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Sample records for pseudoxanthoma elasticum pxe

  1. Zebrafish enpp1 mutants exhibit pathological mineralization, mimicking features of generalized arterial calcification of infancy (GACI and pseudoxanthoma elasticum (PXE

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    Alexander Apschner

    2014-07-01

    Full Text Available In recent years it has become clear that, mechanistically, biomineralization is a process that has to be actively inhibited as a default state. This inhibition must be released in a rigidly controlled manner in order for mineralization to occur in skeletal elements and teeth. A central aspect of this concept is the tightly controlled balance between phosphate, a constituent of the biomineral hydroxyapatite, and pyrophosphate, a physiochemical inhibitor of mineralization. Here, we provide a detailed analysis of a zebrafish mutant, dragonfish (dgf, which is mutant for ectonucleoside pyrophosphatase/phosphodiesterase 1 (Enpp1, a protein that is crucial for supplying extracellular pyrophosphate. Generalized arterial calcification of infancy (GACI is a fatal human disease, and the majority of cases are thought to be caused by mutations in ENPP1. Furthermore, some cases of pseudoxanthoma elasticum (PXE have recently been linked to ENPP1. Similar to humans, we show here that zebrafish enpp1 mutants can develop ectopic calcifications in a variety of soft tissues – most notably in the skin, cartilage elements, the heart, intracranial space and the notochord sheet. Using transgenic reporter lines, we demonstrate that ectopic mineralizations in these tissues occur independently of the expression of typical osteoblast or cartilage markers. Intriguingly, we detect cells expressing the osteoclast markers Trap and CathepsinK at sites of ectopic calcification at time points when osteoclasts are not yet present in wild-type siblings. Treatment with the bisphosphonate etidronate rescues aspects of the dgf phenotype, and we detected deregulated expression of genes that are involved in phosphate homeostasis and mineralization, such as fgf23, npt2a, entpd5 and spp1 (also known as osteopontin. Employing a UAS-GalFF approach, we show that forced expression of enpp1 in blood vessels or the floorplate of mutant embryos is sufficient to rescue the notochord

  2. Efficient molecular diagnostic strategy for ABCC6 in pseudoxanthoma elasticum

    NARCIS (Netherlands)

    Hu, Xiaofeng; Plomp, Astrid; Gorgels, Theo; Brink, Jacoline Ten; Loves, Willem; Mannens, Marcel; de Jong, Paulus T. V. M.; Bergen, Arthur A. B.

    2004-01-01

    Pseudoxanthoma elasticum (PXE) is a hereditary disorder of connective tissue with skin, cardiovascular, and visual involvement. In familial cases, PXE usually segregates in an autosomal recessive fashion. The aim of this manuscript is to describe an efficient strategy for DNA diagnosis of PXE. The

  3. Familial pseudoxanthoma elasticum associated with multiple comedones.

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    Maarouf, Melody; Sharon, Victoria R; Sivamani, Raja K; Prakash, Neha; Bipin, T H; Davis, Tracy; Shi, Vivian Y

    2017-09-15

    Pseudoxanthoma elasticum (PXE) is an autosomal recessive disorder characterized by atypical elastic fibers that causes connective tissue abnormalities of the skin, eyes, and heart, among other organs. The disorder is rare, with a classic presentation of yellow-orange cobblestone-like papules on flexural areas, lax skin, ocular degeneration, and moribund vasculature in multiple organs. There is wide variability in the presentation of the affected organs [1]. We present two sisters with classic cutaneous findings of PXE with the additional unusual findings of numerous open comedones on the neck. To our knowledge, this is the first report of numerous open comedones in familial PXE.

  4. Familial pseudoxanthoma elasticum associated with multiple comedones

    OpenAIRE

    Maarouf, Melody; Sharon, Victoria R; Sivamani, Raja K; Prakash, Neha; Bipin, TH; Davis, Tracy; Shi, Vivian Y

    2017-01-01

    Pseudoxanthoma elasticum (PXE) is an autosomal recessive disorder characterized by atypical elastic fibers that causes connective tissue abnormalities of the skin, eyes, and heart, among other organs. The disorder is rare, with a classic presentation of yellow-orange cobblestone-like papules on flexural areas, lax skin, ocular degeneration, and moribund vasculature in multiple organs. There is wide variability in the presentation of the affected organs [1]. We present two sisters with classic...

  5. Pseudoxanthoma elasticum and nephrocalcinosis: Incidental finding or an infrequent manifestation?

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    Tirthankar Gayen

    2014-01-01

    Full Text Available Pseudoxanthoma elasticum (PXE is an inherited disorder characterized by generalized fragmentation and progressive calcification of elastic tissue. We report two sporadic cases of PXE, both of whom presented with asymptomatic yellowish papules over the flexural sites for cosmetic reasons. Histopathological findings on hematoxylin and eosin and Verhoeff-Van Gieson (VVG staining were classical of PXE. In addition to this, renal calcification was documented on plain radiography of kidneys, ureters, and bladder (KUB in both the cases. Paucity of literature describing the association of nephrocalcinosis with PXE prompted the present report.

  6. Pseudoxanthoma Elasticum - Also a Lung Disease? The Respiratory Affection of Patients with Pseudoxanthoma Elasticum.

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    Simon Pingel

    Full Text Available Pseudoxanthoma elasticum (PXE is an autosomal-recessive mineralisation disorder caused by loss of function mutations in the ABCC6 Gen. Histological findings and data of an autopsy of a PXE-patient suggest a possible pulmonal calcification. So far, there exists no clinical data whether PXE patients actually are at high risk of developing pulmonary disorder.In a cross-sectional study, 35 PXE patients and 15 healthy controls underwent a pulmonary function testing, including spirometry, body plethysmography and carbon monoxide diffusing test. Additionally, PXE patients completed a COPD-Assessment-Test (CAT.We observed in PXE patients normal values for predicted vital capacity (VC%; 96.0±13.0%, predicted total lung capacity (TLC%; 98.2±12.0% and predicted forced expiration volume (FEV1%; 102.5±15.6%, whereas compared to healthy controls the PXE group showed significant diminished values for carbon monoxide diffusing capacity (DLCO, 7.2 ±1.4mmol/min/kPa vs. 8.6 ±1.5 mmol/min/kPa; p = 0.008 and predicted carbon monoxide diffusing capacity (DLCO%; 79.7±11.5% vs. 87.2±6.6%; p = 0.008. 11/35 (31.4% PXE patients showed pathological DLCO% values under 75% (68.5%±5.4%.PXE patients demonstrated a regular lung function testing, but nevertheless they had impaired CO diffusing parameters, which might be associated with a preclinical state of an interstitial lung disease and a risk for restrictive ventilation disorders.

  7. Cerebral involvement in pseudoxanthoma elasticum; case report

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    Eylem Değirmenci

    2013-08-01

    Full Text Available Pseudoxanthoma elasticum (PXE is a rarely seen connective tissue disease which is characterized by progressive fragmentation and calcification of elastic fibers. Generally it is characterized by cutaneus, ocular and vascular system involvement and neurological complications are usually secondary to vascular insufficiency. 43 years old male patient had a progressive dysarthria, ataxia and vision loss which started many years ago referred to our clinic. Loose skin was seen on bilateral his axillar region and neck with atrophic, pale viola macular lesions on his body. There was “angiloid streaks” on fundus examination and skin biopsy showed calcified degenerated elastic fibers on middle and deep dermis. Diffuse white matter lesions were determined on cranial imaging. To keep in mind the diagnosis of rare diseases would be helpful in early diagnosis and treatment, reducing and even preventing systemic complications.

  8. Digital Blood Flow In Pseudoxanthoma Elasticum By Photoplethysmography ( PPG

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    Ghosh Sanjoy

    2002-01-01

    Full Text Available Digital capillary flow in pseudoxanthoma elasticum (PXE was measured by a highly sensitive, non-invasive technique called photoplethysmography (PPG. In total 3 patients (2 females, 1 male of PXE aged between 21 to 37 years suffering for 3 to 8 years were studied along with 3 control (normal subject (2 females, 1 male aged between 20 to 41 years. PPG recordings were done by applying the PPG probe serially to the distal phalanges of all digits of four limbs with Velcro-strap at an ambient temperature of 26-310C and humidity 60-65%. In all cases of PXE the capillary flow was normal in all the digits similar to control subjects.

  9. Complementary angiographic and autofluorescence findings in pseudoxanthoma elasticum.

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    Lee, Thomas K M; Forooghian, Farzin; Cukras, Catherine; Wong, Wai T; Chew, Emily Y; Meyerle, Catherine B

    2010-02-01

    Pseudoxanthoma elasticum (PXE) is a systemic disease with characteristic findings on fundus examination. The fundus findings may be difficult to detect with ophthalmoscopy. A case report is described as follows. A PXE patient had subtle retinal findings on fundoscopy that were more prominently seen using a combination of both fundus autofluorescence (FAF) imaging and indocyanine green (ICG) angiography. The fundus features visualized using each of these two modalities appeared different from each other. FAF imaging and ICG angiography may be able to more prominently detect pathology at the level of the retinal pigment epithelium and Bruch's membrane, respectively. The use of these imaging modalities together may be complementary and useful in the evaluation of patients with PXE.

  10. Retinitis pigmentosa, cutis laxa, and pseudoxanthoma elasticum-like skin manifestations associated with GGCX mutations

    NARCIS (Netherlands)

    Kariminejad, Ariana; Bozorgmehr, Bita; Najafi, Abdolhamid; Khoshaeen, Atefeh; Ghalandari, Maryam; Najmabadi, Hossein; Kariminejad, Mohamad H; Vanakker, Olivier M; Hosen, Mohammad J; Malfait, Fransiska; Quaglino, Daniela; Florijn, Ralph J; Bergen, Arthur A B; Hennekam, Raoul C

    Gamma-glutamyl carboxylase (GGCX) mutations have been reported in patients with a pseudoxanthoma elasticum (PXE)-like phenotype, loose redundant skin, and multiple vitamin K-dependent coagulation factor deficiencies. We report on the clinical findings and molecular results in 13 affected members of

  11. Retinitis pigmentosa, cutis laxa, and pseudoxanthoma elasticum-like skin manifestations associated with GGCX mutations

    NARCIS (Netherlands)

    Kariminejad, Ariana; Bozorgmehr, Bita; Najafi, Abdolhamid; Khoshaeen, Atefeh; Ghalandari, Maryam; Najmabadi, Hossein; Kariminejad, Mohamad H.; Vanakker, Olivier M.; Hosen, Mohammad J.; Malfait, Fransiska; Quaglino, Daniela; Florijn, Ralph J.; Bergen, Arthur A. B.; Hennekam, Raoul C.

    2014-01-01

    Gamma-glutamyl carboxylase (GGCX) mutations have been reported in patients with a pseudoxanthoma elasticum (PXE)-like phenotype, loose redundant skin, and multiple vitamin K-dependent coagulation factor deficiencies. We report on the clinical findings and molecular results in 13 affected members of

  12. Pseudoxanthoma elasticum: clinical, histologic, and genetic studies--a report of two sisters

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    Kaimbo, Dieudonne Kaimbo Wa; Mutosh, Anne; Leys, Anita; Parys-van Ginderdeuren, Rita; Bergen, A. A. B.

    2011-01-01

    CASE 1: A 24-year-old black woman was referred to our clinic in September 1999 by the department of dermatology. She was referred to confirm the diagnosis of pseudoxanthoma elasticum (PXE). Her medical history was normal. Dermatologic examination revealed confluent papules that gave the skin a

  13. Pseudoxanthoma elasticum: A rare cause of gastrointestinal bleed

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    Ishrat H Dar

    2015-01-01

    Full Text Available Causes of obscure gastrointestinal (GI bleed are diverse and rare. The most common cause for GI bleeding of small bowel origin is angiodysplasia, followed by tumors of the small intestine, and various other causes, including small bowel ulcers and aortienteric fistulas. Pseudoxanthoma elasticum (PXE is a rare cause of GI bleed. It is an inherited elastic tissue disorder with degeneration of elastic fibers involving mainly skin, eyes and the cardiovascular system. Upper GI hemorrhage occurs in 13% of cases and is often resistant to nonsurgical methods of treatment. Presented herein is a case of GI bleed in a 65-year-old woman who had PXE and hyperplastic polyps in the stomach.

  14. Generalized arterial calcification of infancy and pseudoxanthoma elasticum: two sides of the same coin

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    Yvonne eNitschke

    2012-12-01

    Full Text Available Generalized arterial calcification of infancy (GACI is associated with biallelic mutations in ENPP1 in the majority of cases, whereas mutations in ABCC6 are known to cause pseudoxanthoma elasticum (PXE. However, ABCC6 mutations account for a significant subset of GACI cases, and ENPP1 mutations can also be associated with PXE lesions. Based on the considerable overlap of GACI and PXE, both entities appear to reflect two ends of a clinical spectrum of ectopic calcification rather than two distinct disorders. ABCC6 and ENPP1 mutations might lead to alterations of the same physiological pathways.

  15. Elastosis perforans serpiginosa in a case of pseudoxanthoma elasticum: A rare association

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    Konakanchi Venkatachalam

    2016-01-01

    Full Text Available Elastosis perforans serpiginosa (EPS, characterized by transepidermal elimination of fragmented elastic fibers, clinically presents as hyperkeratotic papules. EPS is classified into three types: (1 Idiopathic; (2 reactive, with associated connective tissue diseases such as pseudoxanthoma elasticum (PXE, Ehlers–Danlos syndrome, cutis laxa, Marfan syndrome, osteogenesis imperfecta, Down's syndrome; (3 the one that is induced by D-penicillamine. A rare association of EPS with PXE, which is primarily a defect of transmembrane transporter protein with accumulation of certain metabolic compounds and secondary calcification of elastic fibers has been documented in the literature. We report a case of PXE with associated lesions that were histopathologically compatible with EPS.

  16. Vitamin K supplementation increases vitamin K tissue levels but fails to counteract ectopic calcification in a mouse model for pseudoxanthoma elasticum

    NARCIS (Netherlands)

    Gorgels, Theo G. M. F.; Waarsing, Jan H.; Herfs, Marjolein; Versteeg, Daniëlle; Schoensiegel, Frank; Sato, Toshiro; Schlingemann, Reinier O.; Ivandic, Boris; Vermeer, Cees; Schurgers, Leon J.; Bergen, Arthur A. B.

    2011-01-01

    Pseudoxanthoma elasticum (PXE) is an autosomal recessive disorder in which calcification of connective tissue leads to pathology in skin, eye and blood vessels. PXE is caused by mutations in ABCC6. High expression of this transporter in the basolateral hepatocyte membrane suggests that it secretes

  17. Vitamin K supplementation increases vitamin K tissue levels but fails to counteract ectopic calcification in a mouse model for pseudoxanthoma elasticum

    NARCIS (Netherlands)

    T.G.M.F. Gorgels (Theo); J.H. Waarsing (Jan); M. Herfs (Marjolein); D. Versteeg (Daniëlle); F. Schoensiegel (Frank); T. Sato (Toshiro); R.O. Schlingemann (Reinier); B. Ivandic (Boris); C. Vermeer (Cees); L.J. Schurgers (Leon); A.A.B. Bergen (Arthur)

    2011-01-01

    textabstractPseudoxanthoma elasticum (PXE) is an autosomal recessive disorder in which calcification of connective tissue leads to pathology in skin, eye and blood vessels. PXE is caused by mutations in ABCC6. High expression of this transporter in the basolateral hepatocyte membrane suggests that

  18. Administration of vitamin K does not counteract the ectopic mineralization of connective tissues in Abcc6−/− mice, a model for pseudoxanthoma elasticum

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    Jiang, Qiujie; Li, Qiaoli; Grand-Pierre, Alix E; Schurgers, Leon J; Uitto, Jouni

    2011-01-01

    Pseudoxanthoma elasticum (PXE) is a heritable multisystem disorder manifesting with ectopic calcification of peripheral connective tissues, caused by mutations in the ABCC6 gene. Alterations in vitamin K metabolism have been suggested to contribute to the pathomechanisms of the mineralization process. In this study we administered vitamin K or its glutathione conjugate (K3-GSH) into Abcc6−/− mice that recapitulate features of PXE. Oral administration of vitamin K2, in dosages that vastly exce...

  19. Mineralization of elastic fibers and alterations of extracellular matrix in pseudoxanthoma elasticum. Ultrastructure, immunocytochemistry, and X-ray analysis

    International Nuclear Information System (INIS)

    Walker, E.R.; Frederickson, R.G.; Mayes, M.D.

    1989-01-01

    Histologic paraffin sections of pseudoxanthoma elasticum (PXE)-involved skin of forearm and axilla were used for histochemistry and immunohistochemical and analytical electron microscopy to study the progressive mineralization in the dermis of patients with PXE. The von Kossa technique identified mineral deposits throughout the reticular PXE dermis. X-ray analysis revealed patterns of calcium and phosphorus deposition in the von Kossa-positive areas, and the immunohistochemical staining using monoclonal antibodies identified increased chondroitin-6-sulfate in these areas when compared with normal skin. Scanning transmission electron microscopy observation combined with X-ray dot mapping show calcium and phosphorus to be codistributed within the mineralized area. This study confirms by new methods the increase in chondroitin-6-sulfate, alterations in elastin and collagen, and a high calcium and phosphorus elemental distribution matching the mineralized area in the PXE dermis

  20. The Effects of Parenteral K1 Administration in Pseudoxanthoma Elasticum Patients Versus Controls. A Pilot Study

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    Juan Luis Carrillo-Linares

    2018-04-01

    Full Text Available IntroductionPseudoxanthoma elasticum (PXE is a rare disease caused by mutations in the ABCC6 gene. Vitamin K1 is involved in the posttranslational carboxylation of some proteins related to inhibition of the calcification process. Our aim was to investigate, in patients affected by PXE, baseline levels of vitamin K1-dependent proteins and -metabolites and whether parenteral administration of phytomenadione was effective in modulating their levels.MethodsWe included eight PXE patients with typical clinical symptoms (skin, retina, and vascular calcification and two ABCC6 causative mutations; 13 clinically unaffected first-degree patients’ relatives (9 carrying one ABCC6 mutation and 4 non-carriers. We assessed urinary vitamin K1 metabolites and serum Glu- and Gla-OC, Gas6 and undercaboxylated prothrombin (PIVKA-II, at baseline and after 1 and 6 weeks after a single intramuscular injection of 10 mg vitamin K1.ResultsComparison of PXE patients, heterozygous, and non-carriers revealed differences in baseline levels of serum MK-4 and of urinary vitamin K metabolites. The response to phytomenadione administration on vitamin K-dependent proteins was similar in all groups.ConclusionThe physiological axis between vitamin K1 and vitamin K-dependent proteins is preserved; however, differences in the concentration of vitamin K metabolites and of MK-4 suggest that vitamin K1 metabolism/catabolism could be altered in PXE patients.

  1. The vascular phenotype in pseudoxanthoma elasticum and related disorders: Contribution of a genetic disease to the understanding of vascular calcification.

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    Georges eLeftheriotis

    2013-02-01

    Full Text Available Vascular calcification is a complex and dynamic process occurring in various physiological conditions such as aging and exercise or in acquired metabolic disorders like diabetes or chronic renal insufficiency. Arterial calcifications are also observed in several genetic diseases revealing the important role of unbalanced or defective anti- or pro-calcifying factors. Pseudoxanthoma elasticum (PXE is an inherited disease (OMIM 264800 characterized by elastic fiber fragmentation and calcification in various soft conjunctive tissues including the skin, eyes and arterial media. The PXE disease results from mutations in the ABCC6 gene, encoding an ATP-binding cassette transporter primarily expressed in the liver, kidneys suggesting that it is a prototypic metabolic soft-tissue calcifying disease of genetic origin. The clinical expression of the PXE arterial disease is characterized by an increased risk for coronary (myocardial infarction, cerebral (aneurysm and stroke and lower limb peripheral artery disease. However, the structural and functional changes in the arterial wall induced by PXE are still unexplained. The use of a recombinant mouse model inactivated for the Abcc6 gene is an important tool for the understanding of the PXE pathophysiology although the vascular impact in this model remains limited to date. Overlapping of the PXE phenotype with other inherited calcifying diseases could bring important informations to our comprehension of the PXE disease.

  2. The significance of fluorescein angiography in the early diagnosis of lesions on ocular fundus at pseudoxanthoma elasticum patients.

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    Bogdanowski, T; Gluza, J; Rasiewicz, D

    1977-05-27

    The role of fluorescein angiography in early diagnosis of lesions on fundus of the eye at pseudoxanthoma elasticum patients has been shown. The authors show angiographic changes on the basis of three cases of pseudoxanthoma elasticum patients.

  3. Novel mutation in ABCC6 gene in a Japanese pedigree with pseudoxanthoma elasticum and retinitis pigmentosa.

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    Yoshida, S; Honda, M; Yoshida, A; Nakao, S; Goto, Y; Nakamura, T; Fujisawa, K; Ishibashi, T

    2005-02-01

    To report a novel mutation of the ABCC6 gene in a Japanese family that had a case of pseudoxanthoma elasticum (PXE) another with PXE and retinitis pigmentosa. Ophthalmologic examinations were performed, and the ABCC6 gene was analysed by direct genomic sequencing. Fundus examinations of the 48-year-old proband disclosed angioid streaks and a peud'orange appearance of the retina of the both eyes, whereas both of his 25- and 20-year-old daughters had pigmentary degeneration and angioid streaks. In the sibilings, the mixed cone-rod ERG was almost nondetectable, whereas that of the proband was well-preserved. Molecular genetic analysis revealed that the proband has a homozygous nonsense mutation at the 595 bp in the ABCC6, and the siblings were heterozygous for the same mutation. This mutation was not detected in Japanese subjects in the JSNP database (http://snp.ims.u-tokyo.ac.jp/). Our results demonstrated an association between a novel mutation in the ABCC6 gene and PXE in a Japanese family.

  4. An update on the ocular phenotype in patients with pseudoxanthoma elasticum

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    Martin eGliem

    2013-04-01

    Full Text Available Pseudoxanthoma elasticum (PXE is an inherited multi-system disorder characterized by ectopic mineralization and fragmentation of elastic fibres in the skin, the elastic laminae of blood vessels and Bruch membrane in the eye. Biallelic mutations in the ABC transporter gene ABCC6 on chromosome 16 are responsible for the disease.The pathophysiology is incompletely understood. However, there is consent that a metabolic alteration leads to dysfunction in extracellular calcium homeostasis and subsequent calcification of connective tissues rich in elastic fibres. This review summarizes and aims at explaining the variety of phenotypic ocular findings in patients with PXE. Specialised imaging techniques including white light fundus photography, blue light autofluorescence, near-infrared confocal reflectance imaging, high resolution optical coherence tomography, fluorescein and indocyanin green angiography have revealed characteristic lesions at the ocular fundus of PXE patients. These include the classic signs of angioid streaks, peau d’orange, comet lesions and choroidal neovascularisations (CNV, but also the more recently recognised features such as chorioretinal atrophy, subretinal fluid independent from CNV, pattern dystrophy-like changes, debris accumulation under the retinal pigment epithelium, and a decreased fluorescence on late phase indocyanine green angiography.

  5. Pseudoxanthoma Elasticum Treatment with Fractional CO2 Laser

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    Alessandra Grassi Salles, MD, PhD

    2014-09-01

    Full Text Available Summary: Pseudoxanthoma elasticum (PE is a rare genetic disease characterized by calcification and fragmentation of elastic fibers of the skin, retina, and cardiovascular system. We report a case of PE in which fractional carbon dioxide laser treatment was successfully used to achieve improvement of the cervical skin with 2-year follow-up, in a patient with Fitzpatrick skin type IV. After the fifth session, the patient presented with a local herpes infection. The postlaser reaction of the PE skin was similar to that of the normal skin, in terms of the duration of redness, pain, swelling, and duration of crusting. The overall cosmetic result was satisfactory, with improvement in skin texture, irregularity, volume, and distensibility. The herpetic infection reinforces the value of antiviral prophylaxis during laser treatment of extrafacial areas.

  6. Ranibizumab for choroidal neovascularization secondary to pseudoxanthoma elasticum: 4-year results from the PIXEL study in France.

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    Mimoun, Gérard; Ebran, Jean-Marc; Grenet, Typhaine; Donati, Alain; Cohen, Salomon-Yves; Ponthieux, Anne

    2017-08-01

    To evaluate the long-term effectiveness and safety of ranibizumab 0.5 mg in patients with choroidal neovascularization (CNV) secondary to pseudoxanthoma elasticum (PXE) in a real-world setting. A descriptive, observational, multicenter study in a retrospective and prospective cohort was conducted in France that included patients who had received at least one injection of ranibizumab 0.5 mg during the period October 2011 to October 2014, for CNV secondary to PXE. Eligible patients were identified by review of medical records or during routine consultations. The main objectives were to describe patient characteristics, assess changes in best-corrected visual acuity [VA, Early Treatment Diabetic Retinopathy Study (ETDRS) letters] over time, the number and reasons for ranibizumab treatment and overall safety. Of the 72 enrolled patients (98 eyes) from 23 centers, 39 (54.2%) were male and mean [±standard deviation (SD)] age was 59.6 (±8.3) years. The mean VA was 64.6 letters at the first ranibizumab injection, which was maintained at the 1-year follow-up (64.7 letters). Thereafter, the mean VA was stable until the 4-year follow-up. At 4 years, the proportion of eyes with VA gain of ≥15 letters was 3/19 (15.8%) and stable VA (change between -15 and +15 letters) was 10/19 (52.6%). Mean (±SD) annual number of ranibizumab injections was 4.1 (±4.0), lower in the second versus first year. The most common reason for ranibizumab treatment was progression of neovascular activity (42.9%). No deaths or new safety findings were reported. In patients with CNV secondary to PXE, ranibizumab 0.5 mg resulted in stable VA over 4 years with a limited number of injections. Safety findings were consistent with the established safety profile of ranibizumab.

  7. Patients with premature coronary artery disease who carry the ABCC6 R1141X mutation have no Pseudoxanthoma Elasticum phenotype

    NARCIS (Netherlands)

    Wegman, Jurgen J.; Hu, Xiaofeng; Tan, Hendra; Bergen, Arthur A. B.; Trip, Mieke D.; Kastelein, John J. P.; Smulders, Yvo M.

    2005-01-01

    Background: Pseudoxanthoma elasticurn (PXE) is an inherited disorder of elastic tissue. We recently found that heterozygosity for the frequent (0.8% prevalence in Dutch population) R 1141 X mutation in the PXE gene coding for the ABCC6 transporter, is associated with a fourfold risk of premature

  8. Vitamin K supplementation increases vitamin K tissue levels but fails to counteract ectopic calcification in a mouse model for pseudoxanthoma elasticum.

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    Gorgels, Theo G M F; Waarsing, Jan H; Herfs, Marjolein; Versteeg, Daniëlle; Schoensiegel, Frank; Sato, Toshiro; Schlingemann, Reinier O; Ivandic, Boris; Vermeer, Cees; Schurgers, Leon J; Bergen, Arthur A B

    2011-11-01

    Pseudoxanthoma elasticum (PXE) is an autosomal recessive disorder in which calcification of connective tissue leads to pathology in skin, eye and blood vessels. PXE is caused by mutations in ABCC6. High expression of this transporter in the basolateral hepatocyte membrane suggests that it secretes an as-yet elusive factor into the circulation which prevents ectopic calcification. Utilizing our Abcc6 (-/-) mouse model for PXE, we tested the hypothesis that this factor is vitamin K (precursor) (Borst et al. 2008, Cell Cycle). For 3 months, Abcc6 (-/-) and wild-type mice were put on diets containing either the minimum dose of vitamin K required for normal blood coagulation or a dose that was 100 times higher. Vitamin K was supplied as menaquinone-7 (MK-7). Ectopic calcification was monitored in vivo by monthly micro-CT scans of the snout, as the PXE mouse model develops a characteristic connective tissue mineralization at the base of the whiskers. In addition, calcification of kidney arteries was measured by histology. Results show that supplemental MK-7 had no effect on ectopic calcification in Abcc6 ( -/- ) mice. MK-7 supplementation increased vitamin K levels (in skin, heart and brain) in wild-type and in Abcc6 (-/-) mice. Vitamin K tissue levels did not depend on Abcc6 genotype. In conclusion, dietary MK-7 supplementation increased vitamin K tissue levels in the PXE mouse model but failed to counteract ectopic calcification. Hence, we obtained no support for the hypothesis that Abcc6 transports vitamin K and that PXE can be cured by increasing tissue levels of vitamin K.

  9. Disseminated arterial calcification and enhanced myogenic response are associated with abcc6 deficiency in a mouse model of pseudoxanthoma elasticum

    NARCIS (Netherlands)

    Kauffenstein, Gilles; Pizard, A; Le Corre, Y; Vessières, E; Grimaud, L; Toutain, B; Labat, C; Mauras, Y; Gorgels, T G; Bergen, A A; Le Saux, O; Lacolley, P; Lefthériotis, G; Henrion, D; Martin, L

    OBJECTIVE: Pseudoxanthoma elasticum is an inherited metabolic disorder resulting from ABCC6 gene mutations. It is characterized by progressive calcification and fragmentation of elastic fibers in the skin, retina, and the arterial wall. Despite calcium accumulation in the arteries of patients with

  10. Imaging manifestations of acquired elastopathy resembling pseudoxanthoma elasticum in patients with beta thalassaemia major and sickle cell disease

    International Nuclear Information System (INIS)

    Narayana, Harish; Cheng, Ken; Lau, Ken; Harish, Radhika; Bowden, Donald K.

    2016-01-01

    Development of an acquired systemic elastopathy resembling pseudoxanthoma elasticum in patients with chronic haemoglobinopathies such as beta thalassaemia major and sickle cell disease is well documented. There is paucity of any comprehensive literature on the radiological manifestations of this entity. This pictorial review aims to describe and illustrate the multi system and multi modality imaging findings of this condition.

  11. ABCC6 does not transport vitamin K3-glutathione conjugate from the liver: relevance to pathomechanisms of pseudoxanthoma elasticum.

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    Fülöp, Krisztina; Jiang, Qiujie; Wetering, Koen V D; Pomozi, Viola; Szabó, Pál T; Arányi, Tamás; Sarkadi, Balázs; Borst, Piet; Uitto, Jouni; Váradi, András

    2011-11-25

    Vitamin K is a cofactor required for gamma-glutamyl carboxylation of several proteins regulating blood clotting, bone formation and soft tissue mineralization. Vitamin K3 is an important intermediate during conversion of the dietary vitamin K1 to the most abundant vitamin K2 form. It has been suggested that ABCC6 may have a role in transporting vitamin K or its derivatives from the liver to the periphery. This activity is missing in pseudoxanthoma elasticum, a genetic disorder caused by mutations in ABCC6 characterized by abnormal soft tissue mineralization. Here we examined the efflux of the glutathione conjugate of vitamin K3 (VK3GS) from the liver in wild type and Abcc6(-/-) mice, and in transport assays in vitro. We found in liver perfusion experiments that VK3GS is secreted into the inferior vena cava, but we observed no significant difference between wild type and Abcc6(-/-) animals. We overexpressed the human ABCC6 transporter in Sf9 insect and MDCKII cells and assayed its vitamin K3-conjugate transport activity in vitro. We found no measurable transport of VK3GS by ABCC6, whereas ABCC1 transported this compound at high rate in these assays. These results show that VK3GS is not the essential metabolite transported by ABCC6 from the liver and preventing the symptoms of pseudoxanthoma elasticum. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Zebrafish enpp1 mutants exhibit pathological mineralization, mimicking features of generalized arterial calcification of infancy (GACI) and pseudoxanthoma elasticum (PXE)

    NARCIS (Netherlands)

    Apschner, Alexander; Huitema, Leonie F A; Ponsioen, Bas; Peterson-Maduro, Josi; Schulte-Merker, Stefan

    In recent years it has become clear that, mechanistically, biomineralization is a process that has to be actively inhibited as a default state. This inhibition must be released in a rigidly controlled manner in order for mineralization to occur in skeletal elements and teeth. A central aspect of

  13. Zebrafish enpp1 mutants exhibit pathological mineralization, mimicking features of generalized arterial calcification of infancy (GACI) and pseudoxanthoma elasticum (PXE)

    NARCIS (Netherlands)

    Apschner, A.; Huitema, L.F.A.; Ponsioen, B.; Peterson-Maduro, J.; Schulte-Merker, S.

    2014-01-01

    In recent years it has become clear that, mechanistically, biomineralization is a process that has to be actively inhibited as a default state. This inhibition must be released in a rigidly controlled manner in order for mineralization to occur in skeletal elements and teeth. A central aspect of

  14. Descubriendo el pseudoxantoma elástico Discovering the elasticum pseudoxanthoma

    Directory of Open Access Journals (Sweden)

    E Ocampo

    2006-03-01

    Full Text Available Enfermedad hereditaria rara, el pseudoxantoma elástico es un trastorno genético del tejido conectivo, que se caracteriza por fragmentación de las fibras elásticas y posterior calcificación de éstas afectando dermis, vasos sanguíneos y la membrana de Bruch de retina. El patrón de herencia es muy variable, lo que hace posible que esta enfermedad pueda estar subdiagnosticada. La escasa incidencia de esta patología justifica la presentación de dos casos que tuvieron solamente manifestaciones cutáneas.Hereditary disease does not frequent pseudoxanthoma elastic; is a genetic upheaval of the conective weave, that characterizes by fragmentation of elastic fibers and later calcification of these, affecting dermis, blood vessels and membrane of Bruch of retina. The inheritance pattern is very variable which causes that disease; can be subdiagnosed. The litlle incidence of this pathology, causes that in our professional experience we have been able to diagnose two cases in which the manifestations were cutaneous.

  15. Le pseudoxanthome élastique et la myopie

    DEFF Research Database (Denmark)

    Trelohan, A; Milea, D; Martin, L

    2013-01-01

    Refraction in patients with pseudoxanthoma elasticum (PXE) has not yet been studied in the literature. The purpose of our study was to determine if PXE may be associated with myopia, similarly to Marfan syndrome, another collagen-vascular disease.......Refraction in patients with pseudoxanthoma elasticum (PXE) has not yet been studied in the literature. The purpose of our study was to determine if PXE may be associated with myopia, similarly to Marfan syndrome, another collagen-vascular disease....

  16. ABCC6 does not transport vitamin K3-glutathione conjugate from the liver: relevance to pathomechanisms of pseudoxanthoma elasticum

    NARCIS (Netherlands)

    Fülöp, Krisztina; Jiang, Qiujie; van de Wetering, Koen; Pomozi, Viola; Szabó, Pál T.; Arányi, Tamás; Sarkadi, Balázs; Borst, Piet; Uitto, Jouni; Váradi, András

    2011-01-01

    Vitamin K is a cofactor required for gamma-glutamyl carboxylation of several proteins regulating blood clotting, bone formation and soft tissue mineralization. Vitamin K3 is an important intermediate during conversion of the dietary vitamin K1 to the most abundant vitamin K2 form. It has been

  17. Alteraciones ecográficas genitourinarias en el pseudoxantoma elástico Genitourinary echography alterations in the pseudoxanthoma elasticum

    Directory of Open Access Journals (Sweden)

    José Severino Hernández Hernández

    2010-09-01

    Full Text Available Se presenta un paciente del sexo masculino, negro, de 13 años de edad, con diagnóstico de pseudoxantoma elástico. En el estudio ultrasonográfico renal y testicular se observaron imágenes ecorrefringentes en los riñones y testículos, que no emiten sombra acústica ni demuestran alteraciones de la función renal o del sedimento urinario. No se recogieron antecedentes familiares de lesiones cutáneas que hagan recordar la enfermedad. Estos hallazgos, tanto los renales como los testiculares, se han documentado en la literatura médica, por lo que estimamos que su divulgación es interesante, pues se ha planteado que forman parte del fenotipo de la enfermedad.This is the case of a black male sex patient aged 13 diagnosed with elastic. Renal and testicular ultrasonographic study showed echo-refractive images in testes and kidneys without neither acoustic shadow nor alterations of renal function or of the urinary sediment. There was not a family history of cutaneous lesions related with this entity. These renal and testicular findings have been documented in the medical literature, thus, authors recommended that its popularization is interesting since it has been proposed that they are part of the disease phenotype.

  18. New perspectives on rare connective tissue calcifying diseases.

    Science.gov (United States)

    Rashdan, Nabil A; Rutsch, Frank; Kempf, Hervé; Váradi, András; Lefthériotis, Georges; MacRae, Vicky E

    2016-06-01

    Connective tissue calcifying diseases (CTCs) are characterized by abnormal calcium deposition in connective tissues. CTCs are caused by multiple factors including chronic diseases (Type II diabetes mellitus, chronic kidney disease), the use of pharmaceuticals (e.g. warfarin, glucocorticoids) and inherited rare genetic diseases such as pseudoxanthoma elasticum (PXE), generalized arterial calcification in infancy (GACI) and Keutel syndrome (KTLS). This review explores our current knowledge of these rare inherited CTCs, and highlights the most promising avenues for pharmaceutical intervention. Advancing our understanding of rare inherited forms of CTC is not only essential for the development of therapeutic strategies for patients suffering from these diseases, but also fundamental to delineating the mechanisms underpinning acquired chronic forms of CTC. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  19. Molecular docking simulations provide insights in the substrate binding sites and possible substrates of the ABCC6 transporter.

    Directory of Open Access Journals (Sweden)

    Mohammad Jakir Hosen

    Full Text Available The human ATP-binding cassette family C member 6 (ABCC6 gene encodes an ABC transporter protein (ABCC6, primarily expressed in liver and kidney. Mutations in the ABCC6 gene cause pseudoxanthoma elasticum (PXE, an autosomal recessive connective tissue disease characterized by ectopic mineralization of the elastic fibers. The pathophysiology underlying PXE is incompletely understood, which can at least partly be explained by the undetermined nature of the ABCC6 substrates as well as the unknown substrate recognition and binding sites. Several compounds, including anionic glutathione conjugates (N-ethylmaleimide; NEM-GS and leukotriene C4 (LTC4 were shown to be modestly transported in vitro; conversely, vitamin K3 (VK3 was demonstrated not to be transported by ABCC6. To predict the possible substrate binding pockets of the ABCC6 transporter, we generated a 3D homology model of ABCC6 in both open and closed conformation, qualified for molecular docking and virtual screening approaches. By docking 10 reported in vitro substrates in our ABCC6 3D homology models, we were able to predict the substrate binding residues of ABCC6. Further, virtual screening of 4651 metabolites from the Human Serum Metabolome Database against our open conformation model disclosed possible substrates for ABCC6, which are mostly lipid and biliary secretion compounds, some of which are found to be involved in mineralization. Docking of these possible substrates in the closed conformation model also showed high affinity. Virtual screening expands this possibility to explore more compounds that can interact with ABCC6, and may aid in understanding the mechanisms leading to PXE.

  20. Genetics in arterial calcification: pieces of a puzzle and cogs in a wheel.

    Science.gov (United States)

    Rutsch, Frank; Nitschke, Yvonne; Terkeltaub, Robert

    2011-08-19

    Artery calcification reflects an admixture of factors such as ectopic osteochondral differentiation with primary host pathological conditions. We review how genetic factors, as identified by human genome-wide association studies, and incomplete correlations with various mouse studies, including knockout and strain analyses, fit into "pieces of the puzzle" in intimal calcification in human atherosclerosis, and artery tunica media calcification in aging, diabetes mellitus, and chronic kidney disease. We also describe in sharp contrast how ENPP1, CD73, and ABCC6 serve as "cogs in a wheel" of arterial calcification. Specifically, each is a minor component in the function of a much larger network of factors that exert balanced effects to promote and suppress arterial calcification. For the network to normally suppress spontaneous arterial calcification, the "cogs" ENPP1, CD73, and ABCC6 must be present and in working order. Monogenic ENPP1, CD73, and ABCC6 deficiencies each drive a molecular pathophysiology of closely related but phenotypically different diseases (generalized arterial calcification of infancy (GACI), pseudoxanthoma elasticum (PXE) and arterial calcification caused by CD73 deficiency (ACDC)), in which premature onset arterial calcification is a prominent but not the sole feature.

  1. Histology-directed and imaging mass spectrometry: an emerging technology in ectopic calcification

    OpenAIRE

    Taverna, Domenico; Boraldi, Federica; De Santis, Giorgio; Caprioli, Richard M; Quaglino, Daniela

    2015-01-01

    The present study was designed to demonstrate the potential of an optimized histology directed protein identification combined with imaging mass spectrometry technology to reveal and identify molecules associated to ectopic calcification in human tissue. As a proof of concept, mineralized and non-mineralized areas were compared within the same dermal tissue obtained from a patient affected by Pseudoxanthoma elasticum, a genetic disorder characterized by calcification only at specific sites of...

  2. Angioid streaks, clinical course, complications, and current therapeutic management

    Directory of Open Access Journals (Sweden)

    Ilias Georgalas

    2008-12-01

    Full Text Available Ilias Georgalas1, Dimitris Papaconstantinou2, Chrysanthi Koutsandrea2, George Kalantzis2, Dimitris Karagiannis2, Gerasimos Georgopoulos2, Ioannis Ladas21Department of Ophthalmology, “G. Gennimatas” Hospital of Athens, NHS, Athens, Greece; 2Department of Ophthalmology, “G. Gennimatas” Hospital of Athens, University of Athens, Athens, GreeceAbstract: Angioid streaks are visible irregular crack-like dehiscences in Bruch’s membrane that are associated with atrophic degeneration of the overlying retinal pigmented epithelium. Angioid streaks may be associated with pseudoxanthoma elasticum, Paget’s disease, sickle-cell anemia, acromegaly, Ehlers–Danlos syndrome, and diabetes mellitus, but also appear in patients without any systemic disease. Patients with angioid streaks are generally asymptomatic, unless the lesions extend towards the foveola or develop complications such as traumatic Bruch’s membrane rupture or macular choroidal neovascularization (CNV. The visual prognosis in patients with CNV secondary to angioid streaks if untreated, is poor and most treatment modalities, until recently, have failed to limit the devastating impact of CNV in central vision. However, it is likely that treatment with antivascular endothelial growth factor, especially in treatment-naive eyes to yield favorable results in the future and this has to be investigated in future studies.Keywords: angioid streaks, pseudoxanthoma elasticum, choroidal neovascularization

  3. MULTIMODAL IMAGING OF ANGIOID STREAKS ASSOCIATED WITH TURNER SYNDROME.

    Science.gov (United States)

    Chiu, Bing Q; Tsui, Edmund; Hussnain, Syed Amal; Barbazetto, Irene A; Smith, R Theodore

    2018-02-13

    To report multimodal imaging in a novel case of angioid streaks in a patient with Turner syndrome with 10-year follow-up. Case report of a patient with Turner syndrome and angioid streaks followed at Bellevue Hospital Eye Clinic from 2007 to 2017. Fundus photography, fluorescein angiography, and optical coherence tomography angiography were obtained. Angioid streaks with choroidal neovascularization were noted in this patient with Turner syndrome without other systemic conditions previously correlated with angioid streaks. We report a case of angioid streaks with choroidal neovascularization in a patient with Turner syndrome. We demonstrate that angioid streaks, previously associated with pseudoxanthoma elasticum, Ehlers-Danlos syndrome, Paget disease of bone, and hemoglobinopathies, may also be associated with Turner syndrome, and may continue to develop choroidal neovascularization, suggesting the need for careful ophthalmic examination in these patients.

  4. Translating molecular medicine into clinical tools: doomed to fail by neglecting basic preanalytical principles

    Directory of Open Access Journals (Sweden)

    Mannello Ferdinando

    2009-10-01

    Full Text Available Abstract This commentary discusses a study on measurements of matrix metalloproteinase 9 (MMP-9 in serum of pseudoxanthoma elasticum patients recently published in Journal of Molecular Medicine. This study can be considered the typical "obstacle" to effective translational medicine as previously documented in JTM journal. Although serum has been frequently proven as inappropriate sample for determining numerous circulating MMPs, among them MMP-9, there are over and over again studies, as in this case, that measure MMP-9 in serum. Comparative measurements in serum and plasma samples demonstrated higher concentrations for MMP-9 in serum due to the additional release from leukocytes and platelets following the coagulation/fibrinolysis process. From this example it can be concluded that translating basic research discoveries into clinical tools needs a more intensive exchange between basic biomedical research and clinical scientists already in an early stage. Otherwise a lost of translation, as discussed in JTM journal, seems to be inevitable.

  5. Elastic fibers in human skin: quantitation of elastic fibers by computerized digital image analyses and determination of elastin by radioimmunoassay of desmosine.

    Science.gov (United States)

    Uitto, J; Paul, J L; Brockley, K; Pearce, R H; Clark, J G

    1983-10-01

    The elastic fibers in the skin and other organs can be affected in several disease processes. In this study, we have developed morphometric techniques that allow accurate quantitation of the elastic fibers in punch biopsy specimens of skin. In this procedure, the elastic fibers, visualized by elastin-specific stains, are examined through a camera unit attached to the microscope. The black and white images sensing various gray levels are then converted to binary images after selecting a threshold with an analog threshold selection device. The binary images are digitized and the data analyzed by a computer program designed to express the properties of the image, thus allowing determination of the volume fraction occupied by the elastic fibers. As an independent measure of the elastic fibers, alternate tissue sections were used for assay of desmosine, an elastin-specific cross-link compound, by a radioimmunoassay. The clinical applicability of the computerized morphometric analyses was tested by examining the elastic fibers in the skin of five patients with pseudoxanthoma elasticum or Buschke-Ollendorff syndrome. In the skin of 10 healthy control subjects, the elastic fibers occupied 2.1 +/- 1.1% (mean +/- SD) of the dermis. The volume fractions occupied by the elastic fibers in the lesions of pseudoxanthoma elasticum or Buschke-Ollendorff syndrome were increased as much as 6-fold, whereas the values in the unaffected areas of the skin in the same patients were within normal limits. A significant correlation between the volume fraction of elastic fibers, determined by computerized morphometric analyses, and the concentration of desmosine, quantitated by radioimmunoassay, was noted in the total material. These results demonstrate that computerized morphometric techniques are helpful in characterizing disease processes affecting skin. This methodology should also be applicable to other tissues that contain elastic fibers and that are affected in various heritable and

  6. Ectopic mineralization disorders of the extracellular matrix of connective tissue: molecular genetics and pathomechanisms of aberrant calcification.

    Science.gov (United States)

    Li, Qiaoli; Jiang, Qiujie; Uitto, Jouni

    2014-01-01

    Ectopic mineralization of connective tissues is a complex process leading to deposition of calcium phosphate complexes in the extracellular matrix, particularly affecting the skin and the arterial blood vessels and common in age-associated disorders. A number of initiating and contributing metabolic and environmental factors are linked to aberrant mineralization in these diseases, making the identification of precise pathomechanistic pathways exceedingly difficult. However, there has been significant recent progress in understanding the ectopic mineralization processes through study of heritable single-gene disorders, which have allowed identification of discrete pathways and contributing factors leading to aberrant connective tissue mineralization. These studies have provided support for the concept of an intricate mineralization/anti-mineralization network present in peripheral connective tissues, providing a perspective to development of pharmacologic approaches to limit the phenotypic consequences of ectopic mineralization. This overview summarizes the current knowledge of ectopic heritable mineralization disorders, with accompanying animal models, focusing on pseudoxanthoma elasticum and generalized arterial calcification of infancy, two autosomal recessive diseases manifesting with extensive connective tissue mineralization in the skin and the cardiovascular system. © 2013.

  7. [Peripheral artery disease in patients younger than 50 years old: Which etiology?].

    Science.gov (United States)

    Cotard, S; Nouni, A; Jaquinandi, V; Gladu, G; Kaladji, A; Mahé, G

    2016-09-01

    Peripheral arterial disease (PAD) encompasses disease of all arteries of the body except the coronary arteries. The main etiology whatever the patient's age is atherosclerosis. Different etiologies can induce PAD especially when patients are younger than 50 years old and have no cardiovascular risk factors (smoking, hypertension, diabetes…). PAD that appears before 50 years old can be named juvenile PAD (JPAD) although there is no consensus about the definition. The aim of this work is to present the different etiologies of JPAD according to their hereditary, acquired or mixed origins. The following hereditary causes are addressed: Marfan syndrome, Ehlers-Danlos syndrome, homocystinuria, pseudoxanthoma elasticum, osteogenesis imperfecta "mid-aortic" syndrome. Among the acquired etiologies, inflammatory JPADs without extravascular signs such as atherosclerosis and Buerger's disease, inflammatory JPADs with extravascular signs as Takayasu's disease, Behçet's disease and Cogan's syndrome, JPADs like aortitis, embolic JPADs, iatrogenic JPADs, and mechanical or traumatic JPADs are described. Finally, mixed origins as thrombotic disease and fibromuscular dysplasia are presented. This work will assist clinicians in the diagnosis of JPAD. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  8. The mouse as a model for understanding chronic diseases of aging: the histopathologic basis of aging in inbred mice

    Directory of Open Access Journals (Sweden)

    David Harrison

    2011-06-01

    Full Text Available Inbred mice provide a unique tool to study aging populations because of the genetic homogeneity within an inbred strain, their short life span, and the tools for analysis which are available. A large-scale longitudinal and cross-sectional aging study was conducted on 30 inbred strains to determine, using histopathology, the type and diversity of diseases mice develop as they age. These data provide tools that when linked with modern in silico genetic mapping tools, can begin to unravel the complex genetics of many of the common chronic diseases associated with aging in humans and other mammals. In addition, novel disease models were discovered in some strains, such as rhabdomyosarcoma in old A/J mice, to diseases affecting many but not all strains including pseudoxanthoma elasticum, pulmonary adenoma, alopecia areata, and many others. This extensive data set is now available online and provides a useful tool to help better understand strain-specific background diseases that can complicate interpretation of genetically engineered mice and other manipulatable mouse studies that utilize these strains.

  9. [Homozygous ectonucleotide pyrophosphatase/phosphodiesterase 1 variants in a girl with hypophosphatemic rickets and literature review].

    Science.gov (United States)

    Liu, Z Q; Chen, X B; Song, F Y; Gao, K; Qiu, M F; Qian, Y; Du, M

    2017-11-02

    Objective: To investigate the clinical features and genetic characteristics of patients with ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) gene variants. Method: The clinical data of a patient with ENPP1 homozygous variants from Capital Institute of Pediatrics was collected, the related literature was searched from China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, National Center from Biotechnology Information and PubMed by using search term "ENPP1" , "hypophosphatemic rickets" . The literature retrieval was confined from 1980 to February 2017. The clinical manifestations, bone metabolism examinations, X-RAY and genotypes were reviewed. Result: Our patient was an 11 years old girl, with 7 years history of lower limb malformation. She showed significant valgus deformity of the knee (genu valgum). Metabolic examination revealed reduced level of plasma phosphate (0.86 mmol/L), a normal level of plasma calcium (2.30 mmol/L) and an elevated alkaline phosphatase level of 688 IU/L. The calcium-phosphorus product was 25.9. A homozygous nonsense variants of ENPP1 gene, c.783C>G (p.Tyr261X) in exon 7 was identified in the patient. Both parents were heterozygous carriers. Literature review identified 3 Chinese patients from one publication and 17 cases from twenty one publications around the world. None of the patients was found PHEX variants which is the most common variants among hypophosphatemic rickets patients. The disease onset age was 11 months to 10 years. Eight patients had short stature, five patients had the history of generalized arterial calcification of infancy. Four suffered from deafness, three showed localized calcifications of arteries, three patients manifested pseudoxanthoma elasticum and two suffered from ossification of posterior longitudinal ligament. Nine missense variants, six splicing variants and 4 nonsense variants were reported among these twenty patients. c.783C>G was found in two Chinese patients

  10. [Arterial involvements in hereditary dysplasia of the connective tissue].

    Science.gov (United States)

    Beylot, C; Doutre, M S; Beylot-Barry, M; Busquet, M

    1994-03-01

    Arterial involvement is an important feature of the diagnosis and, above all, prognosis of heritable disorders of connective tissue. In pseudoxanthoma elasticum, a progressive occlusive syndrome is associated with hemorrhage and especially with gastrointestinal bleeding. Aneurysms are uncommon. Hypertension occurs frequently. Cutaneous signs (yellowish pseudo xanthomatous papules of the large folds) the ocular changes (angioid streaks) and pathology showing numerous, thickened, fragmented, disorganized, calcified elastic fibers in the deep dermis and arterial walls, allow the diagnosis to be made. In the heterogeneous group of Ehlers-Danlos syndromes, type IV is characterized by sudden spontaneous rupture of the large arteries. Aneurysms and carotido-cavernous fistulae are rather frequent. Owing to friability of the arterial walls, arteriograms and other procedure requiring arterial puncture may prove hazardous and surgery difficult. Such patients have an acrogeric morphotype, and thin, fragile skin, but cutaneous hyperelasticity and joint hyperlaxity are usually minimal. Pathology evidences collagen hypoplasia in the skin and arterial walls. The severity of Marfan syndrome is due to aortic involvement. A fusiform aneurysm of the ascending aorta represents a vital risk of rupture. Aortic root dilatation is associated and responsible of severe aortic regurgitation. Aortic dissection is also a serious threat. Improved surgical techniques for repairing a dilated or dissected aortic root with simultaneous replacement of the aortic valve increases the life expectancy of such patients. Dolichomorphism is the characteristic skeletal abnormality, particularly with arachnodactyly and upward ectopia lentis, which is almost bilateral, is a very frequent feature of Marfan syndrome. The most typical histological finding is aortic cystic median necrosis. The basic defect in Marfan syndrome concerns the fibrillin, whose gene is located on chromosome 15. The three diseases

  11. Epidemiology and genetics of intracranial aneurysms

    Energy Technology Data Exchange (ETDEWEB)

    Caranci, F., E-mail: ferdinandocaranci@libero.it [Unit of Neuroradiology, Department of Diagnostic Radiology and Radiotherapy, Federico II University, Naples (Italy); Briganti, F., E-mail: frabriga@unina.it [Unit of Neuroradiology, Department of Diagnostic Radiology and Radiotherapy, Federico II University, Naples (Italy); Cirillo, L.; Leonardi, M. [Neuroradiology service, Bellaria Hospital, Bologna (Italy); Muto, M., E-mail: mutomar@tiscali.it [Neuroradiology Service Cardarelli Hospital Naples (Italy)

    2013-10-01

    Intracranial aneurysms are acquired lesions (5–10% of the population), a fraction of which rupture leading to subarachnoid hemorrhage with devastating consequences. Until now, the exact etiology of intracranial aneurysms formation remains unclear. The low incidence of subarachnoid hemorrhage in comparison with the prevalence of unruptured IAs suggests that the vast majority of intracranial aneurysms do not rupture and that identifying those at highest risk is important in defining the optimal management. The most important factors predicting rupture are aneurysm size and site. In addition to ambiental factors (smoking, excessive alcohol consumption and hypertension), epidemiological studies have demonstrated a familiar influence contributing to the pathogenesis of intracranial aneurysms, with increased frequency in first- and second-degree relatives of people with subarachnoid hemorrhage. In comparison to sporadic aneurysms, familial aneurysms tend to be larger, more often located at the middle cerebral artery, and more likely to be multiple. Other than familiar occurrence, there are several heritable conditions associated with intracranial aneurysm formation, including autosomal dominant polycystic kidney disease, neurofibromatosis type I, Marfan syndrome, multiple endocrine neoplasia type I, pseudoxanthoma elasticum, hereditary hemorrhagic telangiectasia, and Ehlers-Danlos syndrome type II and IV. The familial occurrence and the association with heritable conditions indicate that genetic factors may play a role in the development of intracranial aneurysms. Genome-wide linkage studies in families and sib pairs with intracranial aneurysms have identified several loci on chromosomes showing suggestive evidence of linkage, particularly on chromosomes 1p34.3–p36.13, 7q11, 19q13.3, and Xp22. For the loci on 1p34.3–p36.13 and 7q11, a moderate positive association with positional candidate genes has been demonstrated (perlecan gene, elastin gene, collagen type 1 A2

  12. Epidemiology and genetics of intracranial aneurysms

    International Nuclear Information System (INIS)

    Caranci, F.; Briganti, F.; Cirillo, L.; Leonardi, M.; Muto, M.

    2013-01-01

    Intracranial aneurysms are acquired lesions (5–10% of the population), a fraction of which rupture leading to subarachnoid hemorrhage with devastating consequences. Until now, the exact etiology of intracranial aneurysms formation remains unclear. The low incidence of subarachnoid hemorrhage in comparison with the prevalence of unruptured IAs suggests that the vast majority of intracranial aneurysms do not rupture and that identifying those at highest risk is important in defining the optimal management. The most important factors predicting rupture are aneurysm size and site. In addition to ambiental factors (smoking, excessive alcohol consumption and hypertension), epidemiological studies have demonstrated a familiar influence contributing to the pathogenesis of intracranial aneurysms, with increased frequency in first- and second-degree relatives of people with subarachnoid hemorrhage. In comparison to sporadic aneurysms, familial aneurysms tend to be larger, more often located at the middle cerebral artery, and more likely to be multiple. Other than familiar occurrence, there are several heritable conditions associated with intracranial aneurysm formation, including autosomal dominant polycystic kidney disease, neurofibromatosis type I, Marfan syndrome, multiple endocrine neoplasia type I, pseudoxanthoma elasticum, hereditary hemorrhagic telangiectasia, and Ehlers-Danlos syndrome type II and IV. The familial occurrence and the association with heritable conditions indicate that genetic factors may play a role in the development of intracranial aneurysms. Genome-wide linkage studies in families and sib pairs with intracranial aneurysms have identified several loci on chromosomes showing suggestive evidence of linkage, particularly on chromosomes 1p34.3–p36.13, 7q11, 19q13.3, and Xp22. For the loci on 1p34.3–p36.13 and 7q11, a moderate positive association with positional candidate genes has been demonstrated (perlecan gene, elastin gene, collagen type 1 A2

  13. Proceedings - BORDEAUX VIVA WINTER SCHOOL - XXXIII LIAC MEETING

    Directory of Open Access Journals (Sweden)

    Thierry Couffinhal

    2017-12-01

    - effects of hyperoxia - L. MONTEIRO-RODRIGUES, Lisbon - Portugal Murine models for investigating vascular ageing - G. FAURY, Grenoble New insights into vascular biology by single cell RNA sequencing - M. VANLANDEWYCK, Stockholm - Sweden Thrombosis in aging - C. JAMES, Bordeaux Retinal vascular imaging - C. HELMER, Bordeaux Lunch of Winter School Meeting Winter School meeting (organizers: A. Bikfalvi & J. Badaut Meet the experts - Round table with experts MATRIX STRUCTURAL AND MECHANICAL STUDIES (Chairmen: I. Brunet & P. Dufourcq Model of pseudoxanthoma elasticum – Vascular calcification and aging, from gene to bedside - L. MARTIN, G. LEFTHERIOTIS, Angers Vascular aging: structure and dynamics of constitutive macromolecules and sub-fragments - V. SAMOUILLAN, Toulouse Tubular scaffolds for applications of vascular tissue engineering - V. LA CARRUBBA, Palermo - Italy Bioprosthetic heart valve aging deterioration and age-related benefits - M. SPINA, Padova - Italy Elastin modification during vascular aging and pathophysiological consequences - L. DUCA, Reims SELECTED ORAL PRESENTATION (Chairmen: M. Laffargue & D. Henrion • MicroRNA expressed in progenitor cells circulating in peripheral blood as prospective biomarkers of agerelated macular degeneration (AMD in its dry and wet form – preliminary data - M. KAWA, Poland • Molecular, conformational and thermal characterization of ventricular Remodeling in a pig model of tachycardia-induced cardiomyopathy - V. LLORENTE CORTES, Barcelona - Spain • Valvular calcification: implication of the Semicarbazide-Sensitive Amine Oxidase (SSAO? - N. MERCIER, Nancy • Vascular calcification during chronic kidney disease: role of the RAGE/Cathepsin S/elastin peptides axis - A. WAHART, Reims VIVA EVENING CONFERENCE (Chairman: T. Couffinhal A short history of the vessel - A. BIKFALVI, Bordeaux 1 December | 1 de Dezembro CELL BIOLOGY AND SIGNALING (Chairwomen: C. Duplàa & V. Llorrente Cortes SELECTED ORAL PRESENTATION • Targeting

  14. Dynamics of a Simple Rotating Structure

    DEFF Research Database (Denmark)

    Brøns, Morten; Hjorth, Poul G.; Kliem, Wolfhard

    1996-01-01

    Small oscillations of an elasticum whose one end is constrained to move in uniform circular motion and whose free end carries a mass, are investigated with Poincare-Lindstedt series. It is demonstrated that the mass traverses a figure-eight shaped curve in a direction determined by the sign of th...

  15. Coriolis Effects in the Dynamics of a Rotating Elastic Structure

    DEFF Research Database (Denmark)

    Brøns, Morten; Hjorth, Poul G.; Kliem, Wolfhard

    1996-01-01

    Small oscillations of a rotating elasticum with a mass at the free end are investigated with Poincare-Lindstedt series. It is shown that the mass moves on a figure-eight shaped curve in a direction determined by the sign of the angular velocity and hence that the Coriolis force influences...

  16. Disk cloning program 'Dolly+' for system management of PC Linux cluster

    International Nuclear Information System (INIS)

    Atsushi Manabe

    2001-01-01

    The Dolly+ is a Linux application program to clone files and disk partition image from a PC to many others. By using several techniques such as logical ring connection, multi threading and pipelining, it could achieve high performance and scalability. For example, in typical condition, installations to a hundred PCs takes almost equivalent time for two PCs. Together with the Intel PXE and the RedHat kickstart, automatic and very fast system installation and upgrading could be performed

  17. Investigation of organic liquid-scintillator optical properties

    Energy Technology Data Exchange (ETDEWEB)

    Winter, Juergen; Feilitzsch, Franz von; Goeger-Neff, Marianne; Lewke, Timo; Meindl, Quirin; Oberauer, Lothar; Potzel, Walter; Todor, Sebastian; Wurm, Michael [Physik Department E15, Technische Universitaet Muenchen, James-Franck-Str., 85748 Garching (Germany); Marrodan Undagoitia, Teresa [Physik Department E15, Technische Universitaet Muenchen, James-Franck-Str., 85748 Garching (Germany); Physik-Institut, Universitaet Zuerich (Switzerland)

    2009-07-01

    The characterization of different organic liquid-scintillator mixtures is an important step towards the design of a large-scale detector such as LENA (Low Energy Neutrino Astronomy). Its physics goals, extending from particle and geological to astrophysical issues, set high demands on the optical properties of the liquid scintillator. Therefore, small-scale experiments are carried out in order to optimize the final scintillator mixture. PXE, LAB, and dodecane are under consideration as solvents. Setups for the determination of scintillator properties are presented, such as attenuation length, light yield, emission spectra, fluorescence decay times, and quenching factors. Furthermore, results are discussed.

  18. Disease Advocacy Organizations Catalyze Translational Research

    Directory of Open Access Journals (Sweden)

    Sharon Fontaine Terry

    2013-06-01

    Full Text Available Disease advocacy organizations have long played an important role in the continuum from basic science to therapy development in rare disease research. PXE International has sometimes led the field in innovative ways, venturing into specific activities that have traditionally been conducted by scientists. As lay founders, we have engaged in gene discovery, gene patenting, diagnostic development, epidemiological studies, clinical trials and therapy research and development. This article will describe the steps that we took, and the ways in which we have scaled these efforts for the larger community.

  19. Kinetics of the processes, plasma parameters, and output characteristics of a UV emitter operating on XeI molecules and iodine molecules and atoms

    Energy Technology Data Exchange (ETDEWEB)

    Shuaibov, A. K.; Grabovaya, I. A.; Minya, A. I.; Homoki, Z. T. [Uzhgorod National University (Ukraine); Kalyuzhnaya, A. G.; Shchedrin, A. I. [National Academy of Sciences of Ukraine, Institute of Physics (Ukraine)

    2011-03-15

    A kinetic model of the processes occurring in the plasma of a high-power low-pressure gas-discharge lamp is presented, and the output characteristics of the lamp are described. The lamp is excited by a longitudinal glow discharge and emits the I{sub 2}(D Prime -A Prime ) 342-nm and XeI(B-X) 253-nm bands and the 206.2-nm spectral line of atomic iodine. When the emitter operates in a sealed-off mode on the p(He): p(Xe): p(I{sub 2}) = 400: 120: (100-200) Pa mixture, the fractions of the UV radiation power of iodine atoms, exciplex molecules of xenon iodide, and iodine molecules comprise 55, 10, and 35%, respectively. At the optimal partial pressure, the maximum total radiation power of the lamp reaches 37 W, the energy efficiency being about 15%.

  20. A General Purpose High Performance Linux Installation Infrastructure

    International Nuclear Information System (INIS)

    Wachsmann, Alf

    2002-01-01

    With more and more and larger and larger Linux clusters, the question arises how to install them. This paper addresses this question by proposing a solution using only standard software components. This installation infrastructure scales well for a large number of nodes. It is also usable for installing desktop machines or diskless Linux clients, thus, is not designed for cluster installations in particular but is, nevertheless, highly performant. The infrastructure proposed uses PXE as the network boot component on the nodes. It uses DHCP and TFTP servers to get IP addresses and a bootloader to all nodes. It then uses kickstart to install Red Hat Linux over NFS. We have implemented this installation infrastructure at SLAC with our given server hardware and installed a 256 node cluster in 30 minutes. This paper presents the measurements from this installation and discusses the bottlenecks in our installation

  1. IPv6 testing and deployment at Prague Tier 2

    Science.gov (United States)

    Kouba, Tomáŝ; Chudoba, Jiří; Eliáŝ, Marek; Fiala, Lukáŝ

    2012-12-01

    Computing Center of the Institute of Physics in Prague provides computing and storage resources for various HEP experiments (D0, Atlas, Alice, Auger) and currently operates more than 300 worker nodes with more than 2500 cores and provides more than 2PB of disk space. Our site is limited to one C-sized block of IPv4 addresses, and hence we had to move most of our worker nodes behind the NAT. However this solution demands more difficult routing setup. We see the IPv6 deployment as a solution that provides less routing, more switching and therefore promises higher network throughput. The administrators of the Computing Center strive to configure and install all provided services automatically. For installation tasks we use PXE and kickstart, for network configuration we use DHCP and for software configuration we use CFEngine. Many hardware boxes are configured via specific web pages or telnet/ssh protocol provided by the box itself. All our services are monitored with several tools e.g. Nagios, Munin, Ganglia. We rely heavily on the SNMP protocol for hardware health monitoring. All these installation, configuration and monitoring tools must be tested before we can switch completely to IPv6 network stack. In this contribution we present the tests we have made, limitations we have faced and configuration decisions that we have made during IPv6 testing. We also present testbed built on virtual machines that was used for all the testing and evaluation.

  2. IPv6 testing and deployment at Prague Tier 2

    International Nuclear Information System (INIS)

    Kouba, Tomáŝ; Chudoba, Jiří; Eliáŝ, Marek; Fiala, Lukáŝ

    2012-01-01

    Computing Center of the Institute of Physics in Prague provides computing and storage resources for various HEP experiments (D0, Atlas, Alice, Auger) and currently operates more than 300 worker nodes with more than 2500 cores and provides more than 2PB of disk space. Our site is limited to one C-sized block of IPv4 addresses, and hence we had to move most of our worker nodes behind the NAT. However this solution demands more difficult routing setup. We see the IPv6 deployment as a solution that provides less routing, more switching and therefore promises higher network throughput. The administrators of the Computing Center strive to configure and install all provided services automatically. For installation tasks we use PXE and kickstart, for network configuration we use DHCP and for software configuration we use CFEngine. Many hardware boxes are configured via specific web pages or telnet/ssh protocol provided by the box itself. All our services are monitored with several tools e.g. Nagios, Munin, Ganglia. We rely heavily on the SNMP protocol for hardware health monitoring. All these installation, configuration and monitoring tools must be tested before we can switch completely to IPv6 network stack. In this contribution we present the tests we have made, limitations we have faced and configuration decisions that we have made during IPv6 testing. We also present testbed built on virtual machines that was used for all the testing and evaluation.

  3. Some characteristics of atmospheric gravity waves observed by radio-interferometry

    Directory of Open Access Journals (Sweden)

    Claude Mercier

    Full Text Available Observations of atmospheric acoustic-gravity waves (AGWs are considered through their effect on the horizontal gradient G of the slant total electron content (slant TEC, which can be directly obtained from two-dimensional radio-interferometric observations of cosmic radio-sources with the Nançay radioheligraph (2.2°E, 47.3°N. Azimuths of propagation can be deduced (modulo 180°. The total database amounts to about 800 h of observations at various elevations, local time and seasons. The main results are:

    a AGWs are partially directive, confirming our previous results.

    b The propagation azimuths considered globally are widely scattered with a preference towards the south.

    c They show a bimodal time distribution with preferential directions towards the SE during daytime and towards the SW during night-time (rather than a clockwise rotation as reported by previous authors.

    d The periods are scattered but are larger during night-time than during daytime by about 60%.

    px;">e The effects observed with the solar radio-sources are significantly stronger than with other radio-sources (particularly at higher elevations, showing the role of the geometry in line of sight-integrated observations.

  4. Power Producer Production Valuation

    Directory of Open Access Journals (Sweden)

    M. Kněžek

    2008-01-01

    Full Text Available The ongoing developments in the electricity market, in particular the establishment of the Prague Energy Exchange (PXE and the associated transfer from campaign-driven sale to continuous trading, represent a significant change for power companies.  Power producing companies can now optimize the sale of their production capacities with the objective of maximizing profit from wholesale electricity and supporting services. The Trading Departments measure the success rate of trading activities by the gross margin (GM, calculated by subtracting the realized sales prices from the realized purchase prices and the production cost, and indicate the profit & loss (P&L to be subsequently calculated by the Control Department. The risk management process is set up on the basis of a business strategy defining the volumes of electricity that have to be sold one year and one month before the commencement of delivery. At the same time, this process defines the volume of electricity to remain available for spot trading (trading limits. 

  5. Radiological strategy in acute stroke in children

    Energy Technology Data Exchange (ETDEWEB)

    Paonessa, Amalia [Dept. of Neuroradiology, University Hospital ' S. Salvatore' , L' Aquila (Italy)], E-mail: apaonessa7@hotmail.com; Limbucci, Nicola [Dept. of Neuroradiology, University Hospital ' S. Salvatore' , L' Aquila (Italy); Tozzi, Elisabetta [Dept. of Pediatrics, University Hospital ' S. Salvatore' , L' Aquila (Italy); Splendiani, Alessandra; Gallucci, Massimo [Dept. of Neuroradiology, University Hospital ' S. Salvatore' , L' Aquila (Italy)

    2010-04-15

    The aim of the study was to estimate the preponderance of patterns of pediatric stroke, ischemic or hemorrhagic, their etiologies and the correct diagnostic protocol for acute management. Forty-one consecutive pediatric patients (age range 5-16 years) with an acute stroke observed in acute phase during a 10-year period, were retrospectively evaluated. Twenty-three patients underwent magnetic resonance imaging (MRI), 3 cases were studied by computed tomography (CT) without MRI, and 15 underwent both CT and MRI studies. In 9 cases, intra-arterial digital subtraction angiography (IADSA) was performed after non-invasive preliminary assessment. Seventeen hemorrhagic (41%) and 24 ischemic (59%) strokes were found. Among hemorrhagic forms, 5 cases were due to arteriovenous malformation (AVM), 7 to cavernoma, and 2 to aneurysm. Among ischemic forms, 2 were due to sickle-cell disease, 1 to hyperomocysteinemia, 1 to moyamoya syndrome, 1 to pseudoxantoma elasticum, 3 to prothrombotic state, 1 to Fabry's disease, 1 concomitant with CO intoxication, 5 to venous sinus thrombosis, and 4 to cardio-embolic state. Etiology remains unknown in 8 cases (20.5%). This study shows a moderate prevalence of ischemic over hemorrhagic strokes. Moreover, personal experience suggests that MRI is always more informative than CT and in selected cases should be the first-choice examination in the acute phase.

  6. Flexibility along the Neck of the Neogene Terror Bird Andalgalornis steulleti (Aves Phorusrhacidae)

    Science.gov (United States)

    Tambussi, Claudia P.; de Mendoza, Ricardo; Degrange, Federico J.; Picasso, Mariana B.

    2012-01-01

    Background Andalgalornis steulleti from the upper Miocene–lower Pliocene (≈6 million years ago) of Argentina is a medium-sized patagornithine phorusrhacid. It was a member of the predominantly South American radiation of ‘terror birds’ (Phorusrhacidae) that were apex predators throughout much of the Cenozoic. A previous biomechanical study suggests that the skull would be prepared to make sudden movements in the sagittal plane to subdue prey. Methodology/Principal Findings We analyze the flexion patterns of the neck of Andalgalornis based on the neck vertebrae morphology and biometrics. The transitional cervical vertebrae 5th and 9th clearly separate regions 1–2 and 2–3 respectively. Bifurcate neural spines are developed in the cervical vertebrae 7th to 12th suggesting the presence of a very intricate ligamentary system and of a very well developed epaxial musculature. The presence of the lig. elasticum interespinale is inferred. High neural spines of R3 suggest that this region concentrates the major stresses during downstrokes. Conclusions/Significance The musculoskeletal system of Andalgalornis seems to be prepared (1) to support a particularly big head during normal stance, and (2) to help the neck (and the head) rising after the maximum ventroflexion during a strike. The study herein is the first interpretation of the potential performance of the neck of Andalgalornis in its entirety and we considered this an important starting point to understand and reconstruct the flexion pattern of other phorusrhacids from which the neck is unknown. PMID:22662194

  7. What are the most fire-dangerous atmospheric circulations in the Eastern-Mediterranean? Analysis of the synoptic wildfire climatology.

    Science.gov (United States)

    Paschalidou, A K; Kassomenos, P A

    2016-01-01

    Wildfire management is closely linked to robust forecasts of changes in wildfire risk related to meteorological conditions. This link can be bridged either through fire weather indices or through statistical techniques that directly relate atmospheric patterns to wildfire activity. In the present work the COST-733 classification schemes are applied in order to link wildfires in Greece with synoptic circulation patterns. The analysis reveals that the majority of wildfire events can be explained by a small number of specific synoptic circulations, hence reflecting the synoptic climatology of wildfires. All 8 classification schemes used, prove that the most fire-dangerous conditions in Greece are characterized by a combination of high atmospheric pressure systems located N to NW of Greece, coupled with lower pressures located over the very Eastern part of the Mediterranean, an atmospheric pressure pattern closely linked to the local Etesian winds over the Aegean Sea. During these events, the atmospheric pressure has been reported to be anomalously high, while anomalously low 500hPa geopotential heights and negative total water column anomalies were also observed. Among the various classification schemes used, the 2 Principal Component Analysis-based classifications, namely the PCT and the PXE, as well as the Leader Algorithm classification LND proved to be the best options, in terms of being capable to isolate the vast amount of fire events in a small number of classes with increased frequency of occurrence. It is estimated that these 3 schemes, in combination with medium-range to seasonal climate forecasts, could be used by wildfire risk managers to provide increased wildfire prediction accuracy. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. p-process xenon isotope anomalies in stardust grains from meteorites

    International Nuclear Information System (INIS)

    Ott, U.

    2013-01-01

    Full text: In measurements on 'bulk' samples of meteorites isotopic variations due to the p-process usually have taken a backseat compared to such in s- or r-isotopes, and, in the best case, can be qualitatively attributed to the p-process, with little to no inferences concerning detailed isotopic yields. The situation is different for grains of stardust that survived in primitive meteorites. In fact, isotopically strange xenon was the key feature that led to the first identification of a stardust mineral, nanodiamonds containing xenon with overabundances of up to a factor of ∼2 in both the r-only (≡H-Xe) and p-only (≡L-Xe) isotopes. Relative excesses of the two r-only isotopes ( 134 Xe, 136 Xe) as well as of the two p-only isotopes ( 124 Xe, 126 Xe) are not equal, hence the processes responsible for HL-xenon must differ from the 'average' r- and p-processes as reflected in solar system abundances. However, while considerable effort has been put into explaining H-Xe, there has been little work on the p-side (L-Xe). Relying on scarce nuclear data, Heymann and Dziczkaniec have studied photodisintegration reactions of Xe and Ba seeds in intermediate zones of supernovae and found that the relative production of the p-Xe isotopes depends sensitively on the yield of the (γ, α) reaction on 128 Ba. Another suggestion - applicable to both the r- and p-anomalies in diamond xenon - is that of a 'rapid separation' between stable Xe isotopes and radioactive precursors produced in the 'standard' p- (as well as r-) process. For the p-isotopes to work, this would require the bulk (87%) of 126 Xe to be produced via the 126 Ba precursor, with a half live of ∼100 minutes, in order to explain the high 124 Xe/ 126 Xe. In contrast to diamond xenon, xenon in silicon carbide contains - besides the component from the s-process in their parent AGB stars - 'almost normal' Xe, with indications for 124 Xe/ 126 Xe being few (∼8)% lower than in solar Xe.

  9. Transfusion regimens in thalassemia intermedia

    Directory of Open Access Journals (Sweden)

    Z. Karakas

    2011-12-01

    Full Text Available Thalassemia intermedia (TI is a heterogeneous disease, in terms of both clinical manifestations and underlying molecular defects. Some TI patients are asymptomatic until adult life, whereas others are symptomatic from early childhood. In contrast with patients with Thalassemia major (TM, the severity of anemia is less and the patients do not require transfusions during at least the first few years of life. Many patients with TI, especially older ones, have been exposed to the multiple long-term effects of chronic anemia and tissue hypoxia and their compensatory reactions, including enhanced erythropoiesis and increased iron absorption. Bone marrow expansion and extramedullary hematopoiesis lead to bone deformities and liver and spleen enlargement. Therapeutic strategies in TI are not clear and different criteria are used to decide the initiation of transfusion and chelation therapy, modulation of fetal hemoglobin production, and hematopoietic stem cell transplantation on an individual basis. The clinical picture of well-treated TM patients with regular transfusionchelation therapy is better from TI patients who have not received adequate transfusion therapy. There is a significant role of early blood transfusion to prevent and treat complications commonly associated with TI, such as extramedullary erythropoiesis and bone deformities, autoimmune hemolytic anemia, leg ulcers, gallstones, pseudoxantoma elasticum, hyperuricosuria, gout and pulmonary hypertension, which are rarely seen in thalassemia major. Nowadays, indications of transfusion in patients with TI are chronic anemia (Hb < 7 g/dL, bone deformities, growth failure, extramedullary erythropoiesis, heart failure, pregnancy and preparation for surgical procedures. Conclusion: Adequate (regular or tailored transfusion therapy is an important treatment modality for increasing the quality of life in patients with thalassemia intermedia during childhood. 就临床表象和潜在的分子缺