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Sample records for inherited skin diseases

  1. Inherited renal cystic diseases.

    PubMed

    Kim, Bohyun; King, Bernard F; Vrtiska, Terri J; Irazabal, Maria V; Torres, Vicente E; Harris, Peter C

    2016-06-01

    A number of inherited renal diseases present with renal cysts and often lead to end-stage renal disease. With recent advances in genetics, increasing number of genes and mutations have been associated with cystic renal diseases. Although genetic testing can provide a definite diagnosis, it is often reserved for equivocal cases or for ongoing investigational research. Therefore, imaging findings are essential in the routine diagnosis, follow-up, and detection of complications in patients with inherited cystic renal diseases. In this article, the most recent classification, genetic analysis, clinical presentations, and imaging findings of inherited cystic renal diseases will be discussed. PMID:27167233

  2. Gene therapies for inherited skin disorders.

    PubMed

    Abdul-Wahab, Alya; Qasim, Waseem; McGrath, John A

    2014-06-01

    Skin is an amenable organ for gene replacement and gene editing therapeutics. Its accessibility makes it well-suited for direct topical gene delivery, grafting of genetically corrected cells, and monitoring of possible adverse events. Monogenic recessive disorders with a clinically severe or life-threatening phenotype provide the best candidate diseases for the introduction of a single normal copy of the gene into the target cell, usually keratinocytes. Preclinical studies have shown impressive results in terms of gene correction using both in vivo and ex vivo approaches. The clinical application of gene replacement or genomic editing as potential therapies for inherited skin disorders, however, has been held back by the inadequacy of delivery vectors and concerns from regulatory agencies regarding safety; thus translation to clinical trials has been slow. Over the past 15 years, cell culture and animal models have shown efficient gene correction techniques as preludes to treat inherited skin disorders such as junctional epidermolysis bullosa, dystrophic epidermolysis bullosa, xeroderma pigmentosum, lamellar ichthyosis and Netherton syndrome, but so far only one patient has been treated in a clinical trial. This article reviews the current status of gene therapies for patients with inherited skin diseases and explores future perspectives. PMID:25085667

  3. Inherited interstitial lung disease.

    PubMed

    Garcia, Christine Kim; Raghu, Ganesh

    2004-09-01

    This article focuses on recent advances in the identification of genes and genetic polymorphisms that have been implicated in the development of human interstitial lung diseases. It focuses on the inherited mendelian diseases in which pulmonary fibrosis is part of the clinical phenotype and the genetics of familial idiopathic pulmonary fibrosis and other rare inherited interstitial lung diseases. The article also reviews the association studies that have been published to date regarding the genetics of sporadic idiopathic pulmonary fibrosis. The reader is directed to recent reviews on human genetic predisposition of sarcoidosis, environmental-related, drug-related, connective tissue related pulmonary fibrosis, and genetic predisposition of fibrosis in animal models. PMID:15331184

  4. Phase I study protocol for ex-vivo lentiviral gene therapy for the inherited skin disease, Netherton Syndrome.

    PubMed

    Di, Wei-Li; Mellerio, Jemima E; Bernadis, Catina; Harper, John; Abdul-Wahab, Alya; Ghani, Sumera; Martinez-Queipo, Magdalena; Hara, Havinder; McNicol, Anne-Marie; McGrath, John; Thrasher, Adrian J; Qasim, Waseem

    2013-10-18

    Netherton syndrome (NS) is a serious inherited skin disorder caused by mutations in the gene SPINK5 (serine protease inhibitor Kazal type 5) which encodes for a serine protease inhibitor LEKTI (lymphoepithelial Kazal type-related inhibitor). Patients with NS have defective keratinization, hair shaft defects, recurrent infections, atopy and a predisposition to skin malignancies. Historically, one in ten infants has died before their first birthday. Currently there are no proven treatments to cure this condition. A SIN-lentiviral vector encoding the codon optimized SPINK5 gene under the control of a 572bp element derived from the human involucrin promoter (INVO) can confer compartment specific LEKTI expression in NS keratinocytes with restoration of normal skin architecture. Here we detail a study protocol for a phase I trial for feasibility and safety evaluations of autologous epidermal sheets generated from ex-vivo gene corrected keratinocyte stem cells, which will be grafted onto patients with mutation proven NS. PMID:24138501

  5. Phase I study protocol for ex vivo lentiviral gene therapy for the inherited skin disease, Netherton syndrome.

    PubMed

    Di, Wei-Li; Mellerio, Jemima E; Bernadis, Catina; Harper, John; Abdul-Wahab, Alya; Ghani, Sumera; Chan, Lucas; Martinez-Queipo, Magdalena; Hara, Havinder; McNicol, Anne-Marie; Farzaneh, Farzin; McGrath, John; Thrasher, Adrian; Qasim, Waseem

    2013-12-01

    Netherton syndrome (NS) is a serious inherited skin disorder caused by mutations in the serine protease inhibitor Kazal type 5 gene (SPINK5), which encodes for a serine protease inhibitor lymphoepithelial Kazal type-related inhibitor (LEKTI). Patients with NS have defective keratinization, hair shaft defects, recurrent infections, atopy, and a predisposition to skin malignancies. Historically, 1 in 10 infants has died before their first birthday. Currently, there are no proven treatments to cure this condition. A SIN-lentiviral vector encoding the codon-optimized SPINK5 gene under the control of a 572 bp element derived from the human involucrin promoter can confer compartment-specific LEKTI expression in NS keratinocytes with restoration of normal skin architecture. Here we detail a study protocol for a phase I trial for feasibility and safety evaluations of autologous epidermal sheets generated from ex vivo gene-corrected keratinocyte stem cells, which will be grafted onto patients with mutation-proven NS. PMID:24329107

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

    PubMed Central

    Monnat, Raymond J.

    2015-01-01

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

  7. Therapies for inherited skin fragility disorders.

    PubMed

    Has, Cristina; Kiritsi, Dimitra

    2015-05-01

    Inherited skin fragility comprises disorders characterized by mechanical induced blistering and erosions within the skin and mucosal membranes as a consequence of mutations in genes encoding proteins involved in intra-epidermal or dermal-epidermal adhesion. As the molecular pathology is largely known, it is a prototype group of disorders for which numerous experimental treatments have been developed. However, it became clear that single therapeutic strategies will not be able to address all molecular and clinical aspects. Significant progress has been achieved in gene, cell and protein therapies. Although the way towards clinical application seems obvious, major challenges must be addressed before these therapies become largely accessible. Until curative treatments will become available, alternative strategies which aim at increasing protein stability, amending apoptosis, inflammation and scarring may alleviate skin fragility and prevent or delay the onset of complications. PMID:25916580

  8. 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

  9. 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

  10. Skin Diseases: Skin Health and Skin Diseases

    MedlinePlus

    ... the sun. Photo: PhotoDisc Care for conditions from acne to wrinkles Did you know that your skin ... other skin conditions. Many skin problems, such as acne, also affect your appearance. Your skin can also ...

  11. PROBABLE QUALITATIVE INHERITANCE OF FULL RED SKIN COLOR IN PEACH

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Red skin color is a desirable trait contributing to the attractiveness of a peach [Prunus persica (L.) Batsch]. Previous reports on the expression and inheritance of red skin color have concluded that it was under the control of multiple genes. However, we recently observed hybrid populations whic...

  12. A triad of bovine inherited diseases (abstract).

    PubMed

    Hill, F I

    2003-02-01

    Three inherited diseases of cattle seen in the past 2 years were described. Familial acantholysis of Angus cattle was seen in 9/54 calves born to cows inadvertently mated to a full sibling bull. Sloughing skin from the joints, nose and palate were seen at 1 day of age, confirmed as suprabasilar clefts on histopathology. A 2-year-old Charolais steer was noted at ante-mortem slaughter inspection with a whole body tremor and nystagmus. Histopathologically, eosinophilic plaques expanded white matter throughout the brain, consistent with a syndrome of 'progressive ataxia' of Charolais cattle. Two calves born from Red Devon cattle had marked hyperkeratosis, microtia and periocular reddening with deep fissuring of the keratin, characteristic of congenital ichthyosis. PMID:16032297

  13. 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.

  14. 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

  15. Malignant skin tumours in patients with inherited ichthyosis.

    PubMed

    Natsuga, K; Akiyama, M; Shimizu, H

    2011-08-01

    Inherited ichthyoses are rare genodermatoses caused by mutations in the genes involved in epidermal development. Although there have been case reports on patients with ichthyosis who developed skin malignancies, it is still unknown whether or not patients with ichthyosis have an increased risk of skin malignancies. Here, we review case series of skin malignancies in patients with ichthyosis and show biological findings which might lead to cancer susceptibility. A survey of the literature revealed 28 cases of inherited ichthyoses with skin malignancy, including 12 cases of keratitis-ichthyosis-deafness (KID) syndrome, seven of autosomal recessive congenital ichthyosis, three of Netherton syndrome and six of miscellaneous ichthyosis. Twenty-four of the 28 cases developed single or multiple squamous cell carcinomas (SCCs). The age at diagnosis of the first skin malignancy ranged from 15 to 54 years. As patients with these particular subtypes of ichthyosis seem to be prone to skin malignancies, including SCC, at an unusually young age, routine cancer surveillance of these patients is strongly recommended. PMID:21517795

  16. 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

  17. 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

  18. 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

  19. 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 ...

  20. Oxidative stress in inherited mitochondrial diseases.

    PubMed

    Hayashi, Genki; Cortopassi, Gino

    2015-11-01

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

  1. 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

  2. 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

  3. Occupational skin disease.

    PubMed

    Peate, W E

    2002-09-15

    Contact dermatitis, the most common occupational skin disease, is characterized by clearly demarcated areas of rash at sites of exposure. The rash improves on removal of the offending agent. In allergic contact dermatitis, even minute exposures to antigenic substances can lead to a skin rash. Common sensitizing agents include nickel and members of the Rhus genus (e.g., poison ivy, poison oak). Severe skin irritants tend to cause immediate red blisters or burns, whereas weaker irritants produce eczematous skin changes over time. An occupational cause should be suspected when rash occurs in areas that are in contact with oil, grease, or other substances. Direct skin testing (patch or scratch) or radioallergosorbent testing may help to identify a specific trigger. Skin cancer can have an occupational link in workers with prolonged exposure to sunlight and certain chemicals, although it can take decades for lesions to develop. In workers with occupational skin disease, workplace changes and protective measures are important to prevent future exposure. PMID:12358214

  4. Chemokines and skin diseases.

    PubMed

    Sugaya, Makoto

    2015-04-01

    Chemokines are small molecules that induce chemotaxis and activation of certain subsets of leukocytes. The expression patterns of chemokines and chemokine receptors are specific to certain organs and cells. Therefore, chemokines are important to elucidate the mechanism of organ-specific human diseases. CCL17 expressed by Langerhans cells, blood endothelial cells, and fibroblasts plays a key role in attracting Th2 cells and tumor cells of adult T-cell leukemia/lymphoma and mycosis fungoides/Sézary syndrome into the skin, developing various Th2-type inflammatory skin diseases as well as cutaneous lymphoma. CCL11 and CCL26 expressed by skin-resident cells, such as fibroblasts, blood endothelial cells, and keratinocytes, induce infiltration of CCR3-expressing cells such as Th2 cells and eosinophils. CCL11 may also serve as an autocrine as well as a paracrine in anaplastic large cell lymphoma. CX3CL1 expressed on blood endothelial cells leads to infiltration of CX3CR1(+) immune cells, such as mast cells, neutrophils, and macrophages, playing important roles in wound healing, tumor immunity, and vasculitis. Biologics targeting chemokines and their receptors are promising strategies for various skin diseases that are resistant to the current therapy. PMID:25182982

  5. Darwin's Pangenesis as a molecular theory of inherited diseases.

    PubMed

    Liu, Yongsheng; Li, Xiuju

    2016-05-10

    Darwin spent much time and effort on the study of inherited diseases and the role of environment in disease development. To explain inherited diseases and a considerable variety of other hereditary phenomena, he formulated a Pangenesis hypothesis, assuming that cells could shed many kinds of molecules capable of diffusion from cell to cell, circulation throughout the body, incorporation into recipient cells, and transmission from parents to offspring. His Pangenesis is now supported by the discovery of circulating DNA, mobile RNAs and prions, and might provide an alternative molecular mechanism underlying the inherited diseases. PMID:26836487

  6. 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

  7. 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

  8. 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. PMID:25792089

  9. [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. PMID:1544613

  10. 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.

  11. Medical Problems in Obstetrics: Inherited Metabolic Disease.

    PubMed

    Murphy, Elaine

    2015-07-01

    An increasing number of women with rare inherited disorders of metabolism are becoming pregnant. Although, in general, outcomes for women and their children are good, there are a number of issues that need to be considered. Currently, limited specific guidance on the management of these conditions in pregnancy is available. Prepregnancy counselling with information on inheritance, options for reproduction, teratogenicity risk, potential impact on maternal health and long-term health of children should be offered. With appropriate specialist management, the teratogenic risk of conditions such as maternal phenylketonuria (PKU) can be eliminated, and the risk of metabolic decompensation in disorders of energy metabolism or intoxication significantly reduced. Multidisciplinary management, and close liaison between obstetricians and other specialists, is required for those women in whom there is cardiac, renal, respiratory, joint or other organ involvement. PMID:26088792

  12. Keratins and skin disease.

    PubMed

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

    2015-06-01

    Mutations in keratin genes cause a diverse spectrum of skin, hair and mucosal disorders. Cutaneous disorders include epidermolysis bullosa simplex, palmoplantar keratoderma, epidermolytic ichthyosis and pachyonychia congenita. Both clinical and laboratory observations confirm a major role for keratins in maintaining epidermal cell-cell adhesion. When normal tissue homeostasis is disturbed, for example, during wound healing and cancer, keratins play an important non-mechanical role. Post-translational modifications including glycosylation and phosphorylation of keratins play an important role in protection of epithelial cells from injury. Keratins also play a role in modulation of the immune response. A current focus in the area of keratins and disease is the development of new treatments including small inhibitory RNA (siRNA) to mutant keratins and small molecules to modulate keratin expression. PMID:25620412

  13. 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

  14. 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

  15. 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…

  16. Parkinson's disease and the skin.

    PubMed

    Gregory, Ralph; Miller, Sarah

    2015-08-01

    The concept that the skin is a mirror of Parkinson's disease dates to the start of the last century. Despite dermatological disorders being recognised as a common non-motor symptom of Parkinson's disease, they are often overlooked. This article reviews the various skin disorders seen in Parkinson's disease and addresses the other dermatological questions that are frequently raised by those attending Parkinson's disease clinics. PMID:25862733

  17. 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 ...

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

    MedlinePlus

    Skip Navigation Bar Home Current Issue Past Issues Skin Diseases Skin and Sun —Not a good mix Past Issues / ... of this page please turn Javascript on. Good skin care begins with sun safety. Whether it is ...

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

    PubMed Central

    Scriver, C. R.

    1982-01-01

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

  20. Strategies for Gene Mapping in Inherited Ophthalmic Diseases.

    PubMed

    Srilekha, Sundar; Rao, Bhavna; Rao, Divya M; Sudha, D; Chandrasekar, Sathya Priya; Pandian, A J; Soumittra, N; Sripriya, S

    2016-01-01

    Gene mapping of inherited ophthalmic diseases such as congenital cataracts, retinal degeneration, glaucoma, age-related macular degeneration, myopia, optic atrophy, and eye malformations has shed more light on the disease pathology, identified targets for research on therapeutics, earlier detection, and treatment options for disease management and patient care. This article details the different approaches to gene identification for both Mendelian and complex eye disorders. PMID:27488070

  1. Genetic Diagnostic Methods for Inherited Eye Diseases

    PubMed Central

    Gabriel, Luis A. R.; Traboulsi, Elias I.

    2011-01-01

    Accurate molecular diagnosis of genetic eye diseases has proven to be of great importance because of the prognostic and therapeutic value of an accurate ascertainment of the underlying genetic mutation. Efforts continue in diagnostic laboratories to develop strategies that allow the discovery of responsible gene/mutations in the individual patient using the least number of assays and economizing on the expenses and time involved in the process. Once the ophthalmologist has made the best possible clinical diagnosis, blood samples are obtained for genetic testing. In this paper we will review the basic laboratory methods utilized to identify the chromosomal or mutational etiology of genetic diseases that affect the eye. PMID:21572730

  2. An Update on Laboratory Diagnosis of Liver Inherited Diseases

    PubMed Central

    Elce, Ausilia; Amato, Felice

    2013-01-01

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

  3. 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)

  4. Noninfectious skin diseases of cattle.

    PubMed

    Manning, T O

    1984-03-01

    The noninfectious bovine skin disorders can best be summarized by four factors: environmental, nutritional, congenital, and neoplastic. This article has attempted to address the etiology, treatment, and prevention of most of these noninfectious diseases. PMID:6740876

  5. Skin Diseases: Cross-section of human skin

    MedlinePlus

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

  6. [Skin 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

  7. 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

  8. 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

  9. Clinical neurogenetics: behavioral management of inherited neurodegenerative disease.

    PubMed

    Wexler, Eric

    2013-11-01

    Psychiatric symptoms often manifest years before overt neurologic signs in patients with inherited neurodegenerative disease. The most frequently cited example of this phenomenon is the early onset of personality changes in "presymptomatic" Huntington patients. In some cases the changes in mood and cognition are even more debilitating than their neurologic symptoms. The goal of this article is to provide the neurologist with a concise primer that can be applied in a busy clinic or private practice. PMID:24176427

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

    PubMed Central

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

    1980-01-01

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

  11. Human Induced Pluripotent Stem Cell Models of Inherited Cardiovascular Diseases.

    PubMed

    Jiang, Wenjian; Lan, Feng; Zhang, Hongjia

    2014-10-16

    Cardiovascular cells derived from patient specific induced Pluripotent Stem Cell (iPSC) harbor gene mutations associated with the pathogenesis of inherited cardiac diseases and congenital heart diseases (CHD). Numerous reports have demonstrated the utilization of human induced Pluripotent Stem Cell (hiPSC) to model cardiac diseases as a means of investigating their underlying mechanisms. So far, they have been shown to investigate the molecular mechanisms of many cardiac disorders, such as long-QT syndrome (LQT), catecholaminergic polymorphic ventricular tachycardia (CPVT), dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), LEOPARD syndrome (LS), arrhythmogenic cardiomyopathy (ACM), Friedreich ataxia (FRDA), Barth syndrome (BTHS), hypoplastic left heart syndrome (HLHS), Marfan syndrome (MFS) and other CHD. This article summarizes the growing body of research related to modeling various cardiac diseases using hiPSCs. Moreover, by reviewing the methods used in previous studies, we propose multiple novel applications of hiPSCs to investigate comprehensive cardiovascular disorders and facilitate drug discovery. PMID:25322695

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

    PubMed Central

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

    2012-01-01

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

  13. Willingness to pay for genetic testing for inherited retinal disease

    PubMed Central

    Tubeuf, Sandy; Willis, Thomas A; Potrata, Barbara; Grant, Hilary; Allsop, Matthew J; Ahmed, Mushtaq; Hewison, Jenny; McKibbin, Martin

    2015-01-01

    This paper investigates the willingness of adults with inherited retinal disease to undergo and pay for diagnostic genetic testing in three hypothetical scenarios and to explore the factors that influence decision making. Fifty patients were presented with three scenarios whereby genetic testing provided increasing information: confirming the diagnosis and inheritance pattern alone, providing additional information on future visual function, and identifying in addition a new treatment which could stabilise their condition. Willingness to pay (WTP) was elicited using an iterative bidding game. Regression analysis was used to investigate the probability of agreeing to and paying for testing. Qualitative data were also reviewed to provide a comprehensive understanding of WTP and decision making. The majority of participants agreed to undergo genetic testing in each of the three scenarios. Scenario 2 was the least acceptable with 78% of participants agreeing to genetic testing. The probability of agreeing to genetic testing decreased with age. Between 72 and 96% of participants reported a WTP for genetic testing. Average WTP was £539, £1516, and £6895 for scenarios 1, 2, and 3 respectively. Older participants and participants with higher incomes were willing to pay more for testing. Qualitative data provided additional detail about the rationale behind participants' decisions. The study suggests that patients with inherited retinal disease were willing to undergo and to pay for diagnostic genetic testing, suggesting that they valued the information it may provide. However, several patients preferred not to receive prognostic information and were less willing to pay for genetic testing that yielded such detail. PMID:24916649

  14. Nutrition and bullous skin diseases.

    PubMed

    Fedeles, Flavia; Murphy, Michael; Rothe, Marti J; Grant-Kels, Jane M

    2010-01-01

    Autoimmune and nonautoimmune bullous diseases can both be associated with significant morbidity and mortality. Although our understanding of the pathogenic mechanisms of these diseases has increased tremendously, there is still much to learn about the various factors affecting their onset, course, and therapy. In recent years, increasing information has been published about the effect of vitamins, minerals, and other nutrients on bullous skin diseases. Some factors are believed to be inducers (thiol and phenol-containing foods in pemphigus), whereas others are believed to be protective (antioxidants in cutaneous porphyrias). This contribution reviews the evidence in the literature of the role of various dietary factors in bullous diseases, including the nonautoimmune and the deficiency dermatoses. Additional studies and new investigations are needed to provide a better understanding of the specific associations of dietary factors with bullous diseases and better management for patients affected by these conditions. PMID:21034987

  15. Towards germline gene therapy of inherited mitochondrial diseases

    PubMed Central

    Tachibana, Masahito; Amato, Paula; Sparman, Michelle; Woodward, Joy; Sanchis, Dario Melguizo; Ma, Hong; Gutierrez, Nuria Marti; Tippner-Hedges, Rebecca; Kang, Eunju; Lee, Hyo-Sang; Ramsey, Cathy; Masterson, Keith; Battaglia, David; Lee, David; Wu, Diana; Jensen, Jeffrey; Patton, Phillip; Gokhale, Sumita; Stouffer, Richard; Mitalipov, Shoukhrat

    2012-01-01

    Mutations in mitochondrial DNA (mtDNA) are associated with serious human diseases and inherited from mother's eggs. Here we investigated the feasibility of mtDNA replacement in human oocytes by spindle transfer (ST). Of 106 human oocytes donated for research, 65 were subjected to reciprocal ST and 33 served as controls. Fertilization rate in ST oocytes (73%) was similar to controls (75%). However, a significant portion of ST zygotes (52%) displayed abnormal fertilization as determined by irregular number of pronuclei. Among normally fertilized ST zygotes, blastocyst development (62%) and embryonic stem cell (ESC) isolation (38%) rates were comparable to controls. All ESC lines derived from ST zygotes displayed normal euploid karyotypes and contained exclusively donor mtDNA. The mtDNA can be efficiently replaced in human oocytes. Although some ST oocytes displayed abnormal fertilization, remaining embryos were capable of developing to blastocysts and producing ESCs similar to controls. PMID:23103867

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

    PubMed

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

    2016-05-01

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

  17. Anaplerotic diet therapy in inherited metabolic disease: therapeutic potential.

    PubMed

    Roe, Charles R; Mochel, Fanny

    2006-01-01

    Beginning with phenylketonuria, dietary therapy for inborn errors has focused primarily on the restriction of the precursor to an affected catabolic pathway in an attempt to limit the production of potential toxins. Anaplerotic therapy is based on the concept that there may exist an energy deficit in these diseases that might be improved by providing alternative substrate for both the citric acid cycle (CAC) and the electron transport chain for enhanced ATP production. This article focuses on this basic problem, as it may relate to most catabolic disorders, and provides our current experience involving inherited diseases of mitochondrial fat oxidation, glycogen storage, and pyruvate metabolism using the anaplerotic compound triheptanoin. The observations have led to a realization that 'inter-organ' signalling and 'nutrient sensors' such as adenylate monophosphate mediated-protein kinase (AMPK) and mTOR (mammalian target of rapamycin) appear to play a significant role in the intermediary metabolism of these diseases. Activated AMPK turns on catabolic pathways to augment ATP production while turning off synthetic pathways that consume ATP. Information is provided regarding the inter-organ requirements for more normal metabolic function during crisis and how anaplerotic therapy using triheptanoin, as a direct source of substrate to the CAC for energy production, appears to be a more successful approach to an improved quality of life for these patients. PMID:16763896

  18. Bacterial diseases of the skin.

    PubMed

    Edlich, Richard F; Winters, Kathryne L; Britt, L D; Long, William B

    2005-01-01

    When considering common bacterial diseases of the skin, rather distinct clinical responses to a variety of bacterial infections have been identified. In these cases, it is the specific site of infection and the attendant inflammatory responses that provide the characteristic clinical picture. When the pyoderma extends just below the stratum corneum, it is called impetigo. Nonbullous impetigo is the most common pediatric skin infection. It usually starts in a traumatized area. The typical lesion begins as an erythematous papule, after which it becomes a unilocular vesicle. When the subcorneal vesicle becomes pustular, it ruptures and eventually becomes a yellow, golden crust that is a hallmark of the disease process. Bullous impetigo is a less common form of impetigo, accounting for fewer than 30% of all impetigo cases. It occurs in infants and is characterized by rapid progression of vesicles to the formation of bullae measuring larger than 5 mm in diameter in previously untraumatized skin. Treatment of nonbullous impetigo must include intervention against the pathogen as well as improvements in the hygiene and living conditions of the patient. A fundamental tenet is to debride the crust (scab) from the wound surface using poloxamer 188. If the lesions are not widespread, topical mupirocin is the treatment of choice. Treatment of bullous impetigo is similar, except that the local cleansing and topical antibiotic must be complemented by systemic antibiotics if there is evidence of disseminating infections. Ecthyma is usually a consequence of failure to treat effectively impetigo. The untreated infection extends deep into the tissue in shallow ulcerations that often heal without scar. Treatment for ecthyma usually requires systemic antibiotics against either staphylococcus or streptococcus. Folliculitis is a pyoderma located within a hair follicle, secondary to follicular occlusion by keratin, overhydration, or either bacterial or fungal infection. Folliculitis may

  19. Charcot-Marie-Tooth disease and related inherited neuropathies.

    PubMed

    Murakami, T; Garcia, C A; Reiter, L T; Lupski, J R

    1996-09-01

    Charcot-Marie-Tooth disease (CMT) was initially described more than 100 years ago by Charcot, Marie, and Tooth. It was only recently, however, that molecular genetic studies of CMT have uncovered the underlying causes of most forms of the diseases. Most cases of CMT1 are associated with a 1.5-Mb tandem duplication in 17p11.2-p12 that encompasses the PMP22 gene. Although many genes may exist in this large duplicated region, PMP22 appears to be the major dosage-sensitive gene. CMT1A is the first autosomal dominant disease associated with a gene dosage effect due to an inherited DNA rearrangement. There is no mutant gene, but instead the disease phenotype results from having 3 copies of a normal gene. Furthermore, these findings suggest that therapeutic intervention in CMT1A duplication patients may be possible by normalizing the amount of PMP22 mRNA levels. Alternatively, CMT1A can be caused by mutations in the PMP22 gene. Other forms of CMT are associated with mutations in the MPZ (CMT1B) and Cx32 (CMTX) genes. Thus, mutations in different genes can cause similar CMT phenotypes. The related but more severe neuropathy, Dejerine-Sottas syndrome (DSS), can also be caused by mutations in the PMP22 and MPZ genes. All 3 genes thus far identified by CMT researchers appear to play an important role in the myelin formation or maintenance of peripheral nerves. CMT1A, CMT1B, CMTX, hereditary neuropathy with liability to pressure palsies (HNPP), and DSS have been called myelin disorders or "myelino-pathies." Other demyelinating forms, CMT1C and CMT-AR, may be caused by mutations of not yet identified myelin genes expressed in Schwann cells. The clinically distinct disease HNPP is caused by a 1.5-Mb deletion in 17p11.2-p12, which spans the same region duplicated in most CMT1A patients. Underexpression of the PMP22 gene causes HNPP just as overexpression of PMP22 causes CMT1A. Thus, 2 different phenotypes can be caused by dosage variations of the same gene. It is apparent that

  20. Hypoglycaemia related to inherited metabolic diseases in adults

    PubMed Central

    2012-01-01

    In non-diabetic adult patients, hypoglycaemia may be related to drugs, critical illness, cortisol or glucagon insufficiency, non-islet cell tumour, insulinoma, or it may be surreptitious. Nevertheless, some hypoglycaemic episodes remain unexplained, and inborn errors of metabolism (IEM) should be considered, particularly in cases of multisystemic involvement. In children, IEM are considered a differential diagnosis in cases of hypoglycaemia. In adulthood, IEM-related hypoglycaemia can persist in a previously diagnosed childhood disease. Hypoglycaemia may sometimes be a presenting sign of the IEM. Short stature, hepatomegaly, hypogonadism, dysmorphia or muscular symptoms are signs suggestive of IEM-related hypoglycaemia. In both adults and children, hypoglycaemia can be clinically classified according to its timing. Postprandial hypoglycaemia can be an indicator of either endogenous hyperinsulinism linked to non-insulinoma pancreatogenic hypoglycaemia syndrome (NIPHS, unknown incidence in adults) or very rarely, inherited fructose intolerance. Glucokinase-activating mutations (one family) are the only genetic disorder responsible for NIPH in adults that has been clearly identified so far. Exercise-induced hyperinsulinism is linked to an activating mutation of the monocarboxylate transporter 1 (one family). Fasting hypoglycaemia may be caused by IEM that were already diagnosed in childhood and persist into adulthood: glycogen storage disease (GSD) type I, III, 0, VI and IX; glucose transporter 2 deficiency; fatty acid oxidation; ketogenesis disorders; and gluconeogenesis disorders. Fasting hypoglycaemia in adulthood can also be a rare presenting sign of an IEM, especially in GSD type III, fatty acid oxidation [medium-chain acyl-CoA dehydrogenase (MCAD), ketogenesis disorders (3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) lyase deficiency, and gluconeogenesis disorders (fructose-1,6-biphosphatase deficiency)]. PMID:22587661

  1. 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

  2. A family with spondyloepimetaphyseal dwarfism: a 'new' dysplasia or Kniest disease with autosomal recessive inheritance?

    PubMed Central

    Farag, T I; Al-Awadi, S A; Hunt, M C; Satyanath, S; Zahran, M; Usha, R; Uma, R

    1987-01-01

    We present an Arab family with some features of Kniest disease. The proband was a six year old boy with rhizomelic short limbed dwarfism, 'dish-like' facies, cleft palate, deafness, and camptodactyly. Most radiological changes were compatible with Kniest disease. Two younger sibs, similarly affected, had died at a few months old, and the pedigree shows strong evidence of autosomal recessive inheritance, unlike previously reported cases of Kniest disease which have shown autosomal dominant inheritance. Images PMID:3681904

  3. 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

  4. [Skin diseases associated with obesity in children].

    PubMed

    Lau, K; Höger, P H

    2013-04-01

    While the impact of obesity on diabetes, cardiovascular disease and carcinoma development has been studied extensively, only little attention has been paid to its influence on the skin. Obesity alters the skin barrier, can induce skin manifestations, and worsens existing skin diseases like psoriasis. Cutaneous manifestations of obesity may be pseudoacanthosis nigricans, fibroma pendulans (skin tags, fibroepithelial polyps) and striae distensae. Obesity is also associated with hyperandrogenism in women and girls, promoting acne vulgaris, hirsutism, and androgenetic alopecia. In addition, there is a pathogenic association between obesity and psoriasis: the release of pro-inflammatory factors from fat tissue results in the worsening of psoriasis; an association between the severity of psoriasis and the body mass index has been shown. Obesity promotes skin infections like erysipelas and intertrigo. PMID:23529600

  5. 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

  6. Skin diseases of old dogs and cats.

    PubMed

    Halliwell, R E

    1990-04-21

    The ageing process tends to predispose dogs and cats to certain skin diseases. Impaired immunosurveillance is believed to render the animals more susceptible to neoplasia which can affect any organ including the skin. Endocrinopathies are also more common in older animals. There are some diseases of internal organs which can affect the skin, and some of these tend to occur with increased frequency in old animals. Finally, seborrhoeic diseases are either more common in older animals, or become increasingly severe with age. PMID:2195753

  7. 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

  8. Common Skin Diseases in Children

    PubMed Central

    Taradash, J. B.

    1976-01-01

    Six common pediatric skin problems are discussed through the use of case histories. Problems of differential diagnosis are outlined, and the various steps and pitfalls in therapy itemized. PMID:21308018

  9. Histologic features of granulomatous skin diseases.

    PubMed

    Mitteldorf, Christina; Tronnier, Michael

    2016-04-01

    Granulomatous disorders affecting the skin belong to a heterogeneous group of diseases, which were predominantly classified based on pathogenetic features. In infections diseases a granuloma is formed if an agent could not be eliminated by the immune system. Typical agents which cause granulomatous reactions are mycobacteria, fungal infections, especially extra European agent, which could effect the skin by, dissemination (e.g. histoplasmosis) or parasites, like leishmaniasis. PMID:27027748

  10. Psychosocial effect of common skin diseases.

    PubMed Central

    Barankin, Benjamin; DeKoven, Joel

    2002-01-01

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

  11. Coinheritance of Gaucher disease and α-thalassemia resulting in confusion between two inherited hematologic diseases

    PubMed Central

    Miri-Moghaddam, Ebrahim; Velayati, Arash; Naderi, Majid; Tayebi, Nahid; Sidransky, Ellen

    2012-01-01

    Gaucher type 1 disease has a wide spectrum of phenotypes ranging from asymptomatic individuals to patients with massive hepatosplenomegaly and bone involvement. In most, anemia, thrombocytopenia and splenomegaly are the primary manifestations at diagnosis, findings shared by the hemoglobinopathies. Here we report the co-inheritance of α-thalassemia and Gaucher disease in a consanguineous family followed in Iran, which resulted in confusion regarding the diagnosis. This report emphasizes the need to independently establish the diagnosis of every affected member of a family to ensure appropriate management and therapeutic decisions. PMID:20846888

  12. 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

  13. Helicobacter pylori and skin autoimmune diseases.

    PubMed

    Magen, Eli; Delgado, Jorge-Shmuel

    2014-02-14

    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

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

    PubMed

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

    2013-04-01

    Environmental compounds have been shown to promote epigenetic transgenerational inheritance of disease. The current study was designed to determine if a hydrocarbon mixture involving jet fuel (JP-8) promotes epigenetic transgenerational inheritance of disease. Gestating F0 generation female rats were transiently exposed during the fetal gonadal development period. The direct exposure F1 generation had an increased incidence of kidney abnormalities in both females and males, prostate and pubertal abnormalities in males, and primordial follicle loss and polycystic ovarian disease in females. The first transgenerational generation is the F3 generation, and the jet fuel lineage had an increased incidence of primordial follicle loss and polycystic ovarian disease in females, and obesity in both females and males. Analysis of the jet fuel lineage F3 generation sperm epigenome identified 33 differential DNA methylation regions, termed epimutations. Observations demonstrate hydrocarbons can promote epigenetic transgenerational inheritance of disease and sperm epimutations, potential biomarkers for ancestral exposures. PMID:23453003

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

    PubMed

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

    2015-08-01

    While skin is readily available for sampling and direct studies of its constituents, an important intermediate step is to design in vitro and/or in vivo models to address scientific or medical questions in dermatology and skin biology. Pioneered more than 30 years ago, human skin equivalents (HSEs) have been refined with better cell culture techniques and media, together with sophisticated cell biology tools including genetic engineering and cell reprogramming. HSEs mimic key elements of human skin biology and have been instrumental in demonstrating the importance of cell-cell interactions in skin homeostasis and the role of a complex cellular microenvironment to coordinate epidermal proliferation, differentiation and pigmentation. HSEs have a wide field of applications from cell biology to dermocosmetics, modelling diseases, drug development, skin ageing, pathophysiology and regenerative medicine. In this article we critically review the major current approaches used to reconstruct organotypic skin models and their application with a particular emphasis on skin biology and pathophysiology of skin disorders. PMID:25939812

  16. Antimicrobial peptides in human skin disease

    PubMed Central

    Kenshi, Yamasaki; Richard, L. Gallo

    2009-01-01

    The skin continuously encounters microbial pathogens. To defend against this, cells of the epidermis and dermis have evolved several innate strategies to prevent infection. Antimicrobial peptides are one of the primary mechanisms used by the skin in the early stages of immune defense. In general, antimicrobial peptides have broad antibacterial activity against gram-positive and negative bacteria and also show antifungal and antiviral activity. The antimicrobial activity of most peptides occurs as a result of unique structural characteristics that enable them to disrupt the microbial membrane while leaving human cell membranes intact. However, antimicrobial peptides also act on host cells to stimulate cytokine production, cell migration, proliferation, maturation, and extracellular matrix synthesis. The production by human skin of antimicrobial peptides such as defensins and cathelicidins occurs constitutively but also greatly increases after infection, inflammation or injury. Some skin diseases show altered expression of antimicrobial peptides, partially explaining the pathophysiology of these diseases. Thus, current research suggests that understanding how antimicrobial peptides modify susceptibility to microbes, influence skin inflammation, and modify wound healing, provides greater insight into the pathophysiology of skin disorders and offers new therapeutic opportunities. PMID:18086583

  17. Influence of Skin Diseases on Fingerprint Recognition

    PubMed Central

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

    2012-01-01

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

  18. 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

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

    PubMed Central

    2012-01-01

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

  20. Human Polyomaviruses in Skin Diseases

    PubMed Central

    Moens, Ugo; Ludvigsen, Maria; Van Ghelue, Marijke

    2011-01-01

    Polyomaviruses are a family of small, nonenveloped viruses with a circular double-stranded DNA genome of ∼5,000 base pairs protected by an icosahedral protein structure. So far, members of this family have been identified in birds and mammals. Until 2006, BK virus (BKV), JC virus (JCV), and simian virus 40 (SV40) were the only polyomaviruses known to circulate in the human population. Their occurrence in individuals was mainly confirmed by PCR and the presence of virus-specific antibodies. Using the same methods, lymphotropic polyomavirus, originally isolated in monkeys, was recently shown to be present in healthy individuals although with much lower incidence than BKV, JCV, and SV40. The use of advanced high-throughput sequencing and improved rolling circle amplification techniques have identified the novel human polyomaviruses KI, WU, Merkel cell polyomavirus, HPyV6, HPyV7, trichodysplasia spinulosa-associated polyomavirus, and HPyV9. The skin tropism of human polyomaviruses and their dermatopathologic potentials are the focus of this paper. PMID:21941687

  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. Skin Diseases: Questions for Your Health Care Provider

    MedlinePlus

    Skip Navigation Bar Home Current Issue Past Issues Skin Diseases Questions for Your Health Care Provider Past ... dermatitis worse? What are the most common irritants? Skin cancer What type of skin cancer do I ...

  3. Viral skin diseases of the rabbit.

    PubMed

    Meredith, Anna L

    2013-09-01

    This article describes the viral skin diseases affecting the domestic rabbit, the most important being myxomatosis. Transmission and pathogenesis, clinical signs, diagnosis, treatment, and control are described and the article will be of interest to veterinary practitioners who treat rabbits. Shope fibroma virus, Shope papilloma virus, and rabbitpox are also discussed. PMID:24018033

  4. 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

  5. Managing Amphibian Disease with Skin Microbiota.

    PubMed

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

    2016-03-01

    The contribution of emerging amphibian diseases to the sixth mass extinction is driving innovative wildlife management strategies, including the use of probiotics. Bioaugmentation of the skin mucosome, a dynamic environment including host and microbial components, may not provide a generalized solution. Multi-omics technologies and ecological context underlie effective implementation. PMID:26916805

  6. Dioxin (TCDD) Induces Epigenetic Transgenerational Inheritance of Adult Onset Disease and Sperm Epimutations

    PubMed Central

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

    2012-01-01

    Environmental compounds can promote epigenetic transgenerational inheritance of adult-onset disease in subsequent generations following ancestral exposure during fetal gonadal sex determination. The current study examined the ability of dioxin (2,3,7,8-tetrachlorodibenzo[p]dioxin, TCDD) to promote epigenetic transgenerational inheritance of disease and DNA methylation epimutations in sperm. Gestating F0 generation females were exposed to dioxin during fetal day 8 to 14 and adult-onset disease was evaluated in F1 and F3 generation rats. The incidences of total disease and multiple disease increased in F1 and F3 generations. Prostate disease, ovarian primordial follicle loss and polycystic ovary disease were increased in F1 generation dioxin lineage. Kidney disease in males, pubertal abnormalities in females, ovarian primordial follicle loss and polycystic ovary disease were increased in F3 generation dioxin lineage animals. Analysis of the F3 generation sperm epigenome identified 50 differentially DNA methylated regions (DMR) in gene promoters. These DMR provide potential epigenetic biomarkers for transgenerational disease and ancestral environmental exposures. Observations demonstrate dioxin exposure of a gestating female promotes epigenetic transgenerational inheritance of adult onset disease and sperm epimutations. PMID:23049995

  7. 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

  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, 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. Molecular advances in genetic skin diseases.

    PubMed

    Siegel, Dawn H; Howard, Renee

    2002-08-01

    The genes for several genetic skin diseases have been identified in recent years. This development improves diagnostic capabilities and genetic counseling, and investigators can now turn to the molecular mechanisms involved in the pathogenesis of these diseases. The identification of the causative genes has led to the generation of mouse models for some genetic skin diseases. A study of the keratin 10 deficient mouse, a model for epidermolytic hyperkeratosis, and a mouse model for Bloom syndrome are reviewed in this article. Several studies also evaluate the relation between genotype and phenotype. In this article, the clinical findings and molecular advances in tuberous sclerosis complex, neurofibromatosis type 1, Bloom syndrome, epidermolytic hyperkeratosis, X-linked ichthyosis, Netherton syndrome, and Hermansky-Pudlak syndrome are reviewed. PMID:12130905

  15. 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. PMID:26702794

  16. Eosinophilic Skin Diseases: A Comprehensive Review.

    PubMed

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

    2016-04-01

    Eosinophilic skin diseases, commonly termed as eosinophilic dermatoses, refer to a broad spectrum of skin diseases characterized by eosinophil infiltration and/or degranulation in skin lesions, with or without blood eosinophilia. The majority of eosinophilic dermatoses lie in the allergy-related group, including allergic drug eruption, urticaria, allergic contact dermatitis, atopic dermatitis, and eczema. Parasitic infestations, arthropod bites, and autoimmune blistering skin diseases such as bullous pemphigoid, are also common. Besides these, there are several rare types of eosinophilic dermatoses with unknown origin, in which eosinophil infiltration is a central component and affects specific tissue layers or adnexal structures of the skin, such as the dermis, subcutaneous fat, fascia, follicles, and cutaneous vessels. Some typical examples are eosinophilic cellulitis, granuloma faciale, eosinophilic pustular folliculitis, recurrent cutaneous eosinophilic vasculitis, and eosinophilic fasciitis. Although tissue eosinophilia is a common feature shared by these disorders, their clinical and pathological properties differ dramatically. Among these rare entities, eosinophilic pustular folliculitis may be associated with human immunodeficiency virus (HIV) infection or malignancies, and some other diseases, like eosinophilic fasciitis and eosinophilic cellulitis, may be associated with an underlying hematological disorder, while others are considered idiopathic. However, for most of these rare eosinophilic dermatoses, the causes and the pathogenic mechanisms remain largely unknown, and systemic, high-quality clinical investigations are needed for advances in better strategies for clinical diagnosis and treatment. Here, we present a comprehensive review on the etiology, pathogenesis, clinical features, and management of these rare entities, with an emphasis on recent advances and current consensus. PMID:25876839

  17. Immunology and skin in health and disease.

    PubMed

    Richmond, Jillian M; Harris, John E

    2014-12-01

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

  18. Ocular manifestations of infectious skin diseases.

    PubMed

    Sadowska-Przytocka, Anna; Czarnecka-Operacz, Magdalena; Jenerowicz, Dorota; Grzybowski, Andrzej

    2016-01-01

    Ocular complications of infectious skin diseases are a common occurrence. Managing the inflamed or infected eye in the emergency setting presents a diagnostic and therapeutic challenge to the emergency physician. Infectious agents may affect any part of the eye. Ocular findings may be the first sign of many infectious diseases, such as, for example, gonorrhea or chlamydia infection. Understanding the various forms of ocular involvement in these conditions is important, because untreated ophthalmic involvement can lead to severe vision loss. This review focuses on the significant ocular manifestations of the most common infectious diseases, including bacterial, viral, fungal, and parasitic infections, that both ophthalmologists and dermatologists may encounter. PMID:26903179

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

    ERIC Educational Resources Information Center

    Pines, Maya

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

  20. 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. PMID:26503961

  1. Current Status of Gene Therapy for Inherited Lung Diseases

    PubMed Central

    Driskell, Ryan R.; Engelhardt, John F.

    2007-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  3. 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

  4. 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

  5. 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

  6. Marek's disease virus and skin interactions.

    PubMed

    Couteaudier, Mathilde; Denesvre, Caroline

    2014-01-01

    Marek's disease virus (MDV) is a highly contagious herpesvirus which induces T-cell lymphoma in the chicken. This virus is still spreading in flocks despite forty years of vaccination, with important economical losses worldwide. The feather follicles, which anchor feathers into the skin and allow their morphogenesis, are considered as the unique source of MDV excretion, causing environmental contamination and disease transmission. Epithelial cells from the feather follicles are the only known cells in which high levels of infectious mature virions have been observed by transmission electron microscopy and from which cell-free infectious virions have been purified. Finally, feathers harvested on animals and dust are today considered excellent materials to monitor vaccination, spread of pathogenic viruses, and environmental contamination. This article reviews the current knowledge on MDV-skin interactions and discusses new approaches that could solve important issues in the future. PMID:24694064

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

    PubMed

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

    2015-11-01

    A recent review identified 60 common inherited renal diseases caused by DNA variants in 132 different genes. These diseases can be diagnosed with DNA sequencing, but each gene probably also has a thousand normal variants. Many more normal variants have been characterised by individual laboratories than are reported in the literature or found in publicly accessible collections. At present, testing laboratories must assess each novel change they identify for pathogenicity, even when this has been done elsewhere previously, and the distinction between normal and disease-associated variants is particularly an issue with the recent surge in exomic sequencing and gene discovery projects. The Human Variome Project recommends the establishment of gene-specific DNA variant databases to facilitate the sharing of DNA variants and decisions about likely disease causation. Databases improve diagnostic accuracy and testing efficiency, and reduce costs. They also help with genotype-phenotype correlations and predictive algorithms. The Human Variome Project advocates databases that use standardised descriptions, are up-to-date, include clinical information and are freely available. Currently, the genes affected in the most common inherited renal diseases correspond to 350 different variant databases, many of which are incomplete or have insufficient clinical details for genotype-phenotype correlations. Assistance is needed from nephrologists to maximise the usefulness of these databases for the diagnosis and management of inherited renal disease. PMID:25384529

  8. 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. PMID:26093993

  9. 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. PMID:27311780

  10. IgG4-related skin disease.

    PubMed

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

    2014-11-01

    IgG4-related disease (IgG4-RD) is a recently established clinical entity characterized by high levels of circulating IgG4, and tissue infiltration of IgG4(+) plasma cells. IgG4-RD exhibits a distinctive fibroinflammatory change involving multiple organs, such as the pancreas and salivary and lacrimal glands. The skin lesions of IgG4-RD have been poorly characterized and may stem not only from direct infiltration of plasma cells but also from IgG4-mediated inflammation. Based on the documented cases together with ours, we categorized the skin lesions into seven subtypes: (1) cutaneous plasmacytosis (multiple papulonodules or indurations on the trunk and proximal part of the limbs), (2) pseudolymphoma and angiolymphoid hyperplasia with eosinophilia (plaques and papulonodules mainly on the periauricular, cheek and mandible regions), (3) Mikulicz disease (palpebral swelling, sicca syndrome and exophthalmos), (4) psoriasis-like eruption (strikingly mimicking psoriasis vulgaris), (5) unspecified maculopapular or erythematous eruptions, (6) hypergammaglobulinaemic purpura (bilateral asymmetrical palpable purpuric lesions on the lower extremities) and urticarial vasculitis (prolonged urticarial lesions occasionally with purpura) and (7) ischaemic digit (Raynaud phenomenon and digital gangrene). It is considered that subtypes 1-3 are induced by direct infiltration of IgG4(+) plasma cells, while the other types (4-7) are caused by secondary mechanisms. IgG4-related skin disease is defined as IgG4(+) plasma-cell-infiltrating skin lesions that form plaques, nodules or tumours (types 1-3), but may manifest secondary lesions caused by IgG4(+) plasma cells and/or IgG4 (types 4-7). PMID:25065694

  11. 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

  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. 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

  14. Oral mucosal manifestations of autoimmune skin diseases.

    PubMed

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

    2015-10-01

    A group of autoimmune diseases is characterised by autoantibodies against epithelial adhesion structures and/or tissue-tropic lymphocytes driving inflammatory processes resulting in specific pathology at the mucosal surfaces and the skin. The most frequent site of mucosal involvement in autoimmune diseases is the oral cavity. Broadly, these diseases include conditions affecting the cell-cell adhesion causing intra-epithelial blistering and those where autoantibodies or infiltration lymphocytes cause a loss of cell-matrix adhesion or interface inflammation. Clinically, patients present with blistering, erosions and ulcers that may affect the skin as well as further mucosal surfaces of the eyes, nose and genitalia. While the autoimmune disease may be suspected based on clinical manifestations, demonstration of tissue-bound and circulating autoantibodies, or lymphocytic infiltrates, by various methods including histological examination, direct and indirect immunofluorescence microscopy, immunoblotting and quantitative immunoassay is a prerequisite for definitive diagnosis. Given the frequency of oral involvement and the fact that oral mucosa is the initially affected site in many cases, the informed practitioner should be well acquainted with diagnostic and therapeutic aspects of autoimmune dermatosis with oral involvement. This paper reviews the pathogenesis and clinical presentation of these conditions in the oral cavity with a specific emphasis on their differential diagnosis and current management approaches. PMID:26117595

  15. 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.

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

    PubMed Central

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

    2014-01-01

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

  17. 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

  18. 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

  19. Psoriasis: experiencing a chronic skin disease.

    PubMed

    Chrissopoulos, A; Cleaver, G

    1996-03-01

    Psoriasis is an incurable chronic skin disease that affects one in fifty people. Psychological factors play a role in the aetiology and experience of psoriasis but there is little pertaining to the psychological experience of psoriasis in research literature. In this study the phenomenological approach is used to describe the everyday experiences of a person with psoriasis. By using Giorgi's (1985) steps of data analysis a description of the lifeworld of the person with psoriasis was compiled. The description presented several essential components of the experience of psoriasis and the results emphasize the effects of the disease on the sufferer's life. Problematic interpersonal relationships, a negative selfconcept, fluctuating moods, loss of control, negativity and loneliness are a part of this experience. It is hoped that knowledge of the world of the psoriasis sufferer will assist the help professions to understanding and empathize with the suffering and limitations that psoriasis brings. PMID:9257576

  20. Skin Diseases: Cross-section of human skin

    MedlinePlus

    ... NIAMS) has a wide range of topics under study and through funding of research outside NIAMS. These include disorders such as psoriasis, atopic dermatitis and other chronic inflammatory skin disorders, acne, and many others. Fall 2008 Issue: Volume 3 ...

  1. 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

  2. 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. PMID:23450734

  3. Sarcoptic Mange: A Zoonotic Ectoparasitic Skin Disease

    PubMed Central

    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. PMID:23450734

  4. 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

  5. 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

  6. 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

  7. Inflammatory Bowel Disease and Skin Cancer: An Assessment of Patient Risk Factors, Knowledge, and Skin Practices

    PubMed Central

    Kimmel, Jessica N.; Taft, Tiffany H.; Keefer, Laurie

    2016-01-01

    Objective. Patients with inflammatory bowel disease (IBD) are at increased risk from skin cancer. Aims include assessing IBD patients' risk factors and knowledge of skin cancer and current skin protection practices to identify gaps in patient education regarding skin cancer prevention in IBD. Methods. IBD patients ≥ 18 years were recruited to complete an online survey. Results. 164 patients (mean age 43.5 years, 63% female) with IBD (67% Crohn's disease, 31% ulcerative colitis, and 2% indeterminate colitis) were included. 12% (n = 19) of patients had a personal history and 34% (n = 55) had a family history of skin cancer. Females scored better on skin protection (16.94/32 versus 14.53/32, P ≤ 0.03) and awareness (35.16/40 versus 32.98/40, P ≤ 0.03). Patients over 40 years old scored better on prevention (17.45/28 versus 15.35/28, P = 0.03). Patients with skin cancer scored better on prevention (20.56/28 versus 15.75/28, P ≤ 0.001) and skin protection (21.47/32 versus 15.33/32, P ≤ 0.001). 61% of patients recognized the link between skin cancer and IBD. Conclusions. The majority of IBD patients are aware of the link between skin cancer and IBD; however, skin protection practices are suboptimal. This emphasizes the role of healthcare professionals in providing further education for skin cancer prevention in the IBD population. PMID:27034838

  8. 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

  9. 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

  10. Bone marrow transplantation in the prevention of intellectual disability due to inherited metabolic disease: ethical issues.

    PubMed

    Louhiala, P

    2009-07-01

    Many inherited metabolic diseases may lead to varying degrees of brain damage and thus also to intellectual disability. Bone marrow transplantation (BMT) has been used for over two decades as a form of secondary prevention to stop or reverse the progress of the disease process in some of these conditions. At the population level the impact of BMT on the prevalence of intellectual disability is minute, but at the individual level its impact on the prognosis of the disease and the well-being of the patient can be substantial. The dark side of BMT use is the burden of side effects, complications and transplantation-related mortality in less successful cases. The ethical issues involved in this therapy are discussed in this review. PMID:19567689

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

    PubMed Central

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

    2015-01-01

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

  12. 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. PMID:26105081

  13. 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

  14. 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

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

    PubMed

    Zhao, Boyang; Pritchard, Justin R

    2016-06-01

    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

  16. [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

  17. Inherited prion disease with 4-octapeptide repeat insertion: disease requires the interaction of multiple genetic risk factors.

    PubMed

    Kaski, Diego N; Pennington, Catherine; Beck, Jon; Poulter, Mark; Uphill, James; Bishop, Matthew T; Linehan, Jaqueline M; O'Malley, Catherine; Wadsworth, Jonathan D F; Joiner, Susan; Knight, Richard S G; Ironside, James W; Brandner, Sebastian; Collinge, John; Mead, Simon

    2011-06-01

    Genetic factors are implicated in the aetiology of sporadic late-onset neurodegenerative diseases. Whether these genetic variants are predominantly common or rare, and how multiple genetic factors interact with each other to cause disease is poorly understood. Inherited prion diseases are highly heterogeneous and may be clinically mistaken for sporadic Creutzfeldt-Jakob disease because of a negative family history. Here we report our investigation of patients from the UK with four extra octapeptide repeats, which suggest that the risk of clinical disease is increased by a combination of the mutation and a susceptibility haplotype on the wild-type chromosome. The predominant clinical syndrome is a progressive cortical dementia with pyramidal signs, myoclonus and cerebellar abnormalities that closely resemble sporadic Creutzfeldt-Jakob disease. Autopsy shows perpendicular deposits of prion protein in the molecular layer of the cerebellum. Identity testing, PRNP microsatellite haplotyping and genealogical work confirm no cryptic close family relationships and suggests multiple progenitor disease haplotypes. All patients were homozygous for methionine at polymorphic codon 129. In addition, at a single nucleotide polymorphism upstream of PRNP thought to confer susceptibility to sporadic Creutzfeldt-Jakob disease (rs1029273), all patients were homozygous for the risk allele (combined P=5.9×10(-5)). The haplotype identified may also be a risk factor in other partially penetrant inherited prion diseases although it does not modify age of onset. Blood expression of PRNP in healthy individuals was modestly higher in carriers of the risk haplotype. These findings may provide a precedent for understanding apparently sporadic neurodegenerative diseases caused by rare high-risk mutations. PMID:21616973

  18. [Netherton syndrome--a rare form of inherited ichtyosis].

    PubMed

    Marttila, Riitta; Tuomiranta, Mirja

    2012-01-01

    Netherton syndrome is a rare skin disease classified into ichtyoses. It has a recessive pattern of inheritance. It is associated with scaly erythrodermia, bamboo hair defect, immunological abnormalities of varying severity, IgE-mediated allergic reactions, infections and defective temperature regulation that often leads to retarded growth and development of a newborn. The phenotype of the disease varies from mild skin symptoms to lethal forms of the disease. We describe two Finnish families, whose children were diagnosed with this disease. PMID:22312831

  19. Functions of the skin microbiota in health and disease

    PubMed Central

    Sanford, James A.; Gallo, Richard L.

    2014-01-01

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

  20. Percutaneous absorption in diseased skin: an overview.

    PubMed

    Chiang, Audris; Tudela, Emilie; Maibach, Howard I

    2012-08-01

    The stratum corneum's (SC) functions include protection from external hazardous environments, prevention of water loss and regulation of body temperature. While intact skin absorption studies are abundant, studies on compromised skin permeability are less common, although products are often used to treat affected skin. We reviewed literature on percutaneous absorption through abnormal skin models. Tape stripping is used to disrupt water barrier function. Studies demonstrated that physicochemical properties influence the stripping effect: water-soluble drugs are more affected. Abrasion did not affect absorption as much. Freezing is commonly used to preserve skin. It does not seem to modify water absorption, but still increases the penetration of compounds. Comparatively, heating the skin consistently increased percutaneous absorption. Removing SC lipids may increase percutaneous absorption of drugs. Many organic solvents are employed to delipidize. Delipidization with chloroform-methanol increased hydrophilic compound permeability, but not lipophilic. Acetone pre-treatment enhanced hydrophilic compound penetration. More data is needed to determine influence on highly lipophilic compound penetration. Sodium lauryl sulfate (SLS) induces irritant dermatitis and is frequently used as a model. Studies revealed that SLS increases hydrophilic compound absorption, but not lipophilic. However, skin irritation with other chemicals increases lipophilic penetration as much as hydrophilic. Animal studies show that UV exposure increases percutaneous absorption whereas human studies do not. Human studies show increased penetration in psoriatic and atopic dermatitis skin. The data summarized here begin to characterize flux alteration associated with damaged skin. Understanding the degree of alteration requires interpretation of involved conditions and the enlarging of our database to a more complete physicochemical spectrum. PMID:22912973

  1. Study on application of optical clearing technique in skin diseases

    NASA Astrophysics Data System (ADS)

    Shan, Hao; Liang, Yanmei; Wang, Jingyi; Li, Yan

    2012-11-01

    So far, the study of the optical clearing is almost always about healthy tissue. However, the ultimate goal is to detect diseases for clinical application. Optical clearing on diseased skins is explored. The effect is evaluated by applying a combined liquid paraffin and glycerol mixed solution on several kinds of diseased skins in vitro. Scanning experiments from optical coherence tomography show that it has different effects among fibroma, pigmented nevus, and seborrheic keratosis. Based on the results, we conclude that different skin diseases have different compositions and structures, and their optical parameters and biological characteristics should be different, which implies that the optical clearing technique may have selectivity and may not be suitable for all kinds of skin diseases.

  2. Metamaterial-based sensor for skin disease diagnostics

    NASA Astrophysics Data System (ADS)

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

    2013-05-01

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

  3. [Inherited GPI deficiency; a new disease with intellectual disability and epilepsy].

    PubMed

    Murakami, Yoshiko; Kinoshita, Taroh

    2015-07-01

    Recently, many cases of inherited GPI deficiency(IGD) are found among individuals with intellectual disability and intractable seizures. To date, about twenty patients have been reported in Japan and up to a hundred in the world. GPI is the glycolipid which anchors 150 kinds of proteins to the plasma membrane. We have found that there are at least 26 genes involved in the biosynthesis or modification of GPI-anchored proteins. IGDs caused by mutations in 12 genes were reported until now. IGD shows a variety of symptoms according to the affected genes and the severity of the mutations. Some patients have hyperphosphatasia and most patients can be diagnosed by the flow cytometric analysis of the blood cells. Early diagnosis and treatment are desirable because the disease progresses even after birth and vitamin B6(pyridoxine) is very effective for some patients with intractable seizures. PMID:26165085

  4. Cargos and genes: insights into vesicular transport from inherited human disease

    PubMed Central

    Gissen, Paul; Maher, Eamonn R

    2007-01-01

    Many cellular functions depend on the correct delivery of proteins to specific intracellular destinations. Mutations that alter protein structure and disrupt trafficking of the protein (the “cargo”) occur in many genetic disorders. In addition, an increasing number of disorders have been linked to mutations in the genes encoding components of the vesicular transport machinery responsible for normal protein trafficking. We review the clinical phenotypes and molecular pathology of such inherited “protein‐trafficking disorders”, which provide seminal insights into the molecular mechanisms of protein trafficking. Further characterisation of this expanding group of disorders will provide a basis for developing new diagnostic techniques and treatment strategies and offer insights into the molecular pathology of common multifactorial diseases that have been linked to disordered trafficking mechanisms. PMID:17526798

  5. Use of recombinant factor VIIa in inherited and acquired von Willebrand disease.

    PubMed

    Sucker, Christoph; Scharf, Rüdiger E; Zotz, Rainer B

    2009-02-01

    Recombinant factor VIIa (rFVIIa) is increasingly used outside the labeled indications for the treatment of life-threatening bleeding episodes after failure of respective standard therapy. In this article, the authors focus on the use of the agent in patients with inherited or acquired von Willebrand disease (vWD). Although the current experience is sparse, published cases indicate the high efficacy of rFVIIa for the treatment of patients refractory to conventional treatment. The agent may be used in patients with congenital vWD complicated by alloantibodies directed against substituted von Willebrand factor or in the presence of concomitant hemostatic defects as well as acquired vWD with hitherto limited therapeutic options. Controlled clinical studies are necessary to define the use of rFVIIa in this clinical setting. PMID:18263636

  6. 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

  7. Universal screening for inherited metabolic diseases in the neonate (and the fetus).

    PubMed

    Scala, Iris; Parenti, Giancarlo; Andria, Generoso

    2012-10-01

    The traditional focus of newborn screening for inherited metabolic diseases is to test infants for medical conditions that may cause significant morbidity and mortality unless treatment is initiated early. A major change began with the application of tandem mass spectrometry to the quantitative analysis of amino acids and acylcarnitines in dried blood spots. Beyond the lack of a consensus on disease selection, the pace of introduction for expanded screening programs has been slow and patchy among and within countries. Universal metabolic screening poses important ethical issues, related to possible ambiguous findings, late-onset diseases, conditions, such as lysosomal storage disorders, with no clear-cut evidence on when and how to start a therapy. The possible application of next generation sequencing to newborn screening has been recently proposed. In the near future it will be also possible to perform a genetic and mutational scan across the whole genome of the fetus in a non-invasive manner by analyzing cell-free fetal DNA in maternal blood as early as the 5th week of gestational age. These high-throughput methods applied to neonatal and non-invasive prenatal screening of genetic diseases, including inborn errors of metabolism, are raising further technical, political and ethical issues. PMID:23025760

  8. 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

  9. Antisense mediated splicing modulation for inherited metabolic diseases: challenges for delivery.

    PubMed

    Pérez, Belen; Vilageliu, Lluisa; Grinberg, Daniel; Desviat, Lourdes R

    2014-02-01

    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

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

    PubMed Central

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

    2014-01-01

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

  11. 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

  12. Skin Diseases: Questions for Your Health Care Provider

    MedlinePlus

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

  13. 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

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

    PubMed

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

    2014-09-01

    Aberrant mitochondrial structure and function influence tissue homeostasis and thereby contribute to multiple human disorders and ageing. Ten per cent of patients with primary mitochondrial disorders present skin manifestations that can be categorized into hair abnormalities, rashes, pigmentation abnormalities and acrocyanosis. Less attention has been paid to the fact that several disorders of the skin are linked to alterations of mitochondrial energy metabolism. This review article summarizes the contribution of mitochondrial pathology to both common and rare skin diseases. We explore the intriguing observation that a wide array of skin disorders presents with primary or secondary mitochondrial pathology and that a variety of molecular defects can cause dysfunctional mitochondria. Among them are mutations in mitochondrial- and nuclear DNA-encoded subunits and assembly factors of oxidative phosphorylation (OXPHOS) complexes; mutations in intermediate filament proteins involved in linking, moving and shaping of mitochondria; and disorders of mitochondrial DNA metabolism, fatty acid metabolism and heme synthesis. Thus, we assume that mitochondrial involvement is the rule rather than the exception in skin diseases. We conclude the article by discussing how improving mitochondrial function can be beneficial for aged skin and can be used as an adjunct therapy for certain skin disorders. Consideration of mitochondrial energy metabolism in the skin creates a new perspective for both dermatologists and experts in metabolic disease. PMID:24980550

  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. 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

  17. Inherited mitochondrial disorders.

    PubMed

    Finsterer, Josef

    2012-01-01

    Though inherited mitochondrial disorders (MIDs) are most well known for their syndromic forms, for which widely known acronyms (MELAS, MERRF, NARP, LHON etc.) have been coined, the vast majority of inherited MIDs presents in a non-syndromic form. Since MIDs are most frequently multisystem disorders already at onset or during the disease course, a MID should be suspected if there is a combination of neurological and non-neurological abnormalities. Neurological abnormalities occurring as a part of a MID include stroke-like episodes, epilepsy, migraine-like headache, movement disorders, cerebellar ataxia, visual impairment, encephalopathy, cognitive impairment, dementia, psychosis, hypopituitarism, aneurysms, or peripheral nervous system disease, such as myopathy, neuropathy, or neuronopathy. Non-neurological manifestations concern the ears, the endocrine organs, the heart, the gastrointestinal tract, the kidneys, the bone marrow, and the skin. Whenever there is an unexplained combination of neurological and non-neurological disease in a patient or kindred, a MID should be suspected and appropriate diagnostic measures initiated. Genetic testing should be guided by the phenotype, the biopsy findings, and the biochemical results. PMID:22399423

  18. Genetic Correction of Stem Cells in the Treatment of Inherited Diseases and Focus on Xeroderma Pigmentosum

    PubMed Central

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

    2013-01-01

    Somatic stem cells ensure tissue renewal along life and healing of injuries. Their safe isolation, genetic manipulation ex vivo and reinfusion in patients suffering from life threatening immune deficiencies (for example, severe combined immunodeficiency (SCID)) have demonstrated the efficacy of ex vivo gene therapy. Similarly, adult epidermal stem cells have the capacity to renew epidermis, the fully differentiated, protective envelope of our body. Stable skin replacement of severely burned patients have proven life saving. Xeroderma pigmentosum (XP) is a devastating disease due to severe defects in the repair of mutagenic DNA lesions introduced upon exposure to solar radiations. Most patients die from the consequences of budding hundreds of skin cancers in the absence of photoprotection. We have developed a safe procedure of genetic correction of epidermal stem cells isolated from XP patients. Preclinical and safety assessments indicate successful correction of XP epidermal stem cells in the long term and their capacity to regenerate a normal skin with full capacities of DNA repair. PMID:24113582

  19. 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

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

    PubMed Central

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

    2012-01-01

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

  1. The eye and the skin in endocrine metabolic diseases.

    PubMed

    Urrets-Zavalía, Julio A; Espósito, Evangelina; Garay, Iliana; Monti, Rodolfo; Ruiz-Lascano, Alejandro; Correa, Leandro; Serra, Horacio M; Grzybowski, Andrzej

    2016-01-01

    The eye and skin may offer critical clues to the diagnosis of a varied spectrum of metabolic diseases from endocrine origin and their different stages of severity, such as diabetes mellitus and Graves disease. On the other hand, such entities may compromise the eye and visual function severely, and awareness of these possible associations is an important step in their diagnosis and management. A large number of less common endocrine diseases may also have significant ocular/visual or skin involvement. Often the etiologic relationship between the endocrine metabolic disease and the ocular compromise is unknown, but diverse pathogenetic mechanisms may act through a common pathologic pathway producing ocular damage, as occur in diabetic retinopathy. This review emphasizes the ocular and skin manifestations of different metabolic diseases of endocrine origin. PMID:26903183

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

    PubMed Central

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

    2015-01-01

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

  3. 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

  4. 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. PMID:26527198

  5. 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

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

    PubMed

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

    2014-03-01

    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

  7. 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. PMID:25688346

  8. 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

  9. Skin Disease in Laminopathy-Associated Premature Aging.

    PubMed

    McKenna, Tomás; Sola Carvajal, Agustín; Eriksson, Maria

    2015-11-01

    The nuclear lamina, a protein network located under the nuclear membrane, has during the past decade found increasing interest due to its significant involvement in a range of genetic diseases, including the segmental premature aging syndromes Hutchinson-Gilford progeria syndrome, restrictive dermopathy, and atypical Werner syndrome. In this review we examine these diseases, some caused by mutations in the LMNA gene, and their skin disease features. Advances within this area might also provide novel insights into the biology of skin aging, as recent data suggest that low levels of progerin are expressed in unaffected individuals and these levels increase with aging. PMID:26290387

  10. 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

  11. 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

  12. Skin testing for allergic diseases: techniques, indications and interpretations.

    PubMed

    Villacorte, G V

    1978-01-01

    Despite significant strides in serologic methodologies, the skin test, when properly done, has remained the single most sensitive and practical assay for specific dermal-bound reaginic antibody. Its value could further be enhanced if and when characterization and standardization of the allergen extracts become a reality. While the technique is simple, the indications and interpretations of allergy skin tests required the expertise of well-trained allergists. A positive skin reaction is no more than a mere supportive laboratory aid in the diagnosis of allergic disease, which is arrived at through a carefully taken detailed history and a meticulously done physical examination. PMID:748833

  13. A Role for Non-B DNA Forming Sequences in Mediating Microlesions Causing Human Inherited Disease.

    PubMed

    Kamat, Mihir Anant; Bacolla, Albino; Cooper, David N; Chuzhanova, Nadia

    2016-01-01

    Missense/nonsense mutations and microdeletions/microinsertions (<21 bp) represent ∼ 76% of all mutations causing human inherited disease, and their occurrence has been associated with sequence motifs (direct, inverted, and mirror repeats; G-quartets) capable of adopting non-B DNA structures. We found that a significant proportion (∼ 21%) of both microdeletions and microinsertions occur within direct repeats, and are explicable by slipped misalignment. A novel mutational mechanism, DNA triplex formation followed by DNA repair, may explain ∼ 5% of microdeletions and microinsertions at mirror repeats. Further, G-quartets, direct, and inverted repeats also appear to play a prominent role in mediating missense mutations, whereas only direct and inverted repeats mediate nonsense mutations. We suggest a mutational mechanism involving slipped strand mispairing, slipped structure formation, and DNA repair, to explain ∼ 15% of missense and ∼ 12% of nonsense mutations yielding perfect direct repeats from imperfect repeats, or the extension of existing direct repeats. Similar proportions of missense and nonsense mutations were explicable by hairpin/loop formation and DNA repair, yielding perfect inverted repeats from imperfect repeats. We also propose a model for single base-pair substitution based on one-electron oxidation reactions at G-quadruplex DNA. Overall, the proposed mechanisms provide support for a role for non-B DNA structures in human gene mutagenesis. PMID:26466920

  14. Ascomycins: promising agents for the treatment of inflammatory skin diseases.

    PubMed

    Paul, C; Graeber, M; Stuetz, A

    2000-01-01

    Ascomycin derivatives represent a novel class of anti-inflammatory macrolactams currently under development for the treatment of skin diseases. The main biological effect of ascomycins is an inhibition of the synthesis of both Th1 and Th2-type cytokines in target cells. Several compounds are being developed with SDZ ASM 981 being at the most advanced stage. It has high anti-inflammatory activity in animal models of skin inflammation and does not induce skin atrophy. Topical application of SDZ ASM 981 was shown to be effective in atopic dermatitis (AD), allergic contact dermatitis and also in psoriasis under semi-occlusive conditions. In patients with AD, SDZ ASM 981 cream led to consistently low systemic exposure even when applied on large areas of skin. SDZ ASM 981 overcomes the drawbacks of current topical therapies of inflammatory skin diseases as its safety profile is better than that of topical corticosteroids. Studies continue to investigate its efficacy and safety in the treatment of inflammatory skin diseases. PMID:11060661

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

    PubMed Central

    2011-01-01

    MicroRNAs (miRNAs) are small noncoding RNA molecules that negatively regulate gene expression via degradation or translational repression of their target messenger RNAs (mRNAs). Recent studies have clearly demonstrated that miRNAs play critical roles in several biologic processes, including cell cycle, differentiation, cell development, cell growth, and apoptosis and that miRNAs are highly expressed in regulatory T (Treg) cells and a wide range of miRNAs are involved in the regulation of immunity and in the prevention of autoimmunity. It has been increasingly reported that miRNAs are associated with various human diseases like autoimmune disease, skin disease, neurological disease and psychiatric disease. Recently, the identification of mi- RNAs in skin has added a new dimension in the regulatory network and attracted significant interest in this novel layer of gene regulation. Although miRNA research in the field of dermatology is still relatively new, miRNAs have been the subject of much dermatological interest in skin morphogenesis and in regulating angiogenesis. In addition, miRNAs are moving rapidly onto center stage as key regulators of neuronal development and function in addition to important contributions to neurodegenerative disorder. Moreover, there is now compelling evidence that dysregulation of miRNA networks is implicated in the development and onset of human neruodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, Tourette's syndrome, Down syndrome, depression and schizophrenia. In this review, I briefly summarize the current studies about the roles of miRNAs in various autoimmune diseases, skin diseases, psychoneurological disorders and mental stress. PMID:22194706

  16. Phenotypic heterogeneity and genetic modification of P102L inherited prion disease in an international series

    PubMed Central

    Webb, T. E. F.; Poulter, M.; Beck, J.; Uphill, J.; Adamson, G.; Campbell, T.; Linehan, J.; Powell, C.; Brandner, S.; Pal, S.; Siddique, D.; Wadsworth, J. D.; Joiner, S.; Alner, K.; Petersen, C.; Hampson, S.; Rhymes, C.; Treacy, C.; Storey, E.; Geschwind, M. D.; Nemeth, A. H.; Wroe, S.; Mead, S.

    2008-01-01

    The largest kindred with inherited prion disease P102L, historically Gerstmann-Sträussler-Scheinker syndrome, originates from central England, with émigrés now resident in various parts of the English-speaking world. We have collected data from 84 patients in the large UK kindred and numerous small unrelated pedigrees to investigate phenotypic heterogeneity and modifying factors. This collection represents by far the largest series of P102L patients so far reported. Microsatellite and genealogical analyses of eight separate European kindreds support multiple distinct mutational events at a cytosine-phosphate diester-guanidine dinucleotide mutation hot spot. All of the smaller P102L kindreds were linked to polymorphic human prion protein gene codon 129M and were not connected by genealogy or microsatellite haplotype background to the large kindred or each other. While many present with classical Gerstmann-Sträussler-Scheinker syndrome, a slowly progressive cerebellar ataxia with later onset cognitive impairment, there is remarkable heterogeneity. A subset of patients present with prominent cognitive and psychiatric features and some have met diagnostic criteria for sporadic Creutzfeldt-Jakob disease. We show that polymorphic human prion protein gene codon 129 modifies age at onset: the earliest eight clinical onsets were all MM homozygotes and overall age at onset was 7 years earlier for MM compared with MV heterozygotes (P = 0.02). Unexpectedly, apolipoprotein E4 carriers have a delayed age of onset by 10 years (P = 0.02). We found a preponderance of female patients compared with males (54 females versus 30 males, P = 0.01), which probably relates to ascertainment bias. However, these modifiers had no impact on a semi-quantitative pathological phenotype in 10 autopsied patients. These data allow an appreciation of the range of clinical phenotype, modern imaging and molecular investigation and should inform genetic counselling of at-risk individuals, with the

  17. Genetic skin diseases related to desmosomes and corneodesmosomes.

    PubMed

    Ishida-Yamamoto, Akemi; Igawa, Satomi

    2014-05-01

    The integrity of the epidermis depends on the cohesion between keratinocytes, and desmosomes are the main adhesion structures. When cells become cornified, desmosomes are modified and transformed into corneodesmosomes. Mutations in the genes encoding desmosomal components underlie several skin diseases including palmoplantar keratoderma and forms of epidermolysis bullosa, indicating the importance of desmosomes as mechanical stress-bearing structures. Other types of genetic defects in a desmosome component (desmoglein 1), a corneodesmosome component (corneodesmosin), and an inhibitor for proteases involved in corneodesmosome degradation (LEKTI) result in three clinically overlapping conditions: SAM syndrome, an inflammatory type of peeling skin disease, and Netherton syndrome. All three result in allergies to multiple allergens due to severe barrier impairment. Conversely, impaired corneodesmosomal degradation due to matriptase mutations could lead to ichthyosis. By discovering the diverse clinical phenotypes of these diseases, we can enrich our understanding of the multifunctional roles of desmosomes and corneodesmosomes in skin biology. PMID:24636350

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

    PubMed

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

    2010-08-13

    Generalized peeling skin disease is an autosomal-recessive ichthyosiform erythroderma characterized by lifelong patchy peeling of the skin. After genome-wide linkage analysis, we have identified a homozygous nonsense mutation in CDSN in a large consanguineous family with generalized peeling skin, pruritus, and food allergies, which leads to a complete loss of corneodesmosin. In contrast to hypotrichosis simplex, which can be associated with specific dominant CDSN mutations, peeling skin disease is characterized by a complete loss of CDSN expression. The skin phenotype is consistent with a recent murine Cdsn knockout model. Using three-dimensional human skin models, we demonstrate that lack of corneodesmosin causes an epidermal barrier defect supposed to account for the predisposition to atopic diseases, and we confirm the role of corneodesmosin as a decisive epidermal adhesion molecule. Therefore, peeling skin disease will represent a new model disorder for atopic diseases, similarly to Netherton syndrome and ichthyosis vulgaris in the recent past. PMID:20691404

  19. 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

  20. 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

  1. 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

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

    PubMed Central

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

    2013-01-01

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

  3. 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

  4. 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

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

    PubMed

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

    2016-01-01

    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. PMID:27095813

  6. 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

  7. 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. PMID:27040351

  8. 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

  9. 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. PMID:21199627

  10. 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…

  11. 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…

  12. 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

  13. 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. PMID:24217593

  14. Tropical Skin Diseases in Children: A Review-Part II.

    PubMed

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

    2016-05-01

    Tropical skin diseases are infectious conditions influenced by factors such as nutrition, housing, and the environment. Migration patterns have caused these conditions to be seen all around the world, not only in developing countries. Many of these diseases have a different presentation in childhood, which changes the diagnostic approach and management options. In this article, we review some of the most common tropical mycobacterial, protozoan, parasitic, and viral dermatologic conditions in children, including their epidemiologic, clinical, diagnostic, and therapeutic aspects. PMID:27039881

  15. 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.

  16. Skin involvement and outcome measures in systemic autoimmune diseases.

    PubMed

    Albrecht, J; Atzeni, F; Baldini, C; Bombardieri, S; Dalakas, M C; Demirkesen, C; Yazici, H; Mat, C; Werth, V P; Sarzi-Puttini, P

    2006-01-01

    This paper focuses on skin manifestations that can be observed in autoimmune diseases such as rheumatoid arthritis (RA), Sjögren syndrome (SS), dermatomyositis (DM) and Behçet syndrome (BS). In RA the most widely recognized skin lesion is the rheumatoid nodule. Other cutaneous manifestations can be observed either non-specific or related to the disease itself and/or to the commonly used drugs. Cutaneous manifestations are considered one of the most typical extraglandular features of primary SS, generally they are distinguished in vasculitic and non vasculitic lesions. Among non-vasculitc lesions, skin dryness (xerosis) has been shown to be very common in pSS while vasculitis lesions include typically flat and palpable purpura and urticarial vasculits. In DM the skin manifestations are also frequent and include a heliotrope rash (blue-purple discoloration) on the upper eyelids with edema, a flat red rash on the face and upper trunk, and erythema of the knuckles with a raised violaceous scaly eruption (Gottron rash). The most frequent mucocutaneous finding in BS is aphthous stomatitis which can not usually be differentiated from idiopatic reccurrent aphthous stomatitis on clinical grounds. The most typical skin manifestations are nodular lesions, which are commonly seen in BS and may be due to panniculitis [erythema nodosum (EN)-like lesions] or superficial thrombophlebitis. PMID:16466625

  17. 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

  18. 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. PMID:26100426

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

    ERIC Educational Resources Information Center

    Pines, Maya

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

  20. 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

  1. Clinical and parasitological aspects of onchocercal skin diseases in Nigeria.

    PubMed

    Dozie, Ikechukwu N S; Onwuliri, Celestine O E; Nwoke, Bertram E B; Onwuliri, Viola A

    2005-07-01

    An assessment of onchocercal skin disease (OSD) conducted in 38 rural communities in the Imo River Basin, Nigeria, between March 1999 and September 2000, showed that depigmentation (DPM) was the most prevalent lesion in persons with skin microfilariae (mf) (26.3%), followed by chronic papular onchodermatitis (CPOD) (18.1%) and acute papular onchodermatitis (APOD) (15.5%). There was no significant difference (P > 0.05) in sex-related prevalence of OSD. While CPOD, lichenified onchodermatitis (LOD) and DPM were more prevalent in subjects over 30 years old, APOD was associated more with those aged less than 30 years. OSD occurred with concomitant itching in nearly 50% of subjects. The geometric mean intensity of infection was 13 mf/mg per skin snip. PMID:16105335

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

    PubMed Central

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

    2009-01-01

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

  3. Biologic Therapy in Inflammatory and Immunomediated Skin Diseases: Safety Profile.

    PubMed

    Ganzetti, Giulia; Campanati, Anna; Molinelli, E; Offidani, A

    2016-01-01

    Biologic treatments have modified the therapeutic armamentarium in the treatment of many dermatological and non- dermatological diseases and data on literature have widely focused on the efficacy and safety of TNF-alpha inhibitors in psoriasis. Although the etiopathogenesis has not completely elucidated, inflammation appears the lait motif unifying the immune-pathogenesis of diverse skin disease, as atopic dermatitis, alopecia areata and hidradenitis suppurativa. Actually, data on the off-label use of biologics in cutaneous immune-mediated inflammatory diseases are scarce and restricted to anecdotal cases and case series. The present review aims to evidence the major off- label use of TNF-alpha inhibitors in dermatology. PMID:26463243

  4. Benign skin disease with pustules in the newborn.

    PubMed

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

    2016-04-01

    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

  5. 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

  6. 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

  7. Marek’s disease virus and skin interactions

    PubMed Central

    2014-01-01

    Marek’s disease virus (MDV) is a highly contagious herpesvirus which induces T-cell lymphoma in the chicken. This virus is still spreading in flocks despite forty years of vaccination, with important economical losses worldwide. The feather follicles, which anchor feathers into the skin and allow their morphogenesis, are considered as the unique source of MDV excretion, causing environmental contamination and disease transmission. Epithelial cells from the feather follicles are the only known cells in which high levels of infectious mature virions have been observed by transmission electron microscopy and from which cell-free infectious virions have been purified. Finally, feathers harvested on animals and dust are today considered excellent materials to monitor vaccination, spread of pathogenic viruses, and environmental contamination. This article reviews the current knowledge on MDV-skin interactions and discusses new approaches that could solve important issues in the future. PMID:24694064

  8. 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.

  9. An atypical Dent's disease phenotype caused by co-inheritance of mutations at CLCN5 and OCRL genes.

    PubMed

    Addis, Maria; Meloni, Cristiana; Tosetto, Enrica; Ceol, Monica; Cristofaro, Rosalba; Melis, Maria Antonietta; Vercelloni, Paolo; Del Prete, Dorella; Marra, Giuseppina; Anglani, Franca

    2013-06-01

    Dent's disease is an X-linked renal tubulopathy caused by mutations mainly affecting the CLCN5 gene. Defects in the OCRL gene, which is usually mutated in patients with Lowe syndrome, have been shown to lead to a Dent-like phenotype called Dent disease 2. However, about 20% of patients with Dent's disease carry no CLCN5/OCRL mutations. The disease's genetic heterogeneity is accompanied by interfamilial and intrafamilial phenotypic heterogeneity. We report on a case of Dent's disease with a very unusual phenotype (dysmorphic features, ocular abnormalities, growth delay, rickets, mild mental retardation) in which a digenic inheritance was discovered. Two different, novel disease-causing mutations were detected, both inherited from the patient's healthy mother, that is a truncating mutation in the CLCN5 gene (A249fs*20) and a donor splice-site alteration in the OCRL gene (c.388+3A>G). The mRNA analysis of the patient's leukocytes revealed an aberrantly spliced OCRL mRNA caused by in-frame exon 6 skipping, leading to a shorter protein, but keeping intact the central inositol 5-phosphatase domain and the C-terminal side of the ASH-RhoGAP domain. Only wild-type mRNA was observed in the mother's leukocytes due to a completely skewed X inactivation. Our results are the first to reveal the effect of an epistatic second modifier in Dent's disease too, which can modulate its expressivity. We surmise that the severe Dent disease 2 phenotype of our patient might be due to an addictive interaction of the mutations at two different genes. PMID:23047739

  10. 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

  11. 78 FR 40486 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-05

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and 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...

  12. Skin gangrene as an extraintestinal manifestation of inflammatory bowel disease*

    PubMed Central

    Komatsu, Yumi Cristina; Capareli, Gabriela Cunha; Boin, Maria Fernanda Feitosa de Camargo; Lellis, Rute; de Freitas, Thaís Helena Proença; Simone, Karine

    2014-01-01

    Inflammatory bowel diseases can commonly present many cutaneous lesions which can contribute to the diagnosis of the disease or its activity. The most frequent cutaneous or mucocutaneous manifestations suggesting ulcerative rectocolitis activity are erythema nodosum (3-10%), pyoderma gangrenosum (5-12%) and aphthous stomatitis (4%). Other reactive skin manifestations related to immunological mechanisms associated with the inflammatory bowel disease are: Sweet's syndrome, arthritis-dermatitis syndrome associated with inflammatory bowel disease and leukocytoclastic vasculitis. We describe the case of a young man with diagnosis of ulcerative rectocolitis, which presented an extensive cutaneous gangrene secondary to microvascular thrombosis. The case represents a dermatologic rarity and should be recognized as a cutaneous manifestation related to the hypercoagulability state observed in the disease's activity. PMID:25387503

  13. Skin gangrene as an extraintestinal manifestation of inflammatory bowel disease.

    PubMed

    Komatsu, Yumi Cristina; Capareli, Gabriela Cunha; Boin, Maria Fernanda Feitosa de Camargo; Lellis, Rute; Freitas, Thaís Helena Proença de; Simone, Karine

    2014-01-01

    Inflammatory bowel diseases can commonly present many cutaneous lesions which can contribute to the diagnosis of the disease or its activity. The most frequent cutaneous or mucocutaneous manifestations suggesting ulcerative rectocolitis activity are erythema nodosum (3-10%), pyoderma gangrenosum (5-12%) and aphthous stomatitis (4%). Other reactive skin manifestations related to immunological mechanisms associated with the inflammatory bowel disease are: Sweet's syndrome, arthritis-dermatitis syndrome associated with inflammatory bowel disease and leukocytoclastic vasculitis. We describe the case of a young man with diagnosis of ulcerative rectocolitis, which presented an extensive cutaneous gangrene secondary to microvascular thrombosis. The case represents a dermatologic rarity and should be recognized as a cutaneous manifestation related to the hypercoagulability state observed in the disease's activity. PMID:25387503

  14. 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

  15. Novel mutation in TSPAN12 leads to autosomal recessive inheritance of congenital vitreoretinal disease with intra-familial phenotypic variability.

    PubMed

    Gal, Moran; Levanon, Erez Y; Hujeirat, Yasir; Khayat, Morad; Pe'er, Jacob; Shalev, Stavit

    2014-12-01

    Developmental malformations of the vitreoretinal vasculature are a heterogeneous group of conditions with various modes of inheritance, and include familial exudative vitreoretinopathy (FEVR), persistent fetal vasculature (PFV), and Norrie disease. We investigated a large consanguineous kindred with multiple affected individuals exhibiting variable phenotypes of abnormal vitreoretinal vasculature, consistent with the three above-mentioned conditions and compatible with autosomal recessive inheritance. Exome sequencing identified a novel c.542G > T (p.C181F) apparently mutation in the TSPAN12 gene that segregated with the ocular disease in the family. The TSPAN12 gene was previously reported to cause dominant and recessive FEVR, but has not yet been associated with other vitreoretinal manifestations. The intra-familial clinical variability caused by a single mutation in the TSPAN12 gene underscores the complicated phenotype-genotype correlation of mutations in this gene, and suggests that there are additional genetic and environmental factors involved in the complex process of ocular vascularization during embryonic development. Our study supports considering PFV, FEVR, and Norrie disease a spectrum of disorders, with clinical and genetic overlap, caused by mutations in distinct genes acting in the Norrin/β-catenin signaling pathway. PMID:25250762

  16. Homozygosity Mapping and Targeted Sanger Sequencing Reveal Genetic Defects Underlying Inherited Retinal Disease in Families from Pakistan

    PubMed Central

    Waheed, Nadia Khalida; Siddiqui, Sorath Noorani; Mustafa, Bilal; Ayub, Humaira; Ali, Liaqat; Ahmad, Shakeel; Micheal, Shazia; Hussain, Alamdar; Shah, Syed Tahir Abbas; Ali, Syeda Hafiza Benish; Ahmed, Waqas; Khan, Yar Muhammad; den Hollander, Anneke I.; Haer-Wigman, Lonneke; Collin, Rob W. J.; Khan, Muhammad Imran; Qamar, Raheel; Cremers, Frans P. M.

    2015-01-01

    Background Homozygosity mapping has facilitated the identification of the genetic causes underlying inherited diseases, particularly in consanguineous families with multiple affected individuals. This knowledge has also resulted in a mutation dataset that can be used in a cost and time effective manner to screen frequent population-specific genetic variations associated with diseases such as inherited retinal disease (IRD). Methods We genetically screened 13 families from a cohort of 81 Pakistani IRD families diagnosed with Leber congenital amaurosis (LCA), retinitis pigmentosa (RP), congenital stationary night blindness (CSNB), or cone dystrophy (CD). We employed genome-wide single nucleotide polymorphism (SNP) array analysis to identify homozygous regions shared by affected individuals and performed Sanger sequencing of IRD-associated genes located in the sizeable homozygous regions. In addition, based on population specific mutation data we performed targeted Sanger sequencing (TSS) of frequent variants in AIPL1, CEP290, CRB1, GUCY2D, LCA5, RPGRIP1 and TULP1, in probands from 28 LCA families. Results Homozygosity mapping and Sanger sequencing of IRD-associated genes revealed the underlying mutations in 10 families. TSS revealed causative variants in three families. In these 13 families four novel mutations were identified in CNGA1, CNGB1, GUCY2D, and RPGRIP1. Conclusions Homozygosity mapping and TSS revealed the underlying genetic cause in 13 IRD families, which is useful for genetic counseling as well as therapeutic interventions that are likely to become available in the near future. PMID:25775262

  17. Chronic granulomatous disease with unusual clinical manifestation, outcome, and pattern of inheritance in an Iranian family.

    PubMed

    Tafti, Saeed F; Tabarsi, Payam; Mansouri, Nahal; Mirsaeidi, Mehdi; Motazedi Ghajar, Mohamad A; Karimi, Shirin; Najar, Hossain M; Mansouri, Davood

    2006-05-01

    CGD is a rare phagocytic disorder manifesting as recurrent, severe bacterial and fungal infections. We describe an Iranian family with eight children, of whom six, five males and one female were diagnosed with CGD resulting in diffuse pulmonary sterile granulomatous lesions. Three died despite multiple courses of antibiotic and antituberculosis medications while three are alive, to date they are asymptomatic but with imaging and pathologic findings of pulmonary granulomatosis, treated with steroids. The parents are healthy. Our report describes the clinical manifestations and outcome in this family. The inheritance pattern suggests an autosomal recessive pattern with high penetrance. PMID:16783468

  18. 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

  19. 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

  20. Management of skin disease in patients with lupus erythematosus.

    PubMed

    Callen, Jeffrey P

    2002-04-01

    Skin disease in patients with lupus erythematosus may be subdivided into two broad categories - those represented by a 'specific' histopathology, the interface dermatitis, and those with changes that are not specific to lupus erythematosus, for example, vasculitis, mucin infiltration, etc. The specific skin lesions that are most common are discoid lupus erythematosus (DLE) and subacute cutaneous lupus erythematosus (SCLE). Evaluation will allow the treating physician to assign a prognosis. Cutaneous lesions can generally be managed with standard therapies. Patients with discoid LE and subacute cutaneous LE are generally photosensitive, and therefore sunscreens, protective clothing and behavioural alteration should be discussed with all patients. Topical corticosteroids are a standard form of therapy, but 'newer' agents such as retinoids, calcipotriene and tacrolimus might be effective. Antimalarial agents are generally effective. Attempts to reduce or stop smoking may aid in the control of cutaneous LE. The choice of alternative therapy is personal, and discussions of the risks and benefits should be carefully documented. PMID:12041952

  1. Drug treatments for skin disease introduced in 2007.

    PubMed

    2008-03-01

    A comprehensive list of drug treatments for skin disease including: Adapalene Gel 0.3% (Differin(R)), Drospirenone/ Ethinyl Estradiol (Yaz(R)), Tretinoin 0.05% Gel (Anthralin(R)), Daptomycin for Injection (CUBICIN(R)), Retapamulin Ointment 1% (Altabax(R)), Tinidazole Tablets (Tindamax(R)), Ciclopirox Topical Solution 8%, Ketoconazole 2% Foam (Extina(R)), Terbinafine Hydrochloride (Lamisil(R)), Desloratadine (Aerius(R)/ Azomyr(R)/ Neoclarityn(R)), Levocetirizine Dihydrochloride (Xyzal(R)), Loratadine Dry Syrup 1% (Claritin(R)) and many other treatments introduced in 2007. PMID:18373042

  2. 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

  3. 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

  4. Inheritance of rainbow trout Oncorhynchus mykiss spleen size and correlation with bacterial cold water disease resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Infectious disease causes substantial loss in aquaculture and selective breeding for increased innate resistance offers an attractive strategy for controlling disease. In 2005, the NCCCWA implemented a selective breeding program to increase rainbow trout survival following challenge with Flavobacte...

  5. Evidence of major genes for resistance to bacterial cold-water disease in rainbow trout using mixed inheritance multiple-threshold models and Bayesian segregation analysis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    PURPOSE: Bacterial cold water disease (BCWD) causes significant economic loss in salmonid aquaculture, and in 2005, a rainbow trout breeding program was initiated at the NCCCWA to select for increased disease survival. The main objectives of this study were to determine the mode of inheritance of di...

  6. '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

  7. Evidence for major gene inheritance of Alzheimer disease in families of patients with and without apolipoprotein E epsilon 4.

    PubMed Central

    Rao, V. S.; Cupples, A.; van Duijn, C. M.; Kurz, A.; Green, R. C.; Chui, H.; Duara, R.; Auerbach, S. A.; Volicer, L.; Wells, J.; van Broeckhoven, C.; Growdon, J. H.; Haines, J. L.; Farrer, L. A.

    1996-01-01

    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 epsilon 4, 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. PMID:8751868

  8. 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.

  9. The role of ion-regulatory membrane proteins of excitation-contraction coupling and relaxation in inherited muscle diseases.

    PubMed

    Froemming, G R; Ohlendieck, K

    2001-01-01

    The excitation-contraction-relaxation cycle of skeletal muscle fibres depends on the finely tuned interplay between the voltage-sensing dihydropyridine receptor, the junctional ryanodine receptor Ca2+-release channel and the sarcoplasmic reticulum Ca2+-ATPase. Inherited diseases of excitation-contraction coupling and muscle relaxation such as malignant hyperthermia, central core disease, hypokalemic periodic paralysis or Brody disease are caused by mutations in these Ca2+-regulatory elements. Over twenty different mutations in the Ca2+-release channel are associated with susceptibility to the pharmacogenetic disorder malignant hyperthermia. Other mutations in the ryanodine receptor trigger central core disease. Primary abnormalities in the alpha-1 subunit of the dihydropyridine receptor underlie the molecular pathogenesis of both hypokalemic periodic paralysis and certain forms of malignant hyperthermia. Some cases of the muscle relaxation disorder named Brody disease were demonstrated to be based on primary abnormalities in the Ca2+-ATPase. Since a variety of other sarcoplasmic reticulum proteins modulate the activity of the voltage sensor, Ca2+-release channel and ion-binding proteins, mutations in these Ca2+-regulatory muscle components might be the underlying cause for novel, not yet fully characterized, genetic muscle disorders. The cell biological analysis of knock-out mice has been helpful in evaluating the biomedical consequences of defects in ion-regulatory muscle proteins. PMID:11145921

  10. 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

  11. [Inherited GPI deficiencies:a new disease with intellectual disability and epilepsy].

    PubMed

    Murakami, Yoshiko; Kinoshita, Taroh

    2015-01-01

    Glycosylphosphatidylinositol (GPI) is a glycolipid, which anchors 150 or more types of proteins to the cell surface. There are at least 26 genes involved in the biosynthesis and transport of GPI-anchored proteins (GPI-APs). Many inherited GPI deficiencies (IGDs) have been recently found using whole-exome sequencing. Patients with IGD have only a partial deficiency because complete GPI deficiency causes embryonic death. The major symptoms of IGDs include intellectual disability, epilepsy, coarse facial features, and multiple organ anomalies. These symptoms vary in severity depending upon the degree of the defect and/or position in the pathway of the affected gene. We clarified a mechanism of hyperphosphatasia, which is characterized by elevated release of tissue-nonspecific alkaline phosphatase. Hyperphosphatasia is observed in some patients with IGDs, such as hyperphosphatasia mental retardation syndrome or Mabry syndrome, caused by mutations in genes in the later stage of GPI biosynthesis. The possibility of IGD should be considered in patients with seizures and intellectual disability. The presence of hyperphosphatasia is strong evidence of IGD. Flow cytometric analysis of GPI-APs on granulocytes is also useful for the detection of IGD. PMID:25803904

  12. 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

  13. INHERITANCE OF RESISTANCE TO RATOON STUNTING DISEASE AND IMPLICATIONS FOR SELECTIN IN FLORIDA

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ratoon Stunting Disease (RSD) (caused by Leifsonia xyli subsp. xyli (Davis et al.) Evtushenko et al.) may impart major economic yield losses in sugarcane, particularly in ratoon crops. Although control may be obtained by mechanical sanitation and the use of disease-free seed-cane, genetic resistance...

  14. 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

  15. 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

  16. 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

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and 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...

  17. 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

  18. INHERITANCE OF RESISTANCE IN STRAWBERRY TO BACTERIAL ANGUALAR LEAFSOPT DISEASE CAUSED BY XANTHOMONAS FRAGARIAE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bacterial angular leafspot disease (Xanthomonas fragariae Kennedy and King) of strawberry (Fragaria species and F. × ananassa Duch. cultivars) has become increasingly important to strawberry fruit and plant production. Strawberry cultivars and species vary in susceptibility to infection. However, ...

  19. 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. PMID:26683869

  20. Concise Review: Patient-Specific Stem Cells to Interrogate Inherited Eye Disease

    PubMed Central

    Giacalone, Joseph C.; Wiley, Luke A.; Burnight, Erin R.; Songstad, Allison E.; Mullins, Robert F.; Stone, Edwin M.

    2016-01-01

    Whether we are driving to work or spending time with loved ones, we depend on our sense of vision to interact with the world around us. Therefore, it is understandable why blindness for many is feared above death itself. Heritable diseases of the retina, such as glaucoma, age-related macular degeneration, and retinitis pigmentosa, are major causes of blindness worldwide. The recent success of gene augmentation trials for the treatment of RPE65-associated Leber congenital amaurosis has underscored the need for model systems that accurately recapitulate disease. With the advent of patient-specific induced pluripotent stem cells (iPSCs), researchers are now able to obtain disease-specific cell types that would otherwise be unavailable for molecular analysis. In the present review, we discuss how the iPSC technology is being used to confirm the pathogenesis of novel genetic variants, interrogate the pathophysiology of disease, and accelerate the development of patient-centered treatments. Significance Stem cell technology has created the opportunity to advance treatments for multiple forms of blindness. Researchers are now able to use a person’s cells to generate tissues found in the eye. This technology can be used to elucidate the genetic causes of disease and develop treatment strategies. In the present review, how stem cell technology is being used to interrogate the pathophysiology of eye disease and accelerate the development of patient-centered treatments is discussed. PMID:26683869

  1. Biology and therapy of inherited retinal degenerative disease: insights from mouse models

    PubMed 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

  2. Evidence for an Inherited Predisposition Contributing to the Risk for Rotator Cuff Disease

    PubMed Central

    Tashjian, Robert Z.; Farnham, James M.; Albright, Frederick S.; Teerlink, Craig C.; Cannon-Albright, Lisa A.

    2009-01-01

    Background: A genetic predisposition has been suggested to contribute to the risk for development of rotator cuff disease on the basis of observed family clusters of close relatives. We used a population-based resource combining genealogical data for Utah with clinical diagnosis data from a large Utah hospital to test the hypothesis of excess familial clustering for rotator cuff disease. Methods: The Utah Population Database contains combined health and genealogical data on over two million Utah residents. Current Procedural Terminology, Fourth Revision, codes (29827, 23412, 23410, and 23420) and International Classification of Diseases, Ninth Revision, codes (726.1, 727.61, and 840.4) entered in patient records were used to identify patients with rotator cuff disease. We tested the hypothesis of excess familial clustering using two well-established methods (the Genealogical Index of Familiality test and the estimation of relative risks in relatives) in the overall study group (3091 patients) and a subgroup of the study group diagnosed before the age of forty years (652 patients). Results: The Genealogical Index of Familiality test in patients diagnosed before the age of forty years showed significant excess relatedness for individuals with rotator cuff disease in close and distant relationships (as distant as third cousins) (p = 0.001). The relative risk of rotator cuff disease in the relatives of patients diagnosed before the age of forty years was significantly elevated for second degree (relative risk = 3.66, p = 0.0076) and third degree (relative risk = 1.81, p = 0.0479) relatives. Conclusions: We analyzed a set of patients with diagnosed rotator cuff disease and a known genealogy to describe the familial clustering of affected individuals. The observations of significant excess relatedness of patients and the significantly elevated risks to both close and distant relatives of patients strongly support a heritable predisposition to rotator cuff disease

  3. 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

  4. Biomedical genetics of the inherited metabolic diseases: the GM2-gangliosidoses.

    PubMed

    Kolodny, E H

    1984-03-01

    Many of the known gene defects result in inborn errors of metabolism that produce irreversible damage to the central nervous system. A variety of new clinical, morphologic, biochemical, and genetic techniques are being used to characterize these disorders more precisely. At the Shriver Center, the different genotypes of GM2-gangliosidosis are distinguished according to the ability of cells in culture to metabolize radioactively-labeled GM2-ganglioside. Large-scale screening for carriers of the trait for Tay-Sachs disease, the most common of the GM2-gangliosidoses, has dramatically reduced the incidence of this disease. Current efforts to isolate the genes for the alpha and beta chains of hexosaminidase A will lay the groundwork for better understanding of the molecular defects in these diseases and offers hope for a possible treatment. PMID:6428229

  5. Functional imaging of inherited retinal disease with a commercial optical coherence tomography device

    NASA Astrophysics Data System (ADS)

    Theelen, T.; Hoyng, C. B.; Klevering, B. J.; Cense, B.

    2011-06-01

    Retinal dystrophies (RD) are blinding diseases affecting visual acuity mostly at young age. Intrinsic optical signals (IOS) on optical coherence tomography (OCT) may give topographical information on injure of retinal function in these patients. We demonstrate light response of the healthy and diseased human retina by IOS on a commercially available spectral-domain OCT. Significant IOS could be measured in the healthy retina and in unchanged retinal sectors of the RD patients. Main responses were located in the outer retina (photoreceptors) and the nerve fiber layer. In affected areas of RD eyes IOS were significantly reduced or even absent. Functional OCT imaging was able to give information about retinal function in RD patients on a micrometer scale. These results could be of value for refined disease analysis and control of upcoming gene therapy studies.

  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. 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

  8. Molecular and Bioenergetic Differences between Cells with African versus European Inherited Mitochondrial DNA Haplogroups: Implications for Population Susceptibility to Diseases

    PubMed Central

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

    2015-01-01

    The geographic origins of populations can be identified by their maternally inherited mitochondrial DNA (mtDNA) haplogroups. This study compared human cybrids (cytoplasmic hybrids), which are cell lines with identical nuclei but mitochondria from different individuals with mtDNA from either the H haplogroup or L haplogroup backgrounds. The most common European haplogroup is H while individuals of maternal African origin are of the L haplogroup. Despite lower mtDNA copy numbers, L cybrids had higher expression levels for nine mtDNA-encoded respiratory complex genes, decreased ATP turnover rates and lower levels of ROS production, parameters which are consistent with more efficient oxidative phosphorylation. Surprisingly, GeneChip arrays showed that the L and H cybrids had major differences in expression of genes of the canonical complement system (5 genes), dermatan/chondroitin sulfate biosynthesis (5 genes) and CCR3 signaling (9 genes). Quantitative nuclear gene expression studies confirmed that L cybrids had (a) lower expression levels of complement pathway and innate immunity genes and (b) increased levels of inflammation-related signaling genes, which are critical in human diseases. Our data support the hypothesis that mtDNA haplogroups representing populations from different geographic origins may play a role in differential susceptibilities to diseases. PMID:24200652

  9. Inheritance of resistance to Okra yellow vein mosaic disease in interspecific crosses of Abelmoschus.

    PubMed

    Jambhale, N D; Nerkar, Y S

    1981-09-01

    Two Abelmoschus species, viz., A. manihot (L.) Medik and A. manihot (L.) Medik ssp. manihot, resistant to Okra yellow vein mosaic (YVM) were crossed to A. esculentus cv. 'Pusa Sawani', a susceptible culture. The hybrids were resistant and partially fertile. Segregation pattern for disease reaction in F2, BC1 and subsequent generations of the two crosses revealed that resistance to YVM is controlled by a single dominant gene in each species. PMID:24276872

  10. 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

  11. iPS cell modeling of Best disease: insights into the pathophysiology of an inherited macular degeneration

    PubMed Central

    Singh, Ruchira; Shen, Wei; Kuai, David; Martin, Jessica M.; Guo, Xiangrong; Smith, Molly A.; Perez, Enio T.; Phillips, M. Joseph; Simonett, Joseph M.; Wallace, Kyle A.; Verhoeven, Amelia D.; Capowski, Elizabeth E.; Zhang, Xiaoqing; Yin, Yingnan; Halbach, Patrick J.; Fishman, Gerald A.; Wright, Lynda S.; Pattnaik, Bikash R.; Gamm, David M.

    2013-01-01

    Best disease (BD) is an inherited degenerative disease of the human macula that results in progressive and irreversible central vision loss. It is caused by mutations in the retinal pigment epithelium (RPE) gene BESTROPHIN1 (BEST1), which, through mechanism(s) that remain unclear, lead to the accumulation of subretinal fluid and autofluorescent waste products from shed photoreceptor outer segments (POSs). We employed human iPS cell (hiPSC) technology to generate RPE from BD patients and unaffected siblings in order to examine the cellular and molecular processes underlying this disease. Consistent with the clinical phenotype of BD, RPE from mutant hiPSCs displayed disrupted fluid flux and increased accrual of autofluorescent material after long-term POS feeding when compared with hiPSC-RPE from unaffected siblings. On a molecular level, RHODOPSIN degradation after POS feeding was delayed in BD hiPSC-RPE relative to unaffected sibling hiPSC-RPE, directly implicating impaired POS handling in the pathophysiology of the disease. In addition, stimulated calcium responses differed between BD and normal sibling hiPSC-RPE, as did oxidative stress levels after chronic POS feeding. Subcellular localization, fractionation and co-immunoprecipitation experiments in hiPSC-RPE and human prenatal RPE further linked BEST1 to the regulation and release of endoplasmic reticulum calcium stores. Since calcium signaling and oxidative stress are critical regulators of fluid flow and protein degradation, these findings likely contribute to the clinical picture of BD. In a larger context, this report demonstrates the potential to use patient-specific hiPSCs to model and study maculopathies, an important class of blinding disorders in humans. PMID:23139242

  12. iPS cell modeling of Best disease: insights into the pathophysiology of an inherited macular degeneration.

    PubMed

    Singh, Ruchira; Shen, Wei; Kuai, David; Martin, Jessica M; Guo, Xiangrong; Smith, Molly A; Perez, Enio T; Phillips, M Joseph; Simonett, Joseph M; Wallace, Kyle A; Verhoeven, Amelia D; Capowski, Elizabeth E; Zhang, Xiaoqing; Yin, Yingnan; Halbach, Patrick J; Fishman, Gerald A; Wright, Lynda S; Pattnaik, Bikash R; Gamm, David M

    2013-02-01

    Best disease (BD) is an inherited degenerative disease of the human macula that results in progressive and irreversible central vision loss. It is caused by mutations in the retinal pigment epithelium (RPE) gene BESTROPHIN1 (BEST1), which, through mechanism(s) that remain unclear, lead to the accumulation of subretinal fluid and autofluorescent waste products from shed photoreceptor outer segments (POSs). We employed human iPS cell (hiPSC) technology to generate RPE from BD patients and unaffected siblings in order to examine the cellular and molecular processes underlying this disease. Consistent with the clinical phenotype of BD, RPE from mutant hiPSCs displayed disrupted fluid flux and increased accrual of autofluorescent material after long-term POS feeding when compared with hiPSC-RPE from unaffected siblings. On a molecular level, RHODOPSIN degradation after POS feeding was delayed in BD hiPSC-RPE relative to unaffected sibling hiPSC-RPE, directly implicating impaired POS handling in the pathophysiology of the disease. In addition, stimulated calcium responses differed between BD and normal sibling hiPSC-RPE, as did oxidative stress levels after chronic POS feeding. Subcellular localization, fractionation and co-immunoprecipitation experiments in hiPSC-RPE and human prenatal RPE further linked BEST1 to the regulation and release of endoplasmic reticulum calcium stores. Since calcium signaling and oxidative stress are critical regulators of fluid flow and protein degradation, these findings likely contribute to the clinical picture of BD. In a larger context, this report demonstrates the potential to use patient-specific hiPSCs to model and study maculopathies, an important class of blinding disorders in humans. PMID:23139242

  13. 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

  14. 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.

  15. 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

  16. MND2: A new mouse model of inherited motor neuron disease

    SciTech Connect

    Jones, J.M.; Albin, R.L.; Feldman, E.L.; Simin, K.; Schuster, T.G.; Dunnick, W.A.; Collins, J.T.; Chrisp, C.E.; Meisler, M.H. ); Taylor, B.A. )

    1993-06-01

    The autosomal recessive mutation mnd2 results in early onset motor neuron disease with rapidly progressive paralysis, severe muscle wasting, regression of thymus and spleen, and death before 40 days of age. mnd2 has been mapped to mouse chromosome 6 with the gene order: centromere-Tcrb-Ly-2-Sftp-3-D6Mit4-mnd2-D6Mit6, D6Mit9-D6Rck132-Raf-1, D6Mit11-D6Mit12-D6Mit14. mnd2 is located within a conserved linkage group with homologs on human chromosome 2p12-p13. Spinal motor neurons of homozygous affected animals are swollen and stain weakly, and electromyography revealed spontaneous activity characteristic of muscle denervation. Myelin staining was normal throughout the neuraxis. The clinical observations are consistent with a primary abnormality of lower motor neuron function. This new animal model will be of value for identification of a genetic defect responsible for motor neuron disease and for evaluation of new therapies. 36 refs., 7 figs., 2 tabs.

  17. Prominent scapulae mimicking an inherited myopathy expands the phenotype of CHD7-related disease.

    PubMed

    O'Grady, Gina L; Ma, Alan; Sival, Deborah; Wong, Monica T Y; Peduto, Tony; Menezes, Manoj P; Young, Helen; Waddell, Leigh; Ghaoui, Roula; Needham, Merrilee; Lek, Monkol; North, Kathryn N; MacArthur, Daniel G; van Ravenswaaij-Arts, Conny Ma; Clarke, Nigel F

    2016-08-01

    CHD7 variants are a well-established cause of CHARGE syndrome, a disabling multi-system malformation disorder that is often associated with deafness, visual impairment and intellectual disability. Less severe forms of CHD7-related disease are known to exist, but the full spectrum of phenotypes remains uncertain. We identified a de novo missense variant in CHD7 in a family presenting with musculoskeletal abnormalities as the main manifestation of CHD7-related disease, representing a new phenotype. The proband presented with prominent scapulae, mild shoulder girdle weakness and only subtle dysmorphic features. Investigation revealed hypoplasia of the trapezius and sternocleidomastoid muscles and semicircular canal defects, but he did not fulfill diagnostic criteria for CHARGE syndrome. Although the shoulders are often sloping and anteverted in CHARGE syndrome, the underlying neuromuscular cause has never been investigated. This report expands the phenotypes associated with CHD7 mutations to include a musculoskeletal presentation, with hypoplasia of the shoulder and neck muscles. CHD7 should be considered in patients presenting in childhood with stable scapular winging, particularly if accompanied by dysmorphic features and balance difficulties. PMID:26813943

  18. 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

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and 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....

  19. 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

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and 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,...

  20. 78 FR 17679 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-22

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and 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...

  1. 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

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and 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,...

  2. 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

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and 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....

  3. 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

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and 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...

  4. 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

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and 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,...

  5. 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

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and 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,...

  6. 77 FR 16246 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-20

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and 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...

  7. 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

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and 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...

  8. 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

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and 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...

  9. 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

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and 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...

  10. 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

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and 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,...

  11. 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

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and 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...

  12. 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

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and 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,...

  13. 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

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and 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,...

  14. 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

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and 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...

  15. 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

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and 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...

  16. 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

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the Federal Advisory Committee... Musculoskeletal and Skin Diseases Special Emphasis Panel; Program Project Grant Review. Date: June 13, 2012....

  17. 76 FR 40385 - National Institute of Arthritis and Musculoskeletal and Skin Diseases Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-08

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and 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...

  18. 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

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and 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,...

  19. 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

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and 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,...

  20. 76 FR 55399 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-07

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and 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,...

  1. 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

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and 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,...

  2. 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

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and 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...

  3. 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

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and 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,...

  4. 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

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and 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,...

  5. 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…

  6. 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

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and 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...

  7. 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

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and 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,...

  8. 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

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and 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....

  9. 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

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and 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...

  10. 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

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and 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....

  11. 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

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and 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:...

  12. 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

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and 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....

  13. 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

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and 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....

  14. 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

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and 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...

  15. 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

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and 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...

  16. 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

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and 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....

  17. 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

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and 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...

  18. 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

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and 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,...

  19. 76 FR 35225 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-16

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and 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:...

  20. 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

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and 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...

  1. 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

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and 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,...

  2. 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

    ... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and 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...

  3. 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

  4. Application of next generation sequencing to molecular diagnosis of inherited diseases.

    PubMed

    Zhang, Wei; Cui, Hong; Wong, Lee-Jun C

    2014-01-01

    Recent development of high throughput, massively parallel sequencing (MPS or next generation sequencing, NGS) technology has revolutionized the molecular diagnosis of human genetic disease. The ability to generate enormous amount of sequence data in a short time at an affordable cost makes this approach ideal for a wide range of applications from sequencing a group of candidate genes, all coding regions (known as exome sequencing) to the entire human genome. The technology brings about an unprecedented application to the identification of the molecular basis of hard-to-diagnose genetic disorders. This chapter reviews the up-to-date published application of next generation sequencing in clinical molecular diagnostic laboratories. We also emphasize the various target gene enrichment methods and their advantages and shortcomings. Obstacles to compliance with regulatory authorities like CLIA/CAP in clinical settings are also briefly discussed. PMID:22576358

  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. 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

  7. The use of reflectance confocal microscopy in selected inflammatory skin diseases.

    PubMed

    Białek-Galas, Kamila; Wielowieyska-Szybińska, Dorota; Dyduch, Grzegorz; Wojas-Pelc, Anna

    2015-06-01

    Reflectance confocal microscopy is a modern, non-invasive diagnostic method that enables real-time imaging of the epidermis and upper layers of the dermis with nearly histological precision and high contrast. The application of this technology to skin imaging during the last years has resulted in progress of dermatological diagnosis, providing virtual access to living skin, without the need for conventional histopathology. The presented method potentially has broad application in the diagnosis of skin diseases. This article provides a summary of the latest reports and previous achievements in the field of reflectance confocal microscopy. General characteristics of confocal images in selected inflammatory skin diseases are presented. PMID:26247522

  8. Seminal transmission of lumpy skin disease virus in heifers.

    PubMed

    Annandale, C H; Holm, D E; Ebersohn, K; Venter, E H

    2014-10-01

    It is known that lumpy skin disease virus (LSDV) can be shed in bull semen following infection and also that artificial insemination (AI) poses a biosecurity risk. However, it is not known whether the use of LSDV infected semen in AI poses a biosecurity risk. The aim of this study was to investigate whether LSDV, transmitted through semen, can infect cows and their embryos. Two controlled trials were performed simultaneously. Eleven young beef heifers, naïve to LSDV, were synchronized using an OvSynch protocol and inseminated on Day 0 with fresh semen spiked with a field strain of LSDV on day 0. Six of the heifers were superovulated on Day 1 using pregnant mare serum gonadotropin, and embryos were flushed from these heifers on Day 6. Blood and serum samples were collected from Day 4 until Day 27 to determine the presence of LSDV by PCR and virus isolation, and the presence of antibodies against LSDV by SNT. The first clinical signs of LSD were noticed on Day 10, followed by severe generalized LSD in three heifers and mild LSD in two more heifers. Two heifers were humanely euthanized due to severe unresponsive stranguria. LSDV was detected by PCR, virus isolation or electron microscopy in blood, embryos and organs of experimentally infected animals; and eight heifers had seroconverted by Day 27. Two control animals were not affected. This is the first report of experimental seminal transmission of LSDV in cattle. PMID:23289592

  9. 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

  10. Toward the molecular basis of inherited prion diseases: NMR structure of the human prion protein with V210I mutation.

    PubMed

    Biljan, Ivana; Ilc, Gregor; Giachin, Gabriele; Raspadori, Andrea; Zhukov, Igor; Plavec, Janez; Legname, Giuseppe

    2011-09-30

    The development of transmissible spongiform encephalopathies (TSEs) is associated with the conversion of the cellular prion protein (PrP(C)) into a misfolded, pathogenic isoform (PrP(Sc)). Spontaneous generation of PrP(Sc) in inherited forms of disease is caused by mutations in gene coding for PrP (PRNP). In this work, we describe the NMR solution-state structure of the truncated recombinant human PrP (HuPrP) carrying the pathological V210I mutation linked to genetic Creutzfeldt-Jakob disease. The three-dimensional structure of V210I mutant consists of an unstructured N-terminal part (residues 90-124) and a well-defined C-terminal domain (residues 125-228). The C-terminal domain contains three α-helices (residues 144-156, 170-194 and 200-228) and a short antiparallel β-sheet (residues 129-130 and 162-163). Comparison with the structure of the wild-type HuPrP revealed that although two structures share similar global architecture, mutation introduces some local structural differences. The observed variations are mostly clustered in the α(2)-α(3) inter-helical interface and in the β(2)-α(2) loop region. Introduction of bulkier Ile at position 210 induces reorientations of several residues that are part of hydrophobic core, thus influencing α(2)-α(3) inter-helical interactions. Another important structural feature involves the alteration of conformation of the β(2)-α(2) loop region and the subsequent exposure of hydrophobic cluster to solvent, which facilitates intermolecular interactions involved in spontaneous generation of PrP(Sc). The NMR structure of V210I mutant offers new clues about the earliest events of the pathogenic conversion process that could be used for the development of antiprion drugs. PMID:21839748

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

    PubMed Central

    Dillon, Michael B.

    2011-01-01

    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. PMID:21450741

  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. Redox Imbalance in T Cell-Mediated Skin Diseases

    PubMed Central

    Pastore, Saveria; Korkina, Liudmila

    2010-01-01

    The skin is permanently exposed to physical, chemical, and biological aggression by the environment. In addition, acute and chronic inflammatory events taking place in the skin are accompanied by abnormal release of pro-oxidative mediators. In this paper, we will briefly overview the homeostatic systems active in the skin to maintain the redox balance and also to counteract abnormal oxidative stress. We will concentrate on the evidence that a local and/or systemic redox dysregulation accompanies the chronic inflammatory disorder events associated to psoriasis, contact dermatitis, and atopic dermatitis. We will also discuss the fact that several well-established treatments for the therapy of chronic inflammatory skin disorders are based on the application of strong physical or chemical oxidants onto the skin, indicating that, in selected conditions, a further increase of the oxidative imbalance may lead to a beneficial outcome. PMID:20847812

  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. PMID:24878038

  16. 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

  17. 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.

  18. 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

  19. Skin microbiota: Microbial community structure and its potential association with health and disease

    PubMed Central

    Rosenthal, Mariana; Goldberg, Deborah; Aiello, Allison; Larson, Elaine; Foxman, Betsy

    2011-01-01

    Skin, the largest human organ, is a complex and dynamic ecosystem inhabited by a multitude of microorganisms. Host demographics and genetics, human behavior, local and regional environmental characteristics, and transmission events may all potentially drive human skin microbiota variability, resulting in an alteration of microbial community structure. This alteration may have important consequences regarding health and disease outcomes among individuals. More specifically, certain diversity patterns of human microbiota may be predictive or diagnostic of disease. The purpose of this review is to briefly describe the skin microbiota, outline the potential determining factors driving its variability, posit the likelihood of an association between the resulting microbial community structure on the skin with disease outcomes among individuals, and finally, to present some challenges and implications for studying the skin microbiota. PMID:21463709

  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. Immunohistochemical detection of 4-hydroxy-2-nonenal adducts in Alzheimer's disease is associated with inheritance of APOE4.

    PubMed Central

    Montine, K. S.; Olson, S. J.; Amarnath, V.; Whetsell, W. O.; Graham, D. G.; Montine, T. J.

    1997-01-01

    Cumulative oxidative damage, including lipid peroxidation, is a central component of cellular aging and is thought to play a role in the pathogenesis of late-onset Alzheimer's disease (AD). Lipid peroxidation produces several cytotoxic aldehydes, one of the most potent being 4-hydroxy-2-nonenal (HNE). We have shown previously that HNE is a potent neurotoxin that covalently modifies and cross-links neuronal cytoskeletal protein in neuroglial cultures, suggesting that HNE may contribute to the pathogenesis of AD. In addition to aging, inheritance of the epsilon 4 allele of APOE is the other major risk factor for development of late-onset AD; however, the mechanisms through which aging and apolipoprotein E isoforms may collaborate in the onset or progression of AD are not known. We tested the hypothesis that HNE may yield a particular type of protein modification, pyrrole adduction, and that this may contribute to the pathogenesis of AD. Our data demonstrated that HNE formed pyrrole adducts with protein. Polyclonal antiserum was raised that specifically recognized HNE pyrrole adducts, and immunohistochemical analysis was performed on hippocampus and temporal cortex of 10 patients with histologically verified AD. Pyramidal neuron cytoplasm was immunoreactive in 4 of 4 APOE4 homozygotes, 2 of 3 APOE3/4 heterozygotes, and none of 3 APOE3 homozygotes (P < 0.05). The pattern of staining was highly suggestive of neurofibrillary tangles as the primary immunoreactive structure. These data suggest that differences in neuronal protein modification by HNE may account in part for the APOE-associated stratification of risk for late-onset AD. Images Figure 2 PMID:9033259

  2. 77 FR 61011 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

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  10. 78 FR 64509 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

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  16. 77 FR 35988 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

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  17. 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

  18. 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. PMID:24148185

  19. Gaucher disease due to saposin C deficiency is an inherited lysosomal disease caused by rapidly degraded mutant proteins.

    PubMed

    Motta, Marialetizia; Camerini, Serena; Tatti, Massimo; Casella, Marialuisa; Torreri, Paola; Crescenzi, Marco; Tartaglia, Marco; Salvioli, Rosa

    2014-11-01

    Saposin (Sap) C is an essential cofactor for the lysosomal degradation of glucosylceramide (GC) by glucosylceramidase (GCase) and its functional impairment underlies a rare variant form of Gaucher disease (GD). Sap C promotes rearrangement of lipid organization in lysosomal membranes favoring substrate accessibility to GCase. It is characterized by six invariantly conserved cysteine residues involved in three intramolecular disulfide bonds, which make the protein remarkably stable to acid environment and degradation. Five different mutations (i.e. p.C315S, p.342_348FDKMCSKdel, p.L349P, p.C382G and p.C382F) have been identified to underlie Sap C deficiency. The molecular mechanism by which these mutations affect Sap C function, however, has not been delineated in detail. Here, we characterized biochemically and functionally four of these gene lesions. We show that all Sap C mutants are efficiently produced, and exhibit lipid-binding properties, modulatory behavior on GCase activity and subcellular localization comparable with those of the wild-type protein. We then delineated the structural rearrangement of these mutants, documenting that most proteins assume diverse aberrant disulfide bridge arrangements, which result in a substantial diminished half-life, and rapid degradation via autophagy. These findings further document the paramount importance of disulfide bridges in the stability of Sap C and provide evidence that accelerated degradation of the Sap C mutants is the underlying pathogenetic mechanism of Sap C deficiency. PMID:24925315

  20. Infliximab-induced skin manifestations in patients with inflammatory bowel disease.

    PubMed

    Eligius Hellström, Alec; Färkkilä, Martti; Kolho, Kaija-Leena

    2016-05-01

    Objective The use of infliximab in rheumatoid and inflammatory bowel diseases (IBD) has been associated with a variety of adverse skin reactions, including paradoxical psoriatic lesions. The prevalence and possible predictors for these lesions were under observation in our cross-sectional prospective study. Material and methods Nurses screened the skin of 118 adult patients with IBD during infliximab infusions between 4 September 2013 and 30 September 2014 based on the structured questionnaire. Data on skin manifestations, concomitant medications, extraintestinal manifestations and inflammatory markers were collected for analysis. Results Non-infectious skin manifestations were observed in 27 (22.9%) patients during the study period, of which eight (29.6%) were new-onset, eight (29.6%) were exacerbations of existing lesions and 11 (40.7%) were baseline lesions that did not worsen during the study. Scaling eczema was the most commonly described skin manifestation (n = 8; 29.6%), followed by exacerbated atopic eczema (n = 5; 18.5%) and plausible infliximab-induced psoriasiform lesions (n = 5; 18.5%). The strongest associating factor for skin manifestations was Crohn's disease, in nearly 80% of afflicted patients. Conclusions Anti-TNF-α therapy is frequently associated with newly onset skin reactions, most commonly in patients with Crohn's disease. Non-infectious skin manifestations can be treated topically and do not require cessation of anti-TNF-α therapy. PMID:26728295

  1. Sequence analysis of attachment gene of lumpy skin disease and sheep poxviruses.

    PubMed

    El-Kenawy, A A; El-Tholoth, M S

    2010-12-01

    In Egypt, protection of cattle against lumpy skin disease (LSD) was carried out using a sheep poxvirus (Kenyan strain) vaccination strategy. In the present study 15 skin nodules from LSD suspected cows and 5 scab samples from sheep pox (SP) suspected sheep were collected. Hyperimmune rabbit sera to Lumpy skin disease virus (LSDV)/Ismailyia88 strain and sheep pox virus (SPV)/ Kenyan vaccinal strain were prepared. The causative agent in the collected samples was identified using immunoflourescence (IF) and immunoperoxidase techniques. Of the 15 skin nodules suspected of LSD, 10 showed a positive reaction and 3 out of 5 skin scabs suspected of sheeppox were found to be positive. An antigenic correlation between field skin isolate of LSDV, tissue culture adapted LSDV/Ismailyia88 strain, field skin isolate of SPV and SPV/Kenyan vaccinal strain was studied using prepared hyperimmune sera. Also, nucleotide sequence of the PCR amplified attachment gene fragments of field skin isolate of LSDV, tissue culture adapted LSDV/Ismailyia88 strain, field skin isolate of SPV and SPV /Kenyan vaccinal strain were compared. The results revealed that the four used viruses were antigenically identical. Sequence analysis indicated that field skin LSDV isolate is more related to tissue culture adapted LSDV/Ismailyia88 strain than to vaccinal SPV/ Kenyan strain and the skin isolate of SPV is more closely related to field skin isolate of LSDV than to SPV/Kenyan vaccinal strain. Thus, further study should be applied on the advantage of a LSD vaccine prepared from LSDV in protection of cattle against LSD compared to the commonly used sheep pox vaccine. PMID:21221919

  2. 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

  3. Inherited Pain

    PubMed Central

    Eberhardt, Mirjam; Nakajima, Julika; Klinger, Alexandra B.; Neacsu, Cristian; Hühne, Kathrin; O'Reilly, Andrias O.; Kist, Andreas M.; Lampe, Anne K.; Fischer, Kerstin; Gibson, Jane; Nau, Carla; Winterpacht, Andreas; Lampert, Angelika

    2014-01-01

    Inherited erythromelalgia (IEM) causes debilitating episodic neuropathic pain characterized by burning in the extremities. Inherited “paroxysmal extreme pain disorder” (PEPD) differs in its clinical picture and affects proximal body areas like the rectal, ocular, or jaw regions. Both pain syndromes have been linked to mutations in the voltage-gated sodium channel Nav1.7. Electrophysiological characterization shows that IEM-causing mutations generally enhance activation, whereas mutations leading to PEPD alter fast inactivation. Previously, an A1632E mutation of a patient with overlapping symptoms of IEM and PEPD was reported (Estacion, M., Dib-Hajj, S. D., Benke, P. J., Te Morsche, R. H., Eastman, E. M., Macala, L. J., Drenth, J. P., and Waxman, S. G. (2008) NaV1.7 Gain-of-function mutations as a continuum. A1632E displays physiological changes associated with erythromelalgia and paroxysmal extreme pain disorder mutations and produces symptoms of both disorders. J. Neurosci. 28, 11079–11088), displaying a shift of both activation and fast inactivation. Here, we characterize a new mutation of Nav1.7, A1632T, found in a patient suffering from IEM. Although transfection of A1632T in sensory neurons resulted in hyperexcitability and spontaneous firing of dorsal root ganglia (DRG) neurons, whole-cell patch clamp of transfected HEK cells revealed that Nav1.7 activation was unaltered by the A1632T mutation but that steady-state fast inactivation was shifted to more depolarized potentials. This is a characteristic normally attributed to PEPD-causing mutations. In contrast to the IEM/PEPD crossover mutation A1632E, A1632T failed to slow current decay (i.e. open-state inactivation) and did not increase resurgent currents, which have been suggested to contribute to high-frequency firing in physiological and pathological conditions. Reduced fast inactivation without increased resurgent currents induces symptoms of IEM, not PEPD, in the new Nav1.7 mutation, A1632T

  4. 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

  5. Phosphorylated α-synuclein in skin nerve fibres differentiates Parkinson's disease from multiple system atrophy.

    PubMed

    Zange, Leonora; Noack, Cornelia; Hahn, Katrin; Stenzel, Werner; Lipp, Axel

    2015-08-01

    Deposition of phosphorylated SNCA (also known as α-synuclein) in cutaneous nerve fibres has been shown pre- and post-mortem in Parkinson's disease. Thus far, no pre-mortem studies investigating the presence of phosphorylated SNCA in skin sympathetic nerve fibres of multiple system atrophy, another synucleinopathy, have been conducted. In this in vivo study, skin from the ventral forearm of 10 patients with multiple system atrophy and 10 with Parkinson's disease, together with six control subjects with essential tremor, were examined by immunohistochemistry. Phosphorylated SNCA deposits in skin sympathetic nerve fibres and dermal nerve fibre density were assessed. All patients with Parkinson's disease expressed phosphorylated SNCA in sympathetic skin nerve fibres, correlating with an age-independent denervation of autonomic skin elements. In contrast, no phosphorylated SNCA was found in autonomic skin nerve fibres of patients with multiple system atrophy and essential tremor control subjects. These findings support that phosphorylated SNCA deposition is causative for nerve fibre degeneration in Parkinson's disease. Moreover, pre-mortem investigation of phosphorylated SNCA in cutaneous nerve fibres may prove a relevant and easily conductible diagnostic procedure to differentiate Parkinson's disease from multiple system atrophy. PMID:26017579

  6. Basic mechanisms of monogenic inheritance.

    PubMed

    Ziegler, A

    1999-01-01

    To revive the appreciation of the importance of genetic studies for the understanding of neurologic diseases inherited in a monogenic fashion. After a description of the basic patterns of monogenic inheritance, the importance of linkage studies for the mapping of a disease gene is mentioned. Furthermore, the term linkage disequilibrium is introduced. Finally, several procedures used in current linkage analyses are briefly mentioned, with the aim of identifying the disease gene. The importance of genetic studies of disease families with many members, preferably from isolated surroundings to favor homogeneity, is stressed. However, such analyses can be performed only as a consequence of a close cooperation between clinicians and research scientists. PMID:10446743

  7. Skin-impedance in Fabry Disease: A prospective, controlled, non-randomized clinical study

    PubMed Central

    Gupta, Surya N; Ries, Markus; Murray, Gary J; Quirk, Jane M; Brady, Roscoe O; Lidicker, Jeffrey R; Schiffmann, Raphael; Moore, David F

    2008-01-01

    Background We previously demonstrated improved sweating after enzyme replacement therapy (ERT) in Fabry disease using the thermo-regularity sweat and quantitative sudomotor axon reflex tests. Skin-impedance, a measure skin-moisture (sweating), has been used in the clinical evaluation of burns and pressure ulcers using the portable dynamic dermal impedance monitor (DDIM) system. Methods We compared skin impedance measurements in hemizygous patients with Fabry disease (22 post 3-years of bi-weekly ERT and 5 ERT naive) and 22 healthy controls. Force compensated skin-moisture values were used for statistical analysis. Outcome measures included 1) moisture reading of the 100th repetitive reading, 2) rate of change, 3) average of 60–110th reading and 4) overall average of all readings. Results All outcome measures showed a significant difference in skin-moisture between Fabry patients and control subjects (p < 0.0001). There was no difference between Fabry patients on ERT and patients naïve to ERT. Increased skin-impedance values for the four skin-impedance outcome measures were found in a small number of dermatome test-sites two days post-enzyme infusions. Conclusion The instrument portability, ease of its use, a relatively short time required for the assessment, and the fact that DDIM system was able to detect the difference in skin-moisture renders the instrument a useful clinical tool. PMID:18990229

  8. 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.

  9. 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

  10. Diet and dermatology: the role of dietary intervention in skin disease.

    PubMed

    Katta, Rajani; Desai, Samir P

    2014-07-01

    For decades, it was thought that many common dermatological conditions had no relationship to diet. Studies from recent years, however, have made it clear that diet may influence outcome. In this review, the authors focus on conditions for which the role of diet has traditionally been an underappreciated aspect of therapy. In some cases, dietary interventions may influence the course of the skin disease, as in acne. In others, dietary change may serve as one aspect of prevention, such as in skin cancer and aging of the skin. In others, dermatological disease may be linked to systemic disease, and dietary changes may affect health outcomes, as in psoriasis. Lastly, systemic medications prescribed for dermatological disease, such as steroids, are known to raise the risk of other diseases, and dietary change may reduce this risk. PMID:25053983

  11. 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.

  12. Role of soluble and cell surface molecules in the pathogenesis of autoimmune skin diseases.

    PubMed

    Drosera, M; Facchetti, F; Landolfo, S; Mondini, M; Nyberg, F; Parodi, A; Santoro, A; Zampieri, S; Doria, A

    2006-01-01

    The skin is one of the most commonly involved tissue in rheumatic autoimmune diseases. Different mechanisms are thought to be implicated in the pathogenesis of skin lesions. In genetically predisposed individuals, ultraviolet (UV) light can contribute to the induction of skin lesions via an inflammatory process. UV light promotes the release of cytokines by keratinocytes and the induction of adhesion molecules on the surface of epidermal cells initiating a cascade of inflammatory events and recruiting immunoinflammatory cells into the skin. In this review data regarding the expression of TNF-alpha in lesional skin tissue from subacute cutaneous lupus erythematosus patients and the role of interferons in the pathogenesis of skin manifestations of rheumatic autoimmune diseases are reported. In addition, an overview on the expression of cellular adhesion molecules in these diseases is provided.UV light can also induce apoptosis in keratinocytes. During this cell death several enzymes became activated. Among them, desoxyribonuclease (DNase) is an enzyme involved in degrading DNA during apoptosis. Data regarding the activity of DNAse in patients with cutaneous lupus erythematosus as a possible risk factor for the development of systemic disease are here reported. PMID:16466628

  13. Elafin is a biomarker of graft versus host disease of the skin

    PubMed Central

    Paczesny, Sophie; Braun, Thomas M; Levine, John E; Hogan, Jason; Crawford, Jeffrey; Coffing, Bryan; Olsen, Stephen; Choi, Sung W; Wang, Hong; Faca, Vitor; Pitteri, Sharon; Zhang, Qing; Chin, Alice; Kitko, Carrie; Mineishi, Shin; Yanik, Gregory; Peres, Edward; Hanauer, David; Wang, Ying; Reddy, Pavan; Hanash, Samir; Ferrara, James LM

    2010-01-01

    Graft-versus-host-disease (GVHD), the major complication of allogeneic bone marrow transplantation (BMT), affects the skin, liver and gastrointestinal (GI) tract. There are no plasma biomarkers specific for any acute GVHD target organ. We used a large scale, quantitative proteomic discovery procedure to identify biomarker candidates of skin GVHD and validated the lead candidate, elafin, by ELISA in samples from 492 patients. Elafin was overexpressed in GVHD skin biopsies. Plasma levels of elafin were significantly higher at the onset of skin GVHD, correlated with the eventual maximum grade of GVHD, and were associated with a greater risk of death relative to other known risk factors (hazard ratio of 1.78). We conclude that elafin has significant diagnostic and prognostic value as a biomarker of skin GVHD. PMID:20371463

  14. Elafin is a biomarker of graft-versus-host disease of the skin.

    PubMed

    Paczesny, Sophie; Braun, Thomas M; Levine, John E; Hogan, Jason; Crawford, Jeffrey; Coffing, Bryan; Olsen, Stephen; Choi, Sung W; Wang, Hong; Faca, Vitor; Pitteri, Sharon; Zhang, Qing; Chin, Alice; Kitko, Carrie; Mineishi, Shin; Yanik, Gregory; Peres, Edward; Hanauer, David; Wang, Ying; Reddy, Pavan; Hanash, Samir; Ferrara, James L M

    2010-01-01

    Graft-versus-host disease (GVHD), the major complication of allogeneic bone marrow transplantation, affects the skin, liver, and gastrointestinal tract. There are no plasma biomarkers specific for any acute GVHD target organ. We used a large-scale quantitative proteomic discovery procedure to identify biomarker candidates of skin GVHD and validated the lead candidate, elafin, with enzyme-linked immunosorbent assay in samples from 492 patients. Elafin was overexpressed in GVHD skin biopsies. Plasma concentrations of elafin were significantly higher at the onset of skin GVHD, correlated with the eventual maximum grade of GVHD, and were associated with a greater risk of death relative to other known risk factors (hazard ratio, 1.78). We conclude that elafin has significant diagnostic and prognostic value as a biomarker of skin GVHD. PMID:20371463

  15. 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

  16. 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

  17. Identification of mast cells in buffy coat preparations from dogs with inflammatory skin diseases.

    PubMed

    Cayatte, S M; McManus, P M; Miller, W H; Scott, D W

    1995-02-01

    In 100 dogs with 4 inflammatory dermatologic diseases, buffy coat preparations from EDTA-treated blood samples were examined cytologically. Fifty-four dogs had atopy, 26 had flea-bite hypersensitivity, 17 had sarcoptic mange, and 3 had food allergy. Twenty-eight dogs had 2 or more concurrent skin diseases; most of these had secondary pyoderma. Dogs did not have mast cell tumors. Thirteen samples contained 1 or more mast cells/4 slides reviewed. This study revealed that dogs with inflammatory skin diseases can have a few to many mast cells evident on cytologic examination of buffy coat preparations. PMID:7751239

  18. Evidence of vertical transmission of lumpy skin disease virus in Rhipicephalus decoloratus ticks.

    PubMed

    Tuppurainen, Eeva S M; Lubinga, Jimmy C; Stoltsz, Wilhelm H; Troskie, Milana; Carpenter, Simon T; Coetzer, Jacobus A W; Venter, Estelle H; Oura, Chris A L

    2013-06-01

    Lumpy skin disease (LSD) is an economically important acute or sub-acute disease of cattle that occurs across Africa and in the Middle East. The aim of this study was to assess whether Rhipicephalus decoloratus ticks were able to transmit lumpy skin disease virus (LSDV) transovarially. Uninfected, laboratory-bred R. decoloratus larvae were placed to feed on experimentally infected "donor" cattle. After completion of the life cycle on donor animals, fully engorged adult female ticks were harvested and allowed to lay eggs. Larvae that hatched from these eggs were then transferred to feed on uninfected "recipient" cattle. The latter became viraemic and showed mild clinical disease with characteristic skin lesions and markedly enlarged precrural and subscapular lymph nodes. This is the first report of transovarial transmission of poxviruses by R. decoloratus ticks, and the importance of this mode of transmission in the spread of LSDV in endemic settings requires further investigation. PMID:23545323

  19. 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

  20. 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.

  1. Pathogenetic and therapeutic implications of the histamine H4 receptor in inflammatory skin diseases and pruritus.

    PubMed

    Gutzmer, Ralf; Gschwandtner, Maria; Rossbach, Kristine; Mommert, Susanne; Werfel, Thomas; Kietzmann, Manfred; Baeumer, Wolfgang

    2011-01-01

    Chronic inflammatory skin diseases such as atopic dermatitis (AD) are clinically characterized by erythematous and pruritic skin lesions, immunologically mediated by an inflammatory infiltrate consisting of T-cells, antigen presenting cells (APC) and eosinophilic granulocytes. Histamine levels are increased in lesions of inflammatory skin diseases. It is likely that histamine also plays a pathogenetic role since various relevant cell types such as T-cells and APC express functional histamine receptors. However, therapeutic blockade of the histamine H1 and H2 receptor is inefficient at least in the treatment of atopic dermatitis. We summarize here current data on the role of the recently described histamine H4 receptor (H4R) in chronic inflammatory skin diseases. The H4R is functionally expressed on relevant cell types such as T-cells, APC and keratinocytes. In murine models of contact hypersensitivity and pruritus, H4R blockade had significant in vivo effects. Taken together, several lines of evidence suggest a role of the H4R in chronic inflammatory skin disease and the H4R might be a therapeutic target for diseases such as AD. PMID:21622248

  2. Gender and ethnic differences in onchocercal skin disease in Oyo State, Nigeria.

    PubMed

    Brieger, W R; Ososanya, O O; Kale, O O; Oshiname, F O; Oke, G A

    1997-06-01

    During preparation for a study on the effects of ivermectin treatment on onchocercal skin disease in the Ifeloju Local Government Area of Oyo State, Nigeria, 1032 adults aged 20 years and older were examined for skin lesions and palpable nodules. It was found that for 4 types of skin lesions, acute papular onchodermatitis (APOD), chronic papular onchodermatitis (CPOD), lichenified onchodermatitis (LOD) and depigmentation (leopard skin), as well as for subcutaneous nodules, females had a significantly higher prevalence than males. Although the area is inhabited primarily by the Yoruba people, the study also included some of the cattle-herding Fulani ethnic group. The reactive skin lesions, APOD, CPOD and LOD, were found to be more common among the Fulani, although there were no significant differences in leopard skin and nodules between both groups. While there is need for further research on both immunological and behavioural factors that may lead to these differences in disease. The need to achieve equity in health programming by ensuring that women and ethnic minorities receive full disease control services is of more immediate concern. PMID:9236819

  3. Molecular therapies for inherited epidermolysis bullosa.

    PubMed

    Has, Cristina

    2016-08-01

    Inherited epidermolysis bullosa (EB) comprises rare genetic disorders characterized by formation of blisters and erosions of skin and mucous membranes after minor mechanical trauma. The molecular basis and the pathomechanisms of the main EB types have been largely deciphered in the past decades. The burden of the disease is high and quality of life strongly affected. The treatment is still symptomatic aiming to support wound healing and resolve complications. Numerous experimental therapeutic approaches for EB have been explored in the last years, most of them dedicated to dystrophic EB. Although gene and cell therapies have been already applied in patients, molecular therapies including gene editing and repurposing of small molecules are currently very attractive. Recent data on the effect of small molecules, like aminoglycosides and angiotensin receptor blockers in preclinical models for dystrophic EB are encouraging. The efficacy in patients remains to be proven in clinical trials. Therapeutic efficacy, as well as unexpected outcomes must be carefully monitored. PMID:27149615

  4. 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

  5. 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

  6. Prevalence of Common Skin Diseases and Their Associated Factors among Military Personnel in Korea: A Cross-sectional Study

    PubMed Central

    Bae, Jung Min; Ha, Beomman; Lee, Hongsun; Park, Chang Keun; Kim, Hyun Joon

    2012-01-01

    This study was conducted to clarify the prevalence of common skin diseases and their associated factors among military personnel in Korea. Four dermatologists visited adjacent military units and examined soldiers. A structured questionnaire that included questions about known skin diseases, demographic information, and questions for the Perceived Stress Index was completed for each participant. The soldiers that had been diagnosed with a skin disease answered one additional questionnaire (Skindex-29) which assess the influence of an individual's skin disease on daily life. Of 1,321 soldiers examined, 798 (60.4%) had one or more skin diseases. The three most common skin problems were acne (35.6%), tinea pedis (15.2%) and atopic dermatitis (5.1%). The diseases closely related to the period of military service were acne, tinea pedis, viral warts and corns. The diseases related to the amount of stress were atopic dermatitis, seborrheic dermatitis, and acne. The most troublesome skin diseases were atopic dermatitis, tinea cruris, and seborrheic dermatitis. These results demonstrated that the prevalence of skin disease among military personnel in Korea is very high, and that some of the skin disorders may have a significant influence on their daily lives. PMID:23091325

  7. Inhibition of collagen synthesis and changes in skin morphology in murine graft-versus-host disease and tight skin mice: effect of halofuginone.

    PubMed

    Levi-Schaffer, F; Nagler, A; Slavin, S; Knopov, V; Pines, M

    1996-01-01

    The effect of halofuginone, a plant alkaloid known to inhibit collagen type I synthesis, on skin collagen content and skin morphology was evaluated in two in vivo models of scleroderma: the murine chronic graft-versus-host disease (cGvHD) and the tight skin mouse. Skin collagen was assessed by hydroxyproline levels in skin biopsies and by immunohistochemistry using anti-collagen type I antibodies. Daily intraperitoneal injections of halofuginone (1 microgram/mouse) for 52 d starting 3 d before spleen cell transplantation, abrogated the increase in skin collagen and prevented the thickening of the dermis and the loss of the subdermal fat, all of which are characteristic of the cGvHD mice. Halofuginone had a minimal effect on collagen content of the control mice. The halofuginone-dependent decrease in skin collagen content was concentration-dependent and was not accompanied by changes in body weight in either the cGvHD or the control mice. Injections of halofuginone (1 microgram/mouse) for 45 d caused a decrease in the collagen content and dermis width in tight skin mice, but did not affect the dermis width of control mice. Collagen content determination from skin biopsies confirmed the immunohistochemical results in the same mice. The low concentration of halofuginone needed to prevent collagen deposition in fibrotic skin without affecting body weight suggests that halofuginone may serve as a novel and promising anti-fibrotic therapy. PMID:8592087

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

    PubMed Central

    Tseng, Wen-Ping

    1977-01-01

    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. ImagesFIGURE 1.FIGURE 2. PMID:908285

  9. 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

  10. 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

  11. 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.

  12. miRNAs in inflammatory skin diseases and their clinical implications.

    PubMed

    Løvendorf, Marianne B; Skov, Lone

    2015-04-01

    miRNAs are a class of non-coding RNA molecules that modulate gene expression post-transcriptionally. They have a major impact on several physiological and pathological cellular processes including modulation of the innate and the adaptive immune system. The role of miRNAs in skin biology is still incomplete; however, it is known that miRNAs are implicated in various cellular processes of both normal and diseased skin. Some miRNAs appear to be consistently deregulated in several different inflammatory skin diseases, including psoriasis and atopic dermatitis, indicating a common role in fundamental biological processes. The clinical implications of miRNAs are intriguing, both from a diagnostic and a therapeutic perspective. Accordingly, there is emerging evidence for the clinical potential of miRNAs as both biomarkers and possible therapeutic targets in skin diseases. Future studies will hopefully establish the biological significance of miRNAs in skin biology, paving the way for new miRNA-based diagnostic and therapeutic applications in dermatology. PMID:25719822

  13. 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.

  14. Development of atopic dermatitis-like skin disease from the chronic loss of epidermal caspase-8.

    PubMed

    Li, Christopher; Lasse, Samuel; Lee, Pedro; Nakasaki, Manando; Chen, Shih-Wei; Yamasaki, Kenshi; Gallo, Richard L; Jamora, Colin

    2010-12-21

    Atopic dermatitis is an inflammatory skin disease that affects approximately 20% of children worldwide. Left untreated, the barrier function of the skin is compromised, increasing susceptibility to dehydration and infection. Despite its prevalence, its multifactorial nature has complicated the unraveling of its etiology. We found that chronic loss of epidermal caspase-8 recapitulates many aspects of atopic dermatitis, including a spongiotic phenotype whereby intercellular adhesion between epidermal keratinocytes is disrupted, adversely affecting tissue architecture and function. Although spongiosis is generally thought to be secondary to edema, we found that suppression of matrix metalloproteinase-2 activity is sufficient to abrogate this defect. p38 MAPK induces matrix metalloproteinase-2 expression to cleave E-cadherin, which mediates keratinocyte cohesion in the epidermis. Thus, the conditional loss of caspase-8, which we previously found to mimic a wound response, can be used to gain insights into how these same wound-healing processes are commandeered in inflammatory skin diseases. PMID:21135236

  15. Inherited neuropathies.

    PubMed

    Chance, P F; Reilly, M

    1994-10-01

    Charcot-Marie-Tooth neuropathy (CMT) type 1 is a genetically heterogeneous group of chronic demyelinating polyneuropathies with loci mapping to chromosome 17 (CMT1A), chromosome 1 (CMT1B), the X chromosome (CMTX), and to another unknown autosome (CMT1C). CMT1A is most often associated with a tandem 1.5-Mb duplication in chromosome 17p11.2-12, or in rare patients may result from a point mutation in the peripheral myelin protein-22 (PMP22) gene. CMT1B is associated with point mutations in the myelin protein zero (P0) gene. The molecular defect in CMT1C is unknown. CMTX is associated with mutations in the connexin 32 gene. CMT2 is an axonal neuropathy of undetermined cause. One form of CMT2 maps to chromosome 1p36 (CMT2A). Dejerine-Sottas disease is a severe, infantile-onset demyelinating polyneuropathy that may be associated with point mutations in either the PMP22 gene or the P0 gene. Hereditary neuropathy with liability to pressure palsies (HNPP) is a recurrent, episodic demyelinating neuropathy. HNPP is associated with a 1.5-Mb deletion in chromosome 17p11.2-12 and may result from reduced expression of the PMP22 gene. Most examples of CMT1A and HNPP are reciprocal duplication or deletion syndromes originating from unequal crossover during germ cell meiosis. Familial amyloid polyneuropathy (FAP) is an autosomal dominant disorder that classically presents with a sensory peripheral neuropathy and early autonomic involvement. Transthyretin (TTR) is the most common constituent amyloid fibril protein deposited in FAP, and there are now 28 point mutations in the TTR gene described in TTR-related FAP. Liver transplantation looks promising as a treatment for TTR-related FAP. PMID:7804455

  16. 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

  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

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. App.), notice is...

  18. 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

    ... rheumatoid arthritis and skin diseases. Date: November 16, 2012. Time: 9:00 a.m. to 12:00 p.m. Agenda: To... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and... unwarranted invasion of personal privacy. Name of Committee: National Institute of Arthritis...

  19. 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

  20. 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

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and Skin Diseases; Amended Notice of Meeting Notice is hereby given of a change in the meeting of the National Institute of Arthritis and...

  1. 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

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. App.), notice is...

  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

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. App.), notice is...

  3. 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... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and Skin Diseases; Amended Notice of Meeting Notice is hereby given of a change in the meeting of...

  4. 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... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and Skin Diseases Amended; Notice of Meeting Notice is hereby given of a change in the meeting of...

  5. 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... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and Skin Diseases; Amended Notice of Meeting Notice is hereby given of a change in the meeting of...

  6. 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

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. App.), notice is hereby given...

  7. 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... HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and Skin Diseases; Amended Notice of Meeting Notice is hereby given of a change in the meeting of...

  8. 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

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. App.), notice is...

  9. 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

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. App.), notice is...

  10. 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

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. App.), notice is...

  11. 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

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. App.), notice is...

  12. 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

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. App.), notice is...

  13. Cathelicidin LL-37: An Antimicrobial Peptide with a Role in Inflammatory Skin Disease

    PubMed Central

    Reinholz, Markus; Ruzicka, Thomas

    2012-01-01

    Chronic inflammatory skin diseases such as atopic dermatitis, psoriasis or rosacea are very common. Although their exact pathogenesis is not completely understood all three diseases are characterized by dysregulation of cutaneous innate immunity. Cathelicidin LL-37 is an important effector molecule of innate immunity in the skin and atopic dermatitis, psoriasis or rosacea show defects in cathelicidin expression, function or processing. In atopic dermatitis, cathelicidin induction might be disturbed resulting in defective antimicrobial barrier function. In contrast, psoriasis is characterized by overexpression of cathelicidin. However to date it is unclear whether pro- or anti-inflammatory functions of cathelicidin predominate in lesional skin in psoriasis. In rosacea, cathelicidin processing is disturbed resulting in peptide fragments causing inflammation, erythema and telangiectasias. In this review, the current evidence on the role of cathelicidin LL-37 in the pathogenesis of inflammatory skin diseases will be outlined. As cathelicidin LL-37 might also serve as a future treatment target potential novel treatment strategies for those diseases will be discussed. PMID:22577261

  14. 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

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. App.), notice is...

  15. 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

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. App.), notice is...

  16. 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

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Arthritis And Musculoskeletal and Skin Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. App.), notice is...

  17. 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

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. App.), notice is...

  18. 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. PMID:26945533

  19. Loss of serum response factor in keratinocytes results in hyperproliferative skin disease in mice

    PubMed Central

    Koegel, Heidi; von Tobel, Lukas; Schäfer, Matthias; Alberti, Siegfried; Kremmer, Elisabeth; Mauch, Cornelia; Hohl, Daniel; Wang, Xiao-Jing; Beer, Hans-Dietmar; Bloch, Wilhelm; Nordheim, Alfred; Werner, Sabine

    2009-01-01

    The transcription factor serum response factor (SRF) plays a crucial role in the development of several organs. However, its role in the skin has not been explored. Here, we show that keratinocytes in normal human and mouse skin expressed high levels of SRF but that SRF expression was strongly downregulated in the hyperproliferative epidermis of wounded and psoriatic skin. Keratinocyte-specific deletion within the mouse SRF locus during embryonic development caused edema and skin blistering, and all animals died in utero. Postnatal loss of mouse SRF in keratinocytes resulted in the development of psoriasis-like skin lesions. These lesions were characterized by inflammation, hyperproliferation, and abnormal differentiation of keratinocytes as well as by disruption of the actin cytoskeleton. Ultrastructural analysis revealed markedly reduced cell-cell and cell-matrix contacts and loss of cell compaction in all epidermal layers. siRNA-mediated knockdown of SRF in primary human keratinocytes revealed that the cytoskeletal abnormalities and adhesion defects were a direct consequence of the loss of SRF. In contrast, the hyperproliferation observed in vivo was an indirect effect that was most likely a consequence of the inflammation. These results reveal that loss of SRF disrupts epidermal homeostasis and strongly suggest its involvement in the pathogenesis of hyperproliferative skin diseases, including psoriasis. PMID:19307725

  20. The role of filaggrin mutations during pregnancy and postpartum: atopic dermatitis and genital skin diseases.

    PubMed

    Bager, P; Wohlfahrt, J; Boyd, H; Thyssen, J P; Melbye, M

    2016-05-01

    Mutations in the epidermal filaggrin gene (FLG) are associated with skin barrier dysfunction (dry skin, less acidic skin, and fissured skin), and atopic dermatitis (AD) with a severe and persistent course. Because pregnancy and delivery further impairs normal skin barrier functions (immune suppression, mechanical stress), we studied the possible role of FLG mutations on the risk of AD flares, genital infections, and postpartum problems related to perineal trauma. FLG-genotyping was performed in a population-based sample of 1837 women interviewed in the 12th and 30th weeks of pregnancy and 6 months postpartum as part of the Danish National Birth Cohort study 1996-2002. We found that FLG mutations also influence pregnancy-related skin disease; thus, women with FLG mutations had an increased risk of AD flares during pregnancy (OR 10.5, 95% CI 3.6-30.5) and of enduring postpartum physical problems linked to perineal trauma during delivery (OR 11.1, 95% CI 1.1-107.7). PMID:26835886

  1. 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 ...

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

    PubMed

    Beitz, Janice M

    2013-06-01

    Parkinson's Disease is a chronic neurodegenerative disorder that is expected to increase in coming decades as the American population continues to age. Although the motor dysfunction (bradykinesia, tremor, rigidity) of Parkinson's Disease is well described in the literature, the nonmotor dysfunction related to autonomic system changes is not as commonly addressed. Ironically, nonmotor changes, such as seborrhea, sialorrhea, hyperhidrosis, and sensory denervation occur earlier in the disease process and exert a profound effect on patients' quality of life. The depletion of dopamine, a critically important neurotransmitter, is the critical pathology of Parkinson's disease. Therapies targeting this abnormality and the effect of insufficient dopamine itself can affect the integumentary system and potentially wound healing. The purpose of this review is to describe changes in the autonomic nervous system due to Parkinson's Disease with a focused overview of common skin and wound care issues that may affect wound care clinician practice. Implications for nurses and other clinicians caring for Parkinson's Disease patients include surveillance for melanoma and other skin cancers, skin protection against excessive moisture or the effects of insufficient moisture, monitoring of wound healing progress, and interventions to prevent or ameliorate complications of immobility. PMID:23749660

  3. 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.

  4. Skin Autofluorescence Is Associated with the Progression of Chronic Kidney Disease: A Prospective Observational Study

    PubMed Central

    Tanaka, Kenichi; Nakayama, Masaaki; Kanno, Makoto; Kimura, Hiroshi; Watanabe, Kimio; Tani, Yoshihiro; Kusano, Yuki; Suzuki, Hodaka; Hayashi, Yoshimitsu; Asahi, Koichi; Sato, Keiji; Miyata, Toshio; Watanabe, Tsuyoshi

    2013-01-01

    Background Advanced glycation end product (AGE) accumulation is thought to be a measure of cumulative metabolic stress that has been reported to independently predict cardiovascular disease in diabetes and renal failure. The aim of this study was to evaluate the association between AGE accumulation, measured as skin autofluorescence, and the progression of renal disease in pre-dialysis patients with chronic kidney disease (CKD). Methods Skin autofluorescence was measured noninvasively with an autofluorescence reader at baseline in 449 pre-dialysis patients with CKD. The primary end point was defined as a doubling of serum creatinine and/or need for dialysis. Results Thirty-three patients were lost to follow-up. Forty six patients reached the primary end point during the follow-up period (Median 39 months). Kaplan-Meier analysis showed a significantly higher risk of development of the primary end points in patients with skin autofluorescence levels above the optimal cut-off level of 2.31 arbitrary units, derived by receiver operator curve analysis. Cox regression analysis revealed that skin autofluorescence was an independent predictor of the primary end point, even after adjustment for age, gender, smoking history, diabetes, estimated glomerular filtration rate and proteinuria (adjusted hazard ratio 2.58, P = 0.004). Conclusions Tissue accumulation of AGEs, measured as skin autofluorescence, is a strong and independent predictor of progression of CKD. Skin autofluorescence may be useful for risk stratification in this group of patients; further studies should clarify whether AGE accumulation could be one of the therapeutic targets to improve the prognosis of CKD. PMID:24349550

  5. Fine-needle aspiration in the diagnosis of equine skin disease and the epidemiology of equine skin cytology submissions in a western Canadian diagnostic laboratory.

    PubMed

    Zachar, Erin K; Burgess, Hilary J; Wobeser, Bruce K

    2016-06-01

    Fine-needle aspiration (FNA) is commonly used to diagnose skin disease in companion animals, but its use in horses appears to be infrequent. Equine veterinarians in western Canada were surveyed to determine their opinions about FNA and 15 years of diagnostic submissions were used to compare the perceived to actual value of FNA in the diagnosis of skin disease in horses. Practitioners viewed FNA as quick, easy, economical, and minimally invasive. However, most veterinarians rarely chose to use FNA due to a perception that sample quality and diagnostic yield were poor and there was a narrow range of diseases the technique could diagnose. Analysis of the FNA cytology samples from a veterinary diagnostic laboratory showed a wide variety of equine skin disease conditions, but the frequency of non-diagnostic results was significantly higher in equine submissions compared to those from dogs and cats. PMID:27247463

  6. The Skindex instruments to measure the effects of skin disease on quality of life.

    PubMed

    Chren, Mary-Margaret

    2012-04-01

    Skindex-29 and Skindex-16 are validated measures of the effects of skin diseases on patients' quality of life. This article reviews the development of both versions of Skindex, discusses their measurement properties and interpretability, and gives examples of how they have been used and adapted for dermatologic research internationally. Studies of quality of life in patients with nonmelanoma skin cancer are described to illustrate the use of Skindex to understand quality of life and to compare effectiveness of different treatments for this highly prevalent condition. PMID:22284137

  7. The role of filaggrin in the skin barrier and disease development.

    PubMed

    Armengot-Carbo, M; Hernández-Martín, Á; Torrelo, A

    2015-03-01

    Filaggrin is a structural protein that is fundamental in the development and maintenance of the skin barrier. The function of filaggrin and its involvement in various cutaneous and extracutaneous disorders has been the subject of considerable research in recent years. Mutations in FLG, the gene that encodes filaggrin, have been shown to cause ichthyosis vulgaris, increase the risk of atopic dermatitis and other atopic diseases, and exacerbate certain conditions. The present article reviews the current knowledge on the role of filaggrin in the skin barrier, FLG mutations, and the consequences of filaggrin deficiency. PMID:24674607

  8. 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

  9. 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. PMID:24249889

  10. Stressed skin? - a molecular psychosomatic update on stress-causes and effects in dermatologic diseases.

    PubMed

    Peters, Eva M J

    2016-03-01

    A pathogenetically relevant link between stress, in terms of psychosocial stress, and disease was first described in the 1970s, when it was proven that viral diseases of mucous membranes (such as rhinovirus and Coxsackie virus infections) develop faster and more severe after stress exposure. Since then, there has been an annual increase in the number of publications which investigate this relationship and break it down to the molecular level. Nevertheless, the evidences for the impact of psychosocial stress on chronic inflammatory skin diseases and skin tumors are hardly known. In the present review, we outline current insights into epidemiology, psychoneuroimmunology, and molecular psychosomatics which demonstrate the manifold disease-relevant interactions between the endocrine, nervous, and immune systems. The focus is on stress-induced shifts in immune balance in exemplary disorders such as atopic dermatitis, psoriasis, and malignant melanoma. The objective of this article is to convey basic psychosomatic knowledge with respect to etiology, symptomatology, and therapeutic options for chronic skin diseases. Particular attention is directed towards the underlying molecular relationships, both from a somatic to mental as well as a mental to somatic perspective. PMID:26972185

  11. Substrate deprivation therapy: a new hope for patients suffering from neuronopathic forms of inherited lysosomal storage diseases.

    PubMed

    Jakóbkiewicz-Banecka, Joanna; Wegrzyn, Alicja; Wegrzyn, Grzegorz

    2007-01-01

    Lysosomal storage diseases are a group of disorders caused by defects in enzymes responsible for degradation of particular compounds in lysosomes. In most cases, these diseases are fatal, and until recently no treatment was available. Introduction of enzyme replacement therapy was a breakthrough in the treatment of some of the diseases. However, while this therapy is effective in reduction of many somatic symptoms, its efficacy in the treatment of the central nervous system is negligible, if any, mainly because of problems with crossing the blood-brain-barrier by intravenously administered enzyme molecules. On the other hand, there are many lysosomal storage diseases in which the central nervous system is affected. Results of very recent studies indicate that in at least some cases, another type of therapy, called substrate deprivation therapy (or substrate reduction therapy) may be effective in the treatment of neuronopathic forms of lysosomal storage diseases. This therapy, based on inhibition of synthesis of the compounds that cannot be degraded in cells of the patients, has been shown to be effective in several animal models of various diseases, and recent reports demonstrate its efficacy in the treatment of patients suffering from Niemann-Pick C disease and Sanfilippo disease. PMID:17998597

  12. 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

  13. The involvement of the JAK-STAT signaling pathway in chronic inflammatory skin disease atopic dermatitis

    PubMed Central

    Bao, Lei; Zhang, Huayi; Chan, Lawrence S

    2013-01-01

    Atopic dermatitis (AD), a common chronic inflammatory skin disease, is characterized by inflammatory cell skin infiltration. The JAK-STAT pathway has been shown to play an essential role in the dysregulation of immune responses in AD, including the exaggeration of Th2 cell response, the activation of eosinophils, the maturation of B cells, and the suppression of regulatory T cells (Tregs). In addition, the JAK-STAT pathway, activated by IL-4, also plays a critical role in the pathogenesis of AD by upregulating epidermal chemokines, pro-inflammatroy cytokines, and pro-angiogenic factors as well as by downregulating antimicrobial peptides (AMPs) and factors responsible for skin barrier function. In this review, we will highlight the recent advances in our understanding of the JAK-STAT pathway in the pathogenesis of AD. PMID:24069552

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

    ClinicalTrials.gov

    2014-06-11

    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

  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. Update on the role of plasmacytoid dendritic cells in inflammatory/autoimmune skin diseases.

    PubMed

    Saadeh, Dana; Kurban, Mazen; Abbas, Ossama

    2016-06-01

    Plasmacytoid dendritic cells (pDCs) represent a specialized dendritic cell population that exhibit plasma cell morphology, express CD4, CD123, blood-derived dendritic cell antigen-2 (BDCA-2) and Toll-like receptor (TLR)7 and TLR9 within endosomal compartments. When activated, pDCs are capable of producing large quantities of type I IFNs (mainly IFN-α/β), which provide antiviral resistance and link the innate and adaptive immunity. While generally lacking from normal skin, pDCs infiltrate the skin and appear to be involved in the pathogenesis of several inflammatory, infectious (especially viral) and neoplastic entities. In recent years, pDC role in inflammatory/autoimmune skin conditions has been extensively studied. Unlike type I IFN-mediated protective immunity that pDCs provide at the level of the skin by regulated sensing of microbial or self-nucleic acids upon skin damage, excessive sensing may elicit IFN-driven inflammatory/autoimmune diseases. In this review, focus will be on the role of pDCs in cutaneous inflammatory/autoimmune dermatoses. PMID:26837058

  19. Causative Agent of Pogosta Disease Isolated from Blood and Skin Lesions

    PubMed Central

    Manni, Tytti; Vaheri, Antti; Vapalahti, Olli

    2004-01-01

    Pogosta disease is a mosquito-borne viral disease in Finland, which is clinically manifested by rash and arthritis; larger outbreaks occur in 7-year intervals. The causative agent of the disease has been suspected of being closely related to Sindbis virus (SINV). We isolated SINV from five patients with acute Pogosta disease during an outbreak in fall 2002 in Finland. One virus strain was recovered from a whole blood sample and four other strains from skin lesions. The etiology of Pogosta disease was confirmed by these first Finnish SINV strains, which also represent the first human SINV isolates from Europe. Phylogenetic analysis indicates that the Finnish SINV strains are closely related to the viral agents isolated from mosquitoes and that cause clinically similar diseases in nearby geographic areas. PMID:15200824

  20. Water outage increases the risk of gastroenteritis and eyes and skin diseases

    PubMed Central

    2011-01-01

    Background The present study used insurance claims data to investigate infections associated with short-term water outage because of constructions or pipe breaks. Methods The present study used medical claims of one million insured persons for 2004-2006. We estimated incidences of gastroenteritis and eye and skin complaints for 10 days before, during, and after 10 days of water supply restriction for outpatient visits and for emergency and in-patient care combined. Results There was an increase in medical services for these complaints in outpatient visits because of water outages. Poisson regression analyses showed that increased risks of medical services were significant for gastroenteritis (relative risk [RR] 1.31, 95% confidence interval [CI] 1.26-1.37), skin disease (RR 1.36, 95% CI 1.30-1.42), and eye disease patients (RR 1.34, 95% CI 1.26-1.44). Similar risks were observed during 10-day lag periods. Compared with those in cool days, risks of medical services are higher when average daily temperature is above 30°C for gastroenteritis (RR 12.1, 95% CI 6.17-23.7), skin diseases (RR 4.48, 95% CI 2.29-8.78), and eye diseases (RR 40.3, 95% CI 7.23-224). Conclusion We suggest promoting personal hygiene education during water supply shortages, particularly during the warm months. PMID:21943080

  1. Skindex, a quality-of-life measure for patients with skin disease: reliability, validity, and responsiveness.

    PubMed

    Chren, M M; Lasek, R J; Quinn, L M; Mostow, E N; Zyzanski, S J

    1996-11-01

    To measure the effects of skin disease on patients' quality of life, we developed a 61-item self-administered survey instrument called Skindex. Skindex has eight scales, each of which addresses a construct, or an abstract component, in a comprehensive conceptual framework: cognitive effects, social effects, depression, fear, embarrassment, anger, physical discomfort, and physical limitations. Item responses are standardized from 0 (no effect) to 100 (maximal effect); a scale score is the average of responses to items addressing a construct. In 201 patients seen by dermatologists, mean scale scores (+/-SD) ranged from 14 (+/-17) for physical limitations to 31 (+/-22) for physical discomfort. Scale scores were reproducible after 72 h (r = 0.68-0.90) and were internally consistent (Cronbach's alpha = 0.76-0.86). Construct validity was assessed in two ways: (i) in a comparison of patients with inflammatory dermatoses and patients with isolated lesions, patients with inflammatory dermatoses had higher scale scores, and (ii) in an exploratory factor analysis, 78% of the common variance was explained by seven factors that correlated with the scale scores of Skindex. Most of the a priori scale scores changed in the expected direction in patients who reported that their skin conditions had improved or worsened after 6 mo. Finally, physicians' judgments of disease severity did not consistently correlate with Skindex scores. These preliminary data suggest that Skindex reliably and responsively measures the effects of skin disease on patients' quality of life and may supplement clinical judgments of disease severity. PMID:8875954

  2. 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

  3. 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

  4. 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

  5. Skin as a route of exposure and sensitization in chronic beryllium disease.

    PubMed Central

    Tinkle, Sally S; Antonini, James M; Rich, Brenda A; Roberts, Jenny R; Salmen, Rebecca; DePree, Karyn; Adkins, Eric J

    2003-01-01

    Chronic beryllium disease is an occupational lung disease that begins as a cell-mediated immune response to beryllium. Although respiratory and engineering controls have significantly decreased occupational beryllium exposures over the last decade, the rate of beryllium sensitization has not declined. We hypothesized that skin exposure to beryllium particles would provide an alternative route for sensitization to this metal. We employed optical scanning laser confocal microscopy and size-selected fluorospheres to demonstrate that 0.5- and 1.0- micro m particles, in conjunction with motion, as at the wrist, penetrate the stratum corneum of human skin and reach the epidermis and, occasionally, the dermis. The cutaneous immune response to chemical sensitizers is initiated in the skin, matures in the local lymph node (LN), and releases hapten-specific T cells into the peripheral blood. Topical application of beryllium to C3H mice generated beryllium-specific sensitization that was documented by peripheral blood and LN beryllium lymphocyte proliferation tests (BeLPT) and by changes in LN T-cell activation markers, increased expression of CD44, and decreased CD62L. In a sensitization-challenge treatment paradigm, epicutaneous beryllium increased murine ear thickness following chemical challenge. These data are consistent with development of a hapten-specific, cell-mediated immune response following topical application of beryllium and suggest a mechanistic link between the persistent rate of beryllium worker sensitization and skin exposure to fine and ultrafine beryllium particles. PMID:12842774

  6. My Retina Tracker™: An On-line International Registry for People Affected with Inherited Orphan Retinal Degenerative Diseases and their Genetic Relatives - A New Resource.

    PubMed

    Fisher, Joan K; Bromley, Russell L; Mansfield, Brian C

    2016-01-01

    My Retina Tracker™ is a new on-line registry for people affected with inherited orphan retinal degenerative diseases, and their unaffected, genetic relatives. Created and supported by the Foundation Fighting Blindness, it is an international resource designed to capture the disease from the perspective of the registry participant and their retinal health care providers. The registry operates under an Institutional Review Board (IRB)-approved protocol and allows sharing of de-identified data with participants, researchers and clinicians. All participants sign an informed consent that includes selecting which data they wish to share. There is no minimum age of participation. Guardians must sign on behalf of minors, and children between the ages of 12 to 17 also sign an informed assent. Participants may compare their disease to others in the registry using graphical interpretations of the aggregate registry data. Researchers and clinicians have two levels of access. The first provides an interface to interrogate all data fields registrants have agreed to share based on their answers in the IRB informed consent. The second provides a route to contact people in the registry who may be eligible for studies or trials, through the Foundation. PMID:26427418

  7. Inherited renal carcinomas.

    PubMed

    Kawashima, Akira; Young, Scott W; Takahashi, Naoki; King, Bernard F; Atwell, Thomas D

    2016-06-01

    Hereditary forms of kidney carcinoma account for 5-8% of all malignant kidney neoplasms. The renal tumors are often multiple and bilateral and occur at an earlier age. Each of the hereditary kidney carcinoma syndromes is associated with specific gene mutations as well as a specific histologic type of kidney carcinoma. The presence of associated extrarenal manifestations may suggest a hereditary kidney cancer syndrome. Radiology is most commonly used to screen and manage patients with hereditary kidney cancer syndromes. This manuscript reviews the clinical and imaging findings of well-defined inherited kidney cancer syndromes including von Hippel-Lindau disease, Birt-Hogg-Dubé syndrome, hereditary papillary renal carcinoma syndrome, hereditary leiomyomatosis and RCC syndrome, tuberous sclerosis complex, and Lynch syndrome. PMID:27108134

  8. Adverse Reactions to Field Vaccination Against Lumpy Skin Disease in Jordan.

    PubMed

    Abutarbush, S M; Hananeh, W M; Ramadan, W; Al Sheyab, O M; Alnajjar, A R; Al Zoubi, I G; Knowles, N J; Bachanek-Bankowska, K; Tuppurainen, E S M

    2016-04-01

    Lumpy skin disease (LSD) is an emerging disease in the Middle East region and has been recently reported in Jordan. The aim of this study was to investigate the adverse reactions that were reported after vaccine administration. Geographical areas enrolled in the study were free of the disease and away from the outbreak governorate. Sixty-three dairy cattle farms, with a total of 19,539 animals, were included in the study. Of those, 56 farms reported adverse clinical signs after vaccine administration. The duration between vaccine administration and appearance of adverse clinical signs ranged from 1 to 20 days (Mean = 10.3, SD ± 3.9). Clinical signs were similar to those observed with natural cases of lumpy skin disease. These were mainly fever, decreased feed intake, decreased milk production and variable sized cutaneous nodules (a few millimetres to around 2 cm in diameter) that could be seen anywhere on the body (head, neck, trunk, perineum), udder, and/or teats. Nodules were raised and firm initially and then formed dry scabs that could be peeled off the skin. The characteristic deep 'sit fast' appearance was rarely seen and most lesions were superficial. Some cattle had swollen lymph nodes, while a few pregnant animals aborted. The percentage of affected cattle ranged from 0.3 to 25% (Mean = 8, SD ± 5.1). Fever, decreased feed intake, and decreased milk production were seen in 83.9, 85.7, and 94.6% in cattle on the affected farms, respectively. All affected cattle displayed skin nodules over their entire bodies, while 33.9 and 7.1% of the affected farms reported nodular lesions present on the udders and teats, respectively. No mortalities were reported due to vaccine adverse reactions. Duration (course) of clinical signs ranged from 3 to 20 days (Mean = 13.7, SD ± 4.1). Two types of LSD vaccines were used by the farmers in this study. The first one was a sheep pox virus (SPPV) vaccine derived from the RM65 isolate [Jovivac, manufactured by Jordan

  9. 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

  10. Interplay of co-inherited diseases can turn benign syndromes in a deadly combination: haemoglobinopathy and bilirubin transport disorder.

    PubMed

    Stolmeijer, T M; van der Berg, A P; Koeze, J; Gouw, A S H; Croles, F N; Sieders, E; Zijlstra, J G

    2015-06-01

    We present a case about a 25-year-old male patient suffering from a rare genetic disorder called Mizuho haemoglobin. He was admitted to the Intensive Care Unit with acute liver and renal failure. During admission he also developed a cardiac tamponade twice. Finally he received a liver transplantation. Hereafter the patient stabilised and his liver and renal functions improved. His symptoms could not be explained solely by his known disease. After searching the literature, similarities between his symptoms and a rare complication of sickle cell disease were found. Molecular diagnostics showed that the patient also suffered from Gilbert's syndrome. Due to his chronic haemolysis, symptoms of this other disease were masked. This stresses the importance of always looking for other causes if symptoms or changes cannot be explained by a known rare disorder. PMID:26087805

  11. 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

  12. 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

  13. 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. PMID:26858557

  14. 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.

  15. 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

  16. Inherited deficiency of second component of complement and HLA haplotype A10,B18 associated with inflammatory bowel disease.

    PubMed

    Slade, J D; Luskin, A T; Gewurz, H; Kraft, S C; Kirsner, J B; Zeitz, H J

    1978-06-01

    A patient with inflammatory bowel disease and sacroiliitis had haplotypes A10,B18 and Aw32,b18 at the major histocompatibility locus. Serum total complement and C2 hemolytic complement activities were undetectable; levels of the remaining C1-C9 components were normal. The parents, both siblings, and a child each had half-normal levels of C2 and either the A10,B18 or the Aw32,b18 hla haplotype. In a second unrelated family, an only child and both parents developed inflammatory bowel disease. The father and child had HLA haplotype A10,B18, but, along with the mother, each had normal serum levels of hemolytic C and C2. Homozygous C2 deficiency, often in association with the A10,B18 haplotype, has previously been linked with various autoimmune diseases and with propensity to infection. Our findings suggest that C2 deficiency or this haplotype also may predispose to inflammatory diseases of the intestine. PMID:666136

  17. Inherited desmosomal disorders.

    PubMed

    Samuelov, Liat; Sprecher, Eli

    2015-06-01

    Desmosomes serve as intercellular junctions in various tissues including the skin and the heart where they play a crucial role in cell-cell adhesion, signalling and differentiation. The desmosomes connect the cell surface to the keratin cytoskeleton and are composed of a transmembranal part consisting mainly of desmosomal cadherins, armadillo proteins and desmoplakin, which form the intracytoplasmic desmosomal plaque. Desmosomal genodermatoses are caused by mutations in genes encoding the various desmosomal components. They are characterized by skin, hair and cardiac manifestations occurring in diverse combinations. Their classification into a separate and distinct clinical group not only recognizes their common pathogenesis and facilitates their diagnosis but might also in the future form the basis for the design of novel and targeted therapies for these occasionally life-threatening diseases. PMID:25487406

  18. 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

  19. Quality of life in patients with skin diseases in central Saudi Arabia

    PubMed Central

    Abolfotouh, Mostafa A; Al-Khowailed, Mohammad S; Suliman, Wijdan E; Al-Turaif, Deema A; Al-Bluwi, Eman; Al-Kahtani, Hassan S

    2012-01-01

    Background Previous national and international studies of quality of life (QoL) in patients with skin diseases have revealed different levels of QoL impairment. The aims of this study were to assess QoL in patients with skin diseases in central Saudi Arabia using the newly validated Skindex-16 instrument and to determine the association between QoL in patients with skin disease, sociodemographic data, and disease characteristics. Methods A cross-sectional study was conducted in 283 adult patients who visited the outpatient dermatology clinics of King Abdulaziz Medical City, Riyadh, Saudi Arabia, over 3 months. The patients were interviewed using a pretested Arabic version of the Skindex-16 to measure the effect of skin disorders on their QoL during the previous 7 days. Patient characteristics, medical history, and clinical findings were collected. Multiple linear regression analyses were used to relate the demographic and clinical characteristics to the percentage mean QoL score, and P ≤ 0.05 was considered to be statistically significant. Results QoL was good in 69% of the respondents, with a total percent mean score of 31.80 ± 20.16. The emotional domain was the most affected (mean percentage score 44.27 ± 27.06), followed by symptoms (31.45 ± 28.40) and functioning (14.61 ± 22.75). After adjustment for potential confounders, poorer QoL was significantly associated with female gender (P = 0.03), older age (P = 0.003), rural origin (P = 0.03), positive family history of the same lesion(s) (P = 0.01), shorter duration of ≤6 months (P = 0.02), generalized spread (P ≤ 0.02), and lack of isotretinoin treatment (P = 0.02). Conclusion . The QoL results in this study were generally more optimistic than those of many previous studies. This discrepancy may be due to biases in questionnaire responses or to cultural differences in experience of skin disease and perception of disability. Significant predictors of QoL were not the same for the three domains of the

  20. 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

  1. 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

  2. Genetic background of skin barrier dysfunction in the pathogenesis of psoriasis vulgaris

    PubMed Central

    Szczerkowska-Dobosz, Aneta; Rębała, Krzysztof; Purzycka-Bohdan, Dorota

    2015-01-01

    Psoriasis is a common inflammatory skin disease. It is known to be a complex condition with multifactorial mode of inheritance, however the associations between particular pathogenic pathways remain unclear. A novel report on the pathogenesis of psoriasis has recently included the genetic determination of the skin barrier dysfunction. In this paper, we focus on specific genetic variants associated with formation of the epidermal barrier and their role in the complex pathogenesis of the disease. PMID:26015782

  3. 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. PMID:25964057

  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 Central

    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.

    2015-01-01

    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 (8), Australia (3), UK (1), and Germany (2). By 2014, 41 ADNI and 24 DIAN autopsies (involving 9 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. PMID:25964057

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. Advanced glycation end-products and skin autofluorescence in end-stage renal disease: a review.

    PubMed

    Arsov, Stefan; Graaff, Reindert; van Oeveren, Wim; Stegmayr, Bernd; Sikole, Aleksandar; Rakhorst, Gerhard; Smit, Andries J

    2014-01-01

    Chronic kidney disease (CKD), especially in its end stage, is marked by extremely high cardiovascular rates of morbidity and mortality; hemodialysis patients have a five-fold shorter life expectancy than healthy subjects of the same age. In CKD the metabolic products that accumulate in the body are so-called uremic toxins. These include advanced glycation end-products (AGE). AGE levels are markedly increased in CKD patients not only because of impaired excretion but also because of increased production. AGE formation has initially been described as a non-enzymatic reaction between proteins and glucose in the so-called Maillard reaction, but they are also more rapidly formed during oxidative stress and subsequent formation of reactive carbonyl compounds like (methyl)glyoxal. AGE accumulate in tissue where they cross-link with proteins, e.g., collagen, inducing tissue stiffening of blood vessels and skin. They may also interact with receptor of AGE (RAGE) and other receptors, which lead to activation of intracellular transduction mechanisms resulting in cytokine release and further tissue damage in CKD. The accumulation of AGE in the skin can be measured non-invasively using autofluorescence. The skin autofluorescence is a strong marker of cardiovascular mortality in CKD. The focus of this review is on the role of tissue and plasma AGE, and of skin autofluorescence as a proxy of tissue AGE accumulation, in the increase in cardiovascular disease in end stage renal disease (ESRD). This review will also present the possibility of reducing the AGE accumulation in ESRD patients using the following five methods: 1) use of low AGE peritoneal dialysis solutions; 2) use of advanced hemodialysis techniques; 3) use of AGE reducing drugs; 4) optimizing the nutrition of hemodialysis patients; and 5) renal transplantation. PMID:23612551

  11. Prevalence of skin diseases in female prisoners in Turkey: analysis of impact of prison conditions and psychological stress.

    PubMed

    Kocatürk, Emek; Kocatürk, Asiye; Kavala, Mukaddes

    2014-01-01

    Prisons have been studied as communal places where risk of contagious diseases and dermatological diseases associated with stress are more frequent. We aimed to investigate the prevalence of skin diseases in female prisoners with special focus on psychological stress. We held a day-time dermatology polyclinic for 6-weeks. The patients were given Beck Depression Inventory (BDI) and a questionnaire on the psychological impact of skin disease. A total of 383 female prisoners were examined; 41 dermatological diseases were diagnosed. Acne was the most prevalent condition (34%), followed by hair loss (19%), dry skin (16%), and eczema (12%). Thirty-six percent of the prisoners felt embarrassed, 34% felt anxious, and 45% felt sad about their skin disease. Fourty seven of the responders were found to be in severe depression according to BDI responses. We could not find any association between BDI results and any kind of skin disease diagnosed in inmates. Our study demonstrates that prisoners have benign and common skin conditions similar to those in the general population. PMID:24813838

  12. What is the discrepancy between drug permeation into/across intact and diseased skins? Atopic dermatitis as a model.

    PubMed

    Fang, Yi-Ping; Yang, Sien-Hung; Lee, Chih-Hung; Aljuffali, Ibrahim A; Kao, Hsiao-Ching; Fang, Jia-You

    2016-01-30

    The discrepancy in drug absorption between healthy and diseased skins is an issue that needs to be elucidated. The present study attempted to explore the percutaneous absorption of drugs via lesional skin by using atopic dermatitis (AD) as a model. Tape-stripping and ovalbumin (OVA) sensitization induced AD-like skin. The lesions were evaluated by physiological parameters, histology, cytokines, and differentiation proteins. The permeants of tacrolimus, 8-methoxypsoralen, methotrexate, and dextran were used to examine in vitro and in vivo cutaneous permeation. Transepidermal water loss (TEWL) increased from 5.2 to 27.4 g/m(2)/h by OVA treatment. AD-like lesions were characterized by hyperplasia, skin redness, desquamation, and infiltration of inflammatory cells. Repeated OVA challenge produced a T-helper 2 (Th2) hypersensitivity accompanied by downregulation of filaggrin, involucrin, and integrin β. Tacrolimus, the most lipophilic permeant, revealed an increase of cutaneous deposition by 2.7-fold in AD-like skin compared to intact skin. The transdermal flux of methotrexate and dextran, the hydrophilic permeants, across AD-like skin increased about 18 times compared to the control skin. Surprisingly, AD-like skin showed less skin deposition of 8-methoxypsoralen than intact skin. This may be because the deficient lipids in the atopic-affected stratum corneum (SC) diminished drug partitioning into the superficial skin layer. The fluorescence and confocal microscopic images demonstrated a broad and deep passage of small-molecular and macromolecular dyes into AD-like skin. The results obtained from this report were advantageous for showing how the lesional skin influenced percutaneous absorption. PMID:26657274

  13. 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

  14. Erythropoietic protoporphyria in the house mouse. A recessive inherited ferrochelatase deficiency with anemia, photosensitivity, and liver disease.

    PubMed Central

    Tutois, S; Montagutelli, X; Da Silva, V; Jouault, H; Rouyer-Fessard, P; Leroy-Viard, K; Guénet, J L; Nordmann, Y; Beuzard, Y; Deybach, J C

    1991-01-01

    A viable autosomal recessive mutation (named fch, or ferrochelatase deficiency) causing jaundice and anemia in mice arose in a mutagenesis experiment using ethylnitrosourea. Homozygotes (fch/fch) display a hemolytic anemia, photosensitivity, cholestasis, and severe hepatic dysfunction. Protoporphyrin is found at high concentration in erythrocytes, serum, and liver. Ferrochelatase activity in various tissues is 2.7-6.3% of normal. Heterozygotes (+/fch) are not anemic and have normal liver function; they are not sensitive to light exposure; ferrochelatase activity is 45-65% of normal. Southern blot analysis using a ferrochelatase cDNA probe reveals no gross deletion of the ferrochelatase gene. This is the first spontaneous form of erythropoietic protoporphyria in the house mouse. Despite the presence in the mouse of clinical and biochemical features infrequent in the human, this mutation may represent a model for the human disease, especially in its severe form. Images PMID:1939658

  15. 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

  16. Skin diseases and conditions among students of a medical college in southern India

    PubMed Central

    Joseph, Nitin; Kumar, Ganesh S; Nelliyanil, Maria

    2014-01-01

    Introduction: Skin diseases are a common problem among young adults. There is paucity of data about it among medical students. This study aimed to find out the pattern of skin disorders and to describe their association with various socio-demographic factors among medical students. Materials and Methods: This cross-sectional study was conducted in June 2011 in a medical college in Mangalore, Karnataka. Two-hundred and seventy eight medical students were chosen from the 4th, 6th and 8th semester through convenient sampling method. Data on hair and skin morbidities suffered over past 1 year and its associated factors were collected using a self-administered questionnaire. Results: Most of the participants 171 (61.5%) were of the age group 20-21 years and majority were females 148 (53.2%). The most common hair/skin morbidities suffered in the past one year were acne 185 (66.6%), hair loss 165 (59.3%), and sun tan 147 (52.9%). Fungal infection (P = 0.051) and severe type of acne (P = 0.041) were seen significantly more among males while hair morbidities like hair loss (P = 0.003), split ends of hairs (P < 0.0001) and dandruff (P =0.006) were seen significantly more among female students. Patterned baldness (P = 0.018) and sun tan (P < 0.0001) were significantly more among non-Mangalorean students than native Mangaloreans. Presence of dandruff was significantly associated with hair loss (P = 0.039) and usage of sunscreen was found to protect from developing sun tans (P = 0.049). Conclusion: Skin disorders, particularly the cosmetic problems are very common among medical students. Gender and place of origin were found to significantly influence the development of certain morbidities. PMID:24616849

  17. 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

  18. Toward the first class of suicide inhibitors of kallikreins involved in skin diseases.

    PubMed

    Tan, Xiao; Soualmia, Feryel; Furio, Laetitia; Renard, Jean-François; Kempen, Isabelle; Qin, Lixian; Pagano, Maurice; Pirotte, Bernard; El Amri, Chahrazade; Hovnanian, Alain; Reboud-Ravaux, Michèle

    2015-01-22

    The inhibition of kallikreins 5 and 7, and possibly kallikrein 14 and matriptase, (that initiates the kallikrein proteolytic cascade) constitutes an innovative way to treat some skin diseases such as Netherton syndrome. We present here the inhibitory properties of coumarin-3-carboxylate derivatives against these enzymes. Our small collection of these versatile organic compounds was enriched by newly synthesized derivatives in order to obtain molecules selective against one, two, three enzymes or acting on the four ones. We evidenced a series of compounds with IC50 values in the nanomolar range. A suicide mechanism was observed against kallikrein 7 whereas the inactivation was either definitive (suicide type) or transient for kallikreins 5 and 14, and matriptase. Most of these potent inhibitors were devoid of cytotoxicity toward healthy human keratinocytes. In situ zymography investigations on skin sections from human kallikrein 5 transgenic mouse revealed significant reduction of the global proteolytic activity by several compounds. PMID:25489658

  19. 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

  20. 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. PMID:22244689

  1. 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

  2. Innate immunity and the role of the antimicrobial peptide cathelicidin in inflammatory skin disease

    PubMed Central

    Roby, Keith D; Nardo, Anna Di

    2013-01-01

    Cathelicidin antimicrobial peptide is an important mediator of the innate immune response. In addition to its potent antimicrobial activity, cathelicidin has been shown to have chemoattractant and angiogenic properties. Recent research has demonstrated that, in addition to its aforementioned functions, cathelicidin plays an important role in the complex pathogenesis of several chronic inflammatory skin diseases. This review will present a concise overview of the role of cathelicidin in infection and in the development of atopic dermatitis, psoriasis, and rosacea. This understanding will direct future research efforts to identify therapeutic approaches that use cathelicidin as a novel drug itself, or aim to modify its expression and regulation. PMID:24489580

  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. 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

  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. 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. PMID:15265721

  7. Impact of daily cooling treatment on skin inflammation in patients with chronic venous disease

    PubMed Central

    Mueller, Martina; King, Dana E.; Madisetti, Mohan; Prentice, Margie

    2015-01-01

    People with chronic venous disease are at high risk for developing venous leg ulcers. Inflammation is posited as a pathological factor for this chronic condition as evidenced by persistently elevated skin temperature. As part of a larger trial to test the effects of a cooling regimen on leg ulcer prevention, the objective of this preliminary study was to evaluate the first 30 days of intense daily cooling. Compared to a placebo control cuff, a gel cuff applied to the most severely affected lower leg skin for 30 minutes daily showed no statistically significant differences between temperatures taken in the home at baseline compared to those measured at the 1 month follow up visit. There were also no differences in temperatures noted between the two groups, although the temperatures in the treatment group were lower 30 minutes after treatment, an indication of adherence. There was no discernable decrease or increase in temperature at a given time point during the 30 day treatment period compared to the control group. It may be better to have patients monitor skin temperature on a daily basis and then apply the cuff as necessary, rather than requiring daily cooling based on baseline measurement. This “prn” approach may provide a sufficient cooling milieu to prevent escalation of inflammation and thwart ulcer occurrence or recurrence. Clinical trials registration #NCT01509599 PMID:25703058

  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. PMID:24373349

  9. 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

  10. Fabry disease: an ultrastructural comparative study of skin in hemizygous and heterozygous patients.

    PubMed

    Navarro, Carmen; Teijeira, Susana; Dominguez, Carmen; Fernandez, Jose M; Rivas, Eloy; Fachal, Carmen; Barrera, Soraya; Rodriguez, Carmen; Iranzo, Pilar

    2006-02-01

    Fabry disease is a rare X-linked lysosomal storage disorder due to alpha galactosidase A deficiency, better known after the advent of a promising treatment, a periodical enzyme replacement. As other hereditary X-linked disorders, females have historically been considered non-affected carriers, although they are, actually, clinically and pathologically affected to a variable degree. Some women are asymptomatic, but the majority present milder forms of the disease and later onset. This wide range of disease expression is supposed to be related to the levels of enzymatic activity, probably in accordance with a skewing of X inactivation. Lysosomal deposits of ceramide trihexoside have been repeatedly documented in a wide range of tissues, including those found in angiokeratoma, the characteristic cutaneous lesion which allowed the definition of Fabry disease. The aim of this study was to investigate whether there was any difference in the amount of dermal lysosomal storage in males and females, thus accounting for the difference in clinical severity of both groups. For that purpose, with electron microscopy and quantitative methods, we studied the extent of lysosomal deposits in dermal fibroblasts of normal-appearing skin in six females and nine men, enzymatically and genetically proven as to have Fabry disease, and results were compared. Our results indicate a statistically significant difference between the two groups regarding both the percentage of dermal fibroblasts bearing stored material, and the storage surface occupied in 100 fibroblasts per case. We suggest that periodical ultrastructural examination of normal-appearing skin could be an indicator of the efficacy of enzyme replacement therapy and could help to evaluate results. PMID:16463201

  11. Skin Diseases: Skin Health and Skin Diseases

    MedlinePlus

    ... suggest over-the-counter (OTC) or prescription drugs. Eczema © 2008 Logical Images, Inc. Eczema —Also known as atopic dermatitis, this is a ... Currently, there is no single test to diagnose eczema, so doctors rely on information about you and ...

  12. [Inherited amino acid transport disorders].

    PubMed

    Igarashi, Y; Tada, K

    1992-07-01

    Disorders due to inherited amino acids transport defect are reviewed. The disorders were categorized into three types of transport defects, namely, brush-border membrane of epithelial cells of small intestine and kidney tubules (Hartnup disease, blue diaper syndrome, cystinuria, iminoglycinuria and lysine malabsorption syndrome), basolateral membrane (lysinuric protein intolerance) and membrane of intracellular organelles (cystinosis and hyperornitinemia-hyperammonemia-homocitrullinuria syndrome). Pathogenesis, clinical feature, laboratory findings, diagnosis, genetics and treatment of these disorders are described, briefly. There is not much data for the transport systems themselves, so that further investigation in molecular and gene levels for transport systems is necessary to clarify the characteristics of the transport and heterogeneity of phenotypes in inherited amino acids transport disorders. PMID:1404888

  13. Clinical application of multiphoton tomography in combination with high-frequency ultrasound for evaluation of skin diseases.

    PubMed

    König, Karsten; Speicher, Marco; Köhler, Martin J; Scharenberg, Rüdiger; Kaatz, Martin

    2010-12-01

    The first-ever application of high-frequency ultrasound combined with multiphoton tomography (MPT) and dermoscopy in a clinical trial is reported. 47 patients with 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 and (iii) dermoscopes. Dermoscopy provides two-dimensional color images of the skin surface with a magnification up to 70 x. Depending on the ultrasonic frequencies from 7.5 MHz to 100 MHz, the signal depth varies from about 1 mm to 80 mm. Vertical ultrasound wide-field images provide fast information on depth and volume of the lesion. The 100 MHz ultrasound allows imaging with resolutions down to 16 μm (axial) and 32 μm (lateral). Multiphoton tomography provides 0.36 x 0.36 x 0.001 mm³ horizontal optical sections of a particular region of interest with submicron resolution down to 200 μm tissue depth. The autofluorescence of mitochondrial coenzymes, keratin, melanin, and elastin as well as the network of collagen structures can be imaged. The combination of ultrasound and MPT opens novel synergistic possibilities in diagnostics of skin diseases with a special focus on the early detection of skin cancer as well as the evaluation of treatments. PMID:20680976

  14. Immunological, hematological, biochemical, and histopathological studies on cows naturally infected with lumpy skin disease

    PubMed Central

    Neamat-Allah, Ahmed N. F.

    2015-01-01

    Aim: Lumpy skin disease (LSD) is an infectious viral disease of cattle caused by LSD virus (LSDV) of the family Poxviridae characterized by skin nodules covering all parts of the body. There are many aspects of LSD remaining unknown, thus immunological, hematological, and biochemical parameters were estimated. Materials and Methods: During an outbreak of LSD in Sharkia governorate from Egypt, 211 cows aging (2-4 years) were examined clinically for the presence of LSD lesions during the period from July to November 2014. A total of 134 cows from those showed lesions suspected to be LSD. Results: Recorded clinical signs were pyrexia with the development of skin nodules of varying sizes which ranged from a few to several hundred sometimes coalesced together. Enlargements of the peripheral lymph nodes. Intracytoplasmic inclusion bodies were noticed in the histopathological examination. Immunological studies revealed a significant decrease of lymphocyte transformation rate, phagocytic % and killing % which was marked within 2 weeks postinfection. LSD resulted in non-significant in hemogram in 1st-2nd day post-infection while a macrocytic hypochromic anemia within 10-14th days post-infection. Leucopenia and lymphopenia were recorded 1st-2nd day post-infection while at 10-14th showed granulocytic leucocytosis. Biochemical analysis revealed hypoproteinemia, hypoalbuminemia, and hyperglobulinemia especially gamma globulins. There were a significant increase in serum alanine aminotransferase, aspartate aminotransferase activities, creatinine level, blood urea nitrogen and creatine phosphokinase Conclusion: LSDV infected cows in early stages revealed leucopenia. Immunosuppressive effect was pronounced later. In late stage revealed hemolytic anemia, leucocytosis and increase of serum CK, which could aid in diagnosis. Disturbance in liver and kidney function tests have been occurred. PMID:27047209

  15. How Is Wilson Disease Inherited?

    MedlinePlus

    ... ATP7B gene have been identified thus far. Testing Methods Available: Linkage analysis (Haplotype analysis) Molecular genetic testing ... genetic counselor who can carefully discuss the best method of testing to perform and the benefits, limitations, ...

  16. The wound/burn guidelines - 4: Guidelines for the management of skin ulcers associated with connective tissue disease/vasculitis.

    PubMed

    Fujimoto, Manabu; Asano, Yoshihide; Ishii, Takayuki; Ogawa, Fumihide; Kawakami, Tamihiro; Kodera, Masanari; Abe, Masatoshi; Isei, Taiki; Ito, Takaaki; Inoue, Yuji; Imafuku, Shinichi; Irisawa, Ryokichi; Ohtsuka, Masaki; Ohtsuka, Mikio; Kadono, Takafumi; Kawaguchi, Masakazu; Kukino, Ryuichi; Kono, Takeshi; Sakai, Keisuke; Takahara, Masakazu; Tanioka, Miki; Nakanishi, Takeshi; Nakamura, Yasuhiro; Hashimoto, Akira; Hasegawa, Minoru; Hayashi, Masahiro; Fujiwara, Hiroshi; Maekawa, Takeo; Matsuo, Koma; Madokoro, Naoki; Yamasaki, Osamu; Yoshino, Yuichiro; Le Pavoux, Andres; Tachibana, Takao; Ihn, Hironobu

    2016-07-01

    The Japanese Dermatological Association prepared guidelines focused on the treatment of skin ulcers associated with connective tissue disease/vasculitis practical in clinical settings of dermatological care. Skin ulcers associated with connective tissue diseases or vasculitis occur on the background of a wide variety of diseases including, typically, systemic sclerosis but also systemic lupus erythematosus (SLE), dermatomyositis, rheumatoid arthritis (RA), various vasculitides and antiphospholipid antibody syndrome (APS). Therefore, in preparing the present guidelines, we considered diagnostic/therapeutic approaches appropriate for each of these disorders to be necessary and developed algorithms and clinical questions for systemic sclerosis, SLE, dermatomyositis, RA, vasculitis and APS. PMID:26972733

  17. 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.

  18. 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

  19. 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

  20. Prevalence of self-medication for skin diseases: a systematic review*

    PubMed Central

    Corrêa-Fissmer, Mariane; Mendonça, Mariana Gaspar; Martins, Anesio Henrique; Galato, Dayani

    2014-01-01

    Self-medication is the selection and use of drugs without medical prescription, to treat diseases or for symptomatic relief. This article is a systematic review on self-medication in skin diseases. A search was conducted on Virtual Health Library and PubMed databases using predetermined descriptors. Two researchers performed the article selection process independently, with the degree of inter-observer agreement measured by the kappa index. The prevalence of self-medication ranged from 6.0 to 45.0%. Topical corticosteroids were the most commonly used therapeutic strategies for self-medication, as found in the reviewed articles. This study revealed that published data on self-medication in dermatology are scarce, although the findings showed that it was a common practice.

  1. Neutrophilic dermatoses and autoinflammatory diseases with skin involvement--innate immune disorders.

    PubMed

    Navarini, Alexander A; Satoh, Takashi K; French, Lars E

    2016-01-01

    Neutrophilic dermatoses (NDs) such as Sweet's syndrome and pyoderma gangrenosum were first described more than 50 years ago and grouped based on their clinical features combined with the typical, neutrophil-rich cutaneous inflammation. In contrast, the recently identified autoinflammatory diseases (ADs) that are also associated with neutrophil granulocyte infiltration of the skin were first characterized based on their genetic architecture. Though both the older ND and the newer AD encompass distinct conditions, they can be seen as parts of a spectrum of innate inflammation. Both groups of diseases show so many overlapping clinical, pathogenetic, histologic, and genetic features that together they should likely be considered as innate immune disorders. PMID:26620372

  2. Demonstration of lumpy skin disease virus infection in Amblyomma hebraeum and Rhipicephalus appendiculatus ticks using immunohistochemistry.

    PubMed

    Lubinga, Jimmy C; Clift, Sarah J; Tuppurainen, Eeva S M; Stoltsz, Wilhem H; Babiuk, Shawn; Coetzer, Jacobus A W; Venter, Estelle H

    2014-03-01

    Lumpy skin disease (LSD) is caused by lumpy skin disease virus (LSDV), a member of the genus Capripoxvirus. Transmission of the virus has been associated with haematophagous insects such as Stomoxys calcitrans as well as Aedes and Culex species of mosquitoes. Recent studies have reported the transmission of the virus by Amblyomma hebraeum, Rhipicephalus appendiculatus, and Rhipicephalus decoloratus ticks and the presence of LSDV in saliva of A. hebraeum and R. appendiculatus ticks. The aim of this study was to determine which tick organs become infected by LSDV following intrastadial infection and transstadial persistence of the virus in A. hebraeum and R. appendiculatus ticks. Nymphal and adult ticks were orally infected by feeding them on LSDV-infected cattle. Partially fed adult ticks were processed for testing while nymphs were fed to repletion and allowed to moult to adults before being processed for testing. The infection in tick organs was determined by testing for the presence of the viral antigen using monoclonal antibodies with immunohistochemical staining. The viral antigen was detected in salivary glands, haemocytes, synganglia, ovaries, testes, fat bodies, and midgut. Since the virus was shown to be able to cross the midgut wall and infect various tick organs, this may indicate potential for biological development and transmission of LSDV in ticks. This study strengthens the previously reported evidence of the occurrence of LSDV in tick saliva. PMID:24287140

  3. 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. PMID:27396816

  4. Epigenetic Inheritance in Rice Plants

    PubMed Central

    Akimoto, Keiko; Katakami, Hatsue; Kim, Hyun-Jung; Ogawa, Emiko; Sano, Cecile M.; Wada, Yuko; Sano, Hiroshi

    2007-01-01

    -for-gene manner, the progeny of Line-2 were apparently resistant while the wild type was highly susceptible without Xa21G expression. Conclusions These results indicated that demethylation was selective in Line-2, and that promoter demethylation abolished the constitutive silencing of Xa21G due to hypermethylation, resulting in acquisition of disease resistance. Both hypomethylation and resistant trait were stably inherited. This is a clear example of epigenetic inheritance, and supports the idea of Lamarckian inheritance which suggested acquired traits to be heritable. PMID:17576658

  5. The contribution of de novo and rare inherited copy number changes to congenital heart disease in an unselected sample of children with conotruncal defects or hypoplastic left heart disease

    PubMed Central

    Ronemus, Michael; Kline, Jennie; Jobanputra, Vaidehi; Williams, Ismee; Anyane-Yeboa, Kwame; Chung, Wendy; Yu, Lan; Wong, Nancy; Awad, Danielle; Yu, Chih-yu; Leotta, Anthony; Kendall, Jude; Yamrom, Boris; Lee, Yoon-ha; Wigler, Michael; Levy, Dan

    2013-01-01

    Congenital heart disease (CHD) is the most common congenital malformation, with evidence of a strong genetic component. We analyzed data from 223 consecutively ascertained families, each consisting of at least one child affected by a conotruncal defect (CNT) or hypoplastic left heart disease (HLHS) and both parents. The NimbleGen HD2-2.1 comparative genomic hybridization platform was used to identify de novo and rare inherited copy number variants (CNVs). Excluding 10 cases with 22q11.2 DiGeorge deletions, we validated de novo CNVs in 8 % of 148 probands with CNTs, 12.7 % of 71 probands with HLHS and none in 4 probands with both. Only 2 % of control families showed a de novo CNV. We also identified a group of ultra-rare inherited CNVs that occurred de novo in our sample, contained a candidate gene for CHD, recurred in our sample or were present in an affected sibling. We confirmed the contribution to CHD of copy number changes in genes such as GATA4 and NODAL and identified several genes in novel recurrent CNVs that may point to novel CHD candidate loci. We also found CNVs previously associated with highly variable pheno-types and reduced penetrance, such as dup 1q21.1, dup 16p13.11, dup 15q11.2-13, dup 22q11.2, and del 2q23.1. We found that the presence of extra-cardiac anomalies was not related to the frequency of CNVs, and that there was no significant difference in CNV frequency or specificity between the probands with CNT and HLHS. In agreement with other series, we identified likely causal CNVs in 5.6 % of our total sample, half of which were de novo. PMID:23979609

  6. Genome-Wide Locations of Potential Epimutations Associated with Environmentally Induced Epigenetic Transgenerational Inheritance of Disease Using a Sequential Machine Learning Prediction Approach

    PubMed Central

    Haque, M. Muksitul; Holder, Lawrence B.; Skinner, Michael K.

    2015-01-01

    Environmentally induced epigenetic transgenerational inheritance of disease and phenotypic variation involves germline transmitted epimutations. The primary epimutations identified involve altered differential DNA methylation regions (DMRs). Different environmental toxicants have been shown to promote exposure (i.e., toxicant) specific signatures of germline epimutations. Analysis of genomic features associated with these epimutations identified low-density CpG regions (<3 CpG / 100bp) termed CpG deserts and a number of unique DNA sequence motifs. The rat genome was annotated for these and additional relevant features. The objective of the current study was to use a machine learning computational approach to predict all potential epimutations in the genome. A number of previously identified sperm epimutations were used as training sets. A novel machine learning approach using a sequential combination of Active Learning and Imbalance Class Learner analysis was developed. The transgenerational sperm epimutation analysis identified approximately 50K individual sites with a 1 kb mean size and 3,233 regions that had a minimum of three adjacent sites with a mean size of 3.5 kb. A select number of the most relevant genomic features were identified with the low density CpG deserts being a critical genomic feature of the features selected. A similar independent analysis with transgenerational somatic cell epimutation training sets identified a smaller number of 1,503 regions of genome-wide predicted sites and differences in genomic feature contributions. The predicted genome-wide germline (sperm) epimutations were found to be distinct from the predicted somatic cell epimutations. Validation of the genome-wide germline predicted sites used two recently identified transgenerational sperm epimutation signature sets from the pesticides dichlorodiphenyltrichloroethane (DDT) and methoxychlor (MXC) exposure lineage F3 generation. Analysis of this positive validation data set

  7. Digenic inheritance in medical genetics

    PubMed Central

    Schäffer, Alejandro A

    2013-01-01

    Digenic inheritance (DI) is the simplest form of inheritance for genetically complex diseases. By contrast with the thousands of reports that mutations in single genes cause human diseases, there are only dozens of human disease phenotypes with evidence for DI in some pedigrees. The advent of high-throughput sequencing (HTS) has made it simpler to identify monogenic disease causes and could similarly simplify proving DI because one can simultaneously find mutations in two genes in the same sample. However, through 2012, I could find only one example of human DI in which HTS was used; in that example, HTS found only the second of the two genes. To explore the gap between expectation and reality, I tried to collect all examples of human DI with a narrow definition and characterise them according to the types of evidence collected, and whether there has been replication. Two strong trends are that knowledge of candidate genes and knowledge of protein–protein interactions (PPIs) have been helpful in most published examples of human DI. By contrast, the positional method of genetic linkage analysis, has been mostly unsuccessful in identifying genes underlying human DI. Based on the empirical data, I suggest that combining HTS with growing networks of established PPIs may expedite future discoveries of human DI and strengthen the evidence for them. PMID:23785127

  8. Oxidative stress in skin fibroblasts cultures from patients with Parkinson's disease

    PubMed Central

    2010-01-01

    Background In the substantia nigra of Parkinson's disease (PD) patients, increased lipid peroxidation, decreased activities of the mitochondrial complex I of the respiratory chain, catalase and glutathione-peroxidase, and decreased levels of reduced glutathione have been reported. These observations suggest that oxidative stress and mitochondrial dysfunction play a role in the neurodegeneration in PD. We assessed enzymatic activities of respiratory chain and other enzymes involved in oxidative processes in skin fibroblasts cultures of patients with PD. Methods We studied respiratory chain enzyme activities, activities of total, Cu/Zn- and Mn-superoxide-dismutase, gluthatione-peroxidase and catalase, and coenzyme Q10 levels in skin fibroblasts cultures from 20 Parkinson's disease (PD) patients and 19 age- and sex- matched healthy controls. Results When compared with controls, PD patients showed significantly lower specific activities for complex V (both corrected by citrate synthase activity and protein concentrations). Oxidized, reduced and total coenzyme Q10 levels (both corrected by citrate synthase and protein concentrations), and activities of total, Cu/Zn- and Mn-superoxide-dismutase, gluthatione-peroxidase and catalase, did not differ significantly between PD-patients and control groups. Values for enzyme activities in the PD group did not correlate with age at onset, duration, scores of the Unified Parkinson's Disease Rating scales and Hoehn-Yahr staging. Conclusions The main result of this study was the decreased activity of complex V in PD patients. This complex synthesizes ATP from ADP using an electrochemical gradient generated by complexes I-IV. These results suggest decreased energetic metabolism in fibroblasts of patients with PD. PMID:20958999

  9. Interacting Symbionts and Immunity in the Amphibian Skin Mucosome Predict Disease Risk and Probiotic Effectiveness

    PubMed Central

    Woodhams, Douglas C.; Brandt, Hannelore; Baumgartner, Simone; Kielgast, Jos; Küpfer, Eliane; Tobler, Ursina; Davis, Leyla R.; Schmidt, Benedikt R.; Bel, Christian; Hodel, Sandro; Knight, Rob; McKenzie, Valerie

    2014-01-01

    Pathogenesis is strongly dependent on microbial context, but development of probiotic therapies has neglected the impact of ecological interactions. Dynamics among microbial communities, host immune responses, and environmental conditions may alter the effect of probiotics in human and veterinary medicine, agriculture and aquaculture, and the proposed treatment of emerging wildlife and zoonotic diseases such as those occurring on amphibians or vectored by mosquitoes. Here we use a holistic measure of amphibian mucosal defenses to test the effects of probiotic treatments and to assess disease risk under different ecological contexts. We developed a non-invasive assay for antifungal function of the skin mucosal ecosystem (mucosome function) integrating host immune factors and the microbial community as an alternative to pathogen exposure experiments. From approximately 8500 amphibians sampled across Europe, we compared field infection prevalence with mucosome function against the emerging fungal pathogen Batrachochytrium dendrobatidis. Four species were tested with laboratory exposure experiments, and a highly susceptible species, Alytes obstetricans, was treated with a variety of temperature and microbial conditions to test the effects of probiotic therapies and environmental conditions on mucosome function. We found that antifungal function of the amphibian skin mucosome predicts the prevalence of infection with the fungal pathogen in natural populations, and is linked to survival in laboratory exposure experiments. When altered by probiotic therapy, the mucosome increased antifungal capacity, while previous exposure to the pathogen was suppressive. In culture, antifungal properties of probiotics depended strongly on immunological and environmental context including temperature, competition, and pathogen presence. Functional changes in microbiota with shifts in temperature provide an alternative mechanistic explanation for patterns of disease susceptibility related

  10. High Prevalence of Skin Diseases and Need for Treatment in a Middle-Aged Population. A Northern Finland Birth Cohort 1966 Study

    PubMed Central

    Sinikumpu, Suvi-Päivikki; Huilaja, Laura; Jokelainen, Jari; Koiranen, Markku; Auvinen, Juha; Hägg, Päivi M.; Wikström, Erika; Timonen, Markku; Tasanen, Kaisa

    2014-01-01

    To determine the overall prevalence of skin diseases a whole-body skin examination was performed for 1,932 members (46-years of age) of the Northern Finland Birth Cohort (NFBC 1966), which is a comprehensive longitudinal research program (N = 12,058). A high prevalence of all skin diseases needing treatment was found (N = 1,158). Half of the cases of skin findings were evaluated to be serious enough to require diagnostic evaluation, treatment or follow-up either in a general health care, occupational health care or a secondary care setting. The remaining half were thought to be slight and self-treatment was advised. Males (70%) had more skin diseases needing treatment than females (52%) (P<0.001). The most common skin finding was a benign skin tumor, which was found in every cohort member. Skin infections (44%), eczemas (27%) and sebaceous gland diseases (27%) were the most common skin diseases in the cohort. Moreover, skin infections and eczemas were more commonly seen in the group with low education compared to those with high education (P<0.005). The results strengthen the postulate that skin diseases are common in an adult population. PMID:24911008

  11. Developmental origins of epigenetic transgenerational inheritance

    PubMed Central

    Hanson, Mark A.; Skinner, Michael K.

    2016-01-01

    Environmental factors can induce epigenetic alterations in the germ cells that can potentially be transmitted transgenerationally. This non-genetic form of inheritance is termed epigenetic transgenerational inheritance and has been shown in a variety of species including plants, flies, worms, fish, rodents, pigs, and humans. This phenomenon operates during specific critical windows of exposure, linked to the developmental biology of the germ cells (sperm and eggs). Therefore, concepts of the developmental origins of transgenerational inheritance of phenotypic variation and subsequent disease risk need to include epigenetic processes affecting the developmental biology of the germ cell. These developmental impacts on epigenetic transgenerational inheritance, in contrast to multigenerational exposures, are the focus of this Perspective. PMID:27390622

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

    PubMed Central

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

    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. PMID:27171415

  13. 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. PMID:27171415

  14. [Genodermatoses with malignant skin tumors].

    PubMed

    Hübinger, L; Frank, J

    2014-06-01

    Cutaneous malignancies can manifest as isolated and sporadic tumors as well as multiple and disseminated tumors. In the latter case they often point to a genetic disease, which either can be restricted to the skin exclusively or also involve extracutaneous organs in the context of a hereditary tumor syndrome. Such hereditary tumor syndromes are clinically and genetically very heterogeneous. Therefore, the prevailing specific skin tumors play an important diagnostic role in the case of complex symptom constellations. Elucidation of the genetic basis of rare monogenetically inherited disorders and syndromes can contribute to a better understanding of the pathogenesis of frequently occurring cutaneous malignancies because the mutated genes often encode proteins, which have a key position in metabolic signaling pathways that are of high significance for the development of targeted therapies. Here we provide an overview of genodermatoses, which are associated with basal cell carcinomas, sebaceous carcinomas, keratoacanthomas, squamous cell carcinomas and malignant melanomas. PMID:24898507

  15. Chronic Pruritus in the Absence of Skin Disease: Pathophysiology, Diagnosis and Treatment.

    PubMed

    Pereira, Manuel P; Kremer, Andreas E; Mettang, Thomas; Ständer, Sonja

    2016-08-01

    Chronic pruritus arises not only from dermatoses, but also, in up to half of cases, from extracutaneous origins. A multitude of systemic, neurological, psychiatric, and somatoform conditions are associated with pruritus in the absence of skin disease. Moreover, pruritus is a frequently observed side effect of many drugs. It is therefore difficult for physicians to make a correct diagnosis. Chronic pruritus patients frequently present to the dermatologist with skin lesions secondary to a long-lasting scratching behavior, such as lichenification and prurigo nodularis. A structured clinical history and physical examination are essential in order to evaluate the pruritus, along with systematic, medical history-adapted laboratory and radiological tests carried out according to the differential diagnosis. For therapeutic reasons, a symptomatic therapy should be promptly initiated parallel to the diagnostic procedures. Once the underlying factor(s) leading to the pruritus are identified, a targeted therapy should be implemented. Importantly, the treatment of accompanying disorders such as sleep disturbances or mental symptoms should be taken into consideration. Even after successful treatment of the underlying cause, pruritus may persist, likely due to chronicity processes including peripheral and central sensitization or impaired inhibition at spinal level. A vast arsenal of topical and systemic agents targeting these pathophysiological mechanisms has been used to deter further chronicity. The therapeutic options currently available are, however, still insufficient for many patients. Thus, future studies aiming to unveil the complex mechanisms underlying chronic pruritus and develop new therapeutic agents are urgently needed. PMID:27216284

  16. Skin Disease in the Uninsured: Diagnoses, Management Decisions, and Referral Outcomes of an Urban Free Clinic.

    PubMed

    Rosenbaum, Brooke E; Freitas, Derek; Nosal, Sarah C; Meydani, Ahou

    2016-01-01

    An understanding of the burden of skin disease in the uninsured population is needed to address the unique barriers they face to access dermatologic care. We conducted a retrospective chart review of patients seen for skin conditions over three years at the New York City (NYC) Free Clinic, a weekly primary care clinic operated by the NYU School of Medicine and the Institute for Family Health. Main outcomes of this study were descriptive analyses of demographic characteristics, diagnoses, management strategies, and referral outcomes, as well as key factors influencing referral to a dermatologist and referral attendance. Diagnosis was a significant predictor of referral (p<.000). The referral attendance rate was 52.5%. Patients older than 50 years were more likely to attend their appointments than younger patients (p=.025). Gender, wait time, and travel distance had no significant association with non-attendance. While demand for dermatologic care by uninsured patients in NYC is high, referral non-attendance remains a substantial barrier to care. PMID:27180711

  17. Scalded skin syndrome

    MedlinePlus

    Ritter disease; Staphylococcal scalded skin syndrome (SSS) ... Scalded skin syndrome (SSS) is caused by infection with certain strains of Staphylococcus bacteria. The bacteria produce a toxin that causes the skin ...

  18. [Therapy of inherited diseases of platelet function. Interdisciplinary S2K guideline of the Permanent Paediatric Committee of the Society of Thrombosis and Haemostasis Research (GTH e. V.)].

    PubMed

    Streif, W; Knöfler, R; Eberl, W; Andres, O; Bakchoul, T; Bergmann, F; Beutel, K; Dittmer, R; Gehrisch, S; Gottstein, S; Halimeh, S; Haselböck, J; Hassenpflug, W-A; Heine, S; Holzhauer, S; King, S; Kirchmaier, C M; Krause, M; Kreuz, W; Lösche, W; Mahnel, R; Maurer, M; Nimtz-Talaska, A; Olivieri, M; Rott, H; Schambeck, Ch M; Schedel, A; Schilling, F H; Schmugge, M; Schneppenheim, R; Scholz, U; Scholz, T; Schulze, H; Siegemund, A; Strauß, G; Sykora, K-W; Wermes, C; Wiegering, V; Wieland, I; Zieger, B; Zotz, R B

    2014-01-01

    Inherited disorders of platelet function are a heterogeneous group. For optimal prevention and management of bleeding, classification and diagnosis of the underlying defect are highly recommended. An interdisciplinary guideline for a diagnostic approach has been published (AWMF # 086-003 S2K; Hämostaseologie 2014; 34: 201-212). Underlying platelet disorder, platelet count, age and clinical situation modify treatment. Exclusive transfusion of platelet concentrates may be inappropriate as potentially adverse effects can outweigh its benefit. A stepwise and individually adjusted approach for restitution and maintenance of haemostasis is recommended. Administration of antifibrinolytics is generally endorsed, but is of particular use in Quebec disease. Restricted to older children, desmopressin is favourable in storage pool disease and unclassified platelet disorders. Although licensed only for patients with Glanzmann thrombasthenia and alloantibodies, in clinical practice rFVIIa is widely used in inherited platelet disorders with severe bleeding tendency. This guideline aims at presenting the best available advice for the management of patients with inherited platelet function disorders. PMID:25370176

  19. Nuclear receptor function in skin health and disease: therapeutic opportunities in the orphan and adopted receptor classes.

    PubMed

    Yin, Kelvin; Smith, Aaron G

    2016-10-01

    The skin forms a vital barrier between an organism's external environment, providing protection from pathogens and numerous physical and chemical threats. Moreover, the intact barrier is essential to prevent water and electrolyte loss without which terrestrial life could not be maintained. Accordingly, acute disruption of the skin through physical or chemical trauma needs to be repaired timely and efficiently as sustained skin pathologies ranging from mild irritations and inflammation through to malignancy impact considerably on morbidity and mortality. The Nuclear Hormone Receptor Family of transcriptional regulators has proven to be highly valuable targets for addressing a range of pathologies, including metabolic syndrome and cancer. Indeed members of the classic endocrine sub-group, such as the glucocorticoid, retinoid, and Vitamin D receptors, represent mainstay treatment strategies for numerous inflammatory skin disorders, though side effects from prolonged use are common. Emerging evidence has now highlighted important functional roles for nuclear receptors belonging to the adopted and orphan subgroups in skin physiology and patho-physiology. This review will focus on these subgroups and explore the current evidence that suggests these nuclear receptor hold great promise as future stand-alone or complementary drug targets in treating common skin diseases and maintaining skin homeostasis. PMID:27544210

  20. Oral mucosal lesions in skin diseased patients attending a dermatologic clinic: a cross-sectional study in Sudan

    PubMed Central

    2011-01-01

    Background So far there have been no studies focusing on the prevalence of a wide spectrum of oral mucosal lesions (OML) in patients with dermatologic diseases. This is noteworthy as skin lesions are strongly associated with oral lesions and could easily be neglected by dentists. This study aimed to estimate the frequency and socio-behavioural correlates of OML in skin diseased patients attending outpatient's facility of Khartoum Teaching Hospital - Dermatology Clinic, Sudan. Methods A cross-sectional hospital-based study was conducted in Khartoum from October 2008 to January 2009. A total of 588 patients (mean age 37.2 ± 16 years, 50.3% females) completed an oral examination and a personal interview of which 544 patients (mean age 37.1 ± 15.9 years, 50% females) with confirmed skin disease diagnosis were included for further analyses. OML were recorded using the World Health Organization criteria (WHO). Biopsy and smear were used as adjuvant techniques for confirmation. Data were analysed using the Statistical Package for Social Science (Version 15.0.1). Cross tabulation and Chi-square with Fisher's exact test were used. Results A total of 438 OML were registered in 315 (57.9%, males: 54.6% versus females: 45.6%, p < 0.05) skin diseased patients. Thus, a certain number of patients had more than one type of OML. Tongue lesions were the most frequently diagnosed OML (23.3%), followed in descending order by white lesions (19.1%), red and blue lesions (11%) and vesiculobullous diseases (6%). OML in various skin diseases were; vesiculobullous reaction pattern (72.2%), lichenoid reaction pattern (60.5%), infectious lesions (56.5%), psoriasiform reaction pattern (56.7%), and spongiotic reaction pattern (46.8%). Presence of OML in skin diseased patients was most frequent in older age groups (62.4% older versus 52.7% younger, p < 0.05), in males (63.2% males versus 52.6% females, p < 0.05), patients with a systemic disease (65.2% with systemic versus 51.9% without