three of the patients); These three patients had family history remarkable for early-onset strokes: mother and two brothers deceased by early strokes (40-50-year-old). Skin biopsy samples were fixed in glutaraldehyde and post-fixed in osmium tetroxyde. After dehydration, tissue samples were embedded in Epon. Ultrathin sections were mounted on copper grids and stained with uranyl acetate and lead citrate as usual and examined with a transmission electron microscope Phillips CM100. In all cases ultrastructural study showed granular osmiophilic material (GOM) in extracellular locations, between degenerating smooth muscle cells in dermal arteries or in their indentations. Deposits of GOM varied in size and electron density. Degeneration and loss of smooth muscle cells (SMCs) leads to abnormal enlargement of the space between these cells Ultrastructural analysis in three cases showed chromatin condensation and peripheral aggregation of nuclear material suggesting cells entry to apoptosis. These aspects and the marked destruction of the vascular wall were correlated with MRI findings and the severity of clinical manifestations at these patients. Our study showed that findings of GOM deposits, degeneration and loss of SMCs (probably by apoptosis), cell adhesion elements disturbance are characteristic for CADASIL disease and sufficient for diagnose of certainty. Moreover, electron microscopy analysis of skin biopsies is a useful tool for a differential diagnosis and can be considered as first choice method

  14. 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.

  15. Skin problems in chronic kidney disease.

    PubMed

    Kuypers, Dirk R J

    2009-03-01

    Skin disorders associated with chronic kidney disease (CKD) can markedly affect a patient's quality of life and can negatively impact their mental and physical health. Uremic pruritus, which is frequently encountered in patients with CKD, is considered to be an inflammatory systemic disease rather than a local skin disorder. Biomarkers of inflammation are increased in patients with uremic pruritus and an imbalance of the endogenous opioidergic system might be involved in the complex pathogenesis of the disease. Treatment options for uremic pruritus include emollients, topical capsaicin cream, ultraviolet B phototherapy, gabapentin, oral activated charcoal and nalfurafine, a kappa-opioid-receptor agonist. Calcific uremic arteriolopathy is triggered by an imbalance of promoters and inhibitors of vascular calcification, caused by the inflammatory changes that occur in uremia. Promising therapeutic strategies for calcific uremic arteriolopathy include bisphosphonates and intravenous sodium thiosulfate. Nephrogenic systemic fibrosis is a devastating condition associated with the use of gadolinium-based contrast agents in patients with CKD. At present, no therapies are available for this complication. Preventive measures include use of iodine-based contrast agents, particularly in patients with CKD stage 4 and 5. If gadolinium contrast is necessary, administration of low volumes of the more stable macrocyclic ionic types of gadolinium-based contrast agent is advocated. Hemodialysis following gadolinium exposure might offer benefits but evidence is lacking. PMID:19190625

  16. 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. PMID:19148755

  17. 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.

  18. Oscar Wilde's skin disease: allergic contact dermatitis?

    PubMed

    Nater, J P

    1992-07-01

    During the last years of his life, Oscar Wilde (1856-1900) suffered from a suppurating otitis media as well as from an unidentified skin disease. The eruption was localized to his face, arms, chest and back and itched severely. A new theory is suggested, based on the fact that Wilde almost certainly used a dye to conceal his rapidly graying hair. He sensitized himself to p-phenylenediamine and developed a stubborn allergic contact dermatitis. Patch testing, the only proof of such a diagnosis, had not yet been devised.

  19. 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.

  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. 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.

  2. 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

  3. Skin microvascular endothelial function as a biomarker in cardiovascular diseases?

    PubMed

    Hellmann, Marcin; Roustit, Matthieu; Cracowski, Jean-Luc

    2015-08-01

    Skin microvascular endothelial function is impaired in many cardiovascular diseases, and could be therefore considered as a representative vascular bed. However, today, available evidence allows considering skin microvascular endothelial function neither as a diagnostic biomarker nor as a prognostic biomarker in cardiovascular diseases. Large follow-up studies using standardized methods should now be conducted to assess the potential predictive value of skin microvascular function in cardiovascular diseases.

  4. [Skin diseases in travellers returning from tropical countries].

    PubMed

    Blum, Johannes; Pletscher, Martin

    2013-06-01

    The most frequently observed skin lesions in travellers returning from tropical countries are insect bite reactions, bacterial skin diseases, creeping eruption and allergic reactions. The article describes these most relevant diseases and their differential diagnosis focussing on the diseases, which are potentially dangerous and which should not be missed, such as resistant staphylococci, chancre of rickettsia or sleeping sickness, cutaneous leishmaniasis or worms, which are not limited to the skin.

  5. Biochemical Basis for Dominant Inheritance, Variable Penetrance, and Maternal Effects in RBP4 Congenital Eye Disease.

    PubMed

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

    2015-04-23

    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, in three families with eye malformations of differing severity, including bilateral anophthalmia. The mutant phenotypes exhibit dominant inheritance, but incomplete penetrance. Maternal transmission 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 the affinity of RBP for its cell surface receptor, STRA6. By occupying STRA6 nonproductively, the dominant-negative proteins 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.

  6. Inheriting vice, acquiring virtue: hereditary disease and moral hygiene in eighteenth-century France.

    PubMed

    Quinlan, Sean M

    2006-01-01

    This essay examines the medical debates over hereditary disease and moral hygiene in France between 1748 and 1790. During this time, which was marked by two formal academic exchanges about pathological inheritance, doctors critically studied the existence of hereditary diseases--including syphilis, arthritis, phthisis, scrofula, rickets, gout, stones, epilepsy, and insanity--and the problems that heredity might pose for curing and preventing these diseases. Amid public debate, doctors first treated heredity with formal skepticism and then embraced the idea. Their changing attitudes stemmed less from epistemological or cognitive reasons than from new cultural beliefs about gender, domesticity, and demographic policy. Fearing moral degeneracy and demographic decline, they argued that a number of social pathologies were truly hereditary and that these diseases spread within the family itself. These beliefs were seemingly confirmed by new clinical studies on tuberculosis. Though doctors conceded that hereditary diseases might limit Enlightenment hopes to perfect society, they also suggested that sexual hygiene and physical education could cure hereditary degeneracy and transcend genealogy and descent. Consequently, they stressed that physical regeneration was a dynamic process, one that stretched from the conjugal bed to weaning and beyond. Rather than accepting the accidents of birth, physicians believed that their patients could self-consciously overcome inherited defects and thus regenerate themselves and even all of society itself. Heredity thus gave doctors an idiom with which to diagnose a felt social crisis and to prescribe appropriate hygienic responses.

  7. Sarcoptic mange: a zoonotic ectoparasitic skin disease.

    PubMed

    Bandi, Kiran Madhusudhan; Saikumar, Chitralekha

    2013-01-01

    A 56-year old man attended the Dermatology Outpatients Department with the complaint of a localized, extremely itchy, erythematous papular lesion of acute onset on the ventral aspect of the right thigh. The patient was referred to the Microbiology Lab for the microscopic detection of the fungal elements. The KOH mount from the skin scrapings showed no fungal elements, but it showed the mites of Sarcopetes scabiei mange. The Sarcoptic Mange is noteworthy because of the fact that it is a zoonotic disease which can easily be passed on to humans. A close contact with infested pet dogs was considered as the main predisposing factor in this case. The response to the antiscabietic treatment was dramatic.

  8. 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

  9. Inpatient detection of cardiac-inherited disease: the impact of improving family history taking

    PubMed Central

    Waddell-Smith, Kathryn E; Donoghue, Tom; Oates, Stephanie; Graham, Amanda; Crawford, Jackie; Stiles, Martin K; Aitken, Andrew; Skinner, Jonathan R

    2016-01-01

    Objectives ‘Idiopathic’ cardiac conditions such as dilated cardiomyopathy (DCM) and resuscitated sudden cardiac death (RSCD) may be familial. We suspected that inpatient cardiology services fail to recognise this. Our objective was to compare diagnostic value of family histories recorded by inpatient cardiology teams with a multigenerational family tree obtained by specially trained allied professionals. Methods 2 experienced cardiology nurses working in 2 tertiary adult cardiac units were trained in cardiac-inherited diseases and family history (FHx) taking, and established as regional coordinators for a National Cardiac Inherited Disease Registry. Over 6 months they sought ‘idiopathic’ cardiology inpatients with conditions with a possible familial basis, reviewed the FHx in the clinical records and pursued a minimum 3-generation family tree for syncope, young sudden death and cardiac disease (full FHx). Results 37 patients (22 males) were selected: mean age 51 years (range 15–79). Admission presentations included (idiopathic) RSCD (14), dyspnoea or heart failure (11), ventricular tachycardia (2), other (10). 3 patients had already volunteered their familial diagnosis to the admitting team. FHx was incompletely elicited in 17 (46%) and absent in 20 (54%). 29 patients (78%) provided a full FHx to the coordinator; 12 of which (41%) were strongly consistent with a diagnosis of a cardiac-inherited disease (DCM 7, hypertrophic cardiomyopathy 3, long QT 1, left ventricular non-compaction 1). Overall, a familial diagnostic rate rose from 3/37(8%) to 12/37 (32%). Conclusions Adult cardiology inpatient teams are poor at recording FHx and need to be reminded of its powerful diagnostic value. PMID:26925241

  10. 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

  11. 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.

  12. 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

  13. 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

  14. Guanine Holes Are Prominent Targets for Mutation in Cancer and Inherited Disease

    PubMed Central

    Bacolla, Albino; Temiz, Nuri A.; Yi, Ming; Ivanic, Joseph; Cer, Regina Z.; Donohue, Duncan E.; Ball, Edward V.; Mudunuri, Uma S.; Wang, Guliang; Jain, Aklank; Volfovsky, Natalia; Luke, Brian T.; Stephens, Robert M.; Cooper, David N.; Collins, Jack R.; Vasquez, Karen M.

    2013-01-01

    Single base substitutions constitute the most frequent type of human gene mutation and are a leading cause of cancer and inherited disease. These alterations occur non-randomly in DNA, being strongly influenced by the local nucleotide sequence context. However, the molecular mechanisms underlying such sequence context-dependent mutagenesis are not fully understood. Using bioinformatics, computational and molecular modeling analyses, we have determined the frequencies of mutation at G•C bp in the context of all 64 5′-NGNN-3′ motifs that contain the mutation at the second position. Twenty-four datasets were employed, comprising >530,000 somatic single base substitutions from 21 cancer genomes, >77,000 germline single-base substitutions causing or associated with human inherited disease and 16.7 million benign germline single-nucleotide variants. In several cancer types, the number of mutated motifs correlated both with the free energies of base stacking and the energies required for abstracting an electron from the target guanines (ionization potentials). Similar correlations were also evident for the pathological missense and nonsense germline mutations, but only when the target guanines were located on the non-transcribed DNA strand. Likewise, pathogenic splicing mutations predominantly affected positions in which a purine was located on the non-transcribed DNA strand. Novel candidate driver mutations and tissue-specific mutational patterns were also identified in the cancer datasets. We conclude that electron transfer reactions within the DNA molecule contribute to sequence context-dependent mutagenesis, involving both somatic driver and passenger mutations in cancer, as well as germline alterations causing or associated with inherited disease. PMID:24086153

  15. The effects of skin disease on the penetration kinetics of hydrocortisone through canine skin in vitro.

    PubMed

    Ahlstrom, Liisa A; Cross, Sheree E; Mills, Paul C

    2011-12-01

    This study investigated the effects of allergic skin disease on the penetration kinetics of hydrocortisone through canine skin in vitro. Full-thickness lesional and nonlesional (normal) skin was removed from the dorsal lumbosacral and dorsocaudal thoracic regions, respectively, of five canine cadavers. The dogs were suspected of having flea allergy dermatitis based on their distribution and types of skin lesions. Nonlesional skin was confirmed to be histologically normal, and the histopathology of the lesional skin was consistent with allergic dermatitis. Excised skin was clipped, mounted in Franz-type diffusion cells, and the transdermal penetration of a saturated, radiolabelled hydrocortisone solution was measured over 30 h. When the penetration data for all five dogs were pooled, a restricted (or residual) maximal likelihood mixed model predicted that the permeability coefficient and pseudosteady-state flux of hydrocortisone was more than twice as great (95% confidence interval 1.55-2.71 times as great; P < 0.0001) through lesional compared with nonlesional skin. There was no significant difference in the lag time for hydrocortisone penetration through lesional compared with nonlesional skin of the dogs. This study has confirmed that the transdermal penetration of hydrocortisone may be altered, typically increased twofold, but could be as high as 10-fold, through lesional compared with nonlesional skin of dogs with suspected flea allergy dermatitis. This is likely to be affected by variables such as disease severity, concurrent infections and interindividual differences in skin characteristics.

  16. Lumpy Skin Disease in Iraq: Study of the Disease Emergence.

    PubMed

    Al-Salihi, K A; Hassan, I Q

    2015-10-01

    This study intends to report the first emergence of lumpy skin disease (LSD) in Iraq, in addition to describing its related clinical signs. In August 2013, 21 cases of four outbreaks developed clinical signs suggestive of LSD in the Nineveh (Mosul) and Baghdad Governorates, which were considered as the first infected foci of LSD in Iraq. The disease was diagnosed tentatively, on the basis of clinical signs and epidemiological features, and it was confirmed as positive by the polymerase chain reaction and histopathological features. In September 2013, eight new outbreaks of LSD also appeared in Baghdad and Nineveh. In 2014, the disease spread rapidly to the governorates of Kirkuk, Salah Al-Din, Al-Anbar, Diyala, Wasit, Babil, Karbala, Najaf, Al-Diwaniyah, Muthanna, Maysan, DhiQar and Basra. The total number of infected cows and calves reported was 7396 and 227, respectively. The apparent morbidity and mortality rates were 9.11% and 0.51%, respectively, while the apparent case-fatality rate was 5.56%. Skin nodules, anorexia, reduce in milk production and decrease in bodyweight were the common clinical signs. Moreover, myiasis and mastitis were seen as complications in some infected animals. Attempts were made to stop the distribution of the disease including quarantine and treatment, control over animal movement and arthropod control. Ring vaccination was used in a 10 km radius zone around the outbreak with live sheep pox vaccine. The highly contagious transboundary nature of the LSD, its endemic distribution in the Iraqi neighbouring countries, and the current armed conflict in the area were the possible factors for the disease being introduced into the country. LSD had spread through the Middle East and Gulf peninsula and could be a cause of danger to the rest of Asia and Europe. International precaution, cooperation and exchange of information could guarantee the prevention and further spread of the disease to the rest of Asia and Europe.

  17. 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. PMID:22859821

  18. 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

  19. [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

  20. [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

  1. Family letters are an effective way to inform relatives about inherited cardiac disease.

    PubMed

    van der Roest, Wilma P; Pennings, José M; Bakker, Marian; van den Berg, Maarten P; van Tintelen, J Peter

    2009-03-01

    Increasing numbers of individuals are being referred to cardiogenetics outpatient clinics with potentially inherited arrhythmia (ARR) or cardiomyopathy (CM). To inform relatives at-risk, we ask index patients to distribute "family letters" containing information on the risks, possible genetic and other screenings, and preventive options. We assessed the responses to these letters in terms of referrals to a cardiologist and/or clinical geneticist. Fifty-six index patients were asked to distribute 249 family letters: 85 in the ARR group and 164 in the CM group. Within a mean follow-up period of 2 years (range 1-5 years) the number of relatives actually referred to the clinical geneticist and/or cardiologist was 57% (142 of 249). There was a significant difference (P < 0.01) between the ARR (80%) and CM groups (45.1%). To verify the results obtained from our files at the cardiogenetics department we sent a questionnaire to 52 index patients (response 50%). This showed that 23/26 (88%) index patients had distributed the letters to their relatives and that for 19/23 index patients one or more relatives had been screened. This is comparable with our files, which showed that 57% of relatives of index patients with a potentially inherited cardiac disease underwent screening, particularly in the ARR group. The actual response was underestimated because some relatives were investigated elsewhere or may still decide to be screened in the future. We conclude that distributing family letters is an effective way to inform and encourage relatives to undergo screening for high-risk inherited cardiac disease.

  2. Skin signs of systemic disease. When the problem is more than skin-deep.

    PubMed

    Holmes, C E; Massa, M C

    1994-12-01

    The cutaneous manifestations of systemic diseases are diverse. In some cases, they are the first signs of an underlying disorder, such as Cowden's disease, dermatomyositis, and Lyme disease. Sister Mary Joseph's nodule (metastatic involvement of the umbilicus) is an ominous sign of internal malignant disease. Drug-induced skin necrosis may result from therapy with coumarin (Coumadin, Panwarfin, Sofarin) or heparin.

  3. Systematic review and meta-analysis to estimate the birth prevalence of five inherited metabolic diseases.

    PubMed

    Moorthie, Sowmiya; Cameron, Louise; Sagoo, Gurdeep S; Bonham, Jim R; Burton, Hilary

    2014-11-01

    Many newborn screening programmes now use tandem mass spectrometry in order to screen for a variety of diseases. However, countries have embraced this technology with a differing pace of change and for different conditions. This has been facilitated by the ability of this diagnostic method to limit analysis to specific metabolites of interest, enabling targeted screening for particular conditions. MS/MS was introduced in 2009 in England to implement newborn bloodspot screening for medium chain acyl-CoA dehydrogenase deficiency (MCADD) raising the possibility of screening for other inherited metabolic disorders. Recently, a pilot screening programme was conducted in order to evaluate the health and economic consequences of screening for five additional inherited metabolic disorders in England. As part of this study we conducted a systematic review and meta-analysis to estimate the birth prevalence of these conditions: maple syrup urine disease, homocystinuria (pyridoxine unresponsive), glutaric aciduria type I, isovaleric acidaemia and long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency including trifunctional protein deficiency. We identified a total of 99 studies that were able to provide information on the prevalence of one or more of the disorders. The vast majority of studies were of screening programmes with some reporting on clinically detected cases. PMID:25022222

  4. 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

  5. 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

  6. Inherited DNA mutations contributing to thrombotic complications in patients with sickle cell disease.

    PubMed

    Zimmerman, S A; Ware, R E

    1998-12-01

    Thrombosis may play an important role in the pathophysiology of certain complications of sickle cell disease (SCD), including stroke and avascular necrosis (AVN). Currently there is no laboratory or clinical parameter that can identify patients who are at highest risk of developing these thrombotic complications. We hypothesized that some patients with SCD have an inherited hypercoagulable state that results in an increased risk of developing stroke or AVN. We examined the role of two common inherited thrombophilic mutations that, in other populations, have been associated with arterial and venous thrombosis and are amenable to screening with DNA restriction enzyme analysis. The C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene and the C1565T mutation in the platelet glycoprotein IIIa (GPIIIa) gene were evaluated. We analyzed genomic DNA from 86 children and adults with SCD, including 16 patients with a history of a clinical stroke and 14 patients with AVN, for the presence of these mutations. The C677T MTHFR mutation was found in 19% of patients with stroke, 14% of patients with AVN, and 14% of patients with neither complication (P = NS). The C1565T GPIIIa mutation was found in 25% of patients with stroke, 14% of patients with AVN, and 18% of patients with neither complication (P = NS). Although each of these mutations is relatively common in patients with SCD, neither is independently associated with an increased risk of developing stroke or AVN. PMID:9840906

  7. Inheritance of resistance to pyrethroids in Triatoma infestans, the main Chagas disease vector in South America.

    PubMed

    Cardozo, R M; Panzera, F; Gentile, A G; Segura, M A; Pérez, R; Díaz, R A; Basombrío, M A

    2010-12-01

    An outbreak of pyrethroid resistance was recently detected in Triatoma infestans from northern Argentina. To analyze the inheritance of the resistant phenotype, we carried out experimental crosses between resistant (R) and susceptible (S) strains captured in Argentina during 2005. The R strain was collected from sprayed houses in the north of the province of Salta while the S strain was collected in the province of Chaco. Both strains were bred in the laboratory for reciprocal crosses (F1), intercrosses (F2) and backcrosses (BC). The descendents were tested by a standard insecticide resistance bioassay. Resistance ratios were 1 for S strain, 103.36 for R strain and 18.34 for F1. The regression lines of F1 generations (R×S and S×R) showed no significant differences and were closer to that of the R parents, indicating that inheritance of deltamethrin resistance in T. infestans is autosomal and incompletely dominant (D=0.20). Chi-square analysis from responses of intercross and backcross progenies rejected the hypothesis of a single gene being responsible for resistance. The minimum number of independent segregation genes was three, as calculated with Lande's method. The genetic basis here described for the resistant phenotype indicate that, under pyrethroid selective pressure, the resistant genotypes could be easily spread to susceptible insects from resistant individuals, posing a major threat to vectorial control of Chagas disease.

  8. 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.

  9. 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.

  10. Wnt Signaling in Skin Development, Homeostasis, and Disease

    PubMed Central

    Lim, Xinhong; Nusse, Roel

    2013-01-01

    The skin and its appendages constitute the largest organ of the body. Its stratified epithelia offer protection from environmental stresses such as dehydration, irradiation, mechanical trauma, and pathogenic infection, whereas its appendages, like hair and sebaceous glands, help regulate body temperature as well as influence animal interaction and social behavior through camouflage and sexual signaling. To respond to and function effectively in a dynamic external environment, the skin and its appendages possess a remarkable ability to regenerate in a carefully controlled fashion. When this finely tuned homeostatic process is disrupted, skin diseases such as cancers may result. At present, the molecular signals that orchestrate cell proliferation, differentiation, and patterning in the skin remain incompletely understood. It is increasingly apparent that many morphogenetic pathways with key roles in development are also important in regulating skin biology. Of these, Wnt signaling has emerged as the dominant pathway controlling the patterning of skin and influencing the decisions of embryonic and adult stem cells to adopt the various cell lineages of the skin and its appendages, as well as subsequently controlling the function of differentiated skin cells. Here we will review established concepts and present recent advances in our understanding of the diverse roles that Wnt signaling plays in skin development, homeostasis, and disease. PMID:23209129

  11. 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

  12. Three-Parent IVF: Gene Replacement for the Prevention of Inherited Mitochondrial Diseases

    PubMed Central

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

    2014-01-01

    Mitochondrial dysfunction has been recognized as a significant cause of a number of serious multi-organ diseases. Tissues with a high metabolic demand such as brain, heart, muscle, CNS are often affected. Mitochondrial disease can be due to mutations in mitochondrial DNA (mtDNA) 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. Since mtDNA 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. PMID:24382342

  13. 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

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

    PubMed

    Marcinkiewicz, Małgorzata; Majewski, Sławomir

    2016-02-01

    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

  15. 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

  16. Thermolabile methylenetetrahydrofolate reductase: an inherited risk factor for coronary artery disease.

    PubMed Central

    Kang, S S; Wong, P W; Susmano, A; Sora, J; Norusis, M; Ruggie, N

    1991-01-01

    Severe methylenetetrahydrofolate reductase (MTHFR) deficiency with less than 2% of normal enzyme activity is characterized by neurological abnormalities, atherosclerotic changes, and thromboembolism. We have discovered a "new" variant of MTHFR deficiency which is characterized by the absence of neurological abnormalities, an enzyme activity of about 50% of the normal value, and distinctive thermolability under specific conditions of heat inactivation. In this study, lymphocyte MTHFR specific activities in the thermolabile variant and control groups were 5.58 +/- 0.91 and 10.33 +/- 2.89 nmol formaldehyde formed/mg protein/h, respectively. The difference was significant (P less than .01). However, there was overlap among the individual values from the two groups. On the other hand, residual MTHFR activity after heat inactivation was 11.2 +/- 1.43% in the thermolabile variant and 36.3 +/- 5.18% in the controls. There was no overlap. Enzyme studies in 10 subjects with thermolabile MTHFR and their family members support the hypothesis that thermolabile MTHFR is inherited as an autosomal recessive trait. To elucidate the association of thermolabile MTHFR with the development of coronary artery disease, we determined the thermostability of lymphocyte MTHFR in 212 patients with proven coronary artery disease and in 202 controls without clinical evidence of atherosclerotic vascular disease. Thermolabile MTHFR was found in 36 (17.0%) cardiac patients and 10 (5.0%) controls. The difference in incidence between the two groups was statistically significant (P less than .01). The average age at onset of clinical coronary artery disease in 36 patients with thermolabile MTHFR was 57.3 +/- 7.6 years (35-72 years). The mean total plasma homocysteine concentration in patients with thermolabile MTHFR was 13.19 +/- 5.32 nmol/ml and was significantly different from the normal mean of 8.50 +/- 2.80 nmol/ml (P less than .05). There was no association between thermolabile MTHFR and other

  17. Contamination Appraisals, Pollution Beliefs, and the Role of Cultural Inheritance in Shaping Disease Avoidance Behavior.

    PubMed

    Feder, Yitzhaq

    2016-08-01

    Despite the upsurge of research on disgust, the implications of this research for the investigation of cultural pollution beliefs has yet to be adequately explored. In particular, the sensitivity of both disgust and pollution to a common set of elicitors (e.g., bodily emissions, disease, and death) suggests a common psychological basis, though several obstacles have prevented an integrative account, including methodological differences between the relevant disciplines. Employing a conciliatory framework that embraces both naturalistic (evolutionary) and humanistic levels of explanation, this article examines the dynamic reciprocal process by which contamination/contagion appraisals in individuals serve to shape-and are in turn shaped by-culture-specific pollution beliefs. This complex interrelationship is illustrated by examining ancient Near Eastern and modern ethnographic documentation of pollution beliefs, highlighting the underappreciated function of these pollution beliefs as folk theories for the spread of infectious disease. By evaluating how pollution beliefs (as also modern germ theory) shape contamination appraisals in individuals, it will be argued that cultural inheritance has played a much larger role in guiding disease avoidance behavior than has been previously recognized.

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

    PubMed

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

    2011-12-01

    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.

  19. A novel mutation (G114V) in the prion protein gene in a family with inherited prion disease.

    PubMed

    Rodriguez, M-M; Peoc'h, K; Haïk, S; Bouchet, C; Vernengo, L; Mañana, G; Salamano, R; Carrasco, L; Lenne, M; Beaudry, P; Launay, J-M; Laplanche, J-L

    2005-04-26

    Inherited prion diseases are characterized by mutations in the PRNP gene encoding the prion protein (PrP). We report a novel missense mutation in the PRNP gene (resulting in a G114V mutation in PrP) in members of a Uruguayan family with clinical and histopathologic features of prion disease. Affected individuals were characterized by an early age at onset, initial neuropsychiatric symptoms, late dementia with prominent pyramidal and extrapyramidal symptoms, and long disease duration.

  20. The skin as a target organ in multisystemic diseases II.

    PubMed

    Tsankov, Nikolai; Kazandjieva, Jana; Darlenski, Razvigor

    2015-01-01

    Progress in medical science has given a new reading to the claim that the skin could be a mirror of the pathological changes found in the internal organs. The concept that we previously promoted is furthered in this issue; namely that the greatest part of skin diseases are systemic ones. In this issue we focus on another group of diseases with systemic involvement and skin manifestations. We review such inflammatory conditions as lichen planus, autoinflammatory syndromes, and pyoderma gangrenosum focusing on their systemic involvement. We have not missed such classic examples of systemic involvement as scleroderma. In this issue we have included two infectious diseases with multi-organ involvement: Lyme disease and Herpes simplex. In contrast to our previous work, we have also addressed neoplastic diseases - namely mycosis fungoides. PMID:26321395

  1. Nucleic acid delivery into skin for the treatment of skin disease: Proofs-of-concept, potential impact, and remaining challenges.

    PubMed

    Zakrewsky, Michael; Kumar, Sunny; Mitragotri, Samir

    2015-12-10

    Nucleic acids (NAs) hold significant potential for the treatment of several diseases. Topical delivery of NAs for the treatment of skin diseases is especially advantageous since it bypasses the challenges associated with systemic administration which suffers from enzymatic degradation, systemic toxicity and lack of targeting to skin. However, the skin's protective barrier function limits the delivery of NAs into skin after topical application. Here, we highlight strategies for enhancing delivery of NAs into skin, and provide evidence that translation of topical NA therapies could have a transformative impact on the treatment of skin diseases.

  2. 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. PMID:24166134

  3. 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.

  4. Initial experience in the treatment of inherited mitochondrial disease with EPI-743.

    PubMed

    Enns, Gregory M; Kinsman, Stephen L; Perlman, Susan L; Spicer, Kenneth M; Abdenur, Jose E; Cohen, Bruce H; Amagata, Akiko; Barnes, Adam; Kheifets, Viktoria; Shrader, William D; Thoolen, Martin; Blankenberg, Francis; Miller, Guy

    2012-01-01

    Inherited mitochondrial respiratory chain disorders are progressive, life-threatening conditions for which there are limited supportive treatment options and no approved drugs. Because of this unmet medical need, as well as the implication of mitochondrial dysfunction as a contributor to more common age-related and neurodegenerative disorders, mitochondrial diseases represent an important therapeutic target. Thirteen children and one adult with genetically-confirmed mitochondrial disease (polymerase γ deficiency, n=4; Leigh syndrome, n=4; MELAS, n=3; mtDNA deletion syndrome, n=2; Friedreich ataxia, n=1) at risk for progressing to end-of-life care within 90 days were treated with EPI-743, a novel para-benzoquinone therapeutic, in a subject controlled, open-label study. Serial measures of safety and efficacy were obtained that included biochemical, neurological, quality-of-life, and brain redox assessments using technetium-99m-hexamethylpropyleneamine oxime (HMPAO) single photon emission computed tomography (SPECT) radionuclide imaging. Twelve patients treated with EPI-743 have survived; one polymerase γ deficiency patient died after developing pneumonia and one patient with Surf-1 deficiency died after completion of the protocol. Of the 12 survivors, 11 demonstrated clinical improvement, with 3 showing partial relapse, and 10 of the survivors also had an improvement in quality-of-life scores at the end of the 13-week emergency treatment protocol. HMPAO SPECT scans correlated with clinical response; increased regional and whole brain HMPAO uptake was noted in the clinical responders and the one subject who did not respond clinically had decreased regional and whole brain HMPAO uptake. EPI-743 has modified disease progression in >90% of patients in this open-label study as assessed by clinical, quality-of-life, and non-invasive brain imaging parameters. Data obtained herein suggest that EPI-743 may represent a new drug for the treatment of inherited mitochondrial

  5. Complement system in dermatological diseases - fire under the skin.

    PubMed

    Panelius, Jaana; Meri, Seppo

    2015-01-01

    The complement system plays a key role in several dermatological diseases. Overactivation, deficiency, or abnormality of the control proteins are often related to a skin disease. Autoimmune mechanisms with autoantibodies and a cytotoxic effect of the complement membrane attack complex on epidermal or vascular cells can cause direct tissue damage and inflammation, e.g., in systemic lupus erythematosus (SLE), phospholipid antibody syndrome, and bullous skin diseases like pemphigoid. By evading complement attack, some microbes like Borrelia spirochetes and staphylococci can persist in the skin and cause prolonged symptoms. In this review, we present the most important skin diseases connected to abnormalities in the function of the complement system. Drugs having an effect on the complement system are also briefly described. On one hand, drugs with free hydroxyl on amino groups (e.g., hydralazine, procainamide) could interact with C4A, C4B, or C3 and cause an SLE-like disease. On the other hand, progress in studies on complement has led to novel anti-complement drugs (recombinant C1-inhibitor and anti-C5 antibody, eculizumab) that could alleviate symptoms in diseases associated with excessive complement activation. The main theme of the manuscript is to show how relevant the complement system is as an immune effector system in contributing to tissue injury and inflammation in a broad range of skin disorders.

  6. Complement System in Dermatological Diseases – Fire Under the Skin

    PubMed Central

    Panelius, Jaana; Meri, Seppo

    2015-01-01

    The complement system plays a key role in several dermatological diseases. Overactivation, deficiency, or abnormality of the control proteins are often related to a skin disease. Autoimmune mechanisms with autoantibodies and a cytotoxic effect of the complement membrane attack complex on epidermal or vascular cells can cause direct tissue damage and inflammation, e.g., in systemic lupus erythematosus (SLE), phospholipid antibody syndrome, and bullous skin diseases like pemphigoid. By evading complement attack, some microbes like Borrelia spirochetes and staphylococci can persist in the skin and cause prolonged symptoms. In this review, we present the most important skin diseases connected to abnormalities in the function of the complement system. Drugs having an effect on the complement system are also briefly described. On one hand, drugs with free hydroxyl on amino groups (e.g., hydralazine, procainamide) could interact with C4A, C4B, or C3 and cause an SLE-like disease. On the other hand, progress in studies on complement has led to novel anti-complement drugs (recombinant C1-inhibitor and anti-C5 antibody, eculizumab) that could alleviate symptoms in diseases associated with excessive complement activation. The main theme of the manuscript is to show how relevant the complement system is as an immune effector system in contributing to tissue injury and inflammation in a broad range of skin disorders. PMID:25688346

  7. 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

  8. 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

  9. 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

  10. 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

  11. Stability and Cu(II) Binding of Prion Protein Variants Related to Inherited Human Prion Diseases

    PubMed Central

    Cereghetti, Grazia M.; Schweiger, Arthur; Glockshuber, Rudi; Van Doorslaer, Sabine

    2003-01-01

    All inherited forms of human prion diseases are linked with mutations in the prion protein (PrP) gene. Here we have investigated the stability and Cu(II) binding properties of three recombinant variants of murine full-length PrP(23–231)-containing destabilizing point mutations that are associated with human Gerstmann-Sträussler-Scheinker disease (F198S), Creutzfeld-Jakob disease (E200K), and fatal familial insomnia (D178N) by electron paramagnetic resonance and circular dichroism spectroscopy. Furthermore, we analyzed the variants H140S, H177S, and H187S of the isolated C-terminal domain of murine PrP, mPrP(121–231), to test a role of the histidine residues in Cu(II) binding. The F198S and E200K variants of PrP(23–231) differed in Cu(II) binding from the wild-type mPrP(23–231). However, circular dichroism spectroscopy indicated that the variants and the wild type did not undergo conformational changes in the presence of Cu(II). The D178N variant showed a high tendency to aggregate at pH 7.4 both with and without Cu(II). At lower pH values, it showed the same Cu(II) binding behavior as the wild type. The analysis allowed for a better location of the Cu(II) binding sites in the C-terminal part of the protein. Our present data indicate that hereditary forms of prion diseases cannot be rationalized on the basis of altered Cu(II) binding or mutation-induced protein destabilization alone. PMID:12609901

  12. Complex inheritance of ABCA4 disease: four mutations in a family with multiple macular phenotypes.

    PubMed

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

    2016-01-01

    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 and copy number variants 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.

  13. [Malassezia and its presumed association with skin diseases in dogs].

    PubMed

    Nagata, Masahiko

    2013-01-01

    Malassezia pachydermatis is the major species in Malassezia isolated from dogs, and there is a presumably Malassezia-associated skin disease,"Malassezia dermatitis" in the dog. The skin lesion is characterized by relatively demarcated erythema with some scaling at the sebum-rich areas, in which lichenification and hyperpigmentation could be involved in the chronic stage. The clinical features suggest that it corresponds to seborrheic dermatitis in humans. Hence, it might be possible to identify essential pathogenesis of the disease by clarifying its differences in humans and animals as a shared disease. PMID:23470954

  14. 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

  15. Caspr1/Paranodin/Neurexin IV is most likely not a common disease-causing gene for inherited peripheral neuropathies.

    PubMed

    Venken, K; Meuleman, J; Irobi, J; Ceuterick, C; Martini, R; De Jonghe, P; Timmerman, V

    2001-08-01

    Contactin associated protein 1 (Caspr1/Paranodin/Neurexin IV) is an axonal transmembrane molecule mainly localised at the paranodal junction. Since molecular alterations in septate-like junctions at the paranodes might have important consequences for the function of the nerve fiber, we considered that Caspr1 could be involved in the pathogenesis of inherited peripheral neuropathies. In this study, we physically mapped the Caspr1 gene on chromosome 17q21.1 and determined its genomic structure. We performed a mutation analysis of the Caspr1 gene in a cohort of 64 unrelated patients afflicted with distinct inherited peripheral neuropathies. Since no disease causing mutations were found, we suggest that Caspr1 is probably not a common cause of inherited peripheral neuropathies. PMID:11496158

  16. 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.

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

    PubMed Central

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

    2016-01-01

    Purpose To compare the efficacy of whole genome sequencing (WGS) with targeted next-generation sequencing (NGS) in the diagnosis of inherited retinal disease (IRD). Design Case series. Participants A total of 562 patients diagnosed with IRD. Methods We performed a direct comparative analysis of current molecular diagnostics with WGS. We retrospectively reviewed the findings from a diagnostic NGS DNA test for 562 patients with IRD. A subset of 46 of 562 patients (encompassing potential clinical outcomes of diagnostic analysis) also underwent WGS, and we compared mutation detection rates and molecular diagnostic yields. In addition, we compared the sensitivity and specificity of the 2 techniques to identify known single nucleotide variants (SNVs) using 6 control samples with publically available genotype data. Main Outcome Measures Diagnostic yield of genomic testing. Results Across known disease-causing genes, targeted NGS and WGS achieved similar levels of sensitivity and specificity for SNV detection. However, WGS also identified 14 clinically relevant genetic variants through WGS that had not been identified by NGS diagnostic testing for the 46 individuals with IRD. These variants included large deletions and variants in noncoding regions of the genome. Identification of these variants confirmed a molecular diagnosis of IRD for 11 of the 33 individuals referred for WGS who had not obtained a molecular diagnosis through targeted NGS testing. Weighted estimates, accounting for population structure, suggest that WGS methods could result in an overall 29% (95% confidence interval, 15–45) uplift in diagnostic yield. Conclusions We show that WGS methods can detect disease-causing genetic variants missed by current NGS diagnostic methodologies for IRD and thereby demonstrate the clinical utility and additional value of WGS. PMID:26872967

  18. 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. PMID:27481041

  19. 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.

  20. "To perpetuate blindness!": attitudes of UK patients with inherited retinal disease towards genetic testing.

    PubMed

    Potrata, Barbara; McKibbin, Martin; Lim, Jennifer Nw; Hewison, Jenny

    2014-07-01

    Availability and accuracy of genetic testing in ophthalmology has increased yet the benefits are unclear especially for those conditions where cure or treatments are limited. To explore attitudes to and patients' understanding of possible advantages and disadvantages of genetic testing for inherited retinal disease, we undertook focus groups in three West Yorkshire towns in the UK. Most of our participants had retinitis pigmentosa and one of the focus groups consisted of participants from (British) Asian ethnic background. Here, we report only those attitudes which were common in all three focus groups. Some of the attitudes have already been reported in the literature. Novel findings include attitudes held towards informed choice and life planning, particularly among more severely affected participants. For example, participants appreciated that genetic testing increases informed choice and enables life planning, but these understandings tended to be in a specific sense: informed choice whether to have children and family planning in order to prevent illness recurrence. We conclude that even though these patients are not a homogeneous group, their attitudes tend to be underpinned by deep anxiety of passing their visual impairment onto their children. In this respect, they differ importantly from a small minority of the deaf who would prefer to have children with hearing loss, and from the more general population who do not believe that blindness is a "severe" enough disability to warrant avoiding having children. PMID:24366860

  1. 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.

  2. 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.

  3. Dolphin pox: a skin disease of cetaceans.

    PubMed Central

    Geraci, J R; Hicks, B D; St Aubin, D J

    1979-01-01

    Poxvirus has been identified morphologically from skin lesions in captive and free-ranging bottlenosed dolphins, Tursiops truncatus and a stranded Atlantic white-sided dolphin, Lagenorhynchus acutus. The lesions, commonly referred to as ring or pinhole lesions, appear as solitary or coalesced circular grey blemishes. Advanced ring lesions may take the form of black punctiform stippled patterns known as "tattoo". Histologically, the stratum externum is thickened, and there is ballooning degeneration and eosinophilic intractyoplasmic inclusions in the stratum intermedium. These includions contain virus particles which exhibit typical poxvirus morphology. Stress, environmental conditions and general health appear to play a major role in the clinical manifestation of dolphin pox. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. Fig. 8. Fig. 9. PMID:232852

  4. [Skin diseases in returning travelers: etiologies according to clinical presentation].

    PubMed

    Monsel, G; Caumes, E

    2010-05-12

    Dermatoses are one of the three most common causes of health problem in returning travelers. These dermatoses include infections, environmental diseases (sunburns, arthropod-related reactions) and superficial injuries. Skin infections are the most common cause of consultation after return. They include bacterial infections of cosmopolitan origin (pyoderma, abcess, cellulites) and tropical diseases (hookworm-related cutaneous cutaneous larva migrans, localized cutaneous leishmaniasis, tungiasis, myiasis...). Travelers abroad must be appropriately vaccinated against tetanus and specifically instructed to avoid arthropods bites and sun overexposure. Travel first aid kits should include antibiotics effective against bacterial skin infection, oral antihistamines and corticosteroid ointments. PMID:20545260

  5. Integrin α3 Mutations with Kidney, Lung, and Skin Disease

    PubMed Central

    Has, Cristina; Spartà, Giuseppina; Kiritsi, Dimitra; Weibel, Lisa; Moeller, Alexander; Vega-Warner, Virginia; Waters, Aoife; He, Yinghong; Anikster, Yair; Esser, Philipp; Straub, Beate K.; Hausser, Ingrid; Bockenhauer, Detlef; Dekel, Benjamin; Hildebrandt, Friedhelm; Bruckner-Tuderman, Leena; Laube, Guido F.

    2012-01-01

    SUMMARY Integrin α3 is a transmembrane integrin receptor subunit that mediates signals between the cells and their microenvironment. We identified three patients with homozygous mutations in the integrin α3 gene that were associated with disrupted basement-membrane structures and compromised barrier functions in kidney, lung, and skin. The patients had a multiorgan disorder that included congenital nephrotic syndrome, interstitial lung disease, and epidermolysis bullosa. The renal and respiratory features predominated, and the lung involvement accounted for the lethal course of the disease. Although skin fragility was mild, it provided clues to the diagnosis. PMID:22512483

  6. 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

    ... Skin Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act... Musculoskeletal and Skin Diseases Special Emphasis Panel; Arthritis and Musculoskeletal and Skin Diseases Clinical... Officer, Scientific Review Branch, National Institute of Arthritis,, Musculoskeletal and Skin...

  7. Exposure, skin protection and occupational skin diseases in the glass-fibre-reinforced plastics industry.

    PubMed

    Tarvainen, K; Jolanki, R; Forsman-Grönholm, L; Estlander, T; Pfäffli, P; Juntunen, J; Kanerva, L

    1993-09-01

    A total of 100 workers, 86 from the glass-fibre-reinforced plastics (GRP) industry, 11 from polystyrene production and 3 from polyester resin coating manufacture, were examined for occupational skin hazards and for evaluation of skin protection. The workers had been exposed to many chemicals. Those working in the GRP industry had also been exposed to glass fibre and to dust produced by finishing work. 94% used protective gloves. 22 workers, all employed in the GRP industry, had contracted occupational skin disorders. 6 had allergic and 12 irritant contact dermatitis. 4 workers had an accidental injury caused by a peroxide catalyst, fire, hot air and constant mechanical friction. Allergic dermatoses were due to natural rubber (latex) (4 cases) in protective gloves, phenol-formaldehyde resin (1 case) and cobalt naphthenate (1 case). Irritant hand dermatoses (5 cases) were caused by the combined hazardous effect of unsaturated polyester or vinyl ester resins, organic solvents, glass fibre and dust from finishing work on the skin. Other cases of irritant dermatoses (7 cases) were due to the dust, promoted by mechanical friction of clothes. Skin disorders in the GRP industry were common (26%) but the symptoms were mild and only 3 patients had been on sick leave because of occupational skin disease. PMID:8222622

  8. 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

  9. 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.

  10. 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.

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

    ClinicalTrials.gov

    2016-07-27

    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

  12. 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.

  13. Tungiasis - A Janus-faced parasitic skin disease.

    PubMed

    Feldmeier, Hermann; Keysers, Anne

    2013-01-01

    Tungiasis is a parasitic skin disease caused by the penetration of female sand fleas (Tunga penetrans). It is acquired when people walk barefoot or rest on soil, where sand fleas have completed the off-host cycle. Tungiasis is a classic poverty-associated disease which belongs to the family of neglected tropical diseases (NTD). It has a Janus-face: while in travellers tungiasis usually is a benign self-limiting skin disease, inhabitants of endemic areas suffer from heavy infestations and severe, frequently debilitating and incapacitating morbidity. We describe the epidemiological and clinical characteristics of travel-associated tungiasis and compare these features to the situation in resource-poor communities in South America and sub-Saharan Africa. PMID:24211240

  14. 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. PMID:17986303

  15. 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…

  16. Simulation of Skin Diseases for Teaching Dermatological Diagnosis.

    ERIC Educational Resources Information Center

    Short, John M.; Hess, Alan C.

    1980-01-01

    A technique for simulating the papulosquamous skin diseases, using a computer, has been developed and tested with medical students and dermatologists to determine whether this type of simulation is suitable for training students in dermatological diagnosis. The results indicate that it appears to be feasible for training students in differential…

  17. Skin Diseases: Questions for Your Health Care Provider

    MedlinePlus

    ... Find Out More medlineplus.gov National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) call 877-226-4267 or visit www.niams.nih.gov National Cancer Institute call 800-422-6237 or visit www.cancer.gov . Psoriasis How do I know I have psoriasis? What ...

  18. 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.

  19. Television depictions about dermatology and skin diseases in Seinfeld.

    PubMed

    Vickers, Jennifer L; Uchida, Tatsuo; Wagner, Richard F

    2010-01-01

    The iconic television situation comedy Seinfeld frequently referenced dermatologists and topics involving the integument, using satire for comedic effect. However, selecting satire to portray an already misunderstood and unknown subject matter may perpetuate incorrect public beliefs and stereotypes about those with skin diseases and diminish cultural sensitivity towards people who have dermatologic conditions and their caregivers.

  20. Epidermal RAF prevents allergic skin disease

    PubMed Central

    Raguz, Josipa; Jeric, Ines; Niault, Theodora; Nowacka, Joanna Daniela; Kuzet, Sanya Eduarda; Rupp, Christian; Fischer, Irmgard; Biggi, Silvia; Borsello, Tiziana; Baccarini, Manuela

    2016-01-01

    The RAS pathway is central to epidermal homeostasis, and its activation in tumors or in Rasopathies correlates with hyperproliferation. Downstream of RAS, RAF kinases are actionable targets regulating keratinocyte turnover; however, chemical RAF inhibitors paradoxically activate the pathway, promoting epidermal proliferation. We generated mice with compound epidermis-restricted BRAF/RAF1 ablation. In these animals, transient barrier defects and production of chemokines and Th2-type cytokines by keratinocytes cause a disease akin to human atopic dermatitis, characterized by IgE responses and local and systemic inflammation. Mechanistically, BRAF and RAF1 operate independently to balance MAPK signaling: BRAF promotes ERK activation, while RAF1 dims stress kinase activation. In vivo, JNK inhibition prevents disease onset, while MEK/ERK inhibition in mice lacking epidermal RAF1 phenocopies it. These results support a primary role of keratinocytes in the pathogenesis of atopic dermatitis, and the animals lacking BRAF and RAF1 in the epidermis represent a useful model for this disease. DOI: http://dx.doi.org/10.7554/eLife.14012.001 PMID:27431613

  1. 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.

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

    PubMed

    Fleischer, Alan B

    2016-01-01

    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. PMID:27617717

  3. 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.

  4. 77 FR 63844 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-17

    ... Skin Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act... Musculoskeletal and Skin Diseases Special Emphasis Panel; NIAMS Small Grants in Musculoskeletal Diseases (R03... Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, 6701...

  5. 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...

  6. Immune sensing of nucleic acids in inflammatory skin diseases.

    PubMed

    Demaria, Olivier; Di Domizio, Jeremy; Gilliet, Michel

    2014-09-01

    Endosomal and cytosolic nucleic acid receptors are important immune sensors required for the detection of infecting or replicating viruses. The intracellular location of these receptors allows viral recognition and, at the same time, avoids unnecessary immune activation to self-nucleic acids that are continuously released by dying host cells. Recent evidence, however, indicates that endogenous factors such as anti-microbial peptides have the ability to break this protective mechanism. Here, we discuss these factors and illustrate how they drive inflammatory responses by promoting immune recognition of self-nucleic acids in skin wounds and inflammatory skin diseases such as psoriasis and lupus.

  7. 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

  8. Inherited thrombophilia: an update.

    PubMed

    Franchini, Massimo; Veneri, Dino

    2005-01-01

    Inherited thrombophilia can be defined as a genetically determined predisposition to develop thromboembolic complications. Inherited prothrombotic risk factors include antithrombin deficiency, protein C and protein S deficiencies, activated protein C resistance due to factor V Leiden mutation, inherited hyperhomocysteinemia, prothrombin G20210A variant, dys- and hyperfibrinogenemia and elevated factor VIII levels. In this review we briefly analyze, from an epidemiologic, laboratory and clinical point of view, the main inherited prothrombotic risk factors. Finally, we discuss the synergism between genetic and acquired prothrombotic risk factors in some conditions such as pregnancy and cardiovascular diseases.

  9. 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.

  10. 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…

  11. 77 FR 9671 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-17

    ... 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...

  12. 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...

  13. 77 FR 67824 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Amended Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-14

    ... 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, November...

  14. 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.

  15. 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. PMID:26210237

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. Occupational Skin Diseases in the San Francisco Bay Area

    PubMed Central

    Gellin, Gerald A.; Wolf, C. Richard; Milby, Thomas H.

    1970-01-01

    From answers by one-third of the practicing dermatologists in the San Francisco Bay Area to a questionnaire on occupational skin diseases, contact dermatitis due to irritants and sensitizers was found to rank first. Poison oak, which is the leading reported cause on “Doctor's First Report of Work Injury” received by the California Department of Industrial Relations, was sixth on the list of the survey, trailing solvents, cleansing agents, petroleum products and epoxy resins. A history of atopic dermatitis was often noted in current cases of occupational diseases of the skin. Avoidance of exposure or limiting the contact with pathogenic substances—through engineering changes, observation of working conditions by physicians, education of workers—appeared to be the best preventive measures. PMID:4255687

  1. 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....

  2. 77 FR 4051 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-26

    ... Skin Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the Federal Advisory Committee... Musculoskeletal and Skin Diseases, Special Emphasis Panel, Osteoarthritis Initiative. Date: February 14, 2012... Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, 6701 Democracy Boulevard,...

  3. 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,...

  4. 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

    ... 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 Clinical Studies Review. Date: June 10, 2010... Skin Diseases, National Institutes of Health, 6701 Democracy Blvd., Suite 800, Bethesda, MD 20817,...

  5. 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,...

  6. 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,...

  7. 77 FR 47653 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-09

    ... 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...

  8. 77 FR 18253 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-27

    ... Skin Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the Federal Advisory Committee... Musculoskeletal and Skin Diseases Special Emphasis Panel; Clinical Trial Review. Date: April 9, 2012. Time: 2 p.m..., Musculoskeletal and Skin Diseases, National Institutes of Health, 6701 Democracy Boulevard, Suite 800,...

  9. 76 FR 6806 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-08

    ... Skin Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the Federal Advisory Committee... Musculoskeletal and Skin Diseases Special Emphasis Panel; Ancillary Studies Grant Review. Date: February 22, 2011... Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, 6701...

  10. 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...

  11. 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

    ... 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 Grants Research Review. Date: October 13, 2011... of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, 6701 Democracy...

  12. 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...

  13. 76 FR 24896 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-03

    ... 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 14,...

  14. 78 FR 25753 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-02

    ... 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 4,...

  15. 76 FR 14035 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-15

    ... 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 and Pathways to..., Scientific Review Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases,...

  16. 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...

  17. 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

    ... 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...

  18. 78 FR 21617 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-11

    ... Skin Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act... Musculoskeletal and Skin Diseases Special Emphasis Panel, NIAMS Small Grant Program for New Investigators (R03..., National Institute of Arthritis, Musculoskeletal and Skin Diseases, NIH, 6701 Democracy Boulevard,...

  19. 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...

  20. 75 FR 54897 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-09

    ... Skin Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the Federal Advisory Committee... Musculoskeletal and Skin Diseases Special Emphasis Panel; Muscle Physiology Review. Date: September 15, 2010. Time... . Name of Committee: National Institute of Arthritis and Musculoskeletal and Skin Diseases...

  1. 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...

  2. 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,...

  3. 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

    ... 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...

  4. 78 FR 18357 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-26

    ... Skin Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act... Musculoskeletal and Skin Diseases Special Emphasis Panel; NIAMS Loan Repayment Program Review. Date: April 15... Arthritis, Musculoskeletal and Skin Diseases, NIH, 6701 Democracy Boulevard, Suite 800, Bethesda, MD...

  5. 78 FR 36789 - National Institute of Arthritis And Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-19

    ... Skin Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act... Musculoskeletal and Skin Diseases Special Emphasis Panel; NIAMS Small Grant Program for New Investigators (R03... Review Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, NIH, 6701...

  6. 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...

  7. 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

    ... 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...

  8. 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

    ... 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...

  9. 78 FR 47327 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-05

    ... 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...

  10. 75 FR 28260 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-20

    ... 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 15,...

  11. 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

    ... 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...

  12. 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...

  13. 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...

  14. 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,...

  15. 77 FR 64814 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-23

    ... Skin Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act... Musculoskeletal and Skin Diseases Special Emphasis Panel; NIAMS clinical trial and planning grant applications in rheumatoid arthritis and skin diseases. Date: November 16, 2012. Time: 9:00 a.m. to 12:00 p.m. Agenda:...

  16. 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

    ... 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..., National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health,...

  17. 75 FR 6046 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-05

    ... Skin Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the Federal Advisory Committee... Musculoskeletal and Skin Diseases Special Emphasis Panel, Ancillary Clinical Studies. Date: February 16, 2010... of Committee: National Institute of Arthritis and Musculoskeletal and Skin Diseases Special...

  18. 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....

  19. 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

    ... 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...

  20. 78 FR 13364 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-27

    ... Skin Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the Federal Advisory Committee... Musculoskeletal and Skin Diseases Special Emphasis Panel; NIAMS BIRT grant review. Date: March 19-20, 2013. Time..., Musculoskeletal and Skin Diseases, National Institutes of Health, 6701 Democracy Plaza, Suite 800, Bethesda,...

  1. 77 FR 75181 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-19

    ... 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: February 5,...

  2. 77 FR 16246 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

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    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,...

  3. 75 FR 48979 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-12

    ... 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...

  4. 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

    ... Skin Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act... Musculoskeletal and Skin Diseases Special Emphasis Panel. Centers of Research Translation Grant Review. Date... Assistance Program Nos. 93.846, Arthritis, Musculoskeletal and Skin Diseases Research, National Institutes...

  5. 78 FR 20118 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-03

    ... 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,...

  6. 76 FR 24892 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-03

    ... 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 Trial Pilot Grant Review. Date: May 12, 2011..., Musculoskeletal and Skin Diseases, National Institutes of Health, 6701 Democracy Boulevard, Suite 800,...

  7. 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

    ... 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...

  8. 78 FR 32261 - National Institute of Arthritis And Musculoskeletal and Skin Diseases; Notice of Closed Meeting

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    2013-05-29

    ... 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...

  9. 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:...

  10. 76 FR 1187 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-07

    ... 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: February 1,...

  11. 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...

  12. 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...

  13. 78 FR 9933 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-12

    ... 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... Democracy Boulevard, Suite 800, National Institute of Arthritis, Musculoskeletal and Skin Diseases,...

  14. 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,...

  15. 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,...

  16. 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

    ... 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... Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, 6701 Democracy Blvd.,...

  17. 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

    ... 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 Applications. Date: July 25, 2012. Time..., Musculoskeletal and Skin Diseases, National Institutes of Health, 6701 Democracy Blvd., Suite 800, MSC...

  18. 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,...

  19. 77 FR 35416 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-13

    ... Skin Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act...: National Institute of Arthritis and Musculoskeletal and Skin Diseases, Special Emphasis Panel; Program..., Musculoskeletal and Skin Diseases, National Institutes of Health, 6701 Democracy Boulevard, Suite 800,...

  20. 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...

  1. 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,...

  2. 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...

  3. 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

    ... 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...

  4. 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,...

  5. 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.

  6. 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.

  7. 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

  8. Clinicopathological Study of Non-Infectious Erythaematous Papulosquamous Skin Diseases

    PubMed Central

    Pai, Muktha; Philipose, Thoppil Reba; Nayarmoole, Umaru

    2016-01-01

    Introduction Papulosquamous diseases are characterized by scaly papules and plaques with similar clinical picture which amounts to confusion and hence, a definitive histopathological diagnosis goes a long way in treatment of such diseases. Aim The aim of the study was to study the histomorphology of non-infectious, erythaematous, papulosquamous lesions of skin with clinicopathological correlation. Materials and Methods Skin biopsies from 150 clinically diagnosed/suspected non-infectious erythaematous, papulosquamous skin diseases were received in the Department of Pathology. The specimens obtained were subjected to formalin fixation and paraffin embedding, stained with haematoxylin and eosin and studied. The lesions were classified as psoriasis, lichen planus, lichen nitidus, lichen striatus, pityriasis rosea and pityriasis rubra pilaris and clinicopathological correlation was done. Results Papulosquamous lesions were common in the elderly. Males were commonly affected except in pityriasis rosea. Among the 150 cases studied, 72 cases (48%) were histopathologically confirmed to be papulosquamous lesions. Psoriasis was the most common lesion. Conclusion Key histopathological features and clinicopathological correlation gives a conclusive diagnosis. The importance of specific histomorphological diagnosis lies in distinguishing these lesions as the treatment and prognosis varies widely. PMID:27504295

  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. Inherited heart disease - what can we expect from the second decade of human iPS cell research?

    PubMed

    Bellin, Milena; Mummery, Christine L

    2016-08-01

    Induced pluripotent stem cells (iPSCs) were first generated 10 years ago. Their ability to differentiate into any somatic cell type of the body including cardiomyocytes has already made them a valuable resource for modelling cardiac disease and drug screening. Initially human iPSCs were used mostly to model known disease phenotypes; more recently, and despite a number of recognised shortcomings, they have proven valuable in providing fundamental insights into the mechanisms of inherited heart disease with unknown genetic cause using surprisingly small cohorts. In this review, we summarise the progress made with human iPSCs as cardiac disease models with special focus on the latest mechanistic insights and related challenges. Furthermore, we suggest emerging solutions that will likely move the field forward.

  11. Arsenic-related Bowen's disease, palmar keratosis, and skin cancer.

    PubMed

    Cöl, M; Cöl, C; Soran, A; Sayli, B S; Oztürk, S

    1999-08-01

    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.

  12. Three-Dimensional Tissue Models of Normal and Diseased Skin

    PubMed Central

    Carlson, Mark W.; Alt-Holland, Addy; Egles, Christophe; Garlick, Jonathan A.

    2010-01-01

    Over the last decade, the development of in vitro, human, three-dimensional (3D) tissue models, known as human skin equivalents (HSEs), has furthered understanding of epidermal cell biology and provided novel experimental systems. Signaling pathways that mediate the linkage between growth and differentiation function optimally when cells are spatially organized to display the architectural features seen in vivo, but are uncoupled and lost in two-dimensional culture systems. HSEs consist of a stratified squamous epithelium grown at an air-liquid interface on a collagen matrix populated with dermal fibroblasts. These 3D tissues demonstrate in vivo–like epithelial differentiation and morphology, and rates of cell division, similar to those found in human skin. This unit describes fabrication of HSEs, allowing the generation of human tissues that mimic the morphology, differentiation, and growth of human skin, as well as disease processes of cancer and wound re-epithelialization, providing powerful new tools for the study of diseases in humans. PMID:19085986

  13. 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. PMID:26831170

  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. Current understanding of genetics and genetic testing and information needs and preferences of adults with inherited retinal disease.

    PubMed

    McKibbin, Martin; Ahmed, Mushtaq; Allsop, Matthew J; Downey, Louise; Gale, Richard; Grant, Hilary Louise; Potrata, Barbara; Willis, Thomas A; Hewison, Jenny

    2014-09-01

    Advances in sequencing technology and the movement of genetic testing into all areas of medicine will increase opportunities for molecular confirmation of a clinical diagnosis. For health-care professionals without formal genetics training, there is a need to know what patients understand about genetics and genetic testing and their information needs and preferences for the disclosure of genetic testing results. These topics were explored during face-to-face interviews with 50 adults with inherited retinal disease, selected in order to provide a diversity of opinions. Participants had variable understanding of genetics and genetic testing, including basic concepts such as inheritance patterns and the risk to dependents, and many did not understand the term 'genetic counselling'. Most were keen for extra information on the risk to others, the process for genetic testing and how to share the information with other family members. Participants were divided as to whether genetic testing should be offered at the time of the initial diagnosis or later. Many would prefer the results to be given by face-to-face consultation, supplemented by further information in a format accessible to those with visual impairment. Health-care professionals and either leaflets or websites of trusted agencies were the preferred sources of information. Permission should be sought for disclosure of genetic information to other family members. The information needs of many patients with inherited retinal disease appear to be unmet. An understanding of their information needs and preferences is required to help health-care professionals provide optimal services that meet patient expectations. PMID:24398793

  16. 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...

  17. 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,...

  18. 76 FR 9031 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-16

    ... 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... Branch and the Laboratory of Skin Biology. Place: National Institutes of Health, Building 31, 31...

  19. 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...

  20. 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...

  1. Stressful life events and skin diseases: disentangling evidence from myth.

    PubMed

    Picardi, A; Abeni, D

    2001-01-01

    The possibility of a causal influence of emotional stress, especially of stressful life events, on the course of various skin diseases has long been postulated. Clinical wisdom and experience, as well as many anecdotal observations and uncontrolled case series, support this opinion. We reviewed the available evidence on the role of stressful life events in triggering or exacerbating skin diseases. The role of stressful events in vitiligo, lichen planus, acne, pemphigus and seborrhoeic dermatitis was either controversial or insufficiently explored. The role of stressful events in psoriasis, alopecia areata, atopic dermatitis and urticaria was apparently clearer. However, only a few studies met acceptable methodological standards for stress measurement. Also, few studies considered common potential confounding factors (e.g. age, duration of illness, familial factors), and no study controlled adequately for the influence of other crucial factors (e.g. discontinuation of treatment, seasonal effects). Adding that the large majority of studies were retrospective, it seems wise to conclude that only preliminary evidence has been published so far on the role of stressful life events in bringing on or worsening any dermatological disease. Further research is mandatory, either in the form of prospective studies or, more feasibly, of well-designed case-control studies with adequate statistical power. Future studies should also pay more attention to protective as well as vulnerability factors in stressful events. Further, it would be important to investigate other sources of psychological stress, such as chronic stress and everyday stress. Measuring stress appraisal, although difficult, would also be important.

  2. 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. PMID:22232373

  3. 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

  4. 'Perfect skin', the media and patients with skin disease: a qualitative study of patients with acne, psoriasis and atopic eczema.

    PubMed

    Magin, Parker; Adams, Jon; Heading, Gaynor; Pond, Dimity

    2011-01-01

    The relationship of skin disease with societal ideals of beauty, and the role of the media in this relationship, has not previously been researched. The overall objective of this study was to explore the psychological effects of skin disease. The theme of the ideal of perfect skin and the role of the media in generating this ideal arose via an inductive study methodology and was explored in the context of respondents' psychological morbidity. A qualitative study, 62 semi-structured interviews were conducted with respondents with acne, eczema or psoriasis recruited from both general practice and specialist dermatology practice in an Australian regional city. Interviews were audiotaped, transcribed and subjected to thematic analysis employing a process of constant comparison in which data collection and analysis were cumulative and concurrent. The themes of perfect skin, societal ideals and media influence emerged from this iterative process. Respondents identified a societal ideal of flawless skin, largely mediated by media portrayals of perfection. Failure to meet this ideal precipitated psychological morbidity in female, but not male, respondents. An appreciation of the pervasive pressures of society and media upon females with skin disease may inform management strategies, particularly psychological management strategies, in patients with skin disease. PMID:21645475

  5. 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.

  6. 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

  7. Secondary nephrogenic diabetes insipidus as a complication of inherited renal diseases

    PubMed Central

    Bockenhauer, D; van’t Hoff, W; Dattani, M.; Lehnhardt, A; Subtirelu, M; Hildebrandt, F; Bichet, DG

    2014-01-01

    Background/Aims Nephrogenic diabetes insipidus (NDI) is a serious condition with large water losses in the urine and risk of hypernatremic dehydration. Unrecognised, repeated episodes of hypernatremic dehydration can lead to permanent brain damage. Primary NDI is due to mutations in either AVPR2 or AQP2. NDI can also occur as a secondary complication, most commonly from obstructive uropathy or chronic lithium therapy. We observed NDI in patients with inherited tubulopathies and aimed to define the clinical and molecular phenotype. Methods We reviewed medical notes of four patients with clinical NDI and an underlying molecularly confirmed diagnosis of nephropathic cystinosis, Bartter syndrome, nephronophthisis and apparent mineralocorticoid excess, respectively. Results The patients all failed to concentrate their urine after DDAVP. None had an identifiable mutation in AVPR2 or AQP2, consistent with secondary NDI. Patients experienced repeated episodes of hypernatraemic dehydration and in two cases NDI was initially thought to be the primary diagnosis, delaying recognition of the underlying problem. Conclusion The recognition of this potential complication is important as it has direct implications for the clinical management. The occurrence of NDI in these conditions provides clues for the etiology of aquaporin deficiency. PMID:20733335

  8. 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

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

    PubMed Central

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

    2016-01-01

    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. PMID:26856745

  10. The Genetics of Canadian Type 3 von Willebrand Disease (VWD): Further Evidence for Co-dominant Inheritance of Mutant Alleles

    PubMed Central

    Bowman, M.; Tuttle, A.; Notley, C.; Brown, C.; Tinlin, S.; Deforest, M.; Leggo, J.; Blanchette, V.S.; Lillicrap, D.; James, P.

    2014-01-01

    Summary Background Type 3 von Willebrand disease (VWD) is the most severe form of the disease and is classically inherited in an autosomal recessive fashion. Objectives The aim of the current study was to investigate the molecular pathogenesis of a Canadian cohort of type 3 VWD patients. Patients/Methods 34 families comprised of 100 individuals were investigated. Phenotypic data, including bleeding scores (BS), von Willebrand factor (VWF) laboratory values, and anti-VWF inhibitor status were included as well as sequence analysis. Results We identified 31 different mutations (20 novel): 8 frameshift, 5 splice site, 9 nonsense, 1 gene conversion, 6 missense, and 2 partial gene deletion mutations. The majority of mutations identified were in the propeptide (42%); index cases (IC) with these mutations exhibited more severe bleeding (BS=22) than those with mutations elsewhere in VWF (BS=13). 62 of 68 (91%) mutant alleles were identified. Twenty-nine IC (85%) had a VWF null genotype identified; 17 homozygous, 12 compound heterozygous. In five IC (15%), two mutant VWF alleles were not identified to explain the type 3 VWD phenotype. In four ICs only one mutant VWF allele was identified and in one IC no mutant VWF alleles were identified. Conclusions We have investigated the molecular pathogenesis of a Canadian cohort of type 3 VWD patients. Obligate carriers are not phenotypically silent in the Canadian population; 48% have been diagnosed with type 1 VWD. In ~50% of families in this study the inheritance pattern for type 3 VWD is co-dominant and not recessive. PMID:23311757

  11. Occupational skin diseases: options for multidisciplinary networking in preventive medicine.

    PubMed

    John, Swen Malte

    2008-10-27

    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 dermatological

  12. 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

  13. 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

  14. Müller Glia Activation in Response to Inherited Retinal Degeneration Is Highly Varied and Disease-Specific

    PubMed Central

    Barber, Amanda C.; West, Emma L.; Smith, Alexander J.; Ali, Robin R.; Pearson, Rachael A.

    2015-01-01

    Despite different aetiologies, most inherited retinal disorders culminate in photoreceptor loss, which induces concomitant changes in the neural retina, one of the most striking being reactive gliosis by Müller cells. It is typically assumed that photoreceptor loss leads to an upregulation of glial fibrilliary acidic protein (Gfap) and other intermediate filament proteins, together with other gliosis-related changes, including loss of integrity of the outer limiting membrane (OLM) and deposition of proteoglycans. However, this is based on a mix of both injury-induced and genetic causes of photoreceptor loss. There are very few longitudinal studies of gliosis in the retina and none comparing these changes across models over time. Here, we present a comprehensive spatiotemporal assessment of features of gliosis in the degenerating murine retina that involves Müller glia. Specifically, we assessed Gfap, vimentin and chondroitin sulphate proteoglycan (CSPG) levels and outer limiting membrane (OLM) integrity over time in four murine models of inherited photoreceptor degeneration that encompass a range of disease severities (Crb1rd8/rd8, Prph2+/Δ307, Rho-/-, Pde6brd1/rd1). These features underwent very different changes, depending upon the disease-causing mutation, and that these changes are not correlated with disease severity. Intermediate filament expression did indeed increase with disease progression in Crb1rd8/rd8 and Prph2+/Δ307, but decreased in the Prph2+/Δ307 and Pde6brd1/rd1 models. CSPG deposition usually, but not always, followed the trends in intermediate filament expression. The OLM adherens junctions underwent significant remodelling in all models, but with differences in the composition of the resulting junctions; in Rho-/- mice, the adherens junctions maintained the typical rod-Müller glia interactions, while in the Pde6brd1/rd1 model they formed predominantly between Müller cells in late stage of degeneration. Together, these results show that

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. Animal models to test hiPS-derived hepatocytes in the context of inherited metabolic liver diseases.

    PubMed

    Dusséaux, Mathilde; Darche, Sylvie; Strick-Marchand, Helene

    2014-01-01

    Human induced pluripotent stem (hiPS) cells are established following reprogramming of somatic cells from a wide variety of tissues. Given the scarcity of adult human hepatocytes, hiPS-derived hepatocytes would be a valuable source of cells to study differentiation programs, model patient-specific diseases, test drug toxicities, and cell transplantation therapies. Although hiPS-derived hepatocytes are extensively characterized in cell culture assays, testing these cells in animal models is necessary to fully evaluate their differentiation profile and their lack of tumorigenicity. Immunodeficient mouse models harboring liver damage are effective hosts in which xenogeneic hepatocytes can engraft, proliferate, and participate in liver regeneration, thus constituting a stringent test of hepatocyte functionality. The in vivo evaluation of disease-specific hiPS-derived hepatocytes should broaden our understanding of the cellular and molecular processes involved in inherited metabolic liver disease phenotypes. Herein, we detail our methods to test the functions of hiPS-derived hepatocytes in the context of the immunodeficient Rag2(-/-)IL2Rγc(-/-)Alb-uPAtg mouse model.

  20. 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

  1. 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

  2. Infantile Refsum disease: an inherited peroxisomal disorder. Comparison with Zellweger syndrome and neonatal adrenoleukodystrophy.

    PubMed

    Poll-The, B T; Saudubray, J M; Ogier, H A; Odièvre, M; Scotto, J M; Monnens, L; Govaerts, L C; Roels, F; Cornelis, A; Schutgens, R B

    1987-09-01

    Three patients affected by infantile Refsum disease are described with mental retardation, minor facial dysmorphia, chorioretinopathy, sensorineural hearing deficit, hepatomegaly, failure to thrive and hypocholesterolaemia. Initially, only an accumulation of phytanic acid was thought to be present. More recent findings showed a biochemical profile very similar to that found in classical Zellweger syndrome or neonatal adrenoleukodystrophy. Morphologically typical peroxisomes were absent in the liver. All three disorders are associated with multiple peroxisomal dysfunction. Because of these similarities pertinent clinical data of our three patients are compared with those of reported patients diagnosed as having infantile Refsum disease, neonatal adrenoleukodystrophy or Zellweger syndrome who survived for several years. Attention is drawn to the difference in severity of clinical features, ranging from infantile Refsum's disease to neonatal adrenoleukodystrophy and, finally, to Zellweger syndrome.

  3. 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

  4. 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.

  5. Molecular and bioenergetic differences between cells with African versus European inherited mitochondrial DNA haplogroups: implications for population susceptibility to diseases.

    PubMed

    Kenney, M Cristina; Chwa, Marilyn; Atilano, Shari R; Falatoonzadeh, Payam; Ramirez, Claudio; Malik, Deepika; Tarek, Mohamed; Del Carpio, Javier Cáceres; Nesburn, Anthony B; Boyer, David S; Kuppermann, Baruch D; Vawter, Marquis P; Jazwinski, S Michal; Miceli, Michael V; Wallace, Douglas C; Udar, Nitin

    2014-02-01

    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 (adenosine triphosphate) turnover rates and lower levels of reactive oxygen species 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 (chemokine, CC motif, receptor 3) 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

  6. 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

  7. 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.

  8. 78 FR 76634 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Amended Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-18

    ... 30, 2013, 78 FR 59945. This teleconference, originally scheduled for October 23, 2013, will be held... 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...

  9. 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

    ..., Bethesda, MD, 20892 which was published in the Federal Register on September 30, 2013, 78 FR 59945. This... 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...

  10. 76 FR 65737 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-24

    ... 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 Grant Review. Date: November 21, 2011... Review Officer, Scientific Review Branch, National Institute of Arthritis, Musculoskeletal and...

  11. 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...

  12. 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...

  13. 78 FR 66029 - National Institute of Arthritis and Musculoskeletal and Skin Diseases Amended; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-04

    ... Road, Bethesda, MD 20852, which was published in the Federal Register on September 23, 2013, 78 FR... Skin Diseases Amended; Notice of Meeting Notice is hereby given of a change in the meeting of the Arthritis and Musculoskeletal and Skin Diseases Clinical Trials Review Committee, October 15, 2013, 8:00...

  14. 75 FR 1792 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-13

    ... 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 Research Grants Review. Date: February 4, 2010.... Bloom, PhD, MBA, Scientific Review Officer, National Institute of Arthritis, Musculoskeletal and...

  15. 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

    ... Democracy Boulevard, Bethesda, MD 20892 which was published in the Federal Register on February 17, 2012, FR... 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...

  16. 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…

  17. [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.

  18. 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.

  19. 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

  20. Pediatric dermatohistopathology--histopathology of skin diseases in newborns and infants.

    PubMed

    Wobser, Marion; Ernestus, Karen; Hamm, Henning

    2015-06-01

    While neonatal skin physiology has been thoroughly examined using non-invasive techniques in recent years, only few systematic studies and review articles addressing the histopathology of neonatal skin have been published thus far. In most cases, histopathological findings of dermatoses in neonatal skin do not significantly differ from those seen in adult skin. Nevertheless, a comprehensive knowledge of embryonic and fetal skin development as well as the microanatomical structure of neonatal skin can contribute to a better understanding of various dermatoses of infancy. In the first part of this review article, we present the histopathological features of such skin diseases, which, though generally rare, almost exclusively appear during the first weeks of life due to distinctive structural and functional features of neonatal skin. The second part is dedicated to classic dermatoses of infancy and their histopathological features.

  1. Mechanism of Polycomb recruitment to CpG islands revealed by inherited disease-associated mutation.

    PubMed

    Caputo, Valentina S; Costa, Joana R; Makarona, Kalliopi; Georgiou, Elisabeth; Layton, D Mark; Roberts, Irene; Karadimitris, Anastasios

    2013-08-15

    How the transcription repressing complex Polycomb interacts with transcriptional regulators at housekeeping genes in somatic cells is not well understood. By exploiting a CpG island (CGI) point mutation causing a Mendelian disease, we show that DNA binding of activating transcription factor (TF) determines histone acetylation and nucleosomal depletion commensurate with Polycomb exclusion from the target promoter. Lack of TF binding leads to reversible transcriptional repression imposed by nucleosomal compaction and consolidated by Polycomb recruitment and establishment of bivalent chromatin status. Thus, within a functional hierarchy of transcriptional regulators, TF binding is the main determinant of Polycomb recruitment to the CGI of a housekeeping gene in somatic cells. PMID:23591993

  2. 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. PMID:26135290

  3. Bullous pemphigoid-like skin blistering disease in a rhesus macaque (Macaca mulatta).

    PubMed

    Kim, Jong-Min; Kim, Hyun-Je; Min, Byoung-Hoon; Shin, Jun-Seop; Jeong, Won Young; Lee, Ga Eul; Kim, Min Sun; Kim, Ju Eun; Park, Chung-Gyu

    2016-08-01

    Autoimmune bullous disease is very uncommon in non-human primates. We observed a bullous skin disease in a male rhesus monkey while conducting porcine islet xenotransplantation. Fifty days after the transplantation, multiple bullous skin lesions were observed. There was no mucosal involvement. Skin biopsy results demonstrated a subepidermal blister with no necrotic keratinocytes. Immunofluorescent staining showed linear IgG deposition at the roof of the blister. These skin lesions spontaneously disappeared. Considering these results, this monkey was diagnosed with bullous pemphigoid (BP). As far as we know, this is the first report of BP in non-human primates.

  4. Bullous pemphigoid-like skin blistering disease in a rhesus macaque (Macaca mulatta).

    PubMed

    Kim, Jong-Min; Kim, Hyun-Je; Min, Byoung-Hoon; Shin, Jun-Seop; Jeong, Won Young; Lee, Ga Eul; Kim, Min Sun; Kim, Ju Eun; Park, Chung-Gyu

    2016-08-01

    Autoimmune bullous disease is very uncommon in non-human primates. We observed a bullous skin disease in a male rhesus monkey while conducting porcine islet xenotransplantation. Fifty days after the transplantation, multiple bullous skin lesions were observed. There was no mucosal involvement. Skin biopsy results demonstrated a subepidermal blister with no necrotic keratinocytes. Immunofluorescent staining showed linear IgG deposition at the roof of the blister. These skin lesions spontaneously disappeared. Considering these results, this monkey was diagnosed with bullous pemphigoid (BP). As far as we know, this is the first report of BP in non-human primates. PMID:27373989

  5. The skin microbiome: potential for novel diagnostic and therapeutic approaches to cutaneous disease

    PubMed Central

    Grice, Elizabeth A.

    2015-01-01

    A vast diversity of microorganisms, including bacteria, fungi, viruses, and arthropods, colonize the human skin. Culture-independent genomic approaches for identifying and characterizing microbial communities have provided glimpses into the topographical, temporal, and interpersonal complexity that defines the skin microbiome. Identification of changes associated with cutaneous disease, including acne, atopic dermatitis, rosacea, and psoriasis, are being established. In this review, our current knowledge of the skin microbiome in health and disease is discussed, with particular attention to potential opportunities to leverage the skin microbiome as a diagnostic, prognostic, and/or therapeutic tool. PMID:25085669

  6. Skin diseases in workers at a perfume factory.

    PubMed

    Schubert, Hans-Jürgen

    2006-08-01

    The aim of this study is to find out the causes of skin diseases in one-third of the staff of a perfume factory, in which 10 different perfume sprays were being manufactured. Site inspection, dermatological examination and patch testing of all 26 persons at risk with 4 perfume oils and 30 ingredients of them. The results showed 6 bottlers were found suffering from allergic contact dermatitis, 2 from irritant contact dermatitis, 12 workers showed different strong reactions to various fragrances. The main causes of allergic contact dermatitis were 2 perfume oils (12 cases) and their ingredients geraniol (12 cases), benzaldehyde(9), cinnamic aldehyde (6), linalool, neroli oil, terpenes of lemon oil and orange oil (4 each). Nobody was tested positive to balsam of Peru. Job changes for office workers, packers or printers to other rooms, where they had no longer contact with fragrances, led to a settling. To conclude, automation and replacement of glass bottles by cartridges from non-fragile materials and using gloves may minimize the risk.

  7. 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.

  8. Activated immune response in an inherited leukodystrophy disease caused by the loss of oligodendrocyte gap junctions.

    PubMed

    Wasseff, Sameh K; Scherer, Steven S

    2015-10-01

    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 lymphocytes and microglia, and involved in leukotrienes/prostaglandins synthesis and chemokines/cytokines interactions and signaling pathways. In accord, immunostaining showed T- and B-cells in the cerebella of mutant mice as well as activated microglia and astrocytes. Thus, in addition to the loss of GJ coupling, there is a prominent immune response in mice lacking both Cx47 and Cx32.

  9. 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

  10. 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.

  11. Skin as a potential source of infectious foot and mouth disease aerosols.

    PubMed

    Dillon, Michael B

    2011-06-22

    This review examines whether exfoliated, virus-infected animal skin cells could be an important source of infectious foot and mouth disease virus (FMDV) aerosols. Infectious material rafting on skin cell aerosols is an established means of transmitting other diseases. The evidence for a similar mechanism for FMDV is: (i) FMDV is trophic for animal skin and FMDV epidermis titres are high, even in macroscopically normal skin; (ii) estimates for FMDV skin cell aerosol emissions appear consistent with measured aerosol emission rates and are orders of magnitude larger than the minimum infectious dose; (iii) the timing of infectious FMDV aerosol emissions is consistent with the timing of high FMDV skin concentrations; (iv) measured FMDV aerosol sizes are consistent with skin cell aerosols; and (v) FMDV stability in natural aerosols is consistent with that expected for skin cell aerosols. While these findings support the hypothesis, this review is insufficient, in and of itself, to prove the hypothesis and specific follow-on experiments are proposed. If this hypothesis is validated, (i) new FMDV detection, management and decontamination approaches could be developed and (ii) the relevance of skin cells to the spread of viral disease may need to be reassessed as skin cells may protect viruses against otherwise adverse environmental conditions.

  12. Skin disease in pregnancy: The approach of the obstetric medicine physician.

    PubMed

    Mehta, Niharika; Chen, Kenneth K; Kroumpouzos, George

    2016-01-01

    This review presents the approach of the obstetric medicine physician to skin disease in pregnancy. It elaborates on common skin-related problems during gestation, such as pruritus, with or without eruption, and drug eruptions. An algorithmic approach to the differential diagnosis of pruritus in pregnancy is outlined. Also, the review focuses on how to diagnose promptly endocrinopathies presenting with skin manifestations in pregnancy, such as Addison disease, diabetes, and hyperthyroidism. The prompt diagnosis of endocrine disorders can help to optimize management and improve outcomes. Finally, the authors outline their approach to minimizing maternal and fetal risks associated with skin disease. The risks associated with obstetric cholestasis, pemphigoid gestationis, and impetigo herpetiformis are discussed. Prompt diagnosis helps to minimize the serious risks associated with certain infections. Preconception counseling and a multidisciplinary approach are crucial to preventing risks associated with rheumatic skin disease and genodermatoses. Challenging, real-life obstetric medicine cases are discussed. PMID:27265069

  13. Yeasts in a hospital for patients with skin diseases

    PubMed Central

    Somerville, Dorothy A.

    1972-01-01

    The incidence and acquisition of Candida albicans and other yeasts in two wards of a skin hospital is described. Carriage rates on the skin in hospital patients is higher than is generally supposed, and cutaneous sites may act as sources of infection with these organisms. PMID:4567312

  14. New experimental models of skin homeostasis and diseases.

    PubMed

    Larcher, F; Espada, J; Díaz-Ley, B; Jaén, P; Juarranz, A; Quintanilla, M

    2015-01-01

    Homeostasis, whose regulation at the molecular level is still poorly understood, is intimately related to the functions of epidermal stem cells. Five research groups have been brought together to work on new in vitro and in vivo skin models through the SkinModel-CM program, under the auspices of the Spanish Autonomous Community of Madrid. This project aims to analyze the functions of DNA methyltransferase 1, endoglin, and podoplanin in epidermal stem cell activity, homeostasis, and skin cancer. These new models include 3-dimensional organotypic cultures, immunodeficient skin-humanized mice, and genetically modified mice. Another aim of the program is to use skin-humanized mice to model dermatoses such as Gorlin syndrome and xeroderma pigmentosum in order to optimize new protocols for photodynamic therapy. PMID:24878038

  15. New experimental models of skin homeostasis and diseases.

    PubMed

    Larcher, F; Espada, J; Díaz-Ley, B; Jaén, P; Juarranz, A; Quintanilla, M

    2015-01-01

    Homeostasis, whose regulation at the molecular level is still poorly understood, is intimately related to the functions of epidermal stem cells. Five research groups have been brought together to work on new in vitro and in vivo skin models through the SkinModel-CM program, under the auspices of the Spanish Autonomous Community of Madrid. This project aims to analyze the functions of DNA methyltransferase 1, endoglin, and podoplanin in epidermal stem cell activity, homeostasis, and skin cancer. These new models include 3-dimensional organotypic cultures, immunodeficient skin-humanized mice, and genetically modified mice. Another aim of the program is to use skin-humanized mice to model dermatoses such as Gorlin syndrome and xeroderma pigmentosum in order to optimize new protocols for photodynamic therapy.

  16. 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. PMID

  17. Differential Features between Chronic Skin Inflammatory Diseases Revealed in Skin-Humanized Psoriasis and Atopic Dermatitis Mouse Models.

    PubMed

    Carretero, Marta; Guerrero-Aspizua, Sara; Illera, Nuria; Galvez, Victoria; Navarro, Manuel; García-García, Francisco; Dopazo, Joaquin; Jorcano, Jose Luis; Larcher, Fernando; del Rio, Marcela

    2016-01-01

    Psoriasis and atopic dermatitis are chronic and relapsing inflammatory diseases of the skin affecting a large number of patients worldwide. Psoriasis is characterized by a T helper type 1 and/or T helper type 17 immunological response, whereas acute atopic dermatitis lesions exhibit T helper type 2-dominant inflammation. Current single gene and signaling pathways-based models of inflammatory skin diseases are incomplete. Previous work allowed us to model psoriasis in skin-humanized mice through proper combinations of inflammatory cell components and disruption of barrier function. Herein, we describe and characterize an animal model for atopic dermatitis using similar bioengineered-based approaches, by intradermal injection of human T helper type 2 lymphocytes in regenerated human skin after partial removal of stratum corneum. In this work, we have extensively compared this model with the previous and an improved version of the psoriasis model, in which T helper type 1 and/or T helper type 17 lymphocytes replace exogenous cytokines. Comparative expression analyses revealed marked differences in specific epidermal proliferation and differentiation markers and immune-related molecules, including antimicrobial peptides. Likewise, the composition of the dermal inflammatory infiltrate presented important differences. The availability of accurate and reliable animal models for these diseases will contribute to the understanding of the pathogenesis and provide valuable tools for drug development and testing. PMID:26763433

  18. Ethnomedicinal plants used in the treatment of skin diseases in Hyderabad Karnataka region, Karnataka, India

    PubMed Central

    Policepatel, Shivakumar Singh; Manikrao, Vidyasagar Gunagambhire

    2013-01-01

    Objective To document traditional medicinal plants knowledge used in treating skin diseases at Hyderabad Karnataka Region. Methods The information on the use of medicinal plants in the treatment of skin diseases was gathered from traditional herbal healers and other villagers through interviews. Results A total of 60 plants species belonging to 57 genera and 34 families were found useful and herewith described them along with the method of drug preparation, mode of administration, probable dosage and duration of treatment. Several new findings on the traditional rural practices were reported. Conclusions The present study revealed that the Hyderabad Karnataka rural people is primarily dependent on medicinal plants for treating skin diseases.

  19. Discovery in Genetic Skin Disease: The Impact of High Throughput Genetic Technologies

    PubMed Central

    Maruthappu, Thiviyani; Scott, Claire A.; Kelsell, David P.

    2014-01-01

    The last decade has seen considerable advances in our understanding of the genetic basis of skin disease, as a consequence of high throughput sequencing technologies including next generation sequencing and whole exome sequencing. We have now determined the genes underlying several monogenic diseases, such as harlequin ichthyosis, Olmsted syndrome, and exfoliative ichthyosis, which have provided unique insights into the structure and function of the skin. In addition, through genome wide association studies we now have an understanding of how low penetrance variants contribute to inflammatory skin diseases such as psoriasis vulgaris and atopic dermatitis, and how they contribute to underlying pathophysiological disease processes. In this review we discuss strategies used to unravel the genes underlying both monogenic and complex trait skin diseases in the last 10 years and the implications on mechanistic studies, diagnostics, and therapeutics. PMID:25093584

  20. Impaired sympathetic skin response in chronic obstructive pulmonary disease.

    PubMed

    Bir, Levent Sinan; Ozkurt, Sibel; Daloğlu, Güner; Kurt, Tülay

    2005-12-01

    The sympathetic skin response (SSR) is considered as one of the indexes of autonomic nervous system functions, especially related with the sudomotor function of unmyelinated sympathetic fibers. SSRs are recorded as the potentials with biphasic or multiphasic waveforms by conventional electromyography. SSRs are evaluated by measuring latency (time from the stimulus to the onset), amplitude, and area (the space under the curve of the waveform). Although dysautonomia is a feature of chronic obstructive pulmonary disease (COPD), as demonstrated by acetylcholine sweat-spot test, there are no data concerning SSR in COPD patients. In this study, we electrophysiologically investigated the sudomotor function of the sympathetic nervous system in patients with COPD. SSRs were recorded in 30 patients with COPD and 21 healthy volunteers. Normal responses were obtained from all subjects in the control group. No response was observed in three patients with COPD. The mean latency, amplitude and area values of the potentials recorded of the remaining 27 patients were compared to the control. The mean latency was longer (p<0.01) and the mean amplitude and area values were lower (p=0.012, p=0.021, respectively) in the patients compared to the control. We also demonstrated significant correlations between the latency, amplitude, or area values of the SSR and two parameters of pulmonary function tests forced expiratory volume one second/forced vital capacity (FEV1/FVC) and FEV1/FVC %. In conclusion, SSR is impaired in patients with COPD, which indicates the dysfunction of the sympathetic nervous system. Furthermore, the degree of impairment in SSR may reflect the severity of airway obstruction in patients with COPD. PMID:16272793

  1. Relationship of skin autofluorescence to cardiovascular disease in Japanese hemodialysis patients.

    PubMed

    Tanaka, Kenichi; Katoh, Tetsuo; Asai, Jun; Nemoto, Fumihiko; Suzuki, Hodaka; Asahi, Koichi; Sato, Keiji; Sakaue, Michiaki; Miyata, Toshio; Watanabe, Tsuyoshi

    2010-06-01

    Advanced glycation end products (AGE) are significantly increased in end-stage renal disease patients and it has been suggested that AGE accumulation is related to the progression of cardiovascular disease. An autofluorescence reader non-invasively assesses AGE accumulation using skin autofluorescence under ultraviolet light. Skin autofluorescence has been reported to be an independent predictor of mortality in Caucasian hemodialysis patients. The aim of this study was to assess whether skin autofluorescence in Japanese hemodialysis patients is related to the presence of cardiovascular disease. In this cross-sectional study, patients on maintenance hemodialysis (N = 128; 59 men, 69 women) were included. AGE accumulation was assessed by skin autofluorescence using an autofluorescence reader. Associations between skin autofluorescence, cardiovascular disease, and other parameters were studied. Skin autofluorescence correlated with age (r = 0.32, P < 0.01), diabetes (r = 0.21, P = 0.02), carotid intima-media thickness (IMT) (r = 0.23, P = 0.02), high-sensitivity C-reactive protein (hsCRP) (r = 0.20, P = 0.03), and plasma pentosidine (r = 0.20, P = 0.03). Each parameter was compared in patients with and without cardiovascular disease; the gender distribution, age, carotid IMT, high-density lipoprotein cholesterol, hsCRP, and skin autofluorescence were significantly related to the presence of cardiovascular disease. Multiple logistic regression analysis identified carotid IMT (OR 6.76), hsCRP (OR 1.41), and skin autofluorescence (OR 2.29) as significant factors for the presence of cardiovascular disease. Increased skin autofluorescence was related to the presence of cardiovascular disease in Asian (non-Caucasian) hemodialysis patients, and therefore an autofluorescence reader might have the potential to be a useful assessment of cardiovascular risk in these patients.

  2. Relationship of skin autofluorescence to cardiovascular disease in Japanese hemodialysis patients.

    PubMed

    Tanaka, Kenichi; Katoh, Tetsuo; Asai, Jun; Nemoto, Fumihiko; Suzuki, Hodaka; Asahi, Koichi; Sato, Keiji; Sakaue, Michiaki; Miyata, Toshio; Watanabe, Tsuyoshi

    2010-06-01

    Advanced glycation end products (AGE) are significantly increased in end-stage renal disease patients and it has been suggested that AGE accumulation is related to the progression of cardiovascular disease. An autofluorescence reader non-invasively assesses AGE accumulation using skin autofluorescence under ultraviolet light. Skin autofluorescence has been reported to be an independent predictor of mortality in Caucasian hemodialysis patients. The aim of this study was to assess whether skin autofluorescence in Japanese hemodialysis patients is related to the presence of cardiovascular disease. In this cross-sectional study, patients on maintenance hemodialysis (N = 128; 59 men, 69 women) were included. AGE accumulation was assessed by skin autofluorescence using an autofluorescence reader. Associations between skin autofluorescence, cardiovascular disease, and other parameters were studied. Skin autofluorescence correlated with age (r = 0.32, P < 0.01), diabetes (r = 0.21, P = 0.02), carotid intima-media thickness (IMT) (r = 0.23, P = 0.02), high-sensitivity C-reactive protein (hsCRP) (r = 0.20, P = 0.03), and plasma pentosidine (r = 0.20, P = 0.03). Each parameter was compared in patients with and without cardiovascular disease; the gender distribution, age, carotid IMT, high-density lipoprotein cholesterol, hsCRP, and skin autofluorescence were significantly related to the presence of cardiovascular disease. Multiple logistic regression analysis identified carotid IMT (OR 6.76), hsCRP (OR 1.41), and skin autofluorescence (OR 2.29) as significant factors for the presence of cardiovascular disease. Increased skin autofluorescence was related to the presence of cardiovascular disease in Asian (non-Caucasian) hemodialysis patients, and therefore an autofluorescence reader might have the potential to be a useful assessment of cardiovascular risk in these patients. PMID:20609188

  3. Sutureless skin closure of amputation stumps in patients with peripheral arterial disease

    PubMed Central

    Hollands, M J; Jones, S M

    1982-01-01

    A sutureless technique of skin closure for the amputation stumps of patients with peripheral vascular disease is described. It offers less trauma to skin flaps, limits access to the wound by exogenous sources of bacterial contamination, and is very acceptable to the patient. PMID:7137833

  4. Sex differences in the incidence of skin and skin-related diseases in Olmsted County, Minnesota, United States, and a comparison with other rates published worldwide.

    PubMed

    Andersen, Louise K; Davis, Mark D P

    2016-09-01

    Many skin and skin-related diseases affect the sexes unequally, with attendant implications for public health and resource allocation. To evaluate better the incidence of skin and skin-related diseases affecting males vs. females, we reviewed published population-based epidemiology studies of skin disorders performed utilizing Rochester Epidemiology Project data. Females had a higher incidence of the following diseases: connective tissue diseases (scleroderma, morphea, dermatomyositis, primary Sjögren syndrome, systemic lupus erythematosus [not in all studies]), pityriasis rosea, herpes progenitalis, condyloma acuminatum, hidradenitis suppurativa, herpes zoster (except in children), erythromelalgia, venous stasis syndrome, and venous ulcers. Males had a higher incidence of psoriasis and psoriatic arthritis, basal cell carcinoma (exception, females aged ≤40 years), squamous cell carcinoma, and lentigo maligna. Incidence rates were equal in males and females for cutaneous malignant melanoma (exception, higher in females aged 18-39 years), lower-extremity cellulitis, cutaneous nontuberculous mycobacterial infection, Behçet disease, delusional infestation, alopecia areata, and bullous pemphigoid. Many of the population-based sex-specific incidence rates of skin and skin-related diseases derived from the Rochester Epidemiology Project are strikingly different from those estimated elsewhere. In general, females are more commonly affected by skin and skin-related diseases. The reasons for this imbalance remain to be determined and are likely multifactorial. PMID:27009931

  5. Climate change and skin disease: a review of the English-language literature.

    PubMed

    Andersen, Louise K; Hercogová, Jana; Wollina, Uwe; Davis, Mark D P

    2012-06-01

    Climate change describes variation in regional or global climates over time. The question of how climate change affects skin disease remains largely unanswered. We reviewed the English-language literature describing the influence of climate change on skin. Relatively few publications detail aspects of how climate change affects skin. Direct effects include the effects of extreme weather events, and indirect effects include the effects of longer-term changes in patterns of infections and infestations worldwide. The effect of climate change on skin is unclear, and more studies on this topic are needed.

  6. [Skin diseases among workers engaged into copper-nickel and aluminium production in Far North].

    PubMed

    Nikitina, N Iu; Petrenko, O D; Isakova, T N

    2004-01-01

    The article covers materials obtained in study of skin diseases in workers engaged into non-ferrous metals production. The authors specified suggestions on prevention of metal allergies among major professions of metallurgy complex in Far North.

  7. 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

    ... Institute of Arthritis and Musculoskeletal and Skin Diseases Special Emphasis Panel; Career Development, Research Training & Pathways to Independence Review. Date: June 20, 2012. Time: 11:00 a.m. to 12:00...

  8. Lumpy Skin Disease in Jordan: Disease Emergence, Clinical Signs, Complications and Preliminary-associated Economic Losses.

    PubMed

    Abutarbush, S M; Ababneh, M M; Al Zoubi, I G; Al Sheyab, O M; Al Zoubi, M G; Alekish, M O; Al Gharabat, R J

    2015-10-01

    The objectives of this study are to report the emergence of lumpy skin disease (LSD) in Jordan and associated clinical signs, complications and preliminary economic losses. In mid-April, 2013, two adult dairy cattle developed clinical signs suggestive of LSD and were confirmed as positive by PCR. The two cases were in Bani Kenanah district, Irbid governorate, on the Jordanian border of Israel and Syria. The disease spread rapidly to all the districts of Irbid governorate. During the month following the emergence of the disease, data were collected related to the epidemiology of the disease and the numbers of affected cattle on the premises. Forty-one dairy cattle holdings were surveyed. The morbidity rate ranged from 3% to 100%, (Mean = 35.1%, SD ±28.5%). The mortality rate ranged from 0% to 20%, (Mean = 1.3%, SD ±4.4%). The case fatality rate ranged from 0% to 100%, (Mean = 6.2%, SD ±22%). The overall morbidity rate was 26%, mortality rate 1.9% and case fatality rate 7.5%. Skin nodules, anorexia, decreased milk production and decreased body weight were common clinical signs, while mastitis and myiasis were seen as complications in a few affected animals. Decreased body weight ranged from 0% to 80%, (Mean = 23.1%, SD ±15.7%). Decreased milk production ranged from 0% to 100%, (Mean = 51.5%, SD ±22.2%). Affected cattle were treated mainly with broad-spectrum antibiotics and anti-inflammatory drugs. The cost of treatment ranged from 0 to 84.3 British Pound/animal, (Mean = 27.9 GBP, SD ±22.5 GBP). LSD continues to spread through the Middle East region and poses a serious threat to the rest of Asia and Europe. International collaboration and communication is warranted to prevent the further spread of the disease to the rest of Asia and Europe.

  9. [Significance and possibilities of histopathologic diagnosis in breed-specific skin diseases].

    PubMed

    Teifke, J P; Löhr, C V; Käufer-Weiss, I; Weiss, E

    1998-07-01

    An increasing number of punch biopsies is submitted for histopathology. Results are often disappointing for the veterinary pathologist as well as the referring veterinarian. Inappropriate timing of sampling, selection and preparation of the biopsy site, type of biopsy, biopsy technique and fixation as well as incomplete histories often contribute to insufficient diagnosis and interpretation of skin lesions. The introduction of this review gives an overview of the requirements for a satisfying evaluation of skin lesions and the limits of diagnostic histopathology on skin samples, especially punch biopsies. The second part summarizes more frequent dermatohistopathological diagnoses according to the pattern analysis of skin lesions, using examples of skin diseases with breed predisposition. Among the described skin lesions are the dermatoses associated with endocrine dysfunction, cutaneous mucinosis, Vogt-Koyanagi-Harada-like syndrome, alopecia of color mutants, dermatomyositis, granulomatous sebadentitis, Malassezia dermatitis, pyoderma and atopic dermatitis. PMID:9710933

  10. Skin autofluorescence is a predictor of cardiovascular disease in chronic kidney disease patients.

    PubMed

    Furuya, Fumihiko; Shimura, Hiroki; Takahashi, Kazuya; Akiyama, Daiichiro; Motosugi, Ai; Ikegishi, Yukinobu; Haraguchi, Kazutaka; Kobayashi, Tetsuro

    2015-02-01

    Accelerated formation and tissue accumulation of advanced glycation end products (AGEs), reflecting cumulative glycemic and oxidative stress, occurs in age-related and chronic diseases like diabetes mellitus (DM) and renal failure, and contributes to vascular damage. Skin autofluorescence (AFR), a noninvasive measurement method, reflects tissue accumulation of AGEs. AFR has been reported to be an independent predictor of mortality in Caucasian hemodialysis patients. We assessed the relationship between levels of AFR and the prevalence of cardiovascular disease (CVD), and clarified the prognostic usefulness of skin AFR levels in Asian (non-Caucasian) hemodialysis (HD) patients. AFR was measured with an autofluorescence reader in 64 HD patients. Overall and cardiovascular mortality was monitored prospectively during the 3-year follow-up. During follow-up, CVD events occurred in 21 patients. The deaths of 10 HD patients were associated with CVD. Multivariate logistic regression analyses showed that initial AFR was an independent risk factor for de novo CVD in HD patients with or without diabetes. When patients were classified on the basis of AFR tertiles, Cochran-Armitage analysis demonstrated that the highest tertile of AFR level showed an increased odds ratio for the prevalence of CVD. These findings suggest that AFR levels can be used to detect the prevalence of CVD in HD patients with or without diabetes.

  11. Skin autofluorescence is a predictor of cardiovascular disease in chronic kidney disease patients.

    PubMed

    Furuya, Fumihiko; Shimura, Hiroki; Takahashi, Kazuya; Akiyama, Daiichiro; Motosugi, Ai; Ikegishi, Yukinobu; Haraguchi, Kazutaka; Kobayashi, Tetsuro

    2015-02-01

    Accelerated formation and tissue accumulation of advanced glycation end products (AGEs), reflecting cumulative glycemic and oxidative stress, occurs in age-related and chronic diseases like diabetes mellitus (DM) and renal failure, and contributes to vascular damage. Skin autofluorescence (AFR), a noninvasive measurement method, reflects tissue accumulation of AGEs. AFR has been reported to be an independent predictor of mortality in Caucasian hemodialysis patients. We assessed the relationship between levels of AFR and the prevalence of cardiovascular disease (CVD), and clarified the prognostic usefulness of skin AFR levels in Asian (non-Caucasian) hemodialysis (HD) patients. AFR was measured with an autofluorescence reader in 64 HD patients. Overall and cardiovascular mortality was monitored prospectively during the 3-year follow-up. During follow-up, CVD events occurred in 21 patients. The deaths of 10 HD patients were associated with CVD. Multivariate logistic regression analyses showed that initial AFR was an independent risk factor for de novo CVD in HD patients with or without diabetes. When patients were classified on the basis of AFR tertiles, Cochran-Armitage analysis demonstrated that the highest tertile of AFR level showed an increased odds ratio for the prevalence of CVD. These findings suggest that AFR levels can be used to detect the prevalence of CVD in HD patients with or without diabetes. PMID:25545539

  12. Single stem cell gene therapy for genetic skin disease.

    PubMed

    Larsimont, Jean-Christophe; Blanpain, Cédric

    2015-04-01

    Stem cell gene therapy followed by transplantation into damaged regions of the skin has been successfully used to treat genetic skin blistering disorder. Usually, many stem cells are virally transduced to obtain a sufficient number of genetically corrected cells required for successful transplantation, as genetic insertion in every stem cell cannot be precisely defined. In this issue of EMBO Molecular Medicine, Droz-Georget Lathion et al developed a new strategy for ex vivo single cell gene therapy that allows extensive genomic and functional characterization of the genetically repaired individual cells before they can be used in clinical settings.

  13. Natural ingredients in atopic dermatitis and other inflammatory skin disease.

    PubMed

    Dohil, Magdalene A

    2013-09-01

    Active naturals in dermatology have been experiencing a renaissance. Many of the naturals that have been known for centuries to be effective for various skin conditions have now been scientifically validated with the unraveling of the pathophysiology behind their medicinal mechanism. This article seeks to present data on the clinical use of key dermatological active naturals such as oatmeal, feverfew, chamomile, aloe vera, licorice, and dexpanthenol, as well as on recent multicenter and international clinical studies that support their efficacy and safety profile for a variety of inflammatory skin conditions. PMID:24002161

  14. Ambient humidity and the skin: the impact of air humidity in healthy and diseased states.

    PubMed

    Goad, N; Gawkrodger, D J

    2016-08-01

    Humidity, along with other climatic factors such as temperature and ultraviolet radiation, can have an important impact on the skin. Limited data suggest that external humidity influences the water content of the stratum corneum. An online literature search was conducted through Pub-Med using combinations of the following keywords: skin, skin disease, humidity, dermatoses, dermatitis, eczema, and mist. Publications included in this review were limited to (i) studies in humans or animals, (ii) publications showing relevance to the field of dermatology, (iii) studies published in English and (iv) publications discussing humidity as an independent influence on skin function. Studies examining environmental factors as composite influences on skin health are only included where the impact of humidity on the skin is also explored in isolation of other environmental factors. A formal systematic review was not feasible for this topic due to the heterogeneity of the available research. Epidemiological studies indicated an increase in eczema with low internal (indoors) humidity and an increase in eczema with external high humidity. Other studies suggest that symptoms of dry skin appear with low humidity internal air-conditioned environments. Murine studies determined that low humidity caused a number of changes in the skin, including the impairment of the desquamation process. Studies in humans demonstrated a reduction in transepidermal water loss (TEWL) (a measure of the integrity of the skin's barrier function) with low humidity, alterations in the water content in the stratum corneum, decreased skin elasticity and increased roughness. Intervention with a humidifying mist increased the water content of the stratum corneum. Conversely, there is some evidence that low humidity conditions can actually improve the barrier function of the skin. Ambient relative humidity has an impact on a range of parameters involved in skin health but the literature is inconclusive. Further

  15. Rapid, noninvasive quantitation of skin disease in systemic sclerosis using optical coherence elastography

    NASA Astrophysics Data System (ADS)

    Du, Yong; Liu, Chih-Hao; Lei, Ling; Singh, Manmohan; Li, Jiasong; Hicks, M. John; Larin, Kirill V.; Mohan, Chandra

    2016-04-01

    Systemic sclerosis (SSc) is a connective tissue disease that results in excessive accumulation of collagen in the skin and internal organs. Overall, SSc has a rare morbidity (276 cases per million adults in the United States), but has a 10-year survival rate of 55%. Currently, the modified Rodnan skin score (mRSS) is assessed by palpation on 17 sites on the body. However, the mRSS assessed score is subjective and may be influenced by the experience of the rheumatologists. In addition, the inherent elasticity of skin may bias the mRSS assessment in the early stage of SSc, such as oedematous. Optical coherence elastography (OCE) is a rapidly emerging technique, which can assess mechanical contrast in tissues with micrometer spatial resolution. In this work, the OCE technique is applied to assess the mechanical properties of skin in both control and bleomycin (BLM) induced SSc-like disease noninvasively. Young's modulus of the BLM-SSc skin was found be significantly higher than that of normal skin, in both the in vivo and in vitro studies (p<0.05). Thus, OCE is able to differentiate healthy and fibrotic skin using mechanical contrast. It is a promising new technology for quantifying skin involvement in SSc in a rapid, unbiased, and noninvasive manner.

  16. Rapid, noninvasive quantitation of skin disease in systemic sclerosis using optical coherence elastography.

    PubMed

    Du, Yong; Liu, Chih-Hao; Lei, Ling; Singh, Manmohan; Li, Jiasong; Hicks, M John; Larin, Kirill V; Mohan, Chandra

    2016-04-30

    Systemic sclerosis (SSc) is a connective tissue disease that results in excessive accumulation of collagen in the skin and internal organs. Overall, SSc has a rare morbidity (276 cases per million adults in the United States), but has a 10-year survival rate of 55%. Currently, the modified Rodnan skin score (mRSS) is assessed by palpation on 17 sites on the body. However, the mRSS assessed score is subjective and may be influenced by the experience of the rheumatologists. In addition, the inherent elasticity of skin may bias the mRSS assessment in the early stage of SSc, such as oedematous. Optical coherence elastography (OCE) is a rapidly emerging technique, which can assess mechanical contrast in tissues with micrometer spatial resolution. In this work, the OCE technique is applied to assess the mechanical properties of skin in both control and bleomycin (BLM) induced SSc-like disease noninvasively. Young’s modulus of the BLM-SSc skin was found be significantly higher than that of normal skin, in both the in vivo and in vitro studies (p<0.05 p<0.05 ). Thus, OCE is able to differentiate healthy and fibrotic skin using mechanical contrast. It is a promising new technology for quantifying skin involvement in SSc in a rapid, unbiased, and noninvasive manner. PMID:27048877

  17. Periodic Acid-Schiff Staining Parallels the Immunoreactivity Seen By Direct Immunofluorescence in Autoimmune Skin Diseases

    PubMed Central

    Abreu Velez, Ana Maria; Upegui Zapata, Yulieth Alexandra; Howard, Michael S

    2016-01-01

    Background: In many countries and laboratories, techniques such as direct immunofluorescence (DIF) are not available for the diagnosis of skin diseases. Thus, these laboratories are limited in the full diagnoses of autoimmune skin diseases, vasculitis, and rheumatologic diseases. In our experience with these diseases and the patient's skin biopsies, we have noted a positive correlation between periodic acid-Schiff (PAS) staining and immunofluorescence patterns; however, these were just empiric observations. In the current study, we aim to confirm these observations, given the concept that the majority of autoantibodies are glycoproteins and should thus be recognized by PAS staining. Aims: To compare direct immunofluorescent and PAS staining, in multiple autoimmune diseases that are known to exhibit specific direct immunofluorescent patterns. Materials and Methods: We studied multiple autoimmune skin diseases: Five cases of bullous pemphigoid, five cases of pemphigus vulgaris, ten cases of cutaneous lupus, ten cases of autoimmune vasculitis, ten cases of lichen planus (LP), and five cases of cutaneous drug reactions (including one case of erythema multiforme). In addition, we utilized 45 normal skin control specimens from plastic surgery reductions. Results: We found a 98% positive correlation between DIF and PAS staining patterns over all the disease samples. Conclusion: We recommend that laboratories without access to DIF always perform PAS staining in addition to hematoxylin and eosin (H&E) staining, for a review of the reactivity pattern. PMID:27114972

  18. Inherited epidermolysis bullosa - the spectrum of complications.

    PubMed

    Murat-Sušić, Slobodna; Husar, Karmela; Skerlev, Mihael; Marinović, Branka; Babić, Irena

    2011-01-01

    Epidermolysis bullosa is a group of inherited diseases that are characterized by skin and mucosal fragility and blister formation. A wide variety of extracutaneous manifestations can develop as well as various complications of the disease such as severe anemia, growth retardation, esophageal stenosis, mutilating deformities of hands and feet, glomerulonephritis leading to chronic renal failure, and many others. One of the most important and often occurring complications is the development of cutaneous squamous cell carcinomas that grow and metastasize quickly. The objective of this paper is to give dermatologists a review of major complications encountered in patients with epidermolysis bullosa. Since these complications occur so often and can be considered to be part of the clinical picture, it is mandatory to develop a multidisciplinary well-educated team involved in follow-up and treatment of these patients. PMID:22185926

  19. Alterations in acetylcholinesterase and choline acetyltransferase activities and neuropeptide levels in the ventral spinal cord of the Wobbler mouse during inherited motoneuron disease.

    PubMed

    Yung, K K; Tang, F; Vacca-Galloway, L L

    1994-02-28

    Enzymatic assays for acetylcholine esterase (AChE) and choline acetyltransferase (ChAT) were applied to dorsal and ventral cervical spinal cord regions taken from the Wobbler mouse, a model for inherited motoneuron disease. Early in the disease, ChAT (but not AChE) activity is significantly greater compared with the control littermate specimens. The high ChAT activity correlates with the high thyrotropin releasing hormone (also leucine-enkephalin) concentrations measured in the Wobbler ventral horn early in the disease. Late in the motoneuron disease, both AChE and ChAT activities are significantly lower than in the control littermate specimens. These data correlate with the high substance P, methionine and leucine enkephalin concentrations measured in the Wobbler ventral horn late in the motoneuron disease.

  20. Presence and Persistence of Foot-and-Mouth Disease Virus in Bovine Skin

    PubMed Central

    Gailiunas, Peter; Cottral, George E.

    1966-01-01

    Gailiunas, Peter (Plum Island Animal Disease Laboratory, Greenport, N. Y.), and George E. Cottral. Presence and persistence of foot-and-mouth disease virus in bovine skin. J. Bacteriol. 91:2333–2338. 1966.—This study established that the seven known antigenic types of foot-and-mouth disease virus (FMDV) have consistent affinity to all areas of bovine skin, even though gross cutaneous lesions usually are found only in the pedal area. Considerable amounts of FMDV were present in skin of 13 different body areas, irrespective of the presence of hair. All skin specimens from the trunk of 50 experimentally infected steers, necropsied from 12 hr to 7 days postinoculation (DPI), contained FMDV in the dermal and epidermal tissues. In skins of some steers, FMDV persisted for as long as 5 days after cessation of viremia. The highest average virus titer, 103.6 plaque-forming units (PFU) per g of skin, was found at 2 DPI. Some areas of the trunk and extremities had titers of approximately 105.0 PFU per g of skin. Characteristic gross lesions were not observed in sampling areas. The present observations have epizootiological importance for hides offered in international trade, because FMDV localized intracutaneously is more difficult to inactivate than virus adhering to hide surfaces. PMID:4287587

  1. Coronary heart disease risk factors in men with light and dark skin in Puerto Rico.

    PubMed Central

    Costas, R; Garcia-Palmieri, M R; Sorlie, P; Hertzmark, E

    1981-01-01

    The association of skin color with coronary heart disease risk factors was studied in 4,000 urban Puerto Rican men. Skin color on the inner upper arm was classified according to the von Luschan color tiles. Using this grading, men were separated into two groups of light or dark skin color. The dark group had a lower socioeconomic status (SES) based on income, education, and occupation. Dark men had slightly higher mean systolic blood pressures (SBP) and lower mean serum cholesterol levels than the light, but the relative weights and cigarette smoking habits of both groups were similar. After controlling for the differences in SES, skin color showed a small but statistically significant association with SBP. Whether this association with skin color represents genetic or environmental influences on SBP could not be determined from this study. PMID:7235099

  2. Steroid synthesis by primary human keratinocytes; implications for skin disease

    SciTech Connect

    Hannen, Rosalind F.; Michael, Anthony E.; Jaulim, Adil; Bhogal, Ranjit; Burrin, Jacky M.; Philpott, Michael P.

    2011-01-07

    Research highlights: {yields} Primary keratinocytes express the steroid enzymes required for cortisol synthesis. {yields} Normal primary human keratinocytes can synthesise cortisol. {yields} Steroidogenic regulators, StAR and MLN64, are expressed in normal epidermis. {yields} StAR expression is down regulated in eczema and psoriatic epidermis. -- Abstract: Cortisol-based therapy is one of the most potent anti-inflammatory treatments available for skin conditions including psoriasis and atopic dermatitis. Previous studies have investigated the steroidogenic capabilities of keratinocytes, though none have demonstrated that these skin cells, which form up to 90% of the epidermis are able to synthesise cortisol. Here we demonstrate that primary human keratinocytes (PHK) express all the elements required for cortisol steroidogenesis and metabolise pregnenolone through each intermediate steroid to cortisol. We show that normal epidermis and cultured PHK express each of the enzymes (CYP11A1, CYP17A1, 3{beta}HSD1, CYP21 and CYP11B1) that are required for cortisol synthesis. These enzymes were shown to be metabolically active for cortisol synthesis since radiometric conversion assays traced the metabolism of [7-{sup 3}H]-pregnenolone through each steroid intermediate to [7-{sup 3}H]-cortisol in cultured PHK. Trilostane (a 3{beta}HSD1 inhibitor) and ketoconazole (a CYP17A1 inhibitor) blocked the metabolism of both pregnenolone and progesterone. Finally, we show that normal skin expresses two cholesterol transporters, steroidogenic acute regulatory protein (StAR), regarded as the rate-determining protein for steroid synthesis, and metastatic lymph node 64 (MLN64) whose function has been linked to cholesterol transport in steroidogenesis. The expression of StAR and MLN64 was aberrant in two skin disorders, psoriasis and atopic dermatitis, that are commonly treated with cortisol, suggesting dysregulation of epidermal steroid synthesis in these patients. Collectively these data

  3. Modelling skin disease: lessons from the worlds of mathematics, physics and computer science.

    PubMed

    Gilmore, Stephen

    2005-05-01

    Theoretical biology is a field that attempts to understand the complex phenomena of life in terms of mathematical and physical principles. Likewise, theoretical medicine employs mathematical arguments and models as a methodology in approaching the complexities of human disease. Naturally, these concepts can be applied to dermatology. There are many possible methods available in the theoretical investigation of skin disease. A number of examples are presented briefly. These include the mathematical modelling of pattern formation in congenital naevi and erythema gyratum repens, an information-theoretic approach to the analysis of genetic networks in autoimmunity, and computer simulations of early melanoma growth. To conclude, an analogy is drawn between the behaviour of well-known physical processes, such as earthquakes, and the spatio-temporal evolution of skin disease. Creating models in skin disease can lead to predictions that can be investigated experimentally or by observation and offer the prospect of unexpected or important insights into pathogenesis.

  4. Inherit Space

    NASA Technical Reports Server (NTRS)

    Giarratano, Joseph C.; Jenks, K. C.

    1997-01-01

    The objective of the proposed research was to begin development of a unique educational tool targeted at educating and inspiring young people 12-16 years old about NASA and the Space Program. Since these young people are the future engineers, scientists and space pioneers, the nurturing of their enthusiasm and interest is of critical importance to the Nation. This summer the basic infrastructure of the tool was developed in the context of an educational game paradigm. The game paradigm has achieved remarkable success in maintaining the interest of young people in a self-paced, student-directed learning environment. This type of environment encourages student exploration and curiosity which are exactly the traits that future space pioneers need to develop to prepare for the unexpected. The Inherit Space Educational Tool is an open-ended learning environment consisting of a finite-state machine classic adventure game paradigm. As the young person explores this world, different obstacles must be overcome. Rewards will be offered such as using the flight simulator to fly around and explore Titan. This simulator was modeled on conventional Earth flight simulators but has been considerably enhanced to add texture mapping of Titan's atmosphere utilizing the latest information from the NASA Galileo Space Probe. Additional scenery was added to provide color VGA graphics of a futuristic research station on Titan as well as an interesting story to keep the youngster's attention. This summer the game infrastructure has been developed as well as the Titan Flight Simulator. A number of other enhancements are planned.

  5. Analysis of Published Criteria for Clinically Inactive Disease in a Large Juvenile Dermatomyositis Cohort Shows That Skin Disease Is Underestimated

    PubMed Central

    Almeida, Beverley; Campanilho‐Marques, Raquel; Arnold, Katie; Pilkington, Clarissa A.; Wedderburn, Lucy R.; Armon, Kate; Briggs, Vanja; Ellis‐Gage, Joe; Roper, Holly; Watts, Joanna; Baildam, Eileen; Hanna, Louise; Lloyd, Olivia; McCann, Liza; Roberts, Ian; McGovern, Ann; Riley, Phil; Al‐Abadi, Eslam; Ryder, Clive; Scott, Janis; Southwood, Taunton; Thomas, Beverley; Amin, Tania; Burton, Deborah; Jackson, Gillian; Van Rooyen, Vanessa; Wood, Mark; Wyatt, Sue; Browne, Michael; Davidson, Joyce; Ferguson, Sue; Gardner‐Medwin, Janet; Martin, Neil; Waxman, Liz; Foster, Helen; Friswell, Mark; Jandial, Sharmila; Qiao, Lisa; Sen, Ethan; Smith, Eve; Stevenson, Vicky; Swift, Alison; Wade, Debbie; Watson, Stuart; Crate, Lindsay; Frost, Anna; Jordan, Mary; Mosley, Ellen; Satyapal, Rangaraj; Stretton, Elizabeth; Venning, Helen; Warrier, Kishore; Almeida, Beverley; Arnold, Katie; Beard, Laura; Brown, Virginia; Campanilho‐Marques, Raquel; Enayat, Elli; Glackin, Yvonne; Halkon, Elizabeth; Hasson, Nathan; Juggins, Audrey; Kassoumeri, Laura; Lunt, Sian; Maillard, Sue; Nistala, Kiran; Pilkington, Clarissa; Simou, Stephanie; Smith, Sally; Varsani, Hemlata; Wedderburn, Lucy; Murray, Kevin; Ioannou, John; Suffield, Linda; Al‐Obaidi, Muthana; Leach, Sam; Lee, Helen; Smith, Helen; Inness, Emma; Kendall, Eunice; Mayers, David; Wilkinson, Nick; Clinch, Jacqui; Pluess‐Hall, Helen

    2015-01-01

    Objective The Pediatric Rheumatology International Trials Organisation (PRINTO) recently published criteria for classification of patients with juvenile dermatomyositis (DM) as having clinically inactive disease. The criteria require that at least 3 of 4 conditions be met, i.e., creatine kinase level ≤150 units/liter, Childhood Myositis Assessment Scale score ≥48, Manual Muscle Testing in 8 muscles score ≥78, and physician's global assessment of overall disease activity (PGA) ≤0.2. The present study was undertaken to test these criteria in a UK cohort of patients with juvenile DM. Methods We assessed 1,114 patient visits for the 4 items in the PRINTO criteria for clinically inactive disease. Each visit was analyzed to determine whether skin disease was present. The Disease Activity Score (DAS) for juvenile DM was determined in 59 patients. Results At 307 of the 1,114 visits, clinically inactive disease was achieved based on the 3 muscle criteria (but with a PGA of >0.2); rash was present at 65.8% of these visits and nailfold capillary abnormalities at 35.2%. When PGA ≤0.2 was one of the 3 criteria that were met, the frequency of skin signs was significantly lower (rash in 23.1% and nailfold capillary abnormalities in 8.7%). If PGA was considered an essential criterion for clinically inactive disease (P‐CID), patients with active skin disease were less likely to be categorized as having clinically inactive disease (a median DAS skin score of 0 [of a possible maximum of 9] in visits where the PGA was ≤0.2, versus a median DAS skin score of 4 in patients meeting the 3 muscle criteria [with a PGA of >0.2]; P < 0.001). Use of the P‐CID led to improvements in the positive predictive value and the positive likelihood ratio (85.4% and 11.0, respectively, compared to 72.9% and 5.1 with the current criteria). Conclusion There was a high frequency of skin disease among patients with juvenile DM who did not meet the PGA criterion for inactive disease but met

  6. Skin and kidney histological changes in graft-versus-host disease (GVHD) after kidney transplantation.

    PubMed

    Pintar, Tadeja; Alessiani, Mario; Pleskovič, Alojz; Pleskovič, Aleš; Zorc-Pleskovič, Ruda; Milutinović, Aleksandra

    2011-05-01

    Kidney transplantation (Ktx) is generally performed during end stage renal disease due to a loss of the kidneys' ability to filter wastes from the circulatory system. Acute graft-versus-host disease (GVHD) after Ktx is a life-threatening complication that progresses to organ failure, systemic complications, and death. The current study evaluated the significance of histologic findings of GVHD as obtained from skin biopsies following Ktx in swine. A swine model of Ktx with tacrolimus-based immunosuppression was used to assess possible correlations between acute-graft-cellular rejection and skin histological findings for prediction of GVHD. Animals were divided into a Ktx treatment group or a control group with no Ktx and skin and kidney biopsies were histologically assessed at postoperative days 0, 15, 30, 45 and 60. Skin samples were analyzed and classified from grade 1 to 4 of skin GVHD and the major histopathological changes of kidney acute cellular rejection were described using Banff's score system. We observed a significant linear correlation between the histological grading values of skin biopsy changes and the histological grading values of kidney biopsies (Kendall's tau_b=0.993) in the Ktx experimental group. No histological changes were observed in controls. Our findings demonstrate the diagnostic value of staging skin GVHD after Ktx and suggest it's future utility for monitoring long term Ktx-induced changes.

  7. Ionic liquids as antimicrobials, solvents, and prodrugs for treating skin disease

    NASA Astrophysics Data System (ADS)

    Zakrewsky, Michael A.

    The skin is the largest organ in the body. It provides a compliant interface for needle-free drug delivery, while avoiding major degradative pathways associated with the GI tract. These can result in improved patient compliance and sustained and controlled release compared to other standard delivery methods such as intravenous injection, subcutaneous injection, and oral delivery. Concurrently, for the treatment of skin related diseases (e.g. bacterial infection, skin cancer, psoriasis, atopic dermatitis, etc.) cutaneous application provides targeted delivery to the disease site, allowing the use of more potent therapeutics with fewer systemic side effects. Unfortunately, the outer layer of the skin -- the stratum corneum (SC) -- presents a significant barrier to most foreign material. This is particularly true for large hydrophilic molecules (>500Da), which must partition through tortuous lipid channels in the SC to penetrate deep tissue layers where the majority of skin-related diseases reside. Interestingly, over the last few decades ionic liquids (ILs) have emerged as a burgeoning class of designer solvents. ILs have been proven beneficial for use in industrial processing, catalysis, pharmaceuticals, and electrochemistry to name a few. The ability to modulate either the cation or anion individually presents an advantageous framework for tuning secondary characteristics without sacrificing the primary function of the IL. Here we report the use of novel ILs for cutaneous drug delivery. Specifically, we demonstrate their potential as potent, broad-spectrum antimicrobials, as solvents for topical delivery of hydrophilic and hydrophobic drugs, and as prodrugs to either reduce the dose-dependent toxicity of drugs that cause skin irritation or enhance delivery of macromolecules into skin and cells. Thus, our results clearly demonstrate ILs holds promise as a transformative platform for treating skin disease.

  8. Puffy skin disease (PSD) in rainbow trout, Oncorhynchus mykiss (Walbaum): a case definition.

    PubMed

    Maddocks, C E; Nolan, E T; Feist, S W; Crumlish, M; Richards, R H; Williams, C F

    2015-07-01

    Puffy skin disease (PSD) is a disease that causes skin pathology in rainbow trout, Oncorhynchus mykiss (Walbaum). Incidence of PSD in UK fish farms and fisheries has increased sharply in the last decade, with growing concern from both industry sectors. This paper provides the first comprehensive case definition of PSD, combining clinical and pathological observations of diseased rainbow trout from both fish farms and fisheries. The defining features of PSD, as summarized in the case definition, were focal lateral flank skin lesions that appeared as cutaneous swelling with pigment loss and petechiae. These were associated with lethargy, poor body condition, inappetance and low level mortality. Epidermal hyperplasia and spongiosis, oedema of the dermis stratum spongiosum and a mild diffuse inflammatory cellularity were typical in histopathology of skin. A specific pathogen or aetiology was not identified. Prevalence and severity of skin lesions was greatest during late summer and autumn, with the highest prevalence being 95%. Atypical lesions seen in winter and spring were suggestive of clinical resolution. PSD holds important implications for both trout aquaculture and still water trout fisheries. This case definition will aid future diagnosis, help avoid confusion with other skin conditions and promote prompt and consistent reporting.

  9. Altered manifestations of skin disease at sites affected by neurological deficit

    PubMed Central

    Azimi, E.; Lerner, E.A.; Elmariah, S.B.

    2014-01-01

    The contribution of the nervous system to inflammation in general and inflammatory skin disease in particular has been underappreciated. It is now apparent that the conventional clinical manifestations of many inflammatory skin diseases require an intact neural component. We reviewed the literature and identified 23 cases of alterations in the appearance or distribution of skin disorders in patients with acquired central or peripheral neural damage or dysfunction. In 19 cases, near or complete resolution of pre-existing skin lesions occurred in areas directly or indirectly supplied by a subsequently injured nervous system. Exacerbation or new onset of skin lesions occurred in only 4 cases. The neural deficits described included damage within the peripheral or central nervous system resulting in pure sensory, pure motor, or combined sensory and motor deficits. These cases highlight the importance of neural innervation and neurogenic inflammation in the development of inflammatory skin disease and prompt further examination of the use of neural blockade as an adjunctive therapy in the treatment of inflammatory dermatoses. PMID:25132518

  10. Nephrotic syndrome of minimal change disease following exposure to mercury-containing skin-lightening cream.

    PubMed

    Zhang, Lin; Liu, Fuyou; Peng, Youming; Sun, Lin; Chen, Chunguo

    2014-01-01

    A 28-year-old female suffered from nephrotic syndrome after a long-term use of mercury-containing, skin-lightening cream. The blood and urinary mercury content of this patient increased with use. Renal biopsy showed minimal change disease. Her symptoms were relieved 6 months after discontinuing use of the cream and receiving sodium dimercaptosulfonate and glucocorticosteroid treatments. Proteinuria disappeared, and blood and urinary mercury levels returned to normal. Previous reports of nephrotic syndrome caused by mercury-containing, skin-lightening creams have mostly been identified as be.ing due to membranous nephropathy. Minimal change disease has been reported in a few case reports published in the English language. Here we report a case of nephrotic syndrome with minimal change disease following exposure to a mercury-containing, skin-lightening cream. We also reviewed relevant published reports to summarize clinical features and treatments and to explore the possible mechanisms involved.

  11. Exposure to ambient bioaerosols is associated with allergic skin diseases in Greater Taipei residents.

    PubMed

    Kallawicha, Kraiwuth; Chuang, Ying-Chih; Lung, Shih-Chun Candice; Han, Bor-Cheng; Ting, Yi-Fang; Chao, Hsing Jasmine

    2016-09-01

    Allergic skin diseases may result from various types of chemical and biological allergens. This study investigated the association between ambient bioaerosol exposure and allergic skin diseases by using the exposure data obtained from land use regression models and interpolated data. Data on daily average outpatient visits for atopic dermatitis (ICD-9-CM 691.8) and contact dermatitis and other eczema (ICD-9-CM 692.9) between November 2011 and August 2012 were obtained from the National Health Insurance Research Database. A generalized estimating equation was used to analyze the associations between the skin diseases and ambient bioaerosol levels. The results indicated that during the study period, contact dermatitis and other eczema were more prevalent than atopic dermatitis in the study area. Most cases were observed in districts of Taipei City and 3 major districts of New Taipei City, namely Xinzhuang, Banqiao, and Xindian. In univariate analysis, most bioaerosols were positively associated with both skin diseases. After adjustment for air pollution and sociodemographic factors, exposure to total fungal spores was significantly associated with atopic dermatitis in males (relative risk [RR] = 1.12; 95% confidence interval [CI] = 1.05-1.19). Contact dermatitis and other eczema had significant relationships with Cladosporium in males (RR = 1.07; 95% CI = 1.02-1.14) and with Aspergillus/Penicillium in females (RR = 1.04; 95% CI = 1.02-1.07). Meteorological parameters, namely wind speed, temperature, and rainfall, were also significantly associated with skin diseases. Our findings reveal that exposure to ambient bioaerosols is a significant and independent risk factor for allergic skin diseases. PMID:27389548

  12. Inherited prion disease A117V is not simply a proteinopathy but produces prions transmissible to transgenic mice expressing homologous prion protein.

    PubMed

    Asante, Emmanuel A; Linehan, Jacqueline M; Smidak, Michelle; Tomlinson, Andrew; Grimshaw, Andrew; Jeelani, Asif; Jakubcova, Tatiana; Hamdan, Shyma; Powell, Caroline; Brandner, Sebastian; Wadsworth, Jonathan D F; Collinge, John

    2013-01-01

    Prions are infectious agents causing fatal neurodegenerative diseases of humans and animals. In humans, these have sporadic, acquired and inherited aetiologies. The inherited prion diseases are caused by one of over 30 coding mutations in the human prion protein (PrP) gene (PRNP) and many of these generate infectious prions as evidenced by their experimental transmissibility by inoculation to laboratory animals. However, some, and in particular an extensively studied type of Gerstmann-Sträussler-Scheinker syndrome (GSS) caused by a PRNP A117V mutation, are thought not to generate infectious prions and instead constitute prion proteinopathies with a quite distinct pathogenetic mechanism. Multiple attempts to transmit A117V GSS have been unsuccessful and typical protease-resistant PrP (PrP(Sc)), pathognomonic of prion disease, is not detected in brain. Pathogenesis is instead attributed to production of an aberrant topological form of PrP, C-terminal transmembrane PrP ((Ctm)PrP). Barriers to transmission of prion strains from one species to another appear to relate to structural compatibility of PrP in host and inoculum and we have therefore produced transgenic mice expressing human 117V PrP. We found that brain tissue from GSS A117V patients did transmit disease to these mice and both the neuropathological features of prion disease and presence of PrP(Sc) was demonstrated in the brains of recipient transgenic mice. This PrP(Sc) rapidly degraded during laboratory analysis, suggesting that the difficulty in its detection in patients with GSS A117V could relate to post-mortem proteolysis. We conclude that GSS A117V is indeed a prion disease although the relative contributions of (Ctm)PrP and prion propagation in neurodegeneration and their pathogenetic interaction remains to be established.

  13. Epidermal dysplasia and Malassezia infection in two West Highland White Terrier siblings: an inherited skin disorder or reaction to severe Malassezia infection?

    PubMed

    Nett, C S; Reichler, I; Grest, P; Hauser, B; Reusch, C E

    2001-10-01

    Two 9-month-old West Highland White Terrier siblings were referred to our clinic with pruritus, alopecia and lichenification. Cytological examination of Scotch tape strippings revealed Malassezia organisms and cocci. Skin biopsy specimens showed epidermal dysplasia. Treatment included bathing with a 2% miconazole/chlorhexidine-containing shampoo, orally administered ketoconazole (5 mg kg-1, every 12 h) and cloxacillin (25 mg kg-1 every 8 h). Six weeks later, the dermal infection had resolved and there was hair regrowth. However, the dogs were still moderately pruritic. Intradermal allergy testing was positive for house dust mites, storage mites and Malassezia. Immunotherapy was initiated, and treatment with ketoconazole and cloxacillin was stopped. Skin biopsies, which were performed in both dogs 4 months after the first presentation, revealed mild superficial perivascular dermatitis. The remaining mild facial pruritus was easily controlled with topical treatment. These two cases indicate that epidermal dysplasia might be an inflammatory or hypersensitivity reaction to the Malassezia infection or a result of excessive self-trauma, rather than a congenital keratinization disorder. PMID:11906654

  14. Epidermal dysplasia and Malassezia infection in two West Highland White Terrier siblings: an inherited skin disorder or reaction to severe Malassezia infection?

    PubMed

    Nett, C S; Reichler, I; Grest, P; Hauser, B; Reusch, C E

    2001-10-01

    Two 9-month-old West Highland White Terrier siblings were referred to our clinic with pruritus, alopecia and lichenification. Cytological examination of Scotch tape strippings revealed Malassezia organisms and cocci. Skin biopsy specimens showed epidermal dysplasia. Treatment included bathing with a 2% miconazole/chlorhexidine-containing shampoo, orally administered ketoconazole (5 mg kg-1, every 12 h) and cloxacillin (25 mg kg-1 every 8 h). Six weeks later, the dermal infection had resolved and there was hair regrowth. However, the dogs were still moderately pruritic. Intradermal allergy testing was positive for house dust mites, storage mites and Malassezia. Immunotherapy was initiated, and treatment with ketoconazole and cloxacillin was stopped. Skin biopsies, which were performed in both dogs 4 months after the first presentation, revealed mild superficial perivascular dermatitis. The remaining mild facial pruritus was easily controlled with topical treatment. These two cases indicate that epidermal dysplasia might be an inflammatory or hypersensitivity reaction to the Malassezia infection or a result of excessive self-trauma, rather than a congenital keratinization disorder.

  15. Cytochrome b5 null mouse: a new model for studying inherited skin disorders and the role of unsaturated fatty acids in normal homeostasis.

    PubMed

    Finn, Robert D; McLaughlin, Lesley A; Hughes, Catherine; Song, Chengli; Henderson, Colin J; Roland Wolf, C

    2011-06-01

    Microsomal cytochrome b (5) is a ubiquitous, 15.2 kDa haemoprotein implicated in a number of cellular processes such as fatty acid desaturation, drug metabolism, steroid hormone biosynthesis and methaemoglobin reduction. As a consequence of these functions this protein has been considered essential for life. Most of the ascribed functions of cytochrome b (5), however, stem from in vitro studies and for this reason we have carried out a germline deletion of this enzyme. We have unexpectedly found that cytochrome b (5) null mice were viable and fertile, with pups being born at expected Mendelian ratios. However, a number of intriguing phenotypes were identified, including altered drug metabolism, methaemoglobinemia and disrupted steroid hormone homeostasis. In addition to these previously identified roles for this protein, cytochrome b (5) null mice displayed skin defects closely resembling those observed in autosomal recessive congenital ichthyosis and retardation of neonatal development, indicating that this protein, possibly as a consequence of its role in the de novo biosynthesis of unsaturated fatty acids, plays a central role in skin development and neonatal nutrition. Results from fatty acid profile analysis of several tissues suggest that cytochrome b (5) plays a role controlling saturated/unsaturated homeostasis. These data demonstrate that regional concentrations of unsaturated fatty acids are controlled by endogenous metabolic pathways and not by diet alone.

  16. Essential Role of microRNA in Skin Physiology and Disease.

    PubMed

    Glavač, Damjan; Ravnik-Glavač, Metka

    2015-01-01

    The identification and characterization of microRNAs (miRNAs) is a rapidly growing area of research also in dermatology. Skin represents the largest organ in the human body, and its morphogenesis has been shown to require a highly coordinated and undisrupted miRNA profile. High expression of several miRNAs in the epidermis and hair follicles is necessary for normal skin development. Profiling studies have identified numerous differentially regulated miRNAs associated with either normal physiological status of the skin or some pathological processes or both. This chapter covers current knowledge of the important roles of miRNAs in the pathogenesis of some skin diseases including systemic lupus erythematosus (SLE), systemic sclerosis (SSc), dermatomyositis (DM), psoriasis (PS), and skin cancer, especially malignant melanoma (MM). In addition, the diagnostic and therapeutic relevance of miRNAs that are involved in pathological processes of the skin are elucidated providing further information for some possible clinical implications especially for their use as therapeutic targets or disease biomarkers. PMID:26663190

  17. Inherited platelet disorders.

    PubMed

    Franchini, Massimo; Lippi, Giuseppe; Veneri, Dino; Targher, Giovanni; Zaffanello, Marco; Guidi, Gian Cesare

    2008-01-01

    Inherited platelet disorders are a rare, but probably underdiagnosed, cause of symptomatic bleeding. They are characterized by abnormalities of platelet number (inherited thrombocytopenias), function (inherited disorders of platelet function) or both. This review briefly discusses the inherited platelet disorders with respect to molecular defects, diagnostic evaluation and treatment strategies.

  18. Exercise and Inherited Arrhythmias.

    PubMed

    Cheung, Christopher C; Laksman, Zachary W M; Mellor, Gregory; Sanatani, Shubhayan; Krahn, Andrew D

    2016-04-01

    Sudden cardiac death (SCD) in an apparently healthy individual is a tragedy that prompts a series of investigations to identify the cause of death and to prevent SCD in potentially at-risk family members. Several inherited channelopathies and cardiomyopathies, including long QT syndrome (LQTS), catecholaminergic polymorphic ventricular cardiomyopathy (CPVT), hypertrophic cardiomyopathy (HCM), and arrhythmogenic right ventricular cardiomyopathy (ARVC) are associated with exercise-related SCD. Exercise restriction has been a historical mainstay of therapy for these conditions. Syncope and cardiac arrest occur during exercise in LQTS and CPVT because of ventricular arrhythmias, which are managed with β-blockade and exercise restriction. Exercise may provoke hemodynamic or ischemic changes in HCM, leading to ventricular arrhythmias. ARVC is a disease of the desmosome, whose underlying disease process is accelerated by exercise. On this basis, expert consensus has erred on the side of caution, recommending rigorous exercise restriction for all inherited arrhythmias. With time, as familiarity with inherited arrhythmia conditions has increased and patients with milder forms of disease are diagnosed, practitioners have questioned the historical rigorous restrictions advocated for all. This change has been driven by the fact that these are often children and young adults who wish to lead active lives. Recent evidence suggests a lower risk of exercise-related arrhythmias in treated patients than was previously assumed, including those with previous symptoms managed with an implantable cardioverter-defibrillator. In this review, we emphasize shared decision making, monitored medical therapy, individual and team awareness of precautions and emergency response measures, and a more permissive approach to recreational and competitive exercise.

  19. Exercise and Inherited Arrhythmias.

    PubMed

    Cheung, Christopher C; Laksman, Zachary W M; Mellor, Gregory; Sanatani, Shubhayan; Krahn, Andrew D

    2016-04-01

    Sudden cardiac death (SCD) in an apparently healthy individual is a tragedy that prompts a series of investigations to identify the cause of death and to prevent SCD in potentially at-risk family members. Several inherited channelopathies and cardiomyopathies, including long QT syndrome (LQTS), catecholaminergic polymorphic ventricular cardiomyopathy (CPVT), hypertrophic cardiomyopathy (HCM), and arrhythmogenic right ventricular cardiomyopathy (ARVC) are associated with exercise-related SCD. Exercise restriction has been a historical mainstay of therapy for these conditions. Syncope and cardiac arrest occur during exercise in LQTS and CPVT because of ventricular arrhythmias, which are managed with β-blockade and exercise restriction. Exercise may provoke hemodynamic or ischemic changes in HCM, leading to ventricular arrhythmias. ARVC is a disease of the desmosome, whose underlying disease process is accelerated by exercise. On this basis, expert consensus has erred on the side of caution, recommending rigorous exercise restriction for all inherited arrhythmias. With time, as familiarity with inherited arrhythmia conditions has increased and patients with milder forms of disease are diagnosed, practitioners have questioned the historical rigorous restrictions advocated for all. This change has been driven by the fact that these are often children and young adults who wish to lead active lives. Recent evidence suggests a lower risk of exercise-related arrhythmias in treated patients than was previously assumed, including those with previous symptoms managed with an implantable cardioverter-defibrillator. In this review, we emphasize shared decision making, monitored medical therapy, individual and team awareness of precautions and emergency response measures, and a more permissive approach to recreational and competitive exercise. PMID:26927864

  20. Gene conversion causing human inherited disease: evidence for involvement of non-B-DNA-forming sequences and recombination-promoting motifs in DNA breakage and repair

    PubMed Central

    Chuzhanova, Nadia; Chen, Jian-Min; Bacolla, Albino; Patrinos, George P.; Férec, Claude; Wells, Robert D.; Cooper, David N.

    2009-01-01

    A variety of DNA sequence motifs including inverted repeats, minisatellites, and the χ recombination hotspot, have been reported in association with gene conversion in human genes causing inherited disease. However, no methodical statistically-based analysis has been performed to formalize these observations. We have performed an in silico analysis of the DNA sequence tracts involved in 27 non-overlapping gene conversion events in 19 different genes reported in the context of inherited disease. We found that gene conversion events tend to occur within (C+G)- and CpG-rich regions and that sequences with the potential to form non-B-DNA structures, and which may be involved in the generation of double-strand breaks that could in turn serve to promote gene conversion, occur disproportionately within maximal converted tracts and/or short flanking regions. Maximal converted tracts were also found to be enriched (p<0.01) in a truncated version of the χ-element (a TGGTGG motif), immunoglobulin heavy chain class switch repeats, translin target sites and several novel motifs including (or overlapping) the classical meiotic recombination hotspot, CCTCCCCT. Finally, gene conversions tend to occur in genomic regions that have the potential to fold into stable hairpin conformations. These findings support the concept that recombination-inducing motifs, in association with alternative DNA conformations, can promote recombination in the human genome. PMID:19431182

  1. Characterization of a conserved aphidicolin-sensitive common fragile site at human 4q22 and mouse 6C1: possible association with an inherited disease and cancer.

    PubMed

    Rozier, Lorène; El-Achkar, Eliane; Apiou, Françoise; Debatisse, Michelle

    2004-09-01

    Fragile sites are classified as common or rare depending on their occurrence in the populations. While rare sites are mainly associated with inherited diseases, common sites have been involved in somatic rearrangements found in the chromosomes of cancer cells. Here we study a mouse locus containing the ionotropic glutamate receptor delta 2 (grid2) gene in which spontaneous chromosome rearrangements occur frequently, giving rise to mutant animals in inbred populations. We identify and clone common fragile sites overlapping the mouse grid2 gene and its human ortholog GRID2, lying respectively at bands 6C1 and 4q22 in a 7-Mb-long region of synteny. These results show a third example of orthologous common sites conserved at the molecular level, and reveal an unexpected link between an inherited disease and an aphidicolin-sensitive region. Recurrent deletions of subregions of band 4q22 have been previously described in human hepatocellular carcinomas. This 15-Mb-long region appears precisely centered on the site described here, which strongly suggests that it also plays a specific role in hepatic carcinogenesis.

  2. Effects and dose--response relationships of skin cancer and blackfoot disease with arsenic.

    PubMed

    Tseng, W P

    1977-08-01

    In a limited area on the southwest coast of Taiwan, where artesian well water with a high concentration of arsenic has been used for more than 60 years, a high prevalence of chronic arsenicism has been observed in recent years. The total population of this "endemic" area is approximately 100,000. A general survey of 40,421 inhabitants and follow-up of 1,108 patients with blackfoot disease were made. Blackfoot disease, so-termed locally, is a peripheral vascular disorder resulting in gangrene of the extremities, especially the feet. The overall prevalence rates for skin cancer was 10.6 per 1000, and for blackfoot disease 8.9 per 1000. Generally speaking, the prevalence increased steadily with age in both diseases. The prevalence rates for skin cancer and blackfoot disease increased with the arsenic content of well water, i.e., the higher the arsenic content, the more patients with skin cancer and blackfoot disease. A dose-response relationship between blackfoot disease and the duration of water intake was also noted. Furthermore, the degree of permanent impairment of function in the patient was directly related to duration of intake of arsenical water and to duration of such intake at the time of onset. The most common cause of death in the patients with skin cancer and blackfoot disease was carcinoma of various sites. The 5-year survival rate after the onset of blackfoot disease was 76.3%; the 10-year survival rate was 63.3% and 15-year survival rate, 52.2%. The 50% survival point was 16 years after onset of the disease.

  3. Immunofluorescence Patterns in Selected Dermatoses, Including Blistering Skin Diseases Utilizing Multiple Fluorochromes

    PubMed Central

    Abreu-Velez, Ana Maria; Calle-Isaza, Juliana; Howard, Michael S.

    2015-01-01

    Background: Autoimmune vesiculobullous disorders represent a heterogeneous group of dermatoses whose diagnosis is made based on clinical history, histologic features, and immunopathologic features. The most commonly used techniques for the diagnosis of these diseases are direct and indirect immunofluorescence (DIF and IIF), including salt-split processing. NaCl split skin is used to determine the level of blister formation, and the localization of autoantibodies relative to the split. Classically, immunofluorescence has been performed with one fluorochrome in the diagnosis of autoimmune bullous skin diseases. Aims: To compare DIF and IIF of the skin, using a single fluorochrome versus multiple fluorochromes. Materials and Methods: We studied 20 autoimmune skin disease cases using fluorescein isothiocyanate (FITC) alone, in comparison to multiple fluorochromes (with or without DNA counterstaining). Results: The use of multiple fluorochromes helped to simultaneously visualize reactivity in multiple skin areas, in contrast to using FITC alone. Conclusions: Using multiple fluorochromes allows simultaneous labeling of two or more antigens within the same cell/or tissue section, assists in colocalization of unknown antigens with known molecules, and helps in ruling out “background” staining. PMID:26605203

  4. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2012.

    PubMed

    Sicherer, Scott H; Leung, Donald Y M

    2013-01-01

    This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin diseases that were reported in the Journal in 2012. Studies support an increase in peanut allergy prevalence in children and exposure to the antibacterial agent triclosan and having filaggrin (FLG) loss-of-function mutations as risk factors for food sensitization. The role of specific foods in causing eosinophilic esophagitis is elucidated by several studies, and microRNA analysis is identified as a possible noninvasive disease biomarker. Studies on food allergy diagnosis emphasize the utility of component testing and the possibility of improved diagnosis through stepped approaches, epitope-binding analysis, and bioinformatics. Treatment studies of food allergy show promise for oral immunotherapy, but tolerance induction remains elusive, and additional therapies are under study. Studies on anaphylaxis suggest an important role for platelet-activating factor and its relationship to the need for prompt treatment with epinephrine. Insights on the pathophysiology and diagnosis of non-IgE-mediated drug allergy are offered, with novel data regarding the interaction of drugs with HLA molecules. Numerous studies support influenza vaccination of persons with egg allergy using modest precautions. Evidence continues to mount that there is cross-talk between skin barrier defects and immune responses in patients with atopic dermatitis. Augmentation of the skin barrier with reduction in skin inflammatory responses will likely lead to the most effective intervention in patients with this common skin disease.

  5. Clinical combination of multiphoton tomography and high frequency ultrasound imaging for evaluation of skin diseases

    NASA Astrophysics Data System (ADS)

    König, K.; Speicher, M.; Koehler, M. J.; Scharenberg, R.; Elsner, P.; Kaatz, M.

    2010-02-01

    For the first time, high frequency ultrasound imaging, multiphoton tomography, and dermoscopy were combined in a clinical study. Different dermatoses such as benign and malign skin cancers, connective tissue diseases, inflammatory skin diseases and autoimmune bullous skin diseases have been investigated with (i) state-of-the-art and highly sophisticated ultrasound systems for dermatology, (ii) the femtosecond-laser multiphoton tomograph DermaInspectTM and (iii) dermoscopes. Dermoscopy provides two-dimensional color imaging of the skin surface with a magnification up to 70x. Ultrasound images are generated from reflections of the emitted ultrasound signal, based on inhomogeneities of the tissue. These echoes are converted to electrical signals. Depending on the ultrasound frequency the penetration depth varies from about 1 mm to 16 mm in dermatological application. The 100-MHz-ultrasound system provided an axial resolution down to 16 μm and a lateral resolution down to 32 μm. In contrast to the wide-field ultrasound images, multiphoton tomography provided horizontal optical sections of 0.36×0.36 mm2 down to 200 μm tissue depth with submicron resolution. The autofluorescence of mitochondrial coenzymes, melanin, and elastin as well as the secondharmonic- generation signal of the collagen network were imaged. The combination of ultrasound and multiphoton tomography provides a novel opportunity for diagnostics of skin disorders.

  6. Topical hypochlorite ameliorates NF-κB–mediated skin diseases in mice

    PubMed Central

    Leung, Thomas H.; Zhang, Lillian F.; Wang, Jing; Ning, Shoucheng; Knox, Susan J.; Kim, Seung K.

    2013-01-01

    Nuclear factor-κB (NF-κB) regulates cellular responses to inflammation and aging, and alterations in NF-κB signaling underlie the pathogenesis of multiple human diseases. Effective clinical therapeutics targeting this pathway remain unavailable. In primary human keratinocytes, we found that hypochlorite (HOCl) reversibly inhibited the expression of CCL2 and SOD2, two NF-κB–dependent genes. In cultured cells, HOCl inhibited the activity of inhibitor of NF-κB kinase (IKK), a key regulator of NF-κB activation, by oxidizing cysteine residues Cys114 and Cys115. In NF-κB reporter mice, topical HOCl reduced LPS-induced NF-κB signaling in skin. We further evaluated topical HOCl use in two mouse models of NF-κB–driven epidermal disease. For mice with acute radiation dermatitis, topical HOCl inhibited the expression of NF-κB–dependent genes, decreased disease severity, and prevented skin ulceration. In aged mice, topical HOCl attenuated age-dependent production of p16INK4a and expression of the DNA repair gene Rad50. Additionally, skin of aged HOCl-treated mice acquired enhanced epidermal thickness and proliferation, comparable to skin in juvenile animals. These data suggest that topical HOCl reduces NF-κB–mediated epidermal pathology in radiation dermatitis and skin aging through IKK modulation and motivate the exploration of HOCl use for clinical aims. PMID:24231355

  7. Discrimination of skin diseases using the multimodal imaging approach

    NASA Astrophysics Data System (ADS)

    Vogler, N.; Heuke, S.; Akimov, D.; Latka, I.; Kluschke, F.; Röwert-Huber, H.-J.; Lademann, J.; Dietzek, B.; Popp, J.

    2012-06-01

    Optical microspectroscopic tools reveal great potential for dermatologic diagnostics in the clinical day-to-day routine. To enhance the diagnostic value of individual nonlinear optical imaging modalities such as coherent anti-Stokes Raman scattering (CARS), second harmonic generation (SHG) or two-photon excited fluorescence (TPF), the approach of multimodal imaging has recently been developed. Here, we present an application of nonlinear optical multimodal imaging with Raman-scattering microscopy to study sizable human-tissue cross-sections. The samples investigated contain both healthy tissue and various skin tumors. This contribution details the rich information content, which can be obtained from the multimodal approach: While CARS microscopy, which - in contrast to spontaneous Raman-scattering microscopy - is not hampered by single-photon excited fluorescence, is used to monitor the lipid and protein distribution in the samples, SHG imaging selectively highlights the distribution of collagen structures within the tissue. This is due to the fact, that SHG is only generated in structures which lack inversion geometry. Finally, TPF reveals the distribution of autofluorophores in tissue. The combination of these techniques, i.e. multimodal imaging, allows for recording chemical images of large area samples and is - as this contribution will highlight - of high clinically diagnostic value.

  8. Design and bioevaluation of a 32P-patch for brachytherapy of skin diseases.

    PubMed

    Salgueiro, M J; Durán, H; Palmieri, M; Pirchio, R; Nicolini, J; Ughetti, R; Papparella, M L; Casale, G; Zubillaga, M

    2008-03-01

    The purpose of this study was to design and evaluate a 32P patch for brachytherapy of skin diseases. We employed Phosphoric-32P-acid and Chromic 32P-phosphate in combination with natural rubber or silicone to produce the patches. Stability studies in vitro to evaluate the leakage of radioactivity, autoradiographic studies to evaluate homogeneity and shielding, as well as therapeutic efficacy in an animal model of skin cancer of the selected 32P patch were performed. The 32P-silicone-patch demonstrated its safety for external application. Tumor growth was arrest and complete regressions of tumors were seen in some other cases with 40 Gy applied in a single-dose scheme. In conclusion, the 32P-silicone-patch is easy to prepare and use in the treatment of skin diseases.

  9. Occupational skin diseases from 1997 to 2004 at the Department of Dermatology, University Hospital of Northern Norway (UNN): an investigation into the course and treatment of occupational skin disease 10–15 years after first consultations with a dermatologist

    PubMed Central

    Braun, Rosemarie; Dotterud, Lars Kåre

    2016-01-01

    Objectives We investigate the impact of occupational skin disease consultations among outpatients at the Dermatological Department, University Hospital, Northern Norway. Study design From 1997 until 2004, 386 patients with occupational skin disease were examined and given advice on skin care, skin disease treatment, skin protection in further work, and on the legal rights of patients with this disease. Ten to fifteen years later, we wanted to look at these patients in terms of their work situation, the current status of their disease, the help they received from the labour offices, and their subjective quality of life. Material and methods In the autumn of 2011 until the spring of 2012, a number of the patients examined in the period from 1997 to 2004 were selected and sent a questionnaire, which they were asked to answer and return, regarding their work situation and the progress and current status of their occupational disease. Results A total of 153 (77%) patients answered the questionnaire; 71% of these patients were still in work, and further 15% had old-age retired, 13% were working until then; 16% had retired early because of disability; 54% had changed jobs because of their occupational skin disease; 86% of the patients indicated that the skin disease had improved since our previous investigation. Conclusions Our investigation into patients with occupational skin disease documented that the majority of patients who had received professional dermatological consultation and intervention offers were still in the labour market and had good control of their skin disease 10–15 years later. We discovered that 71% of the patients were still employed. 13% had remained in work until they became old age pensioners. Only 16% dropped out of work because of disability. These high percentages may indicate that our intervention has contributed positively to patients’ work conditions and the course of their skin disease. PMID:27172061

  10. Three cases of immune-mediated adnexal skin disease treated with cyclosporin.

    PubMed

    Noli, Chiara; Toma, Stefano

    2006-02-01

    Cyclosporin is currently considered a new and interesting drug in veterinary dermatology for the treatment of immune-mediated skin diseases, and a safe and effective alternative to immunosuppressive therapy with glucocorticoids. The authors report a case of granulomatous folliculitis and furunculosis and of sebaceous adenitis in two cats and a case of alopecia areata in a dog, successfully controlled with cyclosporin.

  11. Highlights from special issue: junctional targets of skin and heart diseases.

    PubMed

    Delmar, Mario; Green, Kathleen; Cowin, Pamela

    2014-02-01

    In this issue, guest editors Kathy Green and Mario Delmar, who are leaders in the fields of epidermal desmosomes and heart intercalated discs respectively, have joined forces to collate a two-part series of reviews focused on junctional proteins and genes that are targets of skin and heart diseases.

  12. The Occurrence and Prevalence of Giraffe Skin Disease in Protected Areas of Northern Tanzania.

    PubMed

    Lee, Derek E; Bond, Monica L

    2016-07-01

    Giraffe skin disease (GSD) is a disorder of undetermined etiology that causes lesions on the forelimbs of Masai giraffe ( Giraffa camelopardalis tippelskirchi). We estimated occurrence and prevalence of GSD in six wildlife conservation areas of Tanzania. The disjunct spatial pattern of occurrence implies that environmental factors may influence GSD. PMID:27310168

  13. Near-infrared Hyperspectral Reflectance Imaging for Early Detection of Sour Skin Disease in Vidalia Sweet Onions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sour skin is a major onion disease caused by the bacterium Burkholderia cepacia (B. cepacia). It not only causes substantial economic loss from diseased onions but also could lead to pulmonary infection in humans. It is critical to prevent onions infected by sour skin from entering storage rooms or ...

  14. Prevalence of Skin and Skin-Related Diseases in the Rochester Epidemiology Project and a Comparison with Other Published Prevalence Studies.

    PubMed

    Andersen, Louise K; Davis, Mark D P

    2016-01-01

    In Olmsted County, Minn., USA, reliable, population-based epidemiologic research studies can be performed because of a unique medical records linkage system, the Rochester Epidemiology Project (REP). Our objective was to summarize the epidemiologic data describing the prevalence of skin and skin-related diseases derived from the REP and to compare the findings with those from other studies worldwide. Retrospectively, we reviewed the results of population-based REP studies reporting the prevalence of skin and skin-related diseases over more than 4 decades and compared them to other published prevalences globally. Prevalences from the REP reported per 100,000 persons were as follows: hidradenitis suppurativa, 130.0; psoriasis, 700.0; psoriatic arthritis in 1992, 100.0, and in 2000, 160.0; Behçet disease, 5.2; scleroderma, 13.8; dermatomyositis, 21.42; systemic lupus erythematosus (SLE), from 30.5 to 122.0 suspected SLE, 32.8; combined SLE, 41.8; discoid lupus erythematosus, 27.6, and cutaneous lupus erythematosus, 70.4 and 73.2 (from 2 studies). Many of the population-based prevalences of specific skin and skin-related diseases derived from the REP are different from those estimated globally. Suggested reasons for disparity in the prevalences globally may include differences in the type of reported prevalence, study methodology, geographic areas, ethnic groups, age distribution, and socioeconomic status. PMID:27011206

  15. Panel-based Genetic Diagnostic Testing for Inherited Eye Diseases is Highly Accurate and Reproducible and More Sensitive for Variant Detection Than Exome Sequencing

    PubMed Central

    Bujakowska, Kinga M.; Sousa, Maria E.; Fonseca-Kelly, Zoë D.; Taub, Daniel G.; Janessian, Maria; Wang, Dan Yi; Au, Elizabeth D.; Sims, Katherine B.; Sweetser, David A.; Fulton, Anne B.; Liu, Qin; Wiggs, Janey L.; Gai, Xiaowu; Pierce, Eric A.

    2015-01-01

    Purpose Next-generation sequencing (NGS) based methods are being adopted broadly for genetic diagnostic testing, but the performance characteristics of these techniques have not been fully defined with regard to test accuracy and reproducibility. Methods We developed a targeted enrichment and NGS approach for genetic diagnostic testing of patients with inherited eye disorders, including inherited retinal degenerations, optic atrophy and glaucoma. In preparation for providing this Genetic Eye Disease (GEDi) test on a CLIA-certified basis, we performed experiments to measure the sensitivity, specificity, reproducibility as well as the clinical sensitivity of the test. Results The GEDi test is highly reproducible and accurate, with sensitivity and specificity for single nucleotide variant detection of 97.9% and 100%, respectively. The sensitivity for variant detection was notably better than the 88.3% achieved by whole exome sequencing (WES) using the same metrics, due to better coverage of targeted genes in the GEDi test compared to commercially available exome capture sets. Prospective testing of 192 patients with IRDs indicated that the clinical sensitivity of the GEDi test is high, with a diagnostic rate of 51%. Conclusion The data suggest that based on quantified performance metrics, selective targeted enrichment is preferable to WES for genetic diagnostic testing. PMID:25412400

  16. Inherited ichthyosis: Syndromic forms.

    PubMed

    Yoneda, Kozo

    2016-03-01

    Among diseases that cause ichthyosis as one of the symptoms, there are some diseases that induce abnormalities in organs other than the skin. Of these, diseases with characteristic signs are regarded as syndromes. Although these syndromes are very rare, Netherton syndrome, Sjögren-Larsson syndrome, Conradi-Hünermann-Happle syndrome, Dorfman-Chanarin syndrome, ichthyosis follicularis, atrichia and photophobia (IFAP) syndrome, and Refsum syndrome have been described in texts as representative ones. It is important to know the molecular genetics and pathomechanisms in order to establish an effective therapy and beneficial genetic counseling including a prenatal diagnosis.

  17. Senescent phenotypes of skin fibroblasts from patients with Tangier disease

    SciTech Connect

    Matsuura, Fumihiko . E-mail: fumihiko@imed2.med.osaka-u.ac.jp; Hirano, Ken-ichi; Ikegami, Chiaki; Sandoval, Jose C.; Oku, Hiroyuki; Yuasa-Kawase, Miyako; Tsubakio-Yamamoto, Kazumi; Koseki, Masahiro; Masuda, Daisaku; Tsujii, Ken-ichi; Shimomura, Iichiro; Hori, Masatsugu; Yamashita, Shizuya; Ishigami, Masato; Nishida, Makoto

    2007-06-01

    Tangier disease (TD) is characterized by a deficiency of high density lipoprotein (HDL) in plasma and patients with TD have an increased risk for coronary artery disease (CAD). Recently, we reported that fibroblasts from TD exhibited large and flattened morphology, which is often observed in senescent cells. On the other hand, data have accumulated to show the relationship between cellular senescence and development of atherosclerotic CAD. The aim of the present study was to investigate whether TD fibroblasts exhibited cellular senescence. The proliferation of TD fibroblasts was gradually decreased at population doubling level (PDL) {approx}10 compared with control cells. TD cells practically ceased proliferation at PDL {approx}30. DNA synthesis was markedly decreased in TD fibroblasts. TD cells exhibited a higher positive rate for senescence-associated {beta}-galactosidase (SA-{beta}-gal), which is one of the biomarkers of cellular senescence in vitro. These data showed that TD cells reached cellular senescence at an earlier PDL compared with controls. Although, there was no difference in the telomere length of fibroblasts between TD and controls at the earlier passage (PDL 6), the telomere length of TD cells was shorter than that of controls at the late passage (PDL 25). Taken together, the current study demonstrates that the late-passaged TD fibroblasts showed senescent phenotype in vitro, which might be related to the increased cardiovascular manifestations in TD patients.

  18. Skin in health and diseases in ṛgveda saṃhiṭa: an overview.

    PubMed

    Mukhopadhyay, Amiya Kumar

    2013-11-01

    Ṛgveda is the oldest religious book of the Aryans. It picturises the early lives of the Aryans. We get mention of various diseases in this Veda. Skin - both in health and diseases had caught attention of the Vedic sages. Skin was not merely an organ of attraction and look but its colour was important socially. Mentions of various diseases like leprosy, guinea worm, jaundice etc., are interesting. Mention of different disorders of the nails and hair are also there, though in a very primitive and mystic form. Management strategy was consisted of herbs, amulates, chanting of mantras, touching the body, uses of water and sunrays etc. This may be presumed that this Veda founded the base for the Āyurveda of the later period.

  19. Skin in Health and Diseases in Ṛgveda Saṃhiṭa: An Overview

    PubMed Central

    Mukhopadhyay, Amiya Kumar

    2013-01-01

    Ṛgveda is the oldest religious book of the Aryans. It picturises the early lives of the Aryans. We get mention of various diseases in this Veda. Skin - both in health and diseases had caught attention of the Vedic sages. Skin was not merely an organ of attraction and look but its colour was important socially. Mentions of various diseases like leprosy, guinea worm, jaundice etc., are interesting. Mention of different disorders of the nails and hair are also there, though in a very primitive and mystic form. Management strategy was consisted of herbs, amulates, chanting of mantras, touching the body, uses of water and sunrays etc. This may be presumed that this Veda founded the base for the Āyurveda of the later period. PMID:24249889

  20. [Individual in-patient and out-patient prevention in occupational skin diseases].

    PubMed

    Skudlik, C; Weisshaar, E

    2015-03-01

    Concerning all occupation-related diseases, one-third of those reported in Germany are skin diseases. Among them, contact dermatitis is the most frequent skin disease. It usually presents as hand eczema leading to a loss of function and ability to work as well as reduced quality of life. Due to the high demand a number of prevention programmes were introduced. They comprise measures of secondary (out-patient) and tertiary (in-patient) prevention. Out-patient prevention measures include dermatologist's report and occupation-tailored teaching and prevention programmes. If the occupational skin disease is severe, therapy is not successful or the diagnosis is not clear measures of tertiary prevention can be offered as an in-patient treatment and prevention programme. All this aims to prevent the job loss of the patient. Preventive measures in occupational dermatology have proven to be very effective in recent years, especially measures of individual in-patient and out-patient prevention as components of a complex hierarchical prevention concept. This integrated concept of an in-patient/out-patient disease management reveals remarkable pertinent effectivity for patients with severe occupational dermatoses in risk professions.

  1. Lipid nanoparticles for improved topical application of drugs for skin diseases.

    PubMed

    Schäfer-Korting, Monika; Mehnert, Wolfgang; Korting, Hans-Christian

    2007-07-10

    Due to the lower risk of systemic side effects topical treatment of skin disease appears favourable, yet the stratum corneum counteracts the penetration of xenobiotics into viable skin. Particulate carrier systems may mean an option to improve dermal penetration. Since epidermal lipids are found in high amounts within the penetration barrier, lipid carriers attaching themselves to the skin surface and allowing lipid exchange between the outermost layers of the stratum corneum and the carrier appear promising. Besides liposomes, solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) have been studied intensively. Here we describe the potential of these carrier systems and compare the dermal uptake from SLN and NLC to the one of alternative vehicle systems. A special focus is upon the interactions of active ingredients and the lipid matrix as well as the quantification of dermal penetration. PMID:17544165

  2. The neuroimmune connection interferes with tissue regeneration and chronic inflammatory disease in the skin.

    PubMed

    Peters, Eva M J; Liezmann, Christiane; Klapp, Burghard F; Kruse, Johannes

    2012-07-01

    Research over the past decades has revealed close interactions between the nervous and immune systems that regulate peripheral inflammation and link psychosocial stress with chronic somatic disease. Besides activation of the sympathetic and the hypothalamus-pituitary-adrenal axis, stress leads to increased neurotrophin and neuropeptide production in organs at the self-environment interface. The scope of this short review is to discuss key functions of these stress mediators in the skin, an exemplary stress-targeted and stress-sensitive organ. We will focus on the skin's response to acute and chronic stress in tissue regeneration and pathogenesis of allergic inflammation, psoriasis, and skin cancer to illustrate the impact of local stress-induced neuroimmune interaction on chronic inflammation. PMID:22823443

  3. The neuroimmune connection interferes with tissue regeneration and chronic inflammatory disease in the skin.

    PubMed

    Peters, Eva M J; Liezmann, Christiane; Klapp, Burghard F; Kruse, Johannes

    2012-07-01

    Research over the past decades has revealed close interactions between the nervous and immune systems that regulate peripheral inflammation and link psychosocial stress with chronic somatic disease. Besides activation of the sympathetic and the hypothalamus-pituitary-adrenal axis, stress leads to increased neurotrophin and neuropeptide production in organs at the self-environment interface. The scope of this short review is to discuss key functions of these stress mediators in the skin, an exemplary stress-targeted and stress-sensitive organ. We will focus on the skin's response to acute and chronic stress in tissue regeneration and pathogenesis of allergic inflammation, psoriasis, and skin cancer to illustrate the impact of local stress-induced neuroimmune interaction on chronic inflammation.

  4. Complex Multiple-Nucleotide Substitution Mutations Causing Human Inherited Disease Reveal Novel Insights into the Action of Translesion Synthesis DNA Polymerases.

    PubMed

    Chen, Jian-Min; Férec, Claude; Cooper, David N

    2015-11-01

    Translesion synthesis (TLS) DNA polymerases allow the bypass of unrepaired lesions during DNA replication. Based upon mutational signatures of a subtype of multiple-nucleotide substitution (MNS) mutations causing human inherited disease, we have recently postulated two properties of TLS DNA polymerases in DNA repair, namely, the generation of neo-microhomologies potentiating strand-misalignment, and additional microlesions within the templated inserts when recruited to stalled replication forks. To provide further support for this postulate, we analyzed the mutational signatures of a new and complex subtype of pathogenic MNS mutation. Several mutations containing long templated inserts (8-19 bp) that are highly informative with regard to their underlying mutational mechanisms, harbor imprints of TLS DNA polymerase action. Dissecting the mechanism underlying the generation of the 19-bp insert implicated repeated participation of TLS DNA polymerases in the conversion of a damaged base into a complex MNS lesion through a process of successive template switching and bypass repair. PMID:26172832

  5. Observational Study of the Genetic Architecture of Neutrophil-Mediated Inflammatory Skin Diseases

    ClinicalTrials.gov

    2016-09-26

    Other Specified Inflammatory Disorders of Skin or Subcutaneous Tissue; Pyoderma Gangrenosum; Erosive Pustular Dermatosis of the Scalp; Sweet's Syndrome; Behcet's Disease; Bowel-associated Dermatosis-arthritis Syndrome; Pustular Psoriasis; Acute Generalized Exanthematous Pustulosis; Keratoderma Blenorrhagicum; Sneddon-Wilkinson Disease; IgA Pemphigus; Amicrobial Pustulosis of the Folds; Infantile Acropustulosis; Transient Neonatal Pustulosis; Neutrophilic Eccrine Hidradenitis; Rheumatoid Neutrophilic Dermatitis; Neutrophilic Urticaria; Still's Disease; Erythema Marginatum; Unclassified Periodic Fever Syndromes / Autoinflammatory Syndromes; Dermatitis Herpetiformis; Linear IgA Bullous Dermatosis; Bullous Systemic Lupus Erythematosus; Inflammatory Epidermolysis Bullosa Aquisita; Neutrophilic Dermatosis of the Dorsal Hands (Pustular Vasculitis); Small Vessel Vasculitis Including Urticarial Vasculitis; Erythema Elevatum Diutinum; Medium Vessel Vasculitis

  6. Major histocompatibility complex-conferred resistance to Theiler's virus-induced demyelinating disease is inherited as a dominant trait in B10 congenic mice.

    PubMed

    Patick, A K; Pease, L R; David, C S; Rodriguez, M

    1990-11-01

    Intracerebral inoculation of Theiler's murine encephalomyelitis virus into susceptible strains of mice produces chronic demyelinating disease in the central nervous system characterized by persistent viral infection. Immunogenetic data suggest that genes from both major histocompatibility complex (MHC) and non-MHC loci are important in determining susceptibility or resistance to demyelination. The role of the MHC in determining resistance or susceptibility to disease can be interpreted either as the presence of antigen-presenting molecules that confer resistance to viral infection or as the ability of MHC products to contribute to pathogenesis by acting as viral receptors or by mediating immune attack against virally infected cells. These alternatives can be distinguished by determining whether the contribution of the MHC to resistance is inherited as a recessive or dominant trait. Congenic mice with different MHC haplotypes on identical B10 backgrounds were crossed and quantitatively analyzed for demyelination, infectious virus, and local virus antigen production. F1 hybrid progeny derived from resistant B10 (H-2b), B10.D2 (H-2d), or B10.K (H-2k) and susceptible B10.R111 (H-2r), B10.M (H-2f), or B10.BR (H-2k) parental mice exhibited no or minimal demyelination, indicating that on a B10 background, resistance is inherited as a dominant trait. Although infectious virus, as measured by viral plaque assay, was cleared inefficiently from the central nervous systems of resistant F1 hybrid progeny mice, we found a direct correlation between local viral antigen production and demyelination. These data are consistent with our hypothesis that the immunological basis for resistance is determined by efficient presentation of the viral antigen to the immune system, resulting in local virus clearance and absence of subsequent demyelination.

  7. Major histocompatibility complex-conferred resistance to Theiler's virus-induced demyelinating disease is inherited as a dominant trait in B10 congenic mice.

    PubMed Central

    Patick, A K; Pease, L R; David, C S; Rodriguez, M

    1990-01-01

    Intracerebral inoculation of Theiler's murine encephalomyelitis virus into susceptible strains of mice produces chronic demyelinating disease in the central nervous system characterized by persistent viral infection. Immunogenetic data suggest that genes from both major histocompatibility complex (MHC) and non-MHC loci are important in determining susceptibility or resistance to demyelination. The role of the MHC in determining resistance or susceptibility to disease can be interpreted either as the presence of antigen-presenting molecules that confer resistance to viral infection or as the ability of MHC products to contribute to pathogenesis by acting as viral receptors or by mediating immune attack against virally infected cells. These alternatives can be distinguished by determining whether the contribution of the MHC to resistance is inherited as a recessive or dominant trait. Congenic mice with different MHC haplotypes on identical B10 backgrounds were crossed and quantitatively analyzed for demyelination, infectious virus, and local virus antigen production. F1 hybrid progeny derived from resistant B10 (H-2b), B10.D2 (H-2d), or B10.K (H-2k) and susceptible B10.R111 (H-2r), B10.M (H-2f), or B10.BR (H-2k) parental mice exhibited no or minimal demyelination, indicating that on a B10 background, resistance is inherited as a dominant trait. Although infectious virus, as measured by viral plaque assay, was cleared inefficiently from the central nervous systems of resistant F1 hybrid progeny mice, we found a direct correlation between local viral antigen production and demyelination. These data are consistent with our hypothesis that the immunological basis for resistance is determined by efficient presentation of the viral antigen to the immune system, resulting in local virus clearance and absence of subsequent demyelination. Images PMID:2214025

  8. Signalling in inflammatory skin disease by AP-1 (Fos/Jun).

    PubMed

    Uluçkan, Özge; Guinea-Viniegra, Juan; Jimenez, Maria; Wagner, Erwin F

    2015-01-01

    Skin inflammation is a physiological reaction to tissue injury, pathogen invasion and irritants. During this process, innate and/or adaptive immune cells are activated and recruited to the site of inflammation to either promote or suppress inflammation. The sequential recruitment and activation of immune cells is modulated by a combination of cytokines and chemokines, which are regulated by transcription factors, such as AP-1 (Fos/Jun), NF-κB, NFATs, and STATs. Here we review the present evidence and the underlying mechanisms of how Jun/AP-1 proteins control skin inflammation. Genetically engineered mouse models (GEMMs) in which AP-1 proteins are deleted in the epidermis have revealed that these proteins control cytokine expression at multiple levels. Constitutive epidermal deletion of JunB in mice leads to a multi-organ disease characterised by increased levels of pro-inflammatory cytokines. These JunB-deficient mutant mice display several phenotypes from skin inflammation to a G-CSF-dependent myeloproliferative disease, as well as kidney atrophy and bone loss, reminiscent of psoriasis and systemic lupus erythematosus. Importantly, epidermal deletion of both JunB and c-Jun in an inducible manner in adult mice leads to a psoriasis-like disease, in which the epidermal proteome expression profile is comparable to the one from psoriasis patient samples. In this GEMM and in psoriasis patient-derived material, S100A8/A9-dependent C3/CFB complement activation, as well as a miR-21-dependent TIMP-3/TACE pathway leading to TNF-α shedding, plays causal roles in disease development. The newly identified therapeutic targets from GEMMs together with investigations in human patient samples open up new avenues for therapeutic interventions for psoriasis and related inflammatory skin diseases. PMID:26458100

  9. Signalling in inflammatory skin disease by AP-1 (Fos/Jun).

    PubMed

    Uluçkan, Özge; Guinea-Viniegra, Juan; Jimenez, Maria; Wagner, Erwin F

    2015-01-01

    Skin inflammation is a physiological reaction to tissue injury, pathogen invasion and irritants. During this process, innate and/or adaptive immune cells are activated and recruited to the site of inflammation to either promote or suppress inflammation. The sequential recruitment and activation of immune cells is modulated by a combination of cytokines and chemokines, which are regulated by transcription factors, such as AP-1 (Fos/Jun), NF-κB, NFATs, and STATs. Here we review the present evidence and the underlying mechanisms of how Jun/AP-1 proteins control skin inflammation. Genetically engineered mouse models (GEMMs) in which AP-1 proteins are deleted in the epidermis have revealed that these proteins control cytokine expression at multiple levels. Constitutive epidermal deletion of JunB in mice leads to a multi-organ disease characterised by increased levels of pro-inflammatory cytokines. These JunB-deficient mutant mice display several phenotypes from skin inflammation to a G-CSF-dependent myeloproliferative disease, as well as kidney atrophy and bone loss, reminiscent of psoriasis and systemic lupus erythematosus. Importantly, epidermal deletion of both JunB and c-Jun in an inducible manner in adult mice leads to a psoriasis-like disease, in which the epidermal proteome expression profile is comparable to the one from psoriasis patient samples. In this GEMM and in psoriasis patient-derived material, S100A8/A9-dependent C3/CFB complement activation, as well as a miR-21-dependent TIMP-3/TACE pathway leading to TNF-α shedding, plays causal roles in disease development. The newly identified therapeutic targets from GEMMs together with investigations in human patient samples open up new avenues for therapeutic interventions for psoriasis and related inflammatory skin diseases.

  10. Measuring the Photopic Negative Response: Viability of Skin Electrodes and Variability Across Disease Severities in Glaucoma

    PubMed Central

    Wu, Zhichao; Hadoux, Xavier; Fan Gaskin, Jennifer C.; Sarossy, Marc G.; Crowston, Jonathan G.

    2016-01-01

    Purpose The purpose of this study was to determine the feasibility of measuring the photopic negative response (PhNR) of the full-field electroretinogram (ERG) using skin electrodes compared to conjunctival electrodes and its test–retest variability over a range of disease severities in open-angle glaucoma. Methods Recordings were performed twice (100 sweeps each) within the same session in 43 eyes of 23 participants with glaucoma to determine its intrinsic variability. The ratio between the PhNR and B-wave amplitude (PhNR/B ratio) was determined for each trace and computed across 5 to 100 sweeps of each recording. Spectral-domain optical coherence tomography was used to measure the average peripapillary retinal nerve fiber layer (RNFL) thickness. Results The PhNR/B ratio and its magnitude of variability were not significantly different between skin and conjunctival electrodes (P ≤ 0.197), and the degree of variability decreased substantially with increasing number of sweeps. For skin electrodes, the intraclass correlation coefficient was 0.89 and 0.91 for right and left eyes, respectively. The variability of the PhNR/B ratio decreased with lower RNFL thickness values and larger B-wave amplitudes (P ≤ 0.002). Conclusions Skin electrodes are a viable alternative to conjunctival electrodes when measuring the PhNR in open angle glaucoma, and increasing the number of sweeps substantially reduced its intrinsic variability; the extent of variability was also lower with worsening disease severity. Translational Relevance The feasibility of performing ERG recordings widely across a range of disease severities in glaucoma can be achieved through using skin electrodes and increasing the number of sweeps performed to improve measurement repeatability. PMID:26998406

  11. The Degree of Skin Involvement Identifies Distinct Lung Disease Outcomes and Survival in Systemic Sclerosis

    PubMed Central

    Cottrell, Tricia R.; Wise, Robert A.; Wigley, Fredrick M.; Boin, Francesco

    2016-01-01

    Objective To determine whether pattern of skin involvement can predict clinical features, risk of restrictive lung disease, and survival in a large scleroderma (SSc) cohort. Methods Demographic and clinical data collected over 30 years from 2,205 SSc patients were retrospectively analyzed after subdividing subjects into four subtypes based on pattern of skin fibrosis: Type-0 (no skin involvement), Type-1 (limited to metacarpophalangeal joints), Type-2 (distal to elbows/knees) and Type-3 (proximal to elbows/knees). Clinical features associated with skin subsets were identified by regression analyses. Kaplan-Meier and Cox proportional hazards models were used to compare time to restrictive lung disease (RLD) and survival across subtypes. Results The presence and severity of RLD were positively associated with skin subtype (p<0.001). RLD prevalence incrementally ranged from 51.9% in Type 0 to 76.7% in Type-3 (p<0.001). Type-2 SSc exhibited a distinct phenotype with intermediate risk for RLD relative to Type-1 (higher, p<0.001) and Type-3 (lower, p<0.001), and a unique autoantibody profile, with a prevalence of anti-centromere lower than Type-1 (28.9% vs. 44.1%, p=0.001) and of anti-topoisomerase I similar to Type-3 (p=0.38). These autoantibodies were also found to be significant negative (OR 0.33, p<0.001) and positive (OR 1.6, p=0.01) predictors of RLD risk respectively. Mortality was also intermediate in Type-2 patients relative to Type-3 (p=0.0003) and Type-1 (p=0.066). Conclusions These data suggest that the current classification subdividing SSc into the limited and diffuse cutaneous subtypes misclassifies an intermediate group of patients exhibiting unique autoantibody profile, disease course and clinical outcomes. PMID:23606705

  12. α-Synuclein inclusions in the skin of Parkinson's disease and parkinsonism

    PubMed Central

    Rodríguez-Leyva, Ildefonso; Calderón-Garcidueñas, Ana Laura; Jiménez-Capdeville, María E; Rentería-Palomo, Ana Arely; Hernandez-Rodriguez, Héctor Gerardo; Valdés-Rodríguez, Rodrigo; Fuentes-Ahumada, Cornelia; Torres-Álvarez, Bertha; Sepúlveda-Saavedra, Julio; Soto-Domínguez, Adolfo; Santoyo, Martha E; Rodriguez-Moreno, José Ildefonso; Castanedo-Cázares, Juan Pablo

    2014-01-01

    Objective The presence in the brain of α-synuclein containing Lewy neurites, or bodies, is the histological hallmark of Parkinson's disease (PD). The discovery of α-synuclein aggregates in nerve endings of the heart, digestive tract, and skin has lent support to the concept of PD as a systemic disease. Our goals were, first, to demonstrate the presence of α-synuclein inclusions in the skin and, second, to detect quantitative differences between patients with PD and atypical parkinsonism (AP). Methods Skin biopsies were taken from 67 patients and 20 controls. The biopsies underwent immunohistochemistry (IHC) and immunofluorescence (IF) testing for α-synuclein, whereupon its presence was quantified as the percentage of positive cells. Patients were divided into those with PD and those with AP. AP patients included AP with neurodegenerative disease (proteinopathies) and secondary AP. Results Sixty-seven patients (34 with PD) and 20 controls were recruited. In the PD group, α-synuclein was detected in 58% of the cells in the spinous cell layer (SCL), 62% in the pilosebaceous unit (PSU), and 58% in the eccrine glands (EG). The AP-proteinopathies group showed 7%, 7%, and 0% expression of α-synuclein, respectively. No expression was found in the skin of the control group. Conclusions The expression of α-synuclein in the skin was relatively high in the PD group, scarce in AP, and null for the individuals in the control group. While these findings require further confirmation, this minimally invasive technique may aid in the improvement of the accuracy of PD diagnoses. PMID:25356418

  13. The endocannabinoid system of the skin in health and disease: novel perspectives and therapeutic opportunities

    PubMed Central

    Bíró, Tamás; Tóth, Balázs I.; Haskó, György; Paus, Ralf; Pacher, Pál

    2009-01-01

    The newly discovered endocannabinoid system (ECS; comprising the endogenous lipid mediators endocannabinoids present in virtually all tissues, their G-protein-coupled cannabinoid receptors, biosynthetic pathways and metabolizing enzymes) has been implicated in multiple regulatory functions both in health and disease. Recent studies have intriguingly suggested the existence of a functional ECS in the skin and implicated it in various biological processes (e.g. proliferation, growth, differentiation, apoptosis and cytokine, mediator or hormone production of various cell types of the skin and appendages, such as the hair follicle and sebaceous gland). It seems that the main physiological function of the cutaneous ECS is to constitutively control the proper and well-balanced proliferation, differentiation and survival, as well as immune competence and/or tolerance, of skin cells. The disruption of this delicate balance might facilitate the development of multiple pathological conditions and diseases of the skin (e.g. acne, seborrhea, allergic dermatitis, itch and pain, psoriasis, hair growth disorders, systemic sclerosis and cancer). PMID:19608284

  14. [Inherited bone marrow failure syndromes].

    PubMed

    Okuno, Yusuke

    2016-02-01

    Inherited bone marrow failure syndromes comprise a series of disorders caused by various gene mutations. Genetic tests were formerly difficult to perform because of the large size and number of causative genes. However, recent advances in next-generation sequencing has enabled simultaneous testing of all causative genes to be performed at an acceptable cost. We collaboratively conducted a series of whole-exome sequencing studies of patients with inherited bone marrow failure syndromes and discovered RPS27/RPL27 and FANCT as causative genes of Diamond-Blackfan anemia and Fanconi anemia, respectively. Furthermore, we established a target gene sequencing system to cover 189 genes associated with pediatric blood diseases to assist genetic diagnoses in clinical practice. In this review, discovery of new causative genes and possible roles of next-generation sequencing in the genetic diagnosis of inherited bone marrow failure syndromes are discussed. PMID:26935625

  15. Nongenetic inheritance and transgenerational epigenetics.

    PubMed

    Szyf, Moshe

    2015-02-01

    The idea that inherited genotypes define phenotypes has been paramount in modern biology. The question remains, however, whether stable phenotypes could be also inherited from parents independently of the genetic sequence per se. Recent data suggest that parental experiences can be transmitted behaviorally, through in utero exposure of the developing fetus to the maternal environment, or through either the male or female germline. The challenge is to delineate a plausible mechanism. In the past decade it has been proposed that epigenetic mechanisms are involved in multigenerational transmission of phenotypes and transgenerational inheritance. The prospect that ancestral experiences are written in our epigenome has immense implications for our understanding of human behavior, health, and disease. PMID:25601643

  16. Nongenetic inheritance and transgenerational epigenetics.

    PubMed

    Szyf, Moshe

    2015-02-01

    The idea that inherited genotypes define phenotypes has been paramount in modern biology. The question remains, however, whether stable phenotypes could be also inherited from parents independently of the genetic sequence per se. Recent data suggest that parental experiences can be transmitted behaviorally, through in utero exposure of the developing fetus to the maternal environment, or through either the male or female germline. The challenge is to delineate a plausible mechanism. In the past decade it has been proposed that epigenetic mechanisms are involved in multigenerational transmission of phenotypes and transgenerational inheritance. The prospect that ancestral experiences are written in our epigenome has immense implications for our understanding of human behavior, health, and disease.

  17. Genetic and phenotypic variations of inherited retinal diseases in dogs: the power of within- and across-breed studies

    PubMed Central

    Acland, Gregory M.

    2014-01-01

    Considerable clinical and molecular variations have been known in retinal blinding diseases in man and also in dogs. Different forms of retinal diseases occur in specific breed(s) caused by mutations segregating within each isolated breeding population. While molecular studies to find genes and mutations underlying retinal diseases in dogs have benefited largely from the phenotypic and genetic uniformity within a breed, within- and across-breed variations have often played a key role in elucidating the molecular basis. The increasing knowledge of phenotypic, allelic, and genetic heterogeneities in canine retinal degeneration has shown that the overall picture is rather more complicated than initially thought. Over the past 20 years, various approaches have been developed and tested to search for genes and mutations underlying genetic traits in dogs, depending on the availability of genetic tools and sample resources. Candidate gene, linkage analysis, and genome-wide association studies have so far identified 24 mutations in 18 genes underlying retinal diseases in at least 58 dog breeds. Many of these genes have been associated with retinal diseases in humans, thus providing opportunities to study the role in pathogenesis and in normal vision. Application in therapeutic interventions such as gene therapy has proven successful initially in a naturally occurring dog model followed by trials in human patients. Other genes whose human homologs have not been associated with retinal diseases are potential candidates to explain equivalent human diseases and contribute to the understanding of their function in vision. PMID:22065099

  18. Staphylococcus δ-toxin promotes mouse allergic skin disease by inducing mast cell degranulation

    PubMed Central

    Nakamura, Yuumi; Oscherwitz, Jon; Cease, Kemp B.; Chan, Susana M.; Muñoz-Planillo, Raul; Hasegawa, Mizuho; Villaruz, Amer E.; Cheung, Gordon Y. C.; McGavin, Martin J.; Travers, Jeffrey B.; Otto, Michael; Inohara, Naohiro; Núñez, Gabriel

    2013-01-01

    Atopic dermatitis (AD) is a chronic inflammatory skin disease that affects 15 to 30% of children and ~5% of adults in industrialized countries1. Although the pathogenesis of AD is not fully understood, the disease is mediated by an abnormal immunoglobulin E (IgE) immune response in the setting of skin barrier dysfunction2. Mast cells (MCs) contribute to IgE-mediated allergic disorders including AD3. Upon activation, MCs release their membrane-bound cytosolic granules leading to the release of multiple molecules that are important in the pathogenesis of AD and host defense4. More than 90% of AD patients are colonized with Staphylococcus aureus in the lesional skin whereas most healthy individuals do not harbor the pathogen5. Several Staphylococcal exotoxins (SEs) can act as superantigens and/or antigens in models of AD6. However, the role of these SEs in disease pathogenesis remains unclear. Here, we report that culture supernatants of S. aureus contain potent MC degranulation activity. Biochemical analysis identified δ-toxin as the MC degranulation-inducing factor produced by S. aureus. MC degranulation induced by δ-toxin depended on phosphoinositide 3-kinase (PI3K) and calcium (Ca2+) influx, but unlike that mediated by IgE crosslinking, it did not require the spleen tyrosine kinase (Syk). In addition, IgE enhanced δ-toxin-induced MC degranulation in the absence of antigen. Furthermore, S. aureus isolates recovered from AD patients produced high levels of δ-toxin. Importantly, skin colonization with S. aureus, but not a mutant deficient in δ-toxin, promoted IgE and IL-4 production, as well as inflammatory skin disease. Furthermore, enhancement of IgE production and dermatitis by δ-toxin was abrogated in KitW-sh/W-sh MC-deficient mice and restored by MC reconstitution. These studies identify δ-toxin as a potent inducer of MC degranulation and suggest a mechanistic link between S. aureus colonization and allergic skin disease. PMID:24172897

  19. Effect of living donor liver transplantation on outcome of children with inherited liver disease and hepatocellular carcinoma.

    PubMed

    Ozçay, Figen; Canan, Oğuz; Bilezikçi, Banu; Torgay, Adnan; Karakayali, Hamdi; Haberal, Mehmet

    2006-01-01

    We described six children with heritable liver disease and hepatocellular carcinoma treated with living-related liver transplantation. Underlying liver diseases were type-1 tyrosinemia (three patients), progressive familial intrahepatic cholestasis type II (two patients), and Wilson's disease (one patient). Two of the tumors were found incidentally during liver transplantation. Number of nodules was 12, 15, 3, 2, and 1 (in two patients). Three patients were treated with chemotherapy before the procedure. Chemotherapy was not given to any patient after liver transplantation. The mean follow-up was 17.7 +/- 6 months (range: 7-24). All patients are tumor recurrence free. Both graft and patient survival rates are 100% at a median of 18.5 months follow-up. Physicians in charge of treating children with heritable liver disease should screen them periodically for the development of hepatocellular carcinoma. Liver transplantation may offer these children better survival rates.

  20. The mechanisms of action of nicotinamide and zinc in inflammatory skin disease.

    PubMed

    Fivenson, David P

    2006-01-01

    Nicotinamide (niacinamide), a physiologically active form of niacin (nicotinic acid), in combination with zinc is being assessed in clinical studies for the treatment of inflammatory skin diseases such as acne vulgaris and bullous pemphigoid. The basis for these investigations is the variety of potential mechanisms of action of nicotinamide and zinc, including an anti-inflammatory effect via inhibition of leukocyte chemotaxis, lysosomal enzyme release, lymphocytic transformation, mast cell degranulation, bacteriostatic effect against Propionibacterium acnes, inhibition of vasoactive amines, preservation of intracellular coenzyme homeostasis, and decreased sebum production. Other possible mechanisms involve suppression of vascular permeability and inflammatory cell accumulation, as well as protection against DNA damage. The goal of this paper is to review the pathophysiology of inflammatory skin diseases and discuss the role, mechanisms of action, and safety of nicotinamide and zinc as therapeutic options for these disorders.

  1. Investigation of photothermolysis therapy of human skin diseases using optical phantoms

    NASA Astrophysics Data System (ADS)

    Jedrzejewska-Szczerska, M.; Wróbel, M. S.; Galla, S.; Popov, A. P.; Bykov, A. V.; Tuchin, V. V.; Cenian, A.

    2015-01-01

    Dermatological diseases, such as neurofibroma (Recklinghausen disease) or hemangiomas can be efficiently treated using photothermolysis from laser irradiation. We have utilized a developed 975 nm fiber diode laser as a low-cost alternative over common Nd:YAG lasers. This paper describes the investigations of interaction of 975 nm diode laser radiation-pulses with optical skin phantoms which were designed and manufactured in our laboratory. Such phantoms match the scattering and absorption coefficients of real human skin. Spatial and temporal temperature evolutions during laser irradiation with various laser settings (pulsed and CW mode), were recorded by an IR camera. Subsequent analysis yielded optimum choice of parameters for laser therapy of coetaneous lesions.

  2. Mechanical characteristics of antibacterial epoxy resin adhesive wood biocomposites against skin disease.

    PubMed

    Chen, Zi-Xiang; Zhang, Zhong-Feng; Aqma, Wan Syaidatul

    2016-01-01

    Moldy wood can cause some skin disease. However epoxy resin adhesive (EP) can inhibit mold growth. Therefore, antibacterial EP/wood biocomposites were reinforced and analyzed by the nonlinear finite element. Results show that glass fiber cloth and aluminum foil have the obvious reinforced effect under flat pressure, but this was not the case under side pressure. And when the assemble pattern was presented in 5A way, the strengthening effect was better. The nonlinear finite element showed that the aluminum foil and glass fiber cloth have the obvious reinforced effect. The mutual influence and effect of span, thickness and length on the ultimate bearing capacity of specimen were studied. And the simulation results agreed with the test. It provided a theoretical basis on the preparation of antibacterial EP/wood biocomposites against skin disease.

  3. Mechanical characteristics of antibacterial epoxy resin adhesive wood biocomposites against skin disease

    PubMed Central

    Chen, Zi-xiang; Zhang, Zhong-feng; Aqma, Wan Syaidatul

    2015-01-01

    Moldy wood can cause some skin disease. However epoxy resin adhesive (EP) can inhibit mold growth. Therefore, antibacterial EP/wood biocomposites were reinforced and analyzed by the nonlinear finite element. Results show that glass fiber cloth and aluminum foil have the obvious reinforced effect under flat pressure, but this was not the case under side pressure. And when the assemble pattern was presented in 5A way, the strengthening effect was better. The nonlinear finite element showed that the aluminum foil and glass fiber cloth have the obvious reinforced effect. The mutual influence and effect of span, thickness and length on the ultimate bearing capacity of specimen were studied. And the simulation results agreed with the test. It provided a theoretical basis on the preparation of antibacterial EP/wood biocomposites against skin disease. PMID:26858557

  4. Necrolytic acral erythema: a rare skin disease associated with hepatitis C virus infection*

    PubMed Central

    Botelho, Luciane Francisca Fernandes; Enokihara, Milvia Maria Simões e Silva; Enokihara, Mauro Yoshiaki

    2016-01-01

    Necrolytic acral erythema is a rare skin disease associated with hepatitis C virus infection. We report a case of a 31-year-old woman with hepatitis C virus infection and decreased zinc serum level. Physical examination revealed scaly, lichenified plaques, well-demarcated with an erythematous peripheral rim located on the lower limbs. After blood transfusion and oral zinc supplementation the patient presented an improvement of lesions.

  5. Hidradenitis suppurativa: a common and burdensome, yet under-recognised, inflammatory skin disease

    PubMed Central

    Dufour, Deirdre Nathalie; Emtestam, Lennart; Jemec, Gregor B

    2014-01-01

    Hidradenitis suppurativa (HS) is a chronic, relapsing, inflammatory skin condition that typically occurs after puberty. The primary clinical presentation is painful inflamed nodules or boils in the apocrine gland-bearing regions (armpits, genital area, groin, breasts and buttocks/anus) that progress to abscesses, sinus tracts and scarring. Severity is typically described according to three Hurley categories, with most patients having mild or moderate disease. Estimated prevalence is 1–4% worldwide and HS is three times more common in women than men. Patients’ disease burden includes intense pain, work disability and overall poor quality of life. Although the clinical signs of the disease can often be hidden by clothing, active HS is associated with a malodorous discharge that contributes to the disabling social stigma. Risk factors include smoking and obesity. Comorbidities include inflammatory bowel disease and spondyloarthropathies. The presentation of the disease is distinct, yet HS is not well-recognised except in dermatology clinics. PMID:24567417

  6. Suppression of skin inflammation in keratinocytes and acute/chronic disease models by caffeic acid phenethyl ester.

    PubMed

    Lim, Kyung-Min; Bae, SeungJin; Koo, Jung Eun; Kim, Eun-Sun; Bae, Ok-Nam; Lee, Joo Young

    2015-04-01

    Skin inflammation plays a central role in the pathophysiology and symptoms of diverse chronic skin diseases including atopic dermatitis (AD). In this study, we examined if caffeic acid phenethyl ester (CAPE), a skin-permeable bioactive compound from propolis, was protective against skin inflammation using in vitro cell system and in vivo animal disease models. CAPE suppressed TNF-α-induced NF-κB activation and expression of inflammatory cytokines in human keratinocytes (HaCaT). The potency and efficacy of CAPE were superior to those of a non-phenethyl derivative, caffeic acid. Consistently, topical treatment of CAPE (0.5 %) attenuated 12-O-tetradecanoylphorbol-13-acetate(TPA)-induced skin inflammation on mouse ear as CAPE reduced ear swelling and histologic inflammation scores. CAPE suppressed increased expression of pro-inflammatory molecules such as TNF-α, cyclooxygenase-2 and inducible NO synthase in TPA-stimulated skin. TPA-induced phosphorylation of IκB and ERK was blocked by CAPE suggesting that protective effects of CAPE on skin inflammation is attributed to inhibition of NF-κB activation. Most importantly, in an oxazolone-induced chronic dermatitis model, topical application of CAPE (0.5 and 1 %) was effective in alleviating AD-like symptoms such as increases of trans-epidermal water loss, skin thickening and serum IgE as well as histologic inflammation assessment. Collectively, our results propose CAPE as a promising candidate for a novel topical drug for skin inflammatory diseases.

  7. Suppression of skin inflammation in keratinocytes and acute/chronic disease models by caffeic acid phenethyl ester.

    PubMed

    Lim, Kyung-Min; Bae, SeungJin; Koo, Jung Eun; Kim, Eun-Sun; Bae, Ok-Nam; Lee, Joo Young

    2015-04-01

    Skin inflammation plays a central role in the pathophysiology and symptoms of diverse chronic skin diseases including atopic dermatitis (AD). In this study, we examined if caffeic acid phenethyl ester (CAPE), a skin-permeable bioactive compound from propolis, was protective against skin inflammation using in vitro cell system and in vivo animal disease models. CAPE suppressed TNF-α-induced NF-κB activation and expression of inflammatory cytokines in human keratinocytes (HaCaT). The potency and efficacy of CAPE were superior to those of a non-phenethyl derivative, caffeic acid. Consistently, topical treatment of CAPE (0.5 %) attenuated 12-O-tetradecanoylphorbol-13-acetate(TPA)-induced skin inflammation on mouse ear as CAPE reduced ear swelling and histologic inflammation scores. CAPE suppressed increased expression of pro-inflammatory molecules such as TNF-α, cyclooxygenase-2 and inducible NO synthase in TPA-stimulated skin. TPA-induced phosphorylation of IκB and ERK was blocked by CAPE suggesting that protective effects of CAPE on skin inflammation is attributed to inhibition of NF-κB activation. Most importantly, in an oxazolone-induced chronic dermatitis model, topical application of CAPE (0.5 and 1 %) was effective in alleviating AD-like symptoms such as increases of trans-epidermal water loss, skin thickening and serum IgE as well as histologic inflammation assessment. Collectively, our results propose CAPE as a promising candidate for a novel topical drug for skin inflammatory diseases. PMID:25501505

  8. Patterns of skin disease in a sample of the federal prison population: a retrospective chart review

    PubMed Central

    Gavigan, Geneviève; McEvoy, Alana; Walker, James

    2016-01-01

    Background: Dermatology in vulnerable populations is under-researched. Our objective was to analyze the most commonly referred skin diseases affecting the Correctional Service Canada inmates in Ontario. Methods: An observational, cross-sectional, retrospective chart review of inmate patients seen from 2008 until 2013 was performed. Two groups of patients were included in the analysis: those assessed in-person, and those evaluated by e-consult. Results: In the in-person patient group, the 3 most common diagnoses were acne, psoriasis and other superficial mycoses. For the e-consult group, the 3 most frequent diagnoses were acne, psoriasis and rosacea. There was a clear bias toward more inmates being seen in-person where the service was provided (Collins Bay Institution) than from other correctional institutions in Eastern Ontario. Interpretation: Most of the skin diseases that affected the incarcerated population studied were common afflictions, similar to those affecting the general population, which is in agreement with other studies. Future studies investigating skin diseases in male and female inmates across Canada would bestow more generalizable data. PMID:27398381

  9. Decorative cosmetics improve the quality of life in patients with disfiguring skin diseases.

    PubMed

    Boehncke, Wolf-Henning; Ochsendorf, Falk; Paeslack, Ingrid; Kaufmann, Roland; Zollner, Thomas Matthias

    2002-01-01

    Dermatoses may have a significant impact on a patient's quality of life, namely the relationship to others, self-image and self-esteem. We therefore asked whether the application of decorative cosmetics might increase their quality of life. Twenty female patients (16-69 y) with skin diseases affecting the patients' face (acne, n = 8; rosacea, n = 9; chronic discoid lupus erythematodes, n = 2; vitiligo, n = 1) were investigated. The patients were instructed by a cosmetician how to use decorative cosmetics (Unifiance , La Roche-Posay, France) and applied it daily for 2 weeks. The dermatology quality of life questionnaire (DLQI) was performed before the first application and 2 weeks afterwards. The clinical course was documented by standardised photography. Unifiance was well tolerated and no side effects occurred. It completely masked the unwanted coloration and application resulted in a significant amelioration of the appearance. The mean DLQI score dropped significantly from 9.2 to 5.5 (p = 0.0009). Improvement of quality of life reached statistical significance among patients with acne (2.8 versus 7.8, p = 0.0078) and among individuals with a less severe initial impairment of quality of life (2.4 versus 4.2, p = 0.007). Thus, the use of decorative cosmetics in disfiguring skin diseases is an effective, well-tolerated measure increasing the patients' quality of life. We therefore suggest that decorative cosmetics can complement the treatment of disfiguring skin diseases.

  10. The global burden of disease for skin, lung and bladder cancer caused by arsenic in food

    PubMed Central

    Oberoi, Shilpi; Barchowsky, Aaron; Wu, Felicia

    2014-01-01

    Background Arsenic is a ubiquitous, naturally occurring metalloid that poses a significant human cancer risk. While water consumption provides the majority of human exposure, millions of individuals worldwide are significantly exposed to arsenic through naturally occurring levels of arsenic in grains, vegetables, meats and fish, as well as through food processed with water containing arsenic. Thus, we estimated the global burdens of disease for bladder, lung and skin cancers attributable to inorganic arsenic in food. Methods To determine foodborne inorganic arsenic exposures worldwide, we used World Health Organization estimates of food consumption in thirteen country clusters, in conjunction with reported measurements of total and inorganic arsenic in different foods. We estimated slope factors for arsenic related bladder and lung cancers, and used the US Environmental Protection Agency skin cancer slope factor, to calculate the annual risk of the cancer incidence in males and females within each country cluster. Results We estimated that each year 9,129 to 119,176 additional cases of bladder cancer, 11,844 to 121,442 of lung cancer, and 10,729 to 110,015 of skin cancer worldwide are attributable to inorganic arsenic in food. Conclusions These estimates indicate that foodborne arsenic exposure causes a significant global burden of human disease. Impact Estimating the global cancer burden caused by arsenic exposure in food will support policies that reduce exposure to disease promoting environmental hazards. PMID:24793955

  11. The Loss and Gain of Functional Amino Acid Residues Is a Common Mechanism Causing Human Inherited Disease.

    PubMed

    Lugo-Martinez, Jose; Pejaver, Vikas; Pagel, Kymberleigh A; Jain, Shantanu; Mort, Matthew; Cooper, David N; Mooney, Sean D; Radivojac, Predrag

    2016-08-01

    Elucidating the precise molecular events altered by disease-causing genetic variants represents a major challenge in translational bioinformatics. To this end, many studies have investigated the structural and functional impact of amino acid substitutions. Most of these studies were however limited in scope to either individual molecular functions or were concerned with functional effects (e.g. deleterious vs. neutral) without specifically considering possible molecular alterations. The recent growth of structural, molecular and genetic data presents an opportunity for more comprehensive studies to consider the structural environment of a residue of interest, to hypothesize specific molecular effects of sequence variants and to statistically associate these effects with genetic disease. In this study, we analyzed data sets of disease-causing and putatively neutral human variants mapped to protein 3D structures as part of a systematic study of the loss and gain of various types of functional attribute potentially underlying pathogenic molecular alterations. We first propose a formal model to assess probabilistically function-impacting variants. We then develop an array of structure-based functional residue predictors, evaluate their performance, and use them to quantify the impact of disease-causing amino acid substitutions on catalytic activity, metal binding, macromolecular binding, ligand binding, allosteric regulation and post-translational modifications. We show that our methodology generates actionable biological hypotheses for up to 41% of disease-causing genetic variants mapped to protein structures suggesting that it can be reliably used to guide experimental validation. Our results suggest that a significant fraction of disease-causing human variants mapping to protein structures are function-altering both in the presence and absence of stability disruption. PMID:27564311

  12. The Loss and Gain of Functional Amino Acid Residues Is a Common Mechanism Causing Human Inherited Disease

    PubMed Central

    Lugo-Martinez, Jose; Pejaver, Vikas; Pagel, Kymberleigh A.; Mort, Matthew; Cooper, David N.; Mooney, Sean D.; Radivojac, Predrag

    2016-01-01

    Elucidating the precise molecular events altered by disease-causing genetic variants represents a major challenge in translational bioinformatics. To this end, many studies have investigated the structural and functional impact of amino acid substitutions. Most of these studies were however limited in scope to either individual molecular functions or were concerned with functional effects (e.g. deleterious vs. neutral) without specifically considering possible molecular alterations. The recent growth of structural, molecular and genetic data presents an opportunity for more comprehensive studies to consider the structural environment of a residue of interest, to hypothesize specific molecular effects of sequence variants and to statistically associate these effects with genetic disease. In this study, we analyzed data sets of disease-causing and putatively neutral human variants mapped to protein 3D structures as part of a systematic study of the loss and gain of various types of functional attribute potentially underlying pathogenic molecular alterations. We first propose a formal model to assess probabilistically function-impacting variants. We then develop an array of structure-based functional residue predictors, evaluate their performance, and use them to quantify the impact of disease-causing amino acid substitutions on catalytic activity, metal binding, macromolecular binding, ligand binding, allosteric regulation and post-translational modifications. We show that our methodology generates actionable biological hypotheses for up to 41% of disease-causing genetic variants mapped to protein structures suggesting that it can be reliably used to guide experimental validation. Our results suggest that a significant fraction of disease-causing human variants mapping to protein structures are function-altering both in the presence and absence of stability disruption. PMID:27564311

  13. The emotional impact of chronic and disabling skin disease: a psychoanalytic perspective.

    PubMed

    Koblenzer, Caroline S

    2005-10-01

    This article discusses some major early factors that influence the evolving psychologic development, which in turn helps determine the emotional impact that chronic or disabling skin disease may have on patients' lives. If the emotional environment, encompassed by the infant-caretaker relationship, is less than optimal, the stability of the body image may be compromised, self-esteem diminished, and affect less well handled and the somatic expression of emotional content may ensue. Each of these is important in dermatology, as is the nature of the disease and the capacity of families and of society to adapt. Psoriasis, atopic dermatitis, and acne are used as examples.

  14. Congenital and inherited neurologic diseases in dogs and cats: Legislation and its effect on purchase in Italy.

    PubMed

    Passantino, Annamaria; Masucci, Marisa

    2016-05-01

    Many of the congenital neurologic diseases can result in incapacity or death of the animal. Some of them, such as idiopathic epilepsy and hydrocephalus, exhibit breed or familial predisposition and a genetic basis was proved or suggested. Some diseases can be presumptively diagnosed after a detailed signalment (breed predisposition), history (e.g. family history because many of these defects have familial tendencies), and through physical exam; other diagnostic methods (radiography, computed tomography, magnetic resonance, electrophysiologic tests, etc.) can provide supportive evidence for the congenital defect and help to confirm the diagnosis. Some cases can lead to civil law-suits when the lesions are congenital, but not easily recognizable, or when the lesions are hereditary but tend to became manifest only after some time (more than 12 months after the date of purchase, e.g., after the vice-free guarantee period has expired). Moreover, quite frequently an early diagnosis is not made because there are delays in consulting the veterinarian or the general practitioner veterinarian does not perceive subtle signs. This study was designed to focus on the medico-legal aspects concerning the buying and selling in Italy of dogs and cats affected by congenital and hereditary neurologic diseases that could constitute vice in these animals. While adequate provisions to regulate in detail the various aspects of pet sale have still to be drawn up by legislators, it may be helpful to involve breeders, by obliging them by contract to extend guarantees in the case of hereditary lesions, including neurologic diseases.

  15. Different intestinal permeability patterns in relatives and spouses of patients with Crohn's disease: an inherited defect in mucosal defence?

    PubMed Central

    Soderholm, J; Olaison, G; Lindberg, E; Hannestad, U; Vindels, A; Tysk, C; Jarnerot, G; Sjodahl, R

    1999-01-01

    Background—A familial defect in intestinal barrier function has been found in Crohn's disease. 
Aim—To investigate possible genetic and environmental influences on this barrier defect by studying intestinal permeability in both relatives and spouses of patients with Crohn's disease. 
Subjects—The study included 39 patients with Crohn's disease, 34 healthy first degree relatives, and 22 spouses. Twenty nine healthy volunteers served as controls. 
Methods—Intestinal permeability was assessed as the lactulose:mannitol ratio in five hour urinary excretion after oral load, both before (baseline) and after ingestion of acetylsalicylic acid. The permeability response represents the difference between the two tests. A ratio above the 95th percentile for controls was classified as abnormal. 
Results—Baseline permeability was higher in patients and spouses than in controls. An abnormal baseline permeability was seen in 36% of the patients, 23% of the spouses, 18% of the relatives, and 3% of the controls. After ingestion of acetylsalicylic acid, permeability increased significantly in all groups. Relatives were similar to patients with regard to permeability after exposure to acetylsalicylic acid, whereas spouses were similar to controls. The proportions with an abnormal permeability response to acetylsalicylic acid were 32% in patients, 14% in spouses, 41% in relatives, and 3% in controls. 
Conclusion—The findings suggest that baseline permeability is determined by environmental factors, whereas permeability provoked by acetylsalicylic acid is a function of the genetically determined state of the mucosal barrier, and support the notion that environmental and hereditary factors interact in the pathogenesis of Crohn's disease. 

 Keywords: acetylsalicylic acid; environment; genetics; inflammatory bowel disease; lactulose; mannitol PMID:9862833

  16. Puffy Skin Disease Is an Emerging Transmissible Condition in Rainbow Trout Oncorhynchus mykiss Walbaum

    PubMed Central

    Cano, Irene; Verner-Jeffreys, David W.; van Aerle, Ronny; Paley, Richard K.; Peeler, Edmund J.; Green, Matthew; Rimmer, Georgina S. E.; Savage, Jacqueline; Joiner, Claire L.; Bayley, Amanda E.; Mewett, Jason; Hulland, Jonathan; Feist, Stephen W.

    2016-01-01

    The transmission of puffy skin disease (PSD) to rainbow trout Oncorhynchus mykiss Walbaum was tested in the laboratory by conducting co-habitation challenges with puffy skin (PS)-affected fish (Trojans) collected from the field. Two separate challenges were conducted using Trojans sourced from two different sites and diploid (first trial) or triploid (second trial) naïve fish. PSD-specific clinical signs were observed in both groups of naïve fish, with 66% of the fish sampled during the challenges showing signs of varying severity. The first clinical features of PSD were presented as white oval skin patches on one or both flanks 15–21 days post-challenge (dpc). The extent of the lesions ranged from 10 to 90% of the body surface, depending on the severity of the lesion. Both the severity and number of affected fish increased during the challenge. Macroscopically, oedema of the skin and multifocal petechial haemorrhaging were observed towards the end of the trials. Abnormal fish behaviour consisting of “flashing” and excessive mucous production was noted from 15 dpc onwards. Fish with severe PSD lesions also displayed inappetence and associated emaciation. Rodlet cells were observed in 41% of the fresh skin scrapes analysed from the second trial. Histologically epidermal oedema was observed in 31% of the naive fish showing gross pathology, with additional 12% displaying epidermal hyperplasia, mostly observed at the end of the challenge. Other concomitant features of the PSD lesions in challenged fish were epithelial erosion and sloughing, and occasionally mild or focal inflammation. No consistent pathology of internal organs was observed. The parasites Ichthyophthirius multifiliis and Ichthyobodo necator were observed in skin samples of a proportion of naïve challenged fish and in Trojans but not in control fish. The presence of these and other known fish pathogens in the skin of PSD-fish was confirmed by high-throughput sequencing analysis. In summary, we

  17. Puffy Skin Disease Is an Emerging Transmissible Condition in Rainbow Trout Oncorhynchus mykiss Walbaum.

    PubMed

    Cano, Irene; Verner-Jeffreys, David W; van Aerle, Ronny; Paley, Richard K; Peeler, Edmund J; Green, Matthew; Rimmer, Georgina S E; Savage, Jacqueline; Joiner, Claire L; Bayley, Amanda E; Mewett, Jason; Hulland, Jonathan; Feist, Stephen W

    2016-01-01

    The transmission of puffy skin disease (PSD) to rainbow trout Oncorhynchus mykiss Walbaum was tested in the laboratory by conducting co-habitation challenges with puffy skin (PS)-affected fish (Trojans) collected from the field. Two separate challenges were conducted using Trojans sourced from two different sites and diploid (first trial) or triploid (second trial) naïve fish. PSD-specific clinical signs were observed in both groups of naïve fish, with 66% of the fish sampled during the challenges showing signs of varying severity. The first clinical features of PSD were presented as white oval skin patches on one or both flanks 15-21 days post-challenge (dpc). The extent of the lesions ranged from 10 to 90% of the body surface, depending on the severity of the lesion. Both the severity and number of affected fish increased during the challenge. Macroscopically, oedema of the skin and multifocal petechial haemorrhaging were observed towards the end of the trials. Abnormal fish behaviour consisting of "flashing" and excessive mucous production was noted from 15 dpc onwards. Fish with severe PSD lesions also displayed inappetence and associated emaciation. Rodlet cells were observed in 41% of the fresh skin scrapes analysed from the second trial. Histologically epidermal oedema was observed in 31% of the naive fish showing gross pathology, with additional 12% displaying epidermal hyperplasia, mostly observed at the end of the challenge. Other concomitant features of the PSD lesions in challenged fish were epithelial erosion and sloughing, and occasionally mild or focal inflammation. No consistent pathology of internal organs was observed. The parasites Ichthyophthirius multifiliis and Ichthyobodo necator were observed in skin samples of a proportion of naïve challenged fish and in Trojans but not in control fish. The presence of these and other known fish pathogens in the skin of PSD-fish was confirmed by high-throughput sequencing analysis. In summary, we have

  18. Topical PDT in the Treatment of Benign Skin Diseases: Principles and New Applications

    PubMed Central

    Kim, Miri; Jung, Haw Young; Park, Hyun Jeong

    2015-01-01

    Photodynamic therapy (PDT) uses a photosensitizer, light energy, and molecular oxygen to cause cell damage. Cells exposed to the photosensitizer are susceptible to destruction upon light absorption because excitation of the photosensitizing agents leads to the production of reactive oxygen species and, subsequently, direct cytotoxicity. Using the intrinsic cellular heme biosynthetic pathway, topical PDT selectively targets abnormal cells, while preserving normal surrounding tissues. This selective cytotoxic effect is the basis for the use of PDT in antitumor treatment. Clinically, PDT is a widely used therapeutic regimen for oncologic skin conditions such as actinic keratosis, squamous cell carcinoma in situ, and basal cell carcinoma. PDT has been shown, under certain circumstances, to stimulate the immune system and produce antibacterial, and/or regenerative effects while protecting cell viability. Thus, it may be useful for treating benign skin conditions. An increasing number of studies support the idea that PDT may be effective for treating acne vulgaris and several other inflammatory/infective skin diseases, including psoriasis, rosacea, viral warts, and aging-related changes. This review provides an overview of the clinical investigations of PDT and discusses each of the essential aspects of the sequence: its mechanism of action, common photosensitizers, light sources, and clinical applications in dermatology. Of the numerous clinical trials of PDT in dermatology, this review focuses on those studies that have reported remarkable therapeutic benefits following topical PDT for benign skin conditions such as acne vulgaris, viral warts, and photorejuvenation without causing severe side effects. PMID:26404243

  19. Topical PDT in the Treatment of Benign Skin Diseases: Principles and New Applications.

    PubMed

    Kim, Miri; Jung, Haw Young; Park, Hyun Jeong

    2015-01-01

    Photodynamic therapy (PDT) uses a photosensitizer, light energy, and molecular oxygen to cause cell damage. Cells exposed to the photosensitizer are susceptible to destruction upon light absorption because excitation of the photosensitizing agents leads to the production of reactive oxygen species and, subsequently, direct cytotoxicity. Using the intrinsic cellular heme biosynthetic pathway, topical PDT selectively targets abnormal cells, while preserving normal surrounding tissues. This selective cytotoxic effect is the basis for the use of PDT in antitumor treatment. Clinically, PDT is a widely used therapeutic regimen for oncologic skin conditions such as actinic keratosis, squamous cell carcinoma in situ, and basal cell carcinoma. PDT has been shown, under certain circumstances, to stimulate the immune system and produce antibacterial, and/or regenerative effects while protecting cell viability. Thus, it may be useful for treating benign skin conditions. An increasing number of studies support the idea that PDT may be effective for treating acne vulgaris and several other inflammatory/infective skin diseases, including psoriasis, rosacea, viral warts, and aging-related changes. This review provides an overview of the clinical investigations of PDT and discusses each of the essential aspects of the sequence: its mechanism of action, common photosensitizers, light sources, and clinical applications in dermatology. Of the numerous clinical trials of PDT in dermatology, this review focuses on those studies that have reported remarkable therapeutic benefits following topical PDT for benign skin conditions such as acne vulgaris, viral warts, and photorejuvenation without causing severe side effects. PMID:26404243

  20. Epidermal parasitic skin diseases: a neglected category of poverty-associated plagues

    PubMed Central

    Heukelbach, Jorg

    2009-01-01

    Abstract Epidermal parasitic skin diseases (EPSD) are a heterogeneous category of infectious diseases in which parasite–host interactions are confined to the upper layer of the skin. The six major EPSD are scabies, pediculosis (capitis, corporis and pubis), tungiasis and hookworm-related cutaneous larva migrans. We summarize the current knowledge on EPSD and show that these diseases are widespread, polyparasitism is common, and significant primary and secondary morbidity occurs. We show that poverty favours the presence of animal reservoirs, ensures ongoing transmission, facilitates atypical methods of spreading infectious agents and increases the chances of exposure. This results in an extraordinarily high prevalence and intensity of infestation of EPSD in resource-poor populations. Stigma, lack of access to health care and deficient behaviour in seeking health care are the reasons why EPSD frequently progress untreated and why in resource-poor populations severe morbidity is common. The ongoing uncontrolled urbanization in many developing countries makes it likely that EPSD will remain the overriding parasitic diseases for people living in extreme poverty. We advocate integrating control of EPSD into intervention measures directed against other neglected diseases such as filariasis and intestinal helminthiases. PMID:19274368

  1. Activation of Blood Coagulation in Two Prototypic Autoimmune Skin Diseases: A Possible Link with Thrombotic Risk.

    PubMed

    Cugno, Massimo; Tedeschi, Alberto; Borghi, Alessandro; Bucciarelli, Paolo; Asero, Riccardo; Venegoni, Luigia; Griffini, Samantha; Grovetti, Elena; Berti, Emilio; Marzano, Angelo Valerio

    2015-01-01

    Coagulation activation has been demonstrated in two prototypic autoimmune skin diseases, chronic autoimmune urticaria and bullous pemphigoid, but only the latter is associated with increased thrombotic risk. Two markers of coagulation activation (prothrombin fragment F1+2 and fibrin fragment D-dimer) were measured by immunoenzymatic methods in plasma samples from 30 patients with active chronic autoimmune urticaria, positive for autologous serum skin test, 30 patients with active bullous pemphigoid and 30 healthy subjects. In skin biopsies, tissue factor expression was evaluated by both immunohistochemistry and in situ hybridization. F1+2 and D-dimer levels were higher in active chronic autoimmune urticaria (276.5±89.8 pmol/L and 5.56±4.40 nmol/L, respectively) than in controls (145.2±38.0 pmol/L and 1.06±0.25 nmol/L; P=0.029 and P=0.011) and were much higher in active bullous pemphigoid (691.7±318.7 pmol/L and 15.24±9.09 nmol/L, respectively) (P<0.0001). Tissue factor positivity was evident in skin biopsies of both disorders with higher intensity in bullous pemphigoid. F1+2 and D-dimer, during remission, were markedly reduced in both disorders. These findings support the involvement of coagulation activation in the pathophysiology of both diseases. The strong systemic activation of coagulation in bullous pemphigoid may contribute to increase the thrombotic risk and provides the rationale for clinical trials on anticoagulant treatments in this disease.

  2. Congenital and inherited neurologic diseases in dogs and cats: Legislation and its effect on purchase in Italy.

    PubMed

    Passantino, Annamaria; Masucci, Marisa

    2016-05-01

    Many of the congenital neurologic diseases can result in incapacity or death of the animal. Some of them, such as idiopathic epilepsy and hydrocephalus, exhibit breed or familial predisposition and a genetic basis was proved or suggested. Some diseases can be presumptively diagnosed after a detailed signalment (breed predisposition), history (e.g. family history because many of these defects have familial tendencies), and through physical exam; other diagnostic methods (radiography, computed tomography, magnetic resonance, electrophysiologic tests, etc.) can provide supportive evidence for the congenital defect and help to confirm the diagnosis. Some cases can lead to civil law-suits when the lesions are congenital, but not easily recognizable, or when the lesions are hereditary but tend to became manifest only after some time (more than 12 months after the date of purchase, e.g., after the vice-free guarantee period has expired). Moreover, quite frequently an early diagnosis is not made because there are delays in consulting the veterinarian or the general practitioner veterinarian does not perceive subtle signs. This study was designed to focus on the medico-legal aspects concerning the buying and selling in Italy of dogs and cats affected by congenital and hereditary neurologic diseases that could constitute vice in these animals. While adequate provisions to regulate in detail the various aspects of pet sale have still to be drawn up by legislators, it may be helpful to involve breeders, by obliging them by contract to extend guarantees in the case of hereditary lesions, including neurologic diseases. PMID:27284217

  3. Congenital and inherited neurologic diseases in dogs and cats: Legislation and its effect on purchase in Italy

    PubMed Central

    Passantino, Annamaria; Masucci, Marisa

    2016-01-01

    Many of the congenital neurologic diseases can result in incapacity or death of the animal. Some of them, such as idiopathic epilepsy and hydrocephalus, exhibit breed or familial predisposition and a genetic basis was proved or suggested. Some diseases can be presumptively diagnosed after a detailed signalment (breed predisposition), history (e.g. family history because many of these defects have familial tendencies), and through physical exam; other diagnostic methods (radiography, computed tomography, magnetic resonance, electrophysiologic tests, etc.) can provide supportive evidence for the congenital defect and help to confirm the diagnosis. Some cases can lead to civil law-suits when the lesions are congenital, but not easily recognizable, or when the lesions are hereditary but tend to became manifest only after some time (more than 12 months after the date of purchase, e.g., after the vice-free guarantee period has expired). Moreover, quite frequently an early diagnosis is not made because there are delays in consulting the veterinarian or the general practitioner veterinarian does not perceive subtle signs. This study was designed to focus on the medico-legal aspects concerning the buying and selling in Italy of dogs and cats affected by congenital and hereditary neurologic diseases that could constitute vice in these animals. While adequate provisions to regulate in detail the various aspects of pet sale have still to be drawn up by legislators, it may be helpful to involve breeders, by obliging them by contract to extend guarantees in the case of hereditary lesions, including neurologic diseases. PMID:27284217

  4. Neuropathologic assessment of participants in two multi-center longitudinal observational studies: the Alzheimer Disease Neuroimaging Initiative (ADNI) and the Dominantly Inherited Alzheimer Network (DIAN).

    PubMed

    Cairns, Nigel J; Perrin, Richard J; Franklin, Erin E; Carter, Deborah; Vincent, Benjamin; Xie, Mingqiang; Bateman, Randall J; Benzinger, Tammie; Friedrichsen, Karl; Brooks, William S; Halliday, Glenda M; McLean, Catriona; Ghetti, Bernardino; Morris, John C

    2015-08-01

    It has been hypothesized that the relatively rare autosomal dominant Alzheimer disease (ADAD) may be a useful model of the more frequent, sporadic, late-onset AD (LOAD). Individuals with ADAD have a predictable age at onset and the biomarker profile of ADAD participants in the preclinical stage may be used to predict disease progression and clinical onset. However, the extent to which the pathogenesis and neuropathology of ADAD overlaps with that of LOAD is equivocal. To address this uncertainty, two multicenter longitudinal observational studies, the Alzheimer Disease Neuroimaging Initiative (ADNI) and the Dominantly Inherited Alzheimer Network (DIAN), leveraged the expertise and resources of the existing Knight Alzheimer Disease Research Center (ADRC) at Washington University School of Medicine, St. Louis, Missouri, USA, to establish a Neuropathology Core (NPC). The ADNI/DIAN-NPC is systematically examining the brains of all participants who come to autopsy at the 59 ADNI sites in the USA and Canada and the 14 DIAN sites in the USA (eight), Australia (three), UK (one) and Germany (two). By 2014, 41 ADNI and 24 DIAN autopsies (involving nine participants and 15 family members) had been performed. The autopsy rate in the ADNI cohort in the most recent year was 93% (total since NPC inception: 70%). In summary, the ADNI/DIAN NPC has implemented a standard protocol for all sites to solicit permission for brain autopsy and to send brain tissue to the NPC for a standardized, uniform and state-of-the-art neuropathologic assessment. The benefit to ADNI and DIAN of the implementation of the NPC is very clear. The NPC provides final "gold standard" neuropathological diagnoses and data against which the antecedent observations and measurements of ADNI and DIAN can be compared.

  5. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2011.

    PubMed

    Sicherer, Scott H; Leung, Donald Y M

    2012-01-01

    This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin diseases that were reported in the Journal in 2011. Food allergy appears to be increasing in prevalence and carries a strong economic burden. Risk factors can include dietary ones, such as deficiency of vitamin D and timing of complementary foods, and genetic factors, such as filaggrin loss-of-function mutations. Novel mechanisms underlying food allergy include the role of invariant natural killer T cells and influences of dietary components, such as isoflavones. Among numerous preclinical and clinical treatment studies, promising observations include the efficacy of sublingual and oral immunotherapy, a Chinese herbal remedy showing promising in vitro results, the potential immunotherapeutic effects of having children ingest foods with baked-in milk if they tolerate it, and the use of anti-IgE with or without concomitant immunotherapy. Studies of allergic skin diseases, anaphylaxis, and hypersensitivity to drugs and insect venom are elucidating cellular mechanisms, improved diagnostics, and potential targets for future treatment. The role of skin barrier abnormalities, as well as the modulatory effects of the innate and adaptive immune responses, are major areas of investigation.

  6. Acne: a new model of immune-mediated chronic inflammatory skin disease.

    PubMed

    Antiga, E; Verdelli, A; Bonciani, D; Bonciolini, V; Caproni, M; Fabbri, P

    2015-04-01

    Acne is a chronic inflammatory disease of the sebaceous-pilosebaceous unit. Interestingly, inflammation can be detected by histopathological examination and immuohistochemical analysis even in the apparently non-inflammatory acneic lesions, such as comedones. In the last years, it has been clearly demonstrated that acne development is linked to the combination of predisposing genetic factors and environmental triggers, among which a prominent role is played by the follicular colonization by Propionibacterium acnes (P. acnes). P. acnes displays several activities able to promote the development of acne skin lesions, including the promotion of follicular hyperkeratinisation, the induction of sebogenesis, and the stimulation of an inflammatory response by the secretion of proinflammatory molecules and by the activation of innate immunity, that is followed by a P. acnes-specific adaptive immune response. In addition, P. acnes-independent inflammation mediated by androgens or by a neurogenic activation, followed by the secretion in the skin of pro-inflammatory neuropeptides, can occur in acne lesions. In conclusion, acne can be considered as a model of immune-mediated chronic inflammatory skin disease, characterized by an innate immune response that is not able to control P. acnes followed by a Th1-mediated adaptive immune response, that becomes self-maintaining independently from P. acnes itself. PMID:25876146

  7. Risk of Flood-Related Diseases of Eyes, Skin and Gastrointestinal Tract in Taiwan: A Retrospective Cohort Study.

    PubMed

    Huang, Ling-Ya; Wang, Yu-Chun; Wu, Chin-Ching; Chen, Yi-Chun; Huang, Yu-Li

    2016-01-01

    Floods are known to cause serious environmental damage and health impacts. Studies on flood-related diseases have been primarily on individual events, and limited evidence could be drawn on potential health impacts from floods using large population data. This study used reimbursement records of one million people of the Taiwan National Health Insurance program to compare incident diseases of the eyes, skin and gastrointestinal (GI) tract associated with floods. Incidence rates for the selected diseases were calculated according to outpatient/emergency visit data. The incidence rates were evaluated by flood status: in 10 days before floods, during floods and within 10 days after the floods receded. Outpatient/emergency visit rates for the eye, skin and GI tract diseases were highest after floods and lowest during floods. Results from multivariate Poisson regression analyses showed that, when compared with the incidence in 10 days before floods, the incidence rate ratios (IRR) of diseases within 10 days after floods were 1.15 (95% confidence interval (CI) = 1.10-1.20) for eyes, 1.08 (95% C.I. = 1.05-1.10) for skin, and 1.11 (95% CI = 1.08-1.14) for GI tract, after controlling for covariates. All risks increased with ambient temperature. V-shaped trends were found between age and eye diseases, and between age and GI tract diseases. In contrast, the risk of skin diseases increased with age. In conclusion, more diseases of eyes, skin and GI tract could be diagnosed after the flood.

  8. Cutaneous Surgical Denervation: A Method for Testing the Requirement for Nerves in Mouse Models of Skin Disease.

    PubMed

    Peterson, Shelby C; Brownell, Isaac; Wong, Sunny Y

    2016-01-01

    Cutaneous somatosensory nerves function to detect diverse stimuli that act upon the skin. In addition to their established sensory roles, recent studies have suggested that nerves may also modulate skin disorders including atopic dermatitis, psoriasis and cancer. Here, we describe protocols for testing the requirement for nerves in maintaining a cutaneous mechanosensory organ, the touch dome (TD). Specifically, we discuss methods for genetically labeling, harvesting and visualizing TDs by whole-mount staining, and for performing unilateral surgical denervation on mouse dorsal back skin. Together, these approaches can be used to directly compare TD morphology and gene expression in denervated as well as sham-operated skin from the same animal. These methods can also be readily adapted to examine the requirement for nerves in mouse models of skin pathology. Finally, the ability to repeatedly sample the skin provides an opportunity to monitor disease progression at different stages and times after initiation. PMID:27404892

  9. Effect of Alpinia zerumbet components on antioxidant and skin diseases-related enzymes

    PubMed Central

    2012-01-01

    Background The skin is chronically exposed to endogenous and environmental pro-oxidant agents, leading to the harmful generation of reactive oxygen species. Antioxidant is vital substances which possess the ability to protect the body from damage cause by free radicals induce oxidative stress. Alpinia zerumbet, a traditionally important economic plant in Okinawa, contains several interesting bioactive constituents and possesses health promoting properties. In this regard, we carried out to test the inhibitory effect of crude extracts and isolated compounds from A. zerumbet on antioxidant and skin diseases-related enzymes. Methods The antioxidant activities were examined by DPPH, ABTS and PMS-NADH radical scavenging. Collagenase, elastase, hyaluronidase and tyrosinase were designed for enzymatic activities to investigate the inhibitory properties of test samples using a continuous spectrophotometric assay. The inhibitory capacity of test samples was presented at half maximal inhibitory concentration (IC50). Results The results showed that aqueous extract of the rhizome was found to have greater inhibitory effects than the others on both of antioxidant and skin diseases-related enzymes. Furthermore, 5,6-dehydrokawain (DK), dihydro-5,6-dehydrokawain (DDK) and 8(17),12-labdadiene-15,16-dial (labdadiene), isolated from rhizome, were tested for antioxidant and enzyme inhibitions. We found that DK showed higher inhibitory activities on DPPH, ABTS and PMS-NADH scavenging (IC50 = 122.14 ± 1.40, 110.08 ± 3.34 and 127.78 ± 4.75 μg/ml, respectively). It also had stronger inhibitory activities against collagenase, elastase, hyaluronidase and tyrosinase (IC50 = 24.93 ± 0.97, 19.41 ± 0.61, 19.48 ± 0.24 and 76.67 ± 0.50 μg/ml, respectively) than DDK and labdadiene. Conclusion Our results indicate that the rhizome aqueous extract proved to be the source of bioactive compounds against enzymes responsible for causing skin diseases

  10. Genomic analysis of genetic markers associated with inherited cardiomyopathy (round heart disease) in the turkey (Meleagris gallopavo).

    PubMed

    Reed, K M; Mendoza, K M; Hu, G R; Sullivan, L R; Grace, M W; Chaves, L D; Kooyman, D L

    2007-06-01

    In turkeys, spontaneous cardiomyopathy or round heart (RH) disease is characterised by dilated ventricles and cardiac muscle hypertrophy. Although the aetiology of RH is still unknown, the disease can have a significant economic impact on turkey producers. In an initial attempt to identify genomic regions associated with RH, we utilised the chicken genome sequence to target short DNA sequences (sequence-characterised amplified regions, SCARs) identified in previous studies that had significant differences in frequency distribution between RH+ and RH- turkeys. SCARs were comparatively aligned with the chicken whole-genome sequence to identify flanking regions for primer design. Primers from 32 alignments were tested and target sequences were successfully amplified for 30 loci (94%). Comparative re-sequencing identified putative SNPs in 20 of the 30 loci (67%). Genetically informative SNPs at 16 loci were genotyped in the UMN/NTBF turkey mapping population. As a result of this study, 34 markers were placed on the turkey/chicken comparative map and 15 markers were added to the turkey genetic linkage map. The position of these markers relative to cardiac-related genes is presented. In addition, analysis of genotypes at 109 microsatellite loci presumed to flank the SCAR sequences in the turkey genome identified four significant associations with RH.

  11. Cowden's Disease: Familial Goiter and Skin Hamartomas—A Report of Three Cases

    PubMed Central

    Sogol, Paul B.; Sugawara, Masahiro; Gordon, H. Earl; Shellow, William V. R.; Hernandez, Felix; Hershman, Jerome M.

    1983-01-01

    Multiple hamartoma syndrome (Cowden's disease) consists of characteristic skin lesions of the face, mucous membranes and distal extremities in association with a variety of benign and malignant internal tumors, especially of the thyroid and breast. We describe a family in which the father, daughter and son were found to have goiter associated with the skin lesions of Cowden's disease. Review of the 40 reported cases of this syndrome indicates that thyroid disease occurs in two thirds of patients with Cowden's disease and most often presents as goiter at an early age. Thyroid cancer has occurred in only three (7.5%) of the patients. Surgical removal of the large goiter of the son showed that it was composed of multiple encapsulated follicular adenomas and a few areas of lymphocytic thyroiditis. Studies of the thyroid tissue showed that peroxidase activity was decreased, the thyroglobulin had a reduced content of thyroxine and triiodothyronine (perhaps due to the therapeutic suppression of thyroid-stimulating hormone) and thyroxine 5'-monodeiodinase was greatly increased; increased outer ring monodeiodinase activity may be a characteristic of human follicular adenomas. Images PMID:6636746

  12. Predicted disease susceptibility in a Panamanian amphibian assemblage based on skin peptide defenses.

    PubMed

    Woodhams, Douglas C; Voyles, Jamie; Lips, Karen R; Carey, Cynthia; Rollins-Smith, Louise A

    2006-04-01

    Chytridiomycosis is an emerging infectious disease of amphibians caused by a chytrid fungus, Batrachochytrium dendrobatidis. This panzootic does not equally affect all amphibian species within an assemblage; some populations decline, others persist. Little is known about the factors that affect disease resistance. Differences in behavior, life history, biogeography, or immune function may impact survival. We found that an innate immune defense, antimicrobial skin peptides, varied significantly among species within a rainforest stream amphibian assemblage that has not been exposed to B. dendrobatidis. If exposed, all amphibian species at this central Panamanian site are at risk of population declines. In vitro pathogen growth inhibition by peptides from Panamanian species compared with species with known resistance (Rana pipiens and Xenopus laevis) or susceptibility (Bufo boreas) suggests that of the nine species examined, two species (Centrolene prosoblepon and Phyllomedusa lemur) may demonstrate strong resistance, and the other species will have a higher risk of disease-associated population declines. We found little variation among geographically distinct B. dendrobatidis isolates in sensitivity to an amphibian skin peptide mixture. This supports the hypothesis that B. dendrobatidis is a generalist pathogen and that species possessing an innate immunologic defense at the time of disease emergence are more likely to survive.

  13. Regulation of kallikrein-related peptidases in the skin - from physiology to diseases to therapeutic options.

    PubMed

    Fischer, J; Meyer-Hoffert, U

    2013-09-01

    Kallikrein-related peptidases (KLKs) constitute a family of 15 highly conserved serine proteases, which show a tissue-specific expression profile. This made them valuable tumour expression markers. It became evident that KLKs are involved in many physiological processes like semen liquefaction and skin desquamation. More recently, we have learnt that they are involved in many pathophysiological conditions and diseases making them promising target of therapeutic intervention. Therefore, regulation of KLKs raised the interest of numerous reports. Herein, we summarise the current knowledge on KLKs regulation with an emphasis on skin-relevant KLKs regulation processes. Regulation of KLKs takes place on the level of transcription, on protease activation and on protease inactivation. A variety of protease inhibitors has been described to interact with KLKs including the irreversible serine protease inhibitors (SERPINs) and the reversible serine protease inhibitors of Kazal-type (SPINKs). In an attempt to integrate current knowledge, we propose that KLK regulation has credentials as targets for therapeutic intervention.

  14. Photochemical model of photodynamic therapy applied to skin diseases by a topical photosensitizer

    NASA Astrophysics Data System (ADS)

    Fanjul-Vélez, F.; Salas-García, I.; Fernández-Fernández, L. A.; López-Escobar, M.; Buelta-Carrillo, L.; Ortega-Quijano, N.; Arce-Diego, J. L.

    2009-07-01

    Photodynamic Therapy (PDT) provides a non-invasive, efficient and safe treatment for skin diseases with good cosmetic results. These characteristics make this technique more advantageous than radiotherapy or chemotherapy, which present limitations in a big number of lesions, are painful in many cases and produce non-satisfactory cosmetic results. We present the clinical results obtained at present by this optical technique and a photochemical model of the PDT process applied to the skin by means of a topical photosensitizer, in order to find the optimal PDT parameters. Optical propagation inside the tissue is calculated by means of the three dimensional Beer-Lambert law, due to its facility to be integrated in the differential equations system used to model the photochemical processes involved. With this information it is possible to obtain an initial estimation about the optimal drug dose and the optical power required.

  15. Successful treatment of chronic skin diseases with clobetasol propionate and a hydrocolloid occlusive dressing.

    PubMed

    Volden, G

    1992-01-01

    The lesions of 141 patients with chronic skin diseases unresponsive to therapy were treated once a week with clobetasol propionate lotion left under the completely occlusive patch Duoderm. In 131 patients the lesions resolved completely, while partial remission was observed in the remaining 10. The mean interval to complete remission was: for chronic plaque psoriasis, 12 days; psoriasis on palms and soles, 2.5 weeks; palmoplantar pustulosis, 2.2 weeks; skin lesions of Reiter's syndrome, 3 weeks; chronic lichenified eczema, 2.0 weeks; neurodermatitis, 3.1 weeks; breast eczema, 9 days; discoid lupus erythematosus, 3.7 weeks; lichen planus, 2.8 weeks; sarcoidosis, 4 weeks; and lichen sclerosus et atrophicus, 2 weeks. Other conditions benefitting from the treatment were pompholyx, necrobiosis lipoidica, granuloma annulare and pretibial myxedema. The amount of topical corticosteroids needed was reduced to at most 1/20 and to as little as 1/100, compared with common topical steroid preparations.

  16. Vaccinia viruses isolated from skin infection in horses produced cutaneous and systemic disease in experimentally infected rabbits.

    PubMed

    Cargnelutti, Juliana Felipetto; Schmidt, Candice; Masuda, Eduardo Kenji; Nogueira, Paula Rochelle Kurrle; Weiblen, Rudi; Flores, Eduardo Furtado

    2012-10-01

    The susceptibility of rabbits to two isolates of Vaccinia virus (VACV) recovered from cutaneous disease in horses in Southern Brazil was investigated. Rabbits were inoculated in the ear skin with both VACV isolates, either in single or mixed infection. All inoculated animals presented local skin lesions characterized by hyperaemia, papules, vesicles, pustules and ulcers. Infectious virus was detected in the lungs and intestine of rabbits that died during acute disease. Histological examination of the skin revealed changes characteristic of those associated with members of the genus Orthopoxvirus. These results demonstrate that rabbits develop skin disease accompanied by systemic signs upon intradermal inoculation of these two equine VACV isolates, either alone or in combination, opening the way for using rabbits to study selected aspects of the biology and pathogenesis of VACV infection.

  17. Overexpression of constitutively active BMP-receptor-IB in mouse skin causes an ichthyosis-vulgaris-like disease.

    PubMed

    Yu, Xueyan; Espinoza-Lewis, Ramón A; Sun, Cheng; Lin, Lisong; He, Fenglei; Xiong, Wei; Yang, Jing; Wang, Alun; Chen, Yiping

    2010-12-01

    The skin is the outer layer of protection against the environment. The development and formation of the skin is regulated by several genetic cascades including the bone morphogenetic protein (BMP) signaling pathway, which has been suggested to play an important role during embryonic organ development. Several skin defects and diseases are caused by genetic mutations or disorders. Ichthyosis is a common genetic skin disorder characterized by dry scaly skin. Loss-of-function mutations in the filaggrin (FLG) gene have been identified as the cause of the ichthyosis vulgaris (IV) phenotype; however, the direct regulation of filaggrin expression in vivo is unknown. We present evidence that BMP signaling regulates filaggrin expression in the epidermis. Mice expressing a constitutively active form of BMP-receptor-IB in the developing epidermis exhibit a phenotype resembling IV in humans, including dry flaky skin, compact hyperkeratosis, and an attenuated granular layer associated with a significantly downregulated expression of filaggrin. Regulation of filaggrin expression by BMP signaling has been further confirmed by the application of exogenous BMP2 in skin explants and by a transgenic model overexpressing Noggin in the epidermis. Our results demonstrate that aberrant BMP signaling in the epidermis causes overproliferation and hyperkeratinization, leading to an IV-like skin disease.

  18. [The role of Helicobacter pyroli in the development of skin diseases].

    PubMed

    Deroń, Elzbieta; Kieć-Swierczyńska, Marta

    2002-01-01

    The paper presents the current state-of-the-art concerning the effect of Helicobacter pyroli infection on the progress of some skin diseases (Raynaud's disease, purpura hyperergica, rosacea, prurigo nodularis, atopic dermatitis, chronic urticaria). The attention was turned to the lack of unanimity among authors respective to the effect of Helicobacter pylori on the progress of some skin diseases, especially those of allergic etiology. The methods of bacteria identification were discussed. The methods are as follows: invasive tests involving endoscopy of the upper segment of the alimentary tract--a traumatic test, histologic examination and bacteria culture as well as noninvasive tests: respiratory test and serological tests able to detect the humoral response to infection or examination of the bacteria genetic material by means of PCR. The therapeutic methods used to eradicate effectively the infection, recommended by the Working Group of the Polish Association of Gastroenterology (a three-component treatment for seven days--a drug able to diminish gastric secretion and two antibiotics) are also discussed. PMID:12474414

  19. Phenotypic transition of microglia into astrocyte-like cells associated with disease onset in a model of inherited ALS

    PubMed Central

    Trias, Emiliano; Díaz-Amarilla, Pablo; Olivera-Bravo, Silvia; Isasi, Eugenia; Drechsel, Derek A.; Lopez, Nathan; Bradford, C. Samuel; Ireton, Kyle E.; Beckman, Joseph S.; Barbeito, Luis

    2013-01-01

    Microglia and reactive astrocytes accumulate in the spinal cord of rats expressing the Amyotrophic lateral sclerosis (ALS)-linked SOD1 G93A mutation. We previously reported that the rapid progression of paralysis in ALS rats is associated with the appearance of proliferative astrocyte-like cells that surround motor neurons. These cells, designated as Aberrant Astrocytes (AbA cells) because of their atypical astrocytic phenotype, exhibit high toxicity to motor neurons. However, the cellular origin of AbA cells remains unknown. Because AbA cells are labeled with the proliferation marker Ki67, we analyzed the phenotypic makers of proliferating glial cells that surround motor neurons by immunohistochemistry. The number of Ki67 +AbA cells sharply increased in symptomatic rats, displaying large cell bodies with processes embracing motor neurons. Most were co-labeled with astrocytic marker GFAP concurrently with the microglial markers Iba1 and CD163. Cultures of spinal cord prepared from symptomatic SOD1 G93A rats yielded large numbers of microglia expressing Iba1, CD11b, and CD68. Cells sorted for CD11b expression by flow cytometry transformed into AbA cells within two weeks. During these two weeks, the expression of microglial markers largely disappeared, while GFAP and S100β expression increased. The phenotypic transition to AbA cells was stimulated by forskolin. These findings provide evidence for a subpopulation of proliferating microglial cells in SOD1 G93A rats that undergo a phenotypic transition into AbA cells after onset of paralysis that may promote the fulminant disease progression. These cells could be a therapeutic target for slowing paralysis progression in ALS. PMID:24399933

  20. Inherited epidermolysis bullosa: clinical and therapeutic aspects*

    PubMed Central

    Boeira, Vanessa Lys Simas Yamakawa; Souza, Erica Sales; Rocha, Bruno de Oliveira; Oliveira, Pedro Dantas; de Oliveira, Maria de Fátima Santos Paim; Rêgo, Vitória Regina Pedreira de Almeida; Follador, Ivonise

    2013-01-01

    Inherited epidermolysis bullosa (EB) is a heterogeneous group of genetic disorders that present with skin and, in some cases, mucosal fragility, predisposing patients to the development of blisters and/or erosions after minimal trauma or friction. Children with a recurrent history of these kinds of lesions or neonates that present them in the absence of another reasonable explanation should be investigated. Diagnosis must be based on clinical and histopathological findings. To date, management of inherited EB basically consists in avoiding traumas that trigger lesions, as well as preventing infection and facilitating healing of the wounds with the systematic use of bandages. PMID:23739692

  1. Interleukin-17 inhibitors. A new era in treatment of psoriasis and other skin diseases

    PubMed Central

    Wasilewska, Agnieszka; Winiarska, Marta; Olszewska, Małgorzata

    2016-01-01

    Psoriasis is a chronic skin disease caused by the excessive secretion of inflammatory cytokines. Available therapeutic options include biologic drugs such as tumor necrosis factor alpha inhibitors and interleukin 12/23 (IL-12/23) inhibitors. The recent discovery of IL-17, which contributes to development of psoriasis, opened new possibilities for further treatment modalities. Currently, one anti-IL17 biological agent is approved for the treatment – a fully human monoclonal antibody that targets IL-17A (secukinumab). Further clinical trials, including a humanized IgG4 specific for IL-17 (ixekizumab) and a fully human antibody that targets the IL-17 receptor A (brodalumab). PMID:27605893

  2. A review of nicotinamide: treatment of skin diseases and potential side effects.

    PubMed

    Rolfe, Heidi M

    2014-12-01

    Nicotinamide, also known as niacinamide, is the amide form of vitamin B3. It is a precursor of essential coenzymes for numerous reactions in the body including adenosine triphosphate (ATP) production. Nicotinic acid, also known as niacin, is converted into nicotinamide in the body. The use of topical nicotinamide in the treatment of acne vulgaris; melasma; atopic dermatitis; rosacea; and oral nicotinamide in preventing nonmelanoma skin cancer is discussed. The possible side effects and consequences of excessive nicotinamide exposure are reviewed, including suggestions nicotinamide might have a role in the development of diabetes, Parkinson's disease, and liver damage.

  3. A review of nicotinamide: treatment of skin diseases and potential side effects.

    PubMed

    Rolfe, Heidi M

    2014-12-01

    Nicotinamide, also known as niacinamide, is the amide form of vitamin B3. It is a precursor of essential coenzymes for numerous reactions in the body including adenosine triphosphate (ATP) production. Nicotinic acid, also known as niacin, is converted into nicotinamide in the body. The use of topical nicotinamide in the treatment of acne vulgaris; melasma; atopic dermatitis; rosacea; and oral nicotinamide in preventing nonmelanoma skin cancer is discussed. The possible side effects and consequences of excessive nicotinamide exposure are reviewed, including suggestions nicotinamide might have a role in the development of diabetes, Parkinson's disease, and liver damage. PMID:25399625

  4. The allergy and immunology specialist: what is the role in the treatment of skin disease?

    PubMed

    Charlesworth, Ernest N

    2004-10-01

    The practice of medicine transcends our neat borders of demarcation between the myriad of medical specialties and medical disciplines. There are no two specialties in which this clinical interface is more blurred than the clinical interface between allergy and dermatology. With a background in both dermatology and allergy, I address where the specialty of allergy/ immunology is heading, as we navigate the coastal waters separating my two primary disciplines. I also discuss the tools traditionally used only in dermatology, which are now being used increasing by a vanguard of allergists to aid in the diagnosis and treatment of allergic skin disease.

  5. Interleukin-17 inhibitors. A new era in treatment of psoriasis and other skin diseases.

    PubMed

    Wasilewska, Agnieszka; Winiarska, Marta; Olszewska, Małgorzata; Rudnicka, Lidia

    2016-08-01

    Psoriasis is a chronic skin disease caused by the excessive secretion of inflammatory cytokines. Available therapeutic options include biologic drugs such as tumor necrosis factor alpha inhibitors and interleukin 12/23 (IL-12/23) inhibitors. The recent discovery of IL-17, which contributes to development of psoriasis, opened new possibilities for further treatment modalities. Currently, one anti-IL17 biological agent is approved for the treatment - a fully human monoclonal antibody that targets IL-17A (secukinumab). Further clinical trials, including a humanized IgG4 specific for IL-17 (ixekizumab) and a fully human antibody that targets the IL-17 receptor A (brodalumab). PMID:27605893

  6. Interleukin-17 inhibitors. A new era in treatment of psoriasis and other skin diseases

    PubMed Central

    Wasilewska, Agnieszka; Winiarska, Marta; Olszewska, Małgorzata

    2016-01-01

    Psoriasis is a chronic skin disease caused by the excessive secretion of inflammatory cytokines. Available therapeutic options include biologic drugs such as tumor necrosis factor alpha inhibitors and interleukin 12/23 (IL-12/23) inhibitors. The recent discovery of IL-17, which contributes to development of psoriasis, opened new possibilities for further treatment modalities. Currently, one anti-IL17 biological agent is approved for the treatment – a fully human monoclonal antibody that targets IL-17A (secukinumab). Further clinical trials, including a humanized IgG4 specific for IL-17 (ixekizumab) and a fully human antibody that targets the IL-17 receptor A (brodalumab).

  7. Differential protein analysis of chicken skin infected with Marek΄s disease virus.

    PubMed

    Chen, X; Hu, X; Yu, Ch; Qian, K; Ye, J; Qin, A

    2014-01-01

    The skin and feather follicle epithelia of birds infected with Marek's disease virus (MDV) are the sites of infectious virus particle formation and shedding. However, the host responses and protein networks involved in the production of virus particles in the skin of MDV-infected chickens are poorly understood. This current study aimed to analyze the differential protein expression patterns in skin between MDV-infected and uninfected specific pathogen-free (SPF) chickens 28 days post infection (dpi) by combining two-dimensional electrophoresis (2-DE) and mass spectrometry (MS) analyses. Through 2-DE analysis, our results revealed 23 proteins whose expression changed significantly following infection, of which 16 proteins were confirmed by MS. The identified proteins were functionally classified into 5 groups: immune-related, cell regulatory, cytoskeletal, metabolism-related and transport proteins. A single protein, beta 2-microglobulin, was further confirmed by real-time quantitative PCR. Beta 2-microglobulin expression was significantly increased in the infected group 28 dpi. This indicates that beta 2-microglobulin might play very important roles in the viral evasion from host immune response.

  8. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2013.

    PubMed

    Sicherer, Scott H; Leung, Donald Y M

    2014-02-01

    This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin diseases that were reported in the Journal in 2013. Studies on food allergy suggest that (1) 7.6% of the US population is affected, (2) a "healthy" early diet might prevent food allergy, (3) the skin might be an important route of sensitization, (4) allergen component testing might aid diagnosis, (5) the prognosis of milk allergy might be predictable through early testing, (6) oral or sublingual immunotherapy show promise but also have caveats, and (7) preclinical studies show promising alternative modes of immunotherapy and desensitization. Studies on eosinophilic esophagitis show a relationship to connective tissue disorders and that dietary management is an effective treatment for adults. Markers of anaphylaxis severity have been determined and might inform potential diagnostics and therapeutic targets. Insights on serum tests for drug and insect sting allergy might result in improved diagnostics. Genetic and immune-mediated defects in skin epithelial differentiation contribute to the severity of atopic dermatitis. Novel management approaches to treatment of chronic urticaria, including use of omalizumab, are being identified.

  9. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2014.

    PubMed

    Sicherer, Scott H; Leung, Donald Y M

    2015-02-01

    This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin diseases that were reported in the Journal in 2014. Studies on food allergy suggest worrisomely high rates of peanut allergy and food-induced anaphylaxis-related hospitalizations. Evidence is mounting to support the theory that environmental exposure to peanut, such as in house dust, especially with an impaired skin barrier attributed to atopic dermatitis (AD) and loss of function mutations in the filaggrin gene, is a risk factor for sensitization and allergy. Diagnostic tests are improving, with early studies suggesting the possibility of developing novel cellular tests with increased diagnostic utility. Treatment trials continue to show the promise and limitations of oral immunotherapy, and mechanistic studies are elucidating pathways that might define the degree of efficacy of this treatment. Studies have also provided insights into the prevalence and characteristics of anaphylaxis and insect venom allergy, such as suggesting that baseline platelet-activating factor acetylhydrolase activity levels are related to the severity of reactions. Advances in drug allergy include identification of HLA associations for penicillin allergy and a microRNA biomarker/mechanism for toxic epidermal necrolysis. Research identifying critical events leading to skin barrier dysfunction and the polarized immune pathways that drive AD have led to new therapeutic approaches in the prevention and management of AD.

  10. Mathematical modeling of temperature mapping over skin surface and its implementation in thermal disease diagnostics.

    PubMed

    Deng, Zhong-Shan; Liu, Jing

    2004-09-01

    In non-invasive thermal diagnostics, accurate correlations between the thermal image on skin surface and interior human pathophysiology are often desired, which require general solutions for the bioheat equation. In this study, the Monte Carlo method was implemented to solve the transient three-dimensional bio-heat transfer problem with non-linear boundary conditions (simultaneously with convection, radiation and evaporation) and space-dependent thermal physiological parameters. Detailed computations indicated that the thermal states of biological bodies, reflecting physiological conditions, could be correlated to the temperature or heat flux mapping recorded at the skin surface. The effect of the skin emissivity and humidity, the convective heat transfer coefficient, the relative humidity and temperature of the surrounding air, the metabolic rate and blood perfusion rate in the tumor, and the tumor size and number on the sensitivity of thermography are comprehensively investigated. Moreover, several thermal criteria for disease diagnostic were proposed based on statistical principles. Implementations of this study for the clinical thermal diagnostics are discussed.

  11. A longitudinal application of three health behaviour models in the context of skin protection behaviour in individuals with occupational skin disease.

    PubMed

    Matterne, Uwe; Diepgen, Thomas L; Weisshaar, Elke

    2011-09-01

    Occupational skin disease (OSD) is common, associated with poor prognosis and poses a significant burden to the individual and society. We applied the theory of planned behaviour (TPB), the prototype-willingness model (PWM) and the health action process approach (HAPA) to the prediction and explanation of occupationally relevant skin protection behaviour in individuals with OSD. We used a longitudinal design. In this study, 150 individuals participating in a 3-week inpatient tertiary prevention programme completed measures assessing the constructs of the TPB, PWM and HAPA at admission (T 0), discharge (T 1) and once the individual had returned to work and worked for 4 consecutive weeks (T 2) (n = 117). Intention was measured at T 0 and skin protection behaviour at T 2. Path analysis was used to assess the longitudinal associations of the models' constructs with intention and skin protection behaviour. TPB as well as PWM variables accounted for 30% of variance in behaviour, HAPA variables for 33%. While not all predictions were confirmed by the data, all three models are able to inform us about the formation of skin protection intention and behaviour in individuals with OSD. The findings are discussed in light of future interventions and research. PMID:21678190

  12. CMT subtypes and disease burden in patients enrolled in the Inherited Neuropathies Consortium natural history study: a cross-sectional analysis

    PubMed Central

    Fridman, V; Bundy, B; Reilly, M M; Pareyson, D; Bacon, C; Burns, J; Day, J; Feely, S; Finkel, R S; Grider, T; Kirk, C A; Herrmann, D N; Laurá, M; Li, J; Lloyd, T; Sumner, C J; Muntoni, F; Piscosquito, G; Ramchandren, S; Shy, R; Siskind, C E; Yum, S W; Moroni, I; Pagliano, E; Zuchner, S; Scherer, S S; Shy, M E

    2015-01-01

    Background The international Inherited Neuropathy Consortium (INC) was created with the goal of obtaining much needed natural history data for patients with Charcot-Marie-Tooth (CMT) disease. We analysed clinical and genetic data from patients in the INC to determine the distribution of CMT subtypes and the clinical impairment associated with them. Methods We analysed data from 1652 patients evaluated at 13 INC centres. The distribution of CMT subtypes and pathogenic genetic mutations were determined. The disease burden of all the mutations was assessed by the CMT Neuropathy Score (CMTNS) and CMT Examination Score (CMTES). Results 997 of the 1652 patients (60.4%) received a genetic diagnosis. The most common CMT subtypes were CMT1A/PMP22 duplication, CMT1X/GJB1 mutation, CMT2A/MFN2 mutation, CMT1B/MPZ mutation, and hereditary neuropathy with liability to pressure palsy/PMP22 deletion. These five subtypes of CMT accounted for 89.2% of all genetically confirmed mutations. Mean CMTNS for some but not all subtypes were similar to those previously reported. Conclusions Our findings confirm that large numbers of patients with a representative variety of CMT subtypes have been enrolled and that the frequency of achieving a molecular diagnosis and distribution of the CMT subtypes reflects those previously reported. Measures of severity are similar, though not identical, to results from smaller series. This study confirms that it is possible to assess patients in a uniform way between international centres, which is critical for the planned natural history study and future clinical trials. These data will provide a representative baseline for longitudinal studies of CMT. Clinical trial registration ID number NCT01193075. PMID:25430934

  13. Effective chromatic texture coding for robust skin disease minimal descriptor quantification

    NASA Astrophysics Data System (ADS)

    Fiorini, Rodolfo A.; Crivellini, M.; Codagnone, G.; Dacquino, Gianfranco F.; Libertini, M.; Morresi, A.

    1997-04-01

    Among the various skin diseases skin tumors are the most serious ones and skin melanoma is particularly dangerous. Its malignant evolution lasts about 5 or 6 years and ends with the death of the patient. Early diagnosis is a powerful means of preventing this evolution allowing sudden intervention which increases probability of recover and survival. Purpose of this paper is to present an active support system (ASS) able to reveal and quantify the stage of disease evolution. The work focuses the problem encountered in chromatic information encoding the morphological aspects quantification. A new method is proposed which permits robust and reliable quantification of image data obtained via a digital epiluminescence dermatoscopy apparatus (DELM) designed and built with interesting new features. The image information extraction is based on minimal descriptor set of parameters in order to classify chromatic texture and morphological features. The active support systems is based on DELM technique, taking advantage of polarized light guided by optical fibers. In the purpose to discriminate between malignant and benign melanocytic lesions, several dermatoscopical features have been proposed by different research groups. Nevertheless many are the attempts to reach a reliable and objective classification procedure. We adopt, as reference, the approach used by Stanganelli and Kenet. Through a bioengineering analysis we can organize reference grids that offer the possibility to extract the maximum information content from dermatological data. The classification takes into account the Spread and Intrinsic Descriptors and correspond to the best operative description. Therefore these grids are the more suitable tools for application which require ASS for diagnosis. In fact it is possible to obtain quantitative evaluations too. We propose a method based on geometrical synthetical descriptors. All that permits a reliable early diagnosis of melanotic disease and to follow its

  14. Cytoskeletal Regulation of Inflammation and Its Impact on Skin Blistering Disease Epidermolysis Bullosa Acquisita.

    PubMed

    Kopecki, Zlatko; Ludwig, Ralf J; Cowin, Allison J

    2016-01-01

    Actin remodelling proteins regulate cytoskeletal cell responses and are important in both innate and adaptive immunity. These responses play a major role in providing a fine balance in a cascade of biological events that results in either protective acute inflammation or chronic inflammation that leads to a host of diseases including autoimmune inflammation mediated epidermolysis bullosa acquisita (EBA). This review describes the role of the actin cytoskeleton and in particular the actin remodelling protein called Flightless I (Flii) in regulating cellular inflammatory responses and its subsequent effect on the autoimmune skin blistering disease EBA. It also outlines the potential of an antibody based therapy for decreasing Flii expression in vivo to ameliorate the symptoms associated with EBA. PMID:27420054

  15. Clinical application of versapulse laser in the treatment of skin pigmentation diseases

    NASA Astrophysics Data System (ADS)

    Liu, Chun-Li; Yuan, Wai-Hua; Yuan, Wei-Wei; Fu, Qiang

    1998-11-01

    387 cases of various skin pigmentous diseases were treated by Versapulse 'C' laser in our department Versapulse 'C' laser consist of 4 kinds of laser with wavelength of VP532nm, Q532nrn, Q755nm, Q1064nm. The vascular lesions, prot wine strain, cherry angioma, strawberry nevus, perckles, solar lentigines, melasma and junctional moles were treated by VP532 or Q532 laser; the nevus of Ota and tattoo were treated by Q755 or Q1064 laser. Satisfactory results were obtained in this paper, we also discussed the therapeutic and the main points of varying diseases with varying laser of wavelength, the use of FMLA anesthesia, controlled cold therapy an the physical protection to laser.

  16. Polymorphous light eruption: a common skin disease uncommonly recognized in the Hispanic population

    PubMed Central

    Lew, Robert; Jacob, Jason

    2014-01-01

    Polymorphous light eruption (PMLE) is a common acquired disease entity belonging to the idiopathic photodermatoses that is uncommonly considered in the Hispanic population. The pathogenesis of the disease and the mechanism of adaptation in skin (hardening phenomenon) have yet to be elucidated. PMLE is characterized by recurrent abnormal delayed reactions to sunlight ranging from pruritic erythematous papules, papulovesicles and plaques to erythema multiforme. It commonly occurs in the spring or early summer with a predilection for females. A Pubmed review of the literature shows no case reports or literature regarding PMLE in Hispanics. To the best of our knowledge, we report the first case of a 41-year-old Hispanic female diagnosed with PMLE. A high index of suspicion must remain in this group. Additional studies reviewing epidemiology in this group and detailing similar cases may be suggested. PMID:25988060

  17. Cytoskeletal Regulation of Inflammation and Its Impact on Skin Blistering Disease Epidermolysis Bullosa Acquisita

    PubMed Central

    Kopecki, Zlatko; Ludwig, Ralf J.; Cowin, Allison J.

    2016-01-01

    Actin remodelling proteins regulate cytoskeletal cell responses and are important in both innate and adaptive immunity. These responses play a major role in providing a fine balance in a cascade of biological events that results in either protective acute inflammation or chronic inflammation that leads to a host of diseases including autoimmune inflammation mediated epidermolysis bullosa acquisita (EBA). This review describes the role of the actin cytoskeleton and in particular the actin remodelling protein called Flightless I (Flii) in regulating cellular inflammatory responses and its subsequent effect on the autoimmune skin blistering disease EBA. It also outlines the potential of an antibody based therapy for decreasing Flii expression in vivo to ameliorate the symptoms associated with EBA. PMID:27420054

  18. Non-infectious environmental antigens as a trigger for the initiation of an autoimmune skin disease.

    PubMed

    Qian, Ye; Culton, Donna A; Jeong, Joseph S; Trupiano, Nicole; Valenzuela, Jesus G; Diaz, Luis A

    2016-09-01

    Pemphigus represents a group of organ specific autoimmune blistering disorders of the skin mediated by pathogenic autoantibodies with well-defined antigenic targets. While most of these diseases are sporadic, endemic forms of disease do exist. The endemic form of pemphigus foliaceus (also known as fogo selvagem, FS) exhibits epidemiological features that suggest exposure to hematophagous insect bites are a possible precipitating factor of this autoimmune disease, and provides a unique opportunity to study how environmental factors contribute to autoimmune disease development. FS patients and healthy individuals from endemic regions show an autoreactive IgM response that starts in early childhood and becomes restricted to IgG4 autoantibodies in FS patients. In searching for triggering environmental antigens, we have found that IgG4 and IgE autoantibodies from FS patients cross-react with a salivary antigen from sand flies. The presence of these cross-reactive antibodies and antibody genetic analysis confirming that these antibodies evolve from the same naïve B cells provides compelling evidence that this non-infectious environmental antigen could be the initial target of the autoantibody response in FS. Consequently, FS serves as an ideal model to study the impact of environmental antigens in the development of autoimmune disease.

  19. Self-Reported Tuberculosis Disease and Tuberculin Skin Testing in the New York City House Ballroom Community

    PubMed Central

    Marks, Suzanne M.; Murrill, Chris; Sanchez, Travis; Liu, Kai-lih; Finlayson, Teresa; Guilin, Vincent

    2008-01-01

    Objectives. We sought to describe the history of tuberculosis disease and tuberculin skin testing among the New York City House Ballroom community—a social network of diverse sexual and gender identities or expressions. Methods. Members of the House Ballroom community were convenience sampled, surveyed, and tested for HIV in 2004. We identified characteristics associated with history of tuberculosis, tuberculin skin testing, and test positivity and described the timing of skin testing. Results. Of 504 participants, 1.4% (n=7) reported a history of tuberculosis and 81.1% (n=404 of 498) had received a tuberculin skin test. Of those tested, 16 (4%) had positive results, which indicated latent infection, and 68% had received a test in the 2 years prior to the survey. Participants with health insurance were more likely and those with little education were less likely to have received a skin test. HIV-infected participants (16%) were not more likely to have received a tuberculin skin test compared with non-HIV-infected individuals. Foreign-born participants and self-identified heterosexuals and bisexuals were more likely to have had positive skin tests. Conclusions. Self-reported history of tuberculosis was high among the House Ballroom community. Although many community members had a recent skin test, further efforts should target services to those who are HIV infected, have low education, lack health insurance, or are foreign born. PMID:18048796

  20. A potential role for ixodid (hard) tick vectors in the transmission of lumpy skin disease virus in cattle.

    PubMed

    Tuppurainen, E S M; Stoltsz, W H; Troskie, M; Wallace, D B; Oura, C A L; Mellor, P S; Coetzer, J A W; Venter, E H

    2011-04-01

    Lumpy skin disease (LSD) is an economically important cattle disease. The disease is endemic in many African countries, but outbreaks have also been reported in Madagascar and the Middle East. The aim of this study was to investigate the potential role of ixodid (hard) ticks in the transmission of the disease. Cattle were infected with a virulent, South African field isolate of lumpy skin disease virus (LSDV). Three common African tick species (genera Rhipicephalus, Amblyomma and Rhipicephalus (Boophilus)) in different life cycle stages were fed on the infected animals during the viraemic stage and on skin lesions. Post-feeding, the partially fed male ticks were transferred to the skin of non-infected 'recipient' animals, while females were allowed to lay eggs that were then tested using the polymerase chain reaction (PCR) method and virus isolation. Nymphs were allowed to develop for 2-3 weeks after which time they were tested. The non-infected 'recipient' cattle were closely monitored, both skin and blood samples were tested using PCR and virus isolation, and serum samples were tested by the serum neutralization test. This is the first report showing molecular evidence of potential transmission of LSDV by ixodid ticks. The study showed evidence of transstadial and transovarial transmission of LSDV by R. (B.) decoloratus ticks and mechanical or intrastadial transmission by R. appendiculatus and A. hebraeum ticks.