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Sample records for pseudoxanthoma elasticum pxe

  1. Pseudoxanthoma elasticum

    DEFF Research Database (Denmark)

    List-Jensen, Kamille; Åbom, Anne; Bygum, Anette

    2010-01-01

    During childhood two women developed yellowish xanthoma-like papules on the neck. After dermatological examination and skin biopsy, the diagnosis pseudoxanthoma elasticum (PXE) was made. PXE is a hereditary metabolic disease which has an early onset with characteristic skin lesions. Early diagnos...

  2. Pseudoxanthoma elasticum : Een aandoening met verschillende manifestaties

    NARCIS (Netherlands)

    Tromp, Tycho R.; Kranenburg, Guido; Ossewaarde-van Norel, Annette; Spiering, W

    2016-01-01

    BACKGROUND: Pseudoxanthoma elasticum (PXE) is a rare, autosomal recessive inheritable disorder characterized by progressive elastic fibre calcification. CASE DESCRIPTION: Here we describe two patients with different presentations of PXE. Patient A, an 11-year-old girl, visited the dermatologist

  3. Graviditet kompliceret af pseudoxanthoma elasticum

    DEFF Research Database (Denmark)

    Drue, Henrik Christian; Mogensen, Helle; Olesen, Annette Wind

    2014-01-01

    Pseudoxanthoma elasticum (PXE) is a rare inherited systemic disorder characterized by progressive calcification in the elastic tissue. Information about pregnancy in women with PXE is sparse. We report of a 36-year-old Caucasian woman, diagnosed with PXE, with a dichorionic diamniotic twin...... pregnancy, whose antenatal ultrasound scans showed a hyperechogenic placenta due to calcification. The calcification was confirmed on post-partum placental histology. Both twins, delivered via caesarean section due to maternal bleeding at 27 weeks of gestation suffered from intraventricular haemorrhage....

  4. 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

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

    Science.gov (United States)

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

    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 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 mineralization phenotype

  6. Pseudoxanthoma elasticum: the end of the autosomal dominant segregation myth

    NARCIS (Netherlands)

    Bergen, Arthur A. B.

    2006-01-01

    Pseudoxanthoma elasticum (PXE) is a heritable connective-tissue disorder affecting the eye, skin, and vascular system. Recent publications show that PXE exclusively segregates in an autosomal recessive fashion. However, the lack of an internationally accepted clinical "gold standard" for PXE, our

  7. Pseudoxanthoma Elasticum: A Pediatric Case

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    Melis Çoban

    2015-12-01

    Full Text Available Pseudoxanthoma elasticum (PXE is a multisystemic, metabolic and autosomal recessive inherited disorder affecting especially elastic fibers of skin, retina and blood vessels. The prevalence varies from 1:25,000 to 1:100,000. The average age of onset is 13.5 years. Yellowish papules 1-3 mm in diameter and plaques merging as linear or reticular pattern are mostly on antecubital fossae, popliteal fossae, inguinal region, lower clavicle, neck, axilla, flexural regions as umbilicus and trauma sites. Of the patients, 85% have eye involvement. The first symptom of eye involvement is spot retinal pigmentation. Cardiovascular complications occur usually in adults. The most common and early cardiovascular complication is intermittent claudication. There is no specific treatment for skin signs. Lifestyle changes may have important effects on prognosis. A male patient with 3-year history of yellowish papules on his neck and 1-year history of yellowish papules on his groins, was presented in this case report. This 7-year-old patient received a diagnosis of PXE based on medical story, clinical examination and histopathological findings. This case was presented as PXE is a rare disease and should be diagnosed by the clinician at early ages.

  8. 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.

  9. 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.

  10. Generalized arterial calcification of infancy and pseudoxanthoma elasticum can be caused by mutations in either ENPP1 or ABCC6

    NARCIS (Netherlands)

    Nitschke, Y.; Baujat, G.; Botschen, U.; Wittkampf, T.; du Moulin, M.; Stella, J.; Le Merrer, M.; Guest, G.; Lambot, K.; Tazarourte-Pinturier, M.F.; Chassaing, N.; Roche, O.; Feenstra, I.; Loechner, K.; Deshpande, C.; Garber, S.J.; Chikarmane, R.; Steinmann, B.; Shahinyan, T.; Martorell, L.; Davies, J.; Smith, W.E.; Kahler, S.G.; McCulloch, M.; Wraige, E.; Loidi, L.; Hohne, W.; Martin, L.; Hadj-Rabia, S.; Terkeltaub, R.; Rutsch, F.

    2012-01-01

    Spontaneous pathologic arterial calcifications in childhood can occur in generalized arterial calcification of infancy (GACI) or in pseudoxanthoma elasticum (PXE). GACI is associated with biallelic mutations in ENPP1 in the majority of cases, whereas mutations in ABCC6 are known to cause PXE.

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

    NARCIS (Netherlands)

    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

  12. 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.

  13. 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.

  14. Pseudoxanthoma Elasticum with Elastosis Perforans Serpiginosa

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    K Pavithran

    1983-01-01

    Full Text Available Three cases of pseudoxanthoma elasticum are, reported. Two of them had associated elastosis perforans serpigtnosa on their neck and angiod streaks in the eyes. In addition to the angioid streaks, -drusen′ (colloid bodies also were noted in the near the o tic disc in one case. The third patient had associated psoriatic lesions also.

  15. Does the absence of ABCC6 (multidrug resistance protein 6) in patients with Pseudoxanthoma elasticum prevent the liver from providing sufficient vitamin K to the periphery?

    NARCIS (Netherlands)

    Borst, Piet; van de Wetering, Koen; Schlingemann, Reinier

    2008-01-01

    Pseudoxanthoma elasticum (PXE) is an autosomal recessive disease characterized by a progressive mineralization of connective tissue, resulting in skin, arterial and eye disease. Classical PXE is caused by mutations in the ABCC6 gene, which encodes a member of the ABCC (MRP) family of organic anion

  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. Pseudoxanthoma Elasticum of the Skin with Involvement of the Oral Cavity

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    Flávia Sayuri Matsuo

    2013-01-01

    Full Text Available Pseudoxanthoma elasticum (PXE is an inherited multisystemic disease of elastic fibers that primarily affects the skin and retina. A case of primary PXE of the skin with late involvement of the upper lip is reported. A 55-year-old woman with a previous diagnosis of PXE affecting her skin developed a lesion on her lower lip. An oral examination identified a yellowish macule of undefined limits. A biopsy from her lip was taken and both light and transmission electron microscopies confirmed the presence of fragmented elastic fibers and calcifications on her mucosa, which was compatible with the diagnosis of oral PXE. Since the manifestation of oral PXE is rare in this region, dental practitioners must be aware that this systemic condition may produce oral lesions, which sometimes may mimic other benign diseases of the oral cavity like Fordyce granules. So, the establishment of an appropriate diagnosis is necessary to provide adequate information and attention to the patient.

  19. The contribution of arterial calcification to peripheral arterial disease in pseudoxanthoma elasticum.

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    Georges Leftheriotis

    Full Text Available The contribution of arterial calcification (AC in peripheral arterial disease (PAD and arterial wall compressibility is a matter of debate. Pseudoxanthoma elasticum (PXE, an inherited metabolic disease due to ABCC6 gene mutations, combines elastic fiber fragmentation and calcification in various soft tissues including the arterial wall. Since AC is associated with PAD, a frequent complication of PXE, we sought to determine the role of AC in PAD and arterial wall compressibility in this group of patients.Arterial compressibility and patency were determined by ankle-brachial pressure index (ABI in a cohort of 71 PXE patients (mean age 48 ± SD 14 yrs, 45 women and compared to 30 controls without PAD. Lower limb arterial calcification (LLAC was determined by non-contrast enhanced helicoidal CT-scan. A calcification score (Ca-score was computed for the femoral, popliteal and sub-popliteal artery segments of both legs. Forty patients with PXE had an ABI1.40. LLAC increased with age, significantly more in PXE subjects than controls. A negative association was found between LLAC and ABI (r = -0.363, p = 0.002. The LLAC was independently associated with PXE and age, and ABI was not linked to cardiovascular risk factors.The presence of AC was associated with PAD and PXE without affecting arterial compressibility. PAD in PXE patients is probably due to proximal obstructive lesions developing independently from cardiovascular risk factors.

  20. The contribution of arterial calcification to peripheral arterial disease in pseudoxanthoma elasticum.

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    Leftheriotis, Georges; Kauffenstein, Gilles; Hamel, Jean François; Abraham, Pierre; Le Saux, Olivier; Willoteaux, Serge; Henrion, Daniel; Martin, Ludovic

    2014-01-01

    The contribution of arterial calcification (AC) in peripheral arterial disease (PAD) and arterial wall compressibility is a matter of debate. Pseudoxanthoma elasticum (PXE), an inherited metabolic disease due to ABCC6 gene mutations, combines elastic fiber fragmentation and calcification in various soft tissues including the arterial wall. Since AC is associated with PAD, a frequent complication of PXE, we sought to determine the role of AC in PAD and arterial wall compressibility in this group of patients. Arterial compressibility and patency were determined by ankle-brachial pressure index (ABI) in a cohort of 71 PXE patients (mean age 48 ± SD 14 yrs, 45 women) and compared to 30 controls without PAD. Lower limb arterial calcification (LLAC) was determined by non-contrast enhanced helicoidal CT-scan. A calcification score (Ca-score) was computed for the femoral, popliteal and sub-popliteal artery segments of both legs. Forty patients with PXE had an ABI1.40. LLAC increased with age, significantly more in PXE subjects than controls. A negative association was found between LLAC and ABI (r = -0.363, p = 0.002). The LLAC was independently associated with PXE and age, and ABI was not linked to cardiovascular risk factors. The presence of AC was associated with PAD and PXE without affecting arterial compressibility. PAD in PXE patients is probably due to proximal obstructive lesions developing independently from cardiovascular risk factors.

  1. Added value of infrared, red-free and autofluorescence fundus imaging in pseudoxanthoma elasticum.

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    De Zaeytijd, Julie; Vanakker, Olivier M; Coucke, Paul J; De Paepe, Anne; De Laey, Jean-Jacques; Leroy, Bart P

    2010-04-01

    Pseudoxanthoma elasticum (PXE) is an autosomal recessive disorder caused by mutations in the ABCC6 gene and primarily affects the oculocutaneous and cardiovascular systems. However, the phenotype, including the ophthalmological manifestations, varies in severity. The present study aims to evaluate the added value of novel funduscopic imaging techniques, such as near-infrared reflectance, red-free and autofluorescence imaging in PXE. In 22 molecularly proven PXE patients and 25 obligate carriers, PXE retinopathy was evaluated using funduscopy, white light, red-free, infrared and autofluorescence imaging. At least one characteristic of PXE retinopathy was evident on funduscopy of all eyes. Angioid streaks could be subdivided in those with (brick red) or without (feathered) adjacent RPE alterations. Infrared imaging showed the brick-red-coloured streaks as well-demarcated dark fissures, even when these passed unnoticed on funduscopy. Feathered types were detected as triangular areas of hypoautofluorescence. The peau d'orange was much more visible and much more widespread on infrared imaging, with extension from the posterior pole towards the whole midperiphery. Comets and comet tails were best seen with red-free imaging. Infrared, red-free and autofluorescence imaging are more sensitive than white light funduscopy and imaging in visualising early retinal signs of PXE. In addition, this specialised imaging allows a better appreciation of the extent of lesions. Hence, such imaging increases the chances of making a correct diagnosis early, and aids in the accurate evaluation of evolution of disease in the ophthalmic follow-up of PXE patients.

  2. [Acute arterial thrombosis of the extremity in pseudoxanthoma elasticum].

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    Rodríguez-Camarero, S J; Manchado, P; González, J A; Castro, M A; Rodero, J I; Mateo, A M

    1992-01-01

    We report a case of a patient with an elastic pseudoxanthoma (PXE) who presented an acute ischaemia at the left lower limb. The cause of such ischaemia was a thrombosis into the iliac and femoropopliteal arteries. Patient underwent a surgical procedure. The arteriopathy associated with a PXE rarely cause an arterial major occlusion. We did not found a case of acute arterial thrombotic ischaemia and PXE, treated with direct arterial revascularization in the reviewed literature.

  3. Structural characterization of the skin glycosaminoglycans in patients with pseudoxanthoma elasticum.

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    Maccari, Francesca; Volpi, Nicola

    2008-10-01

    Complex polysaccharides, glycosaminoglycans (GAGs), their amount, and fine structure were determined in the skin (epidermis + dermis) of pseudoxanthoma elasticum (PXE)-affected patients in comparison with healthy subjects. Nonlesional skin GAGs were extracted and specifically determined by enzymatic treatment and high-performance liquid chromatography separation. Dermatan sulfate (DS) and hyaluronic acid (HA) were found to be the major GAG species in normal subjects, with contents of approximately 20% for DS and 58% for HA. The chondroitin sulfate (CS) content (unsaturated six-sulfated disaccharide) was approximately 21%. Skin from patients with PXE showed similar HA (61%), DS (22%), and CS (16.7%) contents. No change in the total charge density or nonsulfated/sulfated GAG ratio was noted in PXE-affected subjects, and no modification of the position of the sulfate groups (4s/6s) on the CS/DS backbone. A significant increase (approximately 88%; P < 0.01) in the total amount of GAGs (HA + DS + CS) was found in the PXE group vs. normal subjects, however. In the skin of PXE-affected patients, the altered metabolic processes produce an increase in the total amount of GAGs able to accumulate salts, in particular calcium ions, within the elastic fibers, producing ion precipitates that affect the organization of the matrix fiber.

  4. Relationship between the distribution of pseudoxanthoma elasticum skin and mucous membrane lesions and cardiovascular involvement.

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    Utani, Atsushi; Tanioka, Miki; Yamamoto, Yosuke; Taki, Reiko; Araki, Eri; Tamura, Hiroshi; Miyachi, Yoshiki

    2010-02-01

    Pseudoxanthoma elasticum (PXE) primarily affects organs that are abundant in elastic fibers, such as the skin, eye and blood vessels, and may eventually cause loss of vision or cardiovascular disease (CVD). Because CVD is a potentially life-threatening complication, its early detection is important for improving the quality of life of PXE patients. To determine the relationship between the distribution of skin and mucous membrane lesions and the prevalence of CVD in patients with PXE, we examined 14 PXE cases who presented between 2004 and 2007. All patients had angioid streaks (AS) and positive pathological findings. The skin lesions in PXE patients are distributed discontinuously and thus the degrees of skin involvement were assessed by determining the presence or absence of PXE skin and mucous membrane lesions in six sites (oral mucosa, neck, periumbilical region, cubital fossa, axillae and inguinal regions). Each site was given a binary score (i.e. present = 1, absent = 0) irrespective of severity and the scores were summed to yield a total distribution score (potential range of 0-6). Four cases had PXE-associated CVD. Their mean distribution score was 5.7, which was significantly higher than the score of the cases without CVD (1.8) (P = 0.0049). There was also significant correlation between the high distribution score (P = 0.0053) as well as CVD (P = 0.029) with the maximum width of AS. A higher distribution score and the presence of oral mucosal lesions were associated with CVD. This scoring method may be useful for predicting the presence of CVD in PXE patients.

  5. ABCC6 prevents ectopic mineralization seen in pseudoxanthoma elasticum by inducing cellular nucleotide release

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    Jansen, Robert S.; Küçükosmanoğlu, Aslı; de Haas, Marcel; Sapthu, Sunny; Otero, Jon Andoni; Hegman, Ilse E. M.; Bergen, Arthur A. B.; Gorgels, Theo G. M. F.; Borst, P.; van de Wetering, Koen

    2013-01-01

    Pseudoxanthoma elasticum (PXE) is an autosomal recessive disease characterized by progressive ectopic mineralization of the skin, eyes, and arteries, for which no effective treatment exists. PXE is caused by inactivating mutations in the gene encoding ATP-binding cassette sub-family C member 6 (ABCC6), an ATP-dependent efflux transporter present mainly in the liver. Abcc6−/− mice have been instrumental in demonstrating that PXE is a metabolic disease caused by the absence of an unknown factor in the circulation, the presence of which depends on ABCC6 in the liver. Why absence of this factor results in PXE has remained a mystery. Here we report that medium from HEK293 cells overexpressing either human or rat ABCC6 potently inhibits mineralization in vitro, whereas medium from HEK293 control cells does not. Untargeted metabolomics revealed that cells expressing ABCC6 excrete large amounts of nucleoside triphosphates, even though ABCC6 itself does not transport nucleoside triphosphates. Extracellularly, ectonucleotidases hydrolyze the excreted nucleoside triphosphates to nucleoside monophosphates and inorganic pyrophosphate (PPi), a strong inhibitor of mineralization that plays a pivotal role in several mineralization disorders similar to PXE. The in vivo relevance of our data are demonstrated in Abcc6−/− mice, which had plasma PPi levels <40% of those found in WT mice. This study provides insight into how ABCC6 affects PXE. Our data indicate that the factor that normally prevents PXE is PPi, which is provided to the circulation in the form of nucleoside triphosphates via an as-yet unidentified but ABCC6-dependent mechanism. PMID:24277820

  6. 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.

  7. Mouse models for pseudoxanthoma elasticum: genetic and dietary modulation of the ectopic mineralization phenotypes.

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    Qiaoli Li

    Full Text Available Pseudoxanthoma elasticum (PXE, a heritable ectopic mineralization disorder, is caused by mutations in the ABCC6 gene. Null mice (Abcc6(-/- recapitulate the genetic, histopathologic and ultrastructural features of PXE, and they demonstrate early and progressive mineralization of vibrissae dermal sheath, which serves as a biomarker of the overall mineralization process. Recently, as part of a mouse aging study at The Jackson Laboratory, 31 inbred mouse strains were necropsied, and two of them, KK/HlJ and 129S1/SvImJ, were noted to have vibrissae dermal mineralization similar to Abcc6(-/- mice. These two strains were shown to harbor a single nucleotide polymorphism (rs32756904 in the Abcc6 gene, which resulted in out-of-frame splicing and marked reduction in ABCC6 protein expression in the liver of these mice. The same polymorphism is present in two additional mouse strains, DBA/2J and C3H/HeJ, with similar reduction in Abcc6 protein levels, yet these mice did not demonstrate tissue mineralization when kept on standard rodent diet. However, all four mouse strains, when placed on experimental diet enriched in phosphate and low in magnesium, developed extensive ectopic mineralization. These results indicate that the genetic background of mice and the mineral composition of their diet can profoundly modulate the ectopic mineralization process predicated on mutations in the Abcc6 gene. These mice provide novel model systems to study the pathomechanisms and the reasons for strain background on phenotypic variability of PXE.

  8. 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.

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

    Science.gov (United States)

    Gliem, Martin; Zaeytijd, Julie De; Finger, Robert P.; Holz, Frank G.; Leroy, Bart P.; Issa, Peter Charbel

    2013-01-01

    Pseudoxanthoma elasticum (PXE) is an inherited multi-system disorder characterized by ectopic mineralization and fragmentation of elastic fibers in the skin, the elastic laminae of blood vessels and Bruch’s membrane in the eye. Biallelic mutations in the ATP-binding cassette (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 fibers. This review summarizes and aims at explaining the variety of phenotypic ocular findings in patients with PXE. Specialized imaging techniques including white light fundus photography, blue light autofluorescence, near-infrared confocal reflectance imaging, high resolution optical coherence tomography, fluorescein and indocyanine green (ICG) 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 neovascularizations (CNVs), but also the more recently recognized features such as chorioretinal atrophy, subretinal fluid independent from CNV, pattern dystrophy-like changes, debris accumulation under the retinal pigment epithelium, reticular drusen and a decreased fluorescence on late phase ICG angiography. PMID:23577018

  10. Pseudoxanthoma elasticum and familial hypercholesterolemia: a deleterious combination of cardiovascular risk factors.

    Science.gov (United States)

    Pisciotta, Livia; Tarugi, Patrizia; Borrini, Claudia; Bellocchio, Antonella; Fresa, Raffaele; Guerra, Deanna; Quaglino, Daniela; Ronchetti, Ivonne; Calandra, Sebastiano; Bertolini, Stefano

    2010-05-01

    Pseudoxanthoma Elasticum (PXE), an autosomal recessive disease due to mutations in ABCC6 gene, is characterised by fragmentation of elastic fibres with involvement of the cardiovascular system. We investigated a 60-year-old female with angina pectoris found to have PXE, associated with elevated plasma LDL-C suspected to be due to autosomal-co-dominant hypercholesterolemia. ABCC6, LDLR, PCSK9 and exon 26 of APOB genes were re-sequenced. Cardiovascular involvement was assessed by coronary angiography, single-photon emission computed tomography (SPECT) and ultrasound examination. The patient was a compound heterozygous for two ABCC6 mutations (p.S317R and p.R1141X) and heterozygous for a novel LDLR mutation (p.R574H). She had severe coronary stenosis and calcification of the arteries of the lower limbs. Treatment with ezetimibe/simvastatin 10/60mg/day, maintained over a 4.5-year period, reduced of LDL-C and the myocardial ischemic area. In PXE patients LDL-lowering treatment might contribute to delay macrovascular complications. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

  11. Non-vascular vision loss in pseudoxanthoma elasticum

    OpenAIRE

    Tsui, Irena; Fuchs, Brian S.; Chou, Chai Lin; Chang, Stanley; Tsang, Stephen H.

    2007-01-01

    Pseudoxanthoma elasticum patients with angioid streaks are well-known to have acute vision loss due to choroidal bleeding. However, chronic vision loss due to macular atrophy is less well characterized. We describe a patient with sub-acute vision loss in one eye due to loss of macular retinal pigment epithelium function. Autofluorescence and pattern electroretinogram were useful adjuncts to help diagnose the source of her vision loss.

  12. Vitamin K reduces hypermineralisation in zebrafish models of PXE and GACI

    NARCIS (Netherlands)

    Mackay, Eirinn William; Apschner, Alexander|info:eu-repo/dai/nl/345732006; Schulte-Merker, Stefan|info:eu-repo/dai/nl/304079499

    2015-01-01

    The mineralisation disorder pseudoxanthoma elasticum (PXE) is associated with mutations in the transporter protein ABCC6. Patients with PXE suffer from calcified lesions in the skin, eyes and vasculature, and PXE is related to a more severe vascular calcification syndrome called generalised arterial

  13. Testicular microlithiasis in a 2-year-old boy with pseudoxanthoma elasticum

    NARCIS (Netherlands)

    Goede, J.; Hack, W.W.M.; Sijstermans, K.; Pierik, F.H.

    2008-01-01

    Pseudoxantoma elasticum (PXE) is a rare chromosomal disorder that results in mineralization of elastic fibers, especially in the skin, eye, and cardiovascular system. Recently, PXE has been associated with testicular microlithiasis (TM),1 which itself might be associated with testicular malignancy.2

  14. Pseudoxanthoma Elasticum Treatment with Fractional CO2 Laser

    Directory of Open Access Journals (Sweden)

    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.

  15. Chondroitin sulfate in normal human plasma is modified depending on the age. Its evaluation in patients with pseudoxanthoma elasticum.

    Science.gov (United States)

    Volpi, Nicola; Maccari, Francesca

    2006-08-01

    Plasma chondroitin sulfate (CS) amount and charge density were determined in 45 healthy volunteers (control group), 45 pseudoxanthoma elasticum (PXE)-affected patients and 19 healthy carriers by using fluorophore-assisted carbohydrate electrophoresis (FACE) and HPLC equipped with postcolumn derivatization and fluorescence detection. The mean values of CS amount were 4.9+/-1.21 for volunteers, 4.7+/-1.40 for PXE subjects and 4.4+/-1.44 for the carriers. No significant differences were found for the three human subjects groups. On the contrary, by considering the age of normal volunteers, a significant increase of plasma CS amount was measured. In fact, the volunteers aging from 17 to 40 years (mean 32.1) showed a CS concentration of 4.3+/-1.30 while the group ranging from 50 to 74 years (mean 56.9) had a value of 5.6+/-1.16 with a significant increase of +30.2%. The same significant increase in CS plasma content with increasing age was measured for PXE-affected and healthy carriers group. Extracted plasma CS was evaluated for the main two unsaturated disaccharides, non-sulfated and 4-monosulfated, and the charge density determined. The mean values were 0.54+/-0.13 for volunteers, 0.60+/-0.15 for PXE subjects and 0.50+/-0.15 for the carriers. A significant increase of +11.1% was found between the PXE patients and healthy human group but no differences were calculated between the control group and the carriers. Furthermore, besides a CS amount, the volunteers aging from 17 to 40 years (mean 32.1) showed a charge density of 0.53+/-0.14 while the group ranging from 50 to 74 years (mean 56.9) had a value of 0.58+/-0.17 with a significant increase of +9.4%. The same trend was measured for the healthy carriers group. The CS charge density of PXE-affected subjects was found to increase significantly more than healthy controls depending on the age. In fact, the PXE patients aging from 10 to 40 years (mean 29.3) showed a charge density of 0.56+/-0.14 while the group ranging

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

    Science.gov (United States)

    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.

  17. Pseudoxantoma elástico perfurante periumbilical e periareolar Periumbilical and periareolar perforating pseudoxanthoma elasticum

    Directory of Open Access Journals (Sweden)

    Aline Lopes Bressan

    2010-10-01

    Full Text Available O pseudoxantoma elástico perfurante periumbilical (PEPP, ou elastose cálcica perfurante, é distúrbio raro e sua patogênese está associada a alteração da fibra elástica, tendo o trauma provável participação. Apresenta-se caso de paciente de 70 anos com quadro de máculas enegrecidas e pápulas encimadas por crostas na região periareolar e periumbilical há mais de dez anos. O exame histopatológico revelou fibras elásticas alteradas, repletas de cálcio, e formação de pertuito na derme com fibras elásticas degradadas no seu interior. O caso descrito corresponde ao PEPP, que nesta paciente também acomete área periareolar bilateralmente.The periumbilical perforating pseudoxanthoma elasticum or perforating calcific elastosis is a rare disorder and its pathogenesis is associated with the alteration of elastic fibers, which may probably result from trauma. We present the case of a 70-year-old woman with long-time blackish maculas and keratotic surface papules on the periareolar and periumbilical regions. The histopathological examination revealed altered elastic fibers, replete with calcium and formation of a path in the dermis with elastic fibers degraded in their interior, confirming the clinical diagnosis.

  18. 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

  19. 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

  20. 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.

  1. Vitamin K reduces hypermineralisation in zebrafish models of PXE and GACI.

    Science.gov (United States)

    Mackay, Eirinn W; Apschner, Alexander; Schulte-Merker, Stefan

    2015-03-15

    The mineralisation disorder pseudoxanthoma elasticum (PXE) is associated with mutations in the transporter protein ABCC6. Patients with PXE suffer from calcified lesions in the skin, eyes and vasculature, and PXE is related to a more severe vascular calcification syndrome called generalised arterial calcification of infancy (GACI). Mutations in ABCC6 are linked to reduced levels of circulating vitamin K. Here, we describe a mutation in the zebrafish (Danio rerio) orthologue abcc6a, which results in extensive hypermineralisation of the axial skeleton. Administration of vitamin K to embryos was sufficient to restore normal levels of mineralisation. Vitamin K also reduced ectopic mineralisation in a zebrafish model of GACI, and warfarin exacerbated the mineralisation phenotype in both mutant lines. These data suggest that vitamin K could be a beneficial treatment for human patients with PXE or GACI. Additionally, we found that abcc6a is strongly expressed at the site of mineralisation rather than the liver, as it is in mammals, which has significant implications for our understanding of the function of ABCC6. © 2015. Published by The Company of Biologists Ltd.

  2. 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....

  3. ABCC6-mediated ATP secretion by the liver is the main source of the mineralization inhibitor inorganic pyrophosphate in the systemic circulation-brief report

    NARCIS (Netherlands)

    Jansen, Robert S.; Duijst, Suzanne; Mahakena, Sunny; Sommer, Daniela; Szeri, Flóra; Váradi, András; Plomp, Astrid; Bergen, Arthur A.; Oude Elferink, Ronald P. J.; Borst, Piet; van de Wetering, Koen

    2014-01-01

    Mutations in ABCC6 underlie the ectopic mineralization disorder pseudoxanthoma elasticum (PXE) and some forms of generalized arterial calcification of infancy, both of which affect the cardiovascular system. Using cultured cells, we recently showed that ATP-binding cassette subfamily C member 6

  4. ABCC6-mediated ATP secretion by the liver is the main source of the mineralization inhibitor inorganic pyrophosphate in the systemic circulation-brief report

    NARCIS (Netherlands)

    Jansen, Robert S; Duijst, Suzanne; Mahakena, Sunny; Sommer, Daniela; Szeri, Flóra; Váradi, András; Plomp, A.S.; Bergen, Arthur A; Oude Elferink, Ronald P J; Borst, Piet; van de Wetering, Koen

    OBJECTIVE: Mutations in ABCC6 underlie the ectopic mineralization disorder pseudoxanthoma elasticum (PXE) and some forms of generalized arterial calcification of infancy, both of which affect the cardiovascular system. Using cultured cells, we recently showed that ATP-binding cassette subfamily C

  5. Heterozygosity for R1141X in ABCC6 and risk of ischemic vascular disease

    DEFF Research Database (Denmark)

    Hornstrup, Louise S; Tybjærg-Hansen, Anne; Haase, Christiane L

    2011-01-01

    Pseudoxanthoma elasticum (PXE) is an autosomal recessive disease caused by loss-of-function mutations in ABCC6 and characterized by elastic calcification leading to dermal, ocular, and ischemic vascular disease. We tested the hypothesis that heterozygosity for R1141X, the most frequent PXE......-causing mutation in Caucasians, associated with risk of ischemic vascular disease, as previous studies suggested 4- to 11-fold risk of ischemic heart disease (IHD) in heterozygotes....

  6. Untargeted Metabolomics Analysis of ABCC6-Deficient Mice Discloses an Altered Metabolic Liver Profile

    DEFF Research Database (Denmark)

    Rasmussen, Mie Rostved; Nielsen, Kirstine Lykke; Christensen, Mia Benedicte Lykke Roest

    2016-01-01

    Loss-of-function mutations in the transmembrane ABCC6 transport protein cause pseudoxanthoma elasticum (PXE), an ectopic, metabolic mineralization disorder that affects the skin, eye, and vessels. ABCC6 is assumed to mediate efflux of one or several small molecule compounds from the liver cytosol...... in acetylation reactions, were accumulated in the liver. None of the identified metabolites seems to explain mineralization in extrahepatic tissues, but the present study now shows that abrogated ABCC6 function does cause alterations in the metabolic profile of the liver in accordance with PXE being a metabolic...

  7. 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.

  8. Founder effect in 20 Afrikaner kindreds with pseudoxanthoma ...

    African Journals Online (AJOL)

    It is suggested that these two groups are the founder groups of present-day PXE patients. Similar genealogical studies have been performed on kindreds with familial polyposis, familial heart block and familial hyper. cholesterolaemia, among other disorders. Due to geographical isolation, political developments and cultural ...

  9. Disease: H00560 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available di A, Uitto J Pseudoxanthoma elasticum: clinical phenotypes, molecular genetics a...l Issa P, Ladewig MS, Gotting C, Szliska C, Scholl HP, Holz FG Pseudoxanthoma elasticum: genetics, clinical

  10. Expression of the human ABCC6 gene is induced by retinoids through the retinoid X receptor.

    Science.gov (United States)

    Ratajewski, Marcin; Bartosz, Grzegorz; Pulaski, Lukasz

    2006-12-01

    Mutations in the human ABCC6 gene are responsible for the disease pseudoxanthoma elasticum, although the physiological function or substrate of the gene product (an ABC transporter known also as MRP6) is not known. We found that the expression of this gene in cells of hepatic origin (where this gene is predominantly expressed in the body) is significantly upregulated by retinoids, acting as agonists of the retinoid X receptor (RXR) rather than the retinoid A receptor (RAR). The direct involvement of this nuclear receptor in the transcriptional regulation of ABCC6 gene expression was confirmed by transient transfection and chromatin immunoprecipitation assays. This constitutes the first direct proof of previously suggested involvement of nuclear hormone receptors in ABCC6 gene expression and the first identification of a transcription factor which may be relevant to regulation of ABCC6 level in tissues and in some PXE patients.

  11. The molecular and physiological roles of ABCC6: more than meets the eye

    Directory of Open Access Journals (Sweden)

    Olivier eLe Saux

    2012-12-01

    Full Text Available Abnormal mineralization occurs in the context of several common conditions, including advanced age, diabetes, hypercholesterolemia, chronic renal failure and certain genetic conditions. Metabolic, mechanical, infectious, and inflammatory injuries promote ectopic mineralization through overlapping yet distinct molecular mechanisms of initiation and progression. The ABCC6 protein is an ATP-dependent transporter primarily found in the plasma membrane of hepatocytes. ABCC6 exports unknown substrates from the liver presumably for systemic circulation. ABCC6 deficiency is the primary cause for chronic and acute forms of ectopic mineralization described in diseases such as pseudoxanthoma elasticum (PXE, β-thalassemia, and generalized arterial calcification of infancy (GACI in humans and dystrophic cardiac calcification (DCC in mice. These pathologies are characterized by mineralization of cardiovascular, ocular, and dermal tissues. PXE and to an extent GACI, are caused by inactivating ABCC6 mutations, whereas the mineralization associated with β-thalassemia patients derives from a liver-specific change in ABCC6 expression. DCC is an acquired phenotype resulting from cardiovascular insults (ischemic injury or hyperlipidemia and secondary to ABCC6 insufficiency. Abcc6-deficient mice develop ectopic calcifications similar to both the human PXE and mouse DCC phenotypes. The precise molecular and cellular mechanism linking deficient hepatic ABCC6 function to distal ectopic mineral deposition is not understood and has captured the attention of many research groups. Our previously published work along with that of others show that ABCC6 influences other modulators of calcification and that it plays a much greater physiological role than originally thought.

  12. PXE International, Inc.

    Science.gov (United States)

    ... Last Name * Email * feed me To prevent automated spam submissions leave this field empty. CAPTCHA This question ... are a human visitor and to prevent automated spam submissions. Math question * 1 + 0 = Solve this simple ...

  13. Mechanisms of arterial remodeling: lessons from genetic diseases

    Directory of Open Access Journals (Sweden)

    Bernard eVan Varik

    2012-12-01

    Full Text Available Vascular disease is still the leading cause of morbidity and mortality in the Western world, and the primary cause of myocardial infarction, stroke, and ischemia. The biology of vascular disease is complex and still poorly understood in terms of causes and consequences. Vascular function is determined by structural and functional properties of the arterial vascular wall. Arterial stiffness, that is a pathological alteration of the vascular wall, ultimately results in target-organ damage and increased mortality. Arterial remodeling is accelerated under conditions that adversely affect the balance between arterial function and structure such as hypertension, atherosclerosis, diabetes mellitus, chronic kidney disease, inflammatory disease, lifestyle aspects (smoking, drugs (vitamin K antagonists and genetic abnormalities (e.g. pseudoxanthoma elasticum, Marfan’s disease. The aim of this review is to provide an overview of the complex mechanisms and different factors that underlie arterial remodeling, learning from single gene defect diseases like PXE, and PXE-like, Marfan’s disease and Keutel syndrome in vascular remodeling.

  14. Treatment of Exudative and Vasogenic Chorioretinal Diseases Including Variants of AMD and Other CNV Related Maculopathy

    Science.gov (United States)

    2012-10-24

    Coats' Disease; Idiopathic Retinal Telangiectasia; Retinal Angiomatous Proliferation; Polypoidal Choroidal Vasculopathy; Pseudoxanthoma Elasticum; Pathological Myopia; Multi-focal Choroiditis; Rubeosis Iridis; Von Hippel Lindau Disease; BEST VITELLIFORM MACULAR DYSTROPHY, MULTIFOCAL (Disorder)

  15. Disease: H01002 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available tion of infancy (GACI) is a rare and often fatal genetic disorder, characterized by calcification of the internal elastic...n both GACI and pseudoxanthoma elasticum (H00560). OMIM: 208000 PMID:22209248 (ge...et 90:25-39 (2012) PMID:22229486 (gene) Li Q, Schumacher W, Jablonski D, Siegel D, Uitto J Cutaneous features of pseudoxanthoma elast...icum in a patient with generalized arterial calcificatio

  16. The ERK1/2-Hepatocyte Nuclear Factor 4α Axis Regulates Human ABCC6 Gene Expression in Hepatocytes*

    OpenAIRE

    de Boussac, Hugues; Ratajewski, Marcin; Sachrajda, Iwona; Köblös, Gabriella; Tordai, Attila; Pulaski, Lukasz; Buday, László; Váradi, András; Arányi, Tamás

    2010-01-01

    ABCC6 mutations are responsible for the development of pseudoxanthoma elasticum, a rare recessive disease characterized by calcification of elastic fibers. Although ABCC6 is mainly expressed in the liver the disease has dermatologic, ocular, and cardiovascular symptoms. We investigated the transcriptional regulation of the gene and observed that hepatocyte growth factor (HGF) inhibits its expression in HepG2 cells via the activation of ERK1/2. Similarly, other factors activating the cascade a...

  17. Near infrared autofluorescence imaging of retinal diseases.

    Science.gov (United States)

    Skondra, Dimitra; Papakostas, Thanos D; Hunter, Rebecca; Vavvas, Demetrios G

    2012-01-01

    Near infrared autofluorescence (excitation 787 nm, emission >800 nm) is a non-invasive imaging technology that provides information on the distribution of melanin within the retinal pigment epithelial cell/choroid complex. This review contains an introduction to near infrared autofluorescence imaging methods. Characteristics of near infrared imaging in a variety of retinal diseases, including age-related macular degeneration, choroidal nevus, retinal degenerations, retinal dystrophies, central serous chorioretinopathy, pseudoxanthoma elasticum and chloroquine retinopathy, are summarized.

  18. Numerical Simulations of a Vibrating Elasticum

    DEFF Research Database (Denmark)

    Sinclair, Robert

    1999-01-01

    Two robust numerical algorithms for simulating the dynamics of a clamped, massless, incompressibleelasticum with a unit point mass at the free end are presented, along with some first results concerning various modes of oscillation, and further data with some relevance to the question of whether...

  19. 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

  20. Papulosis fibrosa blanca del cuello White Fibrous Papulosis Of The Neck

    Directory of Open Access Journals (Sweden)

    JE Restifo

    2009-12-01

    Full Text Available Presentamos el caso de una mujer de 55 años afectada por Papulosis Fibrosa Blanca del Cuello, que había sido diagnosticada como Pseudoxantoma Elástico. Son cuadros que pueden confundirse y es menester el diagnóstico diferencial, porque nuestra paciente de buen pronóstico tenía un diagnóstico ominoso.We report the case of a woman 55 years old affected by Fibrous Papulosis of the Neck, that was diagnosed as pseudoxanthoma elasticum. These are entities that may be confused but we emphasize the differential diagnosis, since in our case, a patient with good prognosis had an ominous diagnosis.

  1. 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.

  2. [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.

  3. Transcriptional regulation of the ABCC6 gene and the background of impaired function of missense disease-causing mutations

    Directory of Open Access Journals (Sweden)

    Tamás eArányi

    2013-03-01

    Full Text Available The human ABCC6 gene encodes an ABC transporter protein expressed primarily in the liver and to a lesser extent in the kidneys and the intestines. We review here the mechanisms of this restricted tissue-specific expression and the role of hepatocyte nuclear factor 4α which is responsible for the expression pattern. Detailed analyses uncovered further regulators of the expression of the gene pointing to an intronic primate-specific regulator region, an activator of the expression of the gene by binding C/EBPbeta, which interacts with other proteins acting in the proximal promoter. This regulatory network is affected by various environmental stimuli including oxidative stress and the ERK1/2 pathway. We also review here the structural and functional consequences of disease-causing missense mutations of ABCC6. A significant clustering of the missense disease-causing mutations was found at the domain-domain interfaces. This clustering means that the domain contacts are much less permissive to amino acid replacements than the rest of the protein. We summarize the experimental methods resulting in the identification of mutants with preserved transport activity but failure in intracellular targeting. These mutants are candidates for functional rescue by chemical chaperons. The results of such research can provide the basis of future allele-specific therapy of ABCC6-mediated disorders like pseudoxanthoma elasticum or the generalized arterial calcification in infancy.

  4. 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.

  5. Extracardiac medical and neuromuscular implications in restrictive cardiomyopathy.

    Science.gov (United States)

    Stöllberger, Claudia; Finsterer, Josef

    2007-08-01

    Restrictive cardiomyopathy (RCMP) is characterized by restrictive filling and reduced diastolic volume of either or both ventricles with normal or near-normal systolic function and wall thickness. It may occur idiopathically or as a cardiac manifestation of systemic diseases such as scleroderma, amyloidosis, Churg-Strauss syndrome, cystinosis, sarcoidosis, lymphoma, Gaucher's disease, hemochromatosis, Fabry's disease, pseudoxanthoma elasticum, hypereosinophilic syndrome, carcinoid, Noonan's syndrome, reactive arthritis, or Werner's syndrome and various neuromuscular disorders. Whereas in idiopathic RCMP the therapeutic options are only treatment of cardiac congestion, in cases with an underlying disorder, a causal therapy may be available. Patients with RCMP should be investigated as soon as the cardiac diagnosis is established for extracardiac diseases to detect a possibly treatable cause of RCMP before the disease becomes intractable. These investigations include a diligent clinical history and examination, blood tests, and ophthalmologic, otologic, dermatologic, gastroenterologic, nephrologic, hematologic, and neurologic examinations. If extracardiac examinations do not reveal a plausible cause for RCMP, endomyocardial biopsy is indicated. (c) 2007 Wiley Periodicals, Inc.

  6. The ABCC6 Transporter as a Paradigm for Networking from an Orphan Disease to Complex Disorders.

    Science.gov (United States)

    De Vilder, Eva Y G; Hosen, Mohammad Jakir; Vanakker, Olivier M

    2015-01-01

    The knowledge on the genetic etiology of complex disorders largely results from the study of rare monogenic disorders. Often these common and rare diseases show phenotypic overlap, though monogenic diseases generally have a more extreme symptomatology. ABCC6, the gene responsible for pseudoxanthoma elasticum, an autosomal recessive ectopic mineralization disorder, can be considered a paradigm gene with relevance that reaches far beyond this enigmatic orphan disease. Indeed, common traits such as chronic kidney disease or cardiovascular disorders have been linked to the ABCC6 gene. While during the last decade the awareness of the wide ramifications of ABCC6 has increased significantly, the gene itself and the transmembrane transporter it encodes have not unveiled all of the mysteries that surround them. To gain more insights, multiple approaches are being used including next-generation sequencing, computational methods, and various "omics" technologies. Much effort is made to place the vast amount of data that is gathered in an integrated system-biological network; the involvement of ABCC6 in common disorders provides a good view on the wide implications and potential of such a network. In this review, we summarize the network approaches used to study ABCC6 and the role of this gene in several complex diseases.

  7. THE EXPANDING CLINICAL SPECTRUM OF CHOROIDAL EXCAVATION IN MACULAR DYSTROPHIES.

    Science.gov (United States)

    Battaglia Parodi, Maurizio; Casalino, Giuseppe; Iacono, Pierluigi; Introini, Ugo; Adamyan, Tatevik; Bandello, Francesco

    2017-08-09

    To assess the prevalence and the clinical course of focal choroidal excavation (FCE) in patients affected by macular dystrophies. Prospective case series. All the patients underwent a complete ophthalmologic examination, including best-corrected visual acuity and spectral domain optical coherence tomography. The presence of choroidal neovascularization (CNV) was assessed on the basis of the leakage detected on fluorescein angiography. A total of 162 eyes from 81 patients with macular dystrophy were included in the study. FCE was diagnosed in seven eyes (4.3% of the eyes), including four eyes with Best vitelliform dystrophy, two eyes with pattern dystrophy associated with pseudoxanthoma elasticum, and one case of Stargardt disease. In eyes with FCE and macular dystrophy, the mean best-corrected visual acuity was 0.4 ± 0.1 logarithm of the minimum angle of resolution (approximately corresponding to 20/50 Snellen equivalent) at baseline and was stable to 0.41 ± 0.1 logarithm of the minimum angle of resolution (approximately corresponding to 20/50 Snellen equivalent) at the final visit. In four of these seven eyes, FCE was associated with a subfoveal CNV. The CNV was managed with one intravitreal anti-vascular endothelial growth factor injection, achieving the complete anatomical stabilization of the CNV and recovery of the best-corrected visual acuity. Focal choroidal excavation can be infrequently encountered in patients with macular dystrophies. The presence of CNV may complicate FCE in these patients, and anti-vascular endothelial growth factor seems to be an effective treatment with no progression of FCE over time.

  8. ABCC6 Gene Analysis in 20 Japanese Patients with Angioid Streaks Revealing Four Frequent and Two Novel Variants and Pseudodominant Inheritance

    Directory of Open Access Journals (Sweden)

    Satoshi Katagiri

    2017-01-01

    Full Text Available Purpose. To report the spectrum of ABCC6 variants in Japanese patients with angioid streaks (AS. Patients and Methods. This was a single-center cohort study. The medical records of 20 patients with AS from 18 unrelated Japanese families were retrospectively reviewed. Screening of the ABCC6 gene (exons 1 to 31 was performed using PCR-based Sanger sequencing. Results. Eight ABCC6 variants were identified as candidate disease-causing variants. These eight variants included five known variants (p.Q378X, p.R419Q, p.V848CfsX83, p.R1114C, and p.R1357W, one previously reported variant (p.N428S of unknown significance, and two novel variants (c.1939C>T [p.H647Y] and c.3374C>T [p.S1125F]; the three latter variants were determined to be variants of significance. The following four variants were frequently identified: p.V848CfsX83 (14/40 alleles, 35.0%, p.Q378X (7/40 alleles, 17.5%, p.R1357W (6/40 alleles, 15.0%, and p.R419Q (4/40 alleles, 10.0%. The ABCC6 variants were identified in compound heterozygous or homozygous states in 13 of 18 probands. Two families showed a pseudodominant inheritance pattern. Pseudoxanthoma elasticum was seen in 15 of 17 patients (88.2% who underwent dermatological examination. Conclusions. We identified disease-causing ABCC6 variants that were in homozygous or compound heterozygous states in 13 of 18 families (72.2%. Our results indicated that ABCC6 variants play a significant role in patients with AS in the Japanese population.

  9. Multidrug resistance-associated proteins and implications in drug development.

    Science.gov (United States)

    Liu, Ya-He; Di, Yuan-Ming; Zhou, Zhi-Wei; Mo, Sui-Lin; Zhou, Shu-Feng

    2010-01-01

    1. The multidrug resistance-associated proteins (MRPs) belong to the ATP-binding cassette superfamily (ABCC family) of transporters that are expressed differentially in the liver, kidney, intestine and blood-brain barrier. There are nine human MRPs that transport a structurally diverse array of endo- and xenobiotics as well as their conjugates. 2. Multidrug resistance-associated protein 1 can be distinguished from MRP2 and MRP3 by its higher affinity for leukotriene C(4). Unlike MRP1, MRP2 functions in the extrusion of endogenous organic anions, such as bilirubin glucuronide and certain anticancer agents. In addition to the transport of glutathione and glucuronate conjugates, MRP3 has the additional capability of mediating the transport of monoanionic bile acids. 3. Both MRP4 and MRP5 are able to mediate the transport of cyclic nucleotides and confer resistance to certain antiviral and anticancer nucleotide analogues. Hereditary deficiency of MRP6 results in pseudoxanthoma elasticum. In the body, MRP6 is involved in the transport of glutathione conjugates and the cyclic pentapeptide BQ123. 4. Various MRPs show considerable differences in tissue distribution, substrate specificity and proposed physiological function. These proteins play a role in drug disposition and excretion and thus are implicated in drug toxicity and drug interactions. Increased efflux of natural product anticancer drugs and other anticancer agents mediated by MRPs from cancer cells is associated with tumour resistance. 5. A better understanding of the function and regulating mechanisms of MRPs could help minimize and avoid drug toxicity and unfavourable drug-drug interactions, as well as help overcome drug resistance.

  10. Function of prokaryotic and eukaryotic ABC proteins in lipid transport.

    Science.gov (United States)

    Pohl, Antje; Devaux, Philippe F; Herrmann, Andreas

    2005-03-21

    ATP binding cassette (ABC) proteins of both eukaryotic and prokaryotic origins are implicated in the transport of lipids. In humans, members of the ABC protein families A, B, C, D and G are mutated in a number of lipid transport and metabolism disorders, such as Tangier disease, Stargardt syndrome, progressive familial intrahepatic cholestasis, pseudoxanthoma elasticum, adrenoleukodystrophy or sitosterolemia. Studies employing transfection, overexpression, reconstitution, deletion and inhibition indicate the transbilayer transport of endogenous lipids and their analogs by some of these proteins, modulating lipid transbilayer asymmetry. Other proteins appear to be involved in the exposure of specific lipids on the exoplasmic leaflet, allowing their uptake by acceptors and further transport to specific sites. Additionally, lipid transport by ABC proteins is currently being studied in non-human eukaryotes, e.g. in sea urchin, trypanosomatides, arabidopsis and yeast, as well as in prokaryotes such as Escherichia coli and Lactococcus lactis. Here, we review current information about the (putative) role of both pro- and eukaryotic ABC proteins in the various phenomena associated with lipid transport. Besides providing a better understanding of phenomena like lipid metabolism, circulation, multidrug resistance, hormonal processes, fertilization, vision and signalling, studies on pro- and eukaryotic ABC proteins might eventually enable us to put a name on some of the proteins mediating transbilayer lipid transport in various membranes of cells and organelles. It must be emphasized, however, that there are still many uncertainties concerning the functions and mechanisms of ABC proteins interacting with lipids. In particular, further purification and reconstitution experiments with an unambiguous role of ATP hydrolysis are needed to demonstrate a clear involvement of ABC proteins in lipid transbilayer asymmetry.

  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. 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

  13. Pseudoxanthomaelasticum with congestive heart failure: A case report

    African Journals Online (AJOL)

    Pseudoxanthomaelasticum (PXE) is a rare systemic disease of connective tissue primarily affecting the skin, retinae, and cardiovascular system. Clinically it has high hetrogenicity in age of onset, extent and severity of disease. Its cardiovascular effect has a wide clinical spectrum extending from mental fatigue to early death ...

  14. 98 EAST AFRICAN MEDICAL JOURNAL

    African Journals Online (AJOL)

    2008-02-12

    Feb 12, 2008 ... published on this association. The first report of extensive diffuse connective tissue disorder, of the pseudoxanthoma type was by Lippman et al in1985. They described seven sicklers with extensive connective tissue disorder including mitral valve prolapse (9). It has also been described in thalassemia.

  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. 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...

  17. 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.

  18. 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.

  19. A novel thermoalkaliphilic xylanase from Gordonia sp. is salt, solvent and surfactant tolerant.

    Science.gov (United States)

    Kashyap, Radhika; Monika; Subudhi, Enketeswara

    2014-12-01

    Two aerobic bacterial consortia namely Con T and Con R were developed by enrichment technique from termite gut and cow dung respectively, using xylan as a sole carbon source. Molecular characterization of Con R based on 16S rRNA sequence analysis showed the presence of Pannonibacter sp. R-3 and Pseudoxanthomas sp. R-5. On the other hand, Con T showed the presence of Pseudoxanthomas sp. T-5, Cellulosimicrobium sp. T-21, and Gordonia sp. T-30. Being the maximum xylanase producer among the five isolates and being a novel xylanase producing bacterial genus, Gordonia sp. T-30 was selected. Xylanase produced by Gordonia sp. T-30 showed optimum activity at 60 °C and pH 9. Xylanase was 95% stable for 120 min at pH 9.0 and 98% stable at 60 °C for 90 min. Xylanase activity was stimulated in the presence of organic solvents such as petroleum ether, acetone, diethyl ether, n-hexane, and benzene. Detergent like cetyltrimethylammonium bromide and presence of NaCl also accelerated the xylanase function. Comparative evaluation was studied between sterilized and non-sterilized solid fermentation to produce xylanase by Gordonia sp. T-30 using various agricultural residues as growth substrate in cost effective manner. Industrially important features endowed by this xylanase make it a very promising candidate for food, feed, and fuel industry. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. 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%.

  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. Scintillation light production, propagation and detection in the Stereo reactor antineutrino experiment

    Science.gov (United States)

    Buck, Christian; Lindner, Manfred; Roca, Christian

    2017-09-01

    The Stereo experiment’s detector has been optimized to observe reactor antineutrinos via inverse beta decay within a 1800 liter volume filled with Gadolinium-doped organic liquid scintillator (LS). The main requirements for the scintillator in Stereo are compatibility with detector materials as the acrylic vessels, transparency, light yield, pulse shape discrimination capabilities as well as chemical and optical stability over several years of data taking. With these conditions in mind, the composition of the LS is mainly a mix of 75% LAB, 20%PXE and 5% DIN combined with the two wavelength-shifters PPO and Bis-MSB. The final admixture after the full scale production lead to an attenuation length of more than 5 meters for optical photons of 430 nm. The scintillation light produced in the Gd-loaded target volume and the Gd-free outer crown is detected by 48 eight inch PMTs on top of the detector. A correct performance of the PMTs has been ensured through several tests. Common characteristics for PMTs as gain, single photoelectron peak, time behaviour, dark rate and afterpulse ratio were measured resulting in a complete agreement with the manufacturer values.

  3. 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. 

  4. 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.

  5. Spin Polarization Spectroscopy of Alkali-Noble Gas Interatomic Potentials

    Science.gov (United States)

    Mironov, Andrey E.; Goldshlag, William; Eden, J. Gary

    2017-06-01

    We report a new laser spectroscopic technique capable of detecting weak state-state interactions in diatomic molecules. Specifically, a weak interaction has been observed between the 6pσ antibonding orbital of the CsXe (B ^2Σ^+_{1/2}) state and a 5dσ MO associated with a 5dΛ (Λ = 0, 1) state. Thermal Cs-rare gas collision pairs are photoexcited by a circularly-polarized optical field having a wavelength within the B ^2Σ^+_{1/2} \\longleftarrow X ^2Σ^+_{1/2} (free\\longleftarrowfree) continuum. Subsequent dissociation of the B ^2Σ^+_{1/2} transient diatomic selectively populates the F= 4, 5 hyperfine levels of the Cs 6p ^2P_{3/2} state, and circularly-polarized (σ^+) amplified spontaneous emission (ASE) is generated on the Cs D_2 line. The dependence of Cs 6p spin polarization on the Cs(6p)-Xe internuclear separation (R), clearly shows an interaction between the CsXe(B ^2Σ^+_{1/2}) state and a 5dΛ (Λ = 0, 1) potential of the diatomic molecule.

  6. Degradation of acephate by Enterobacter asburiae, Bacillus cereus and Pantoea agglomerans isolated from diamondback moth Plutella xylostella (L), a pest of cruciferous crops.

    Science.gov (United States)

    Ramya, Shanivarsanthe Leelesh; Venkatesan, Thiruvengadam; Murthy, Kottilingam Srinivasa; Jalali, Sushil Kumar; Varghese, Abraham

    2016-07-01

    Acephate-degrading bacterial isolates were isolated from the larval gut of diamondback moth Plutella xylostella, a notorious pest of cruciferous crops worldwide that has developed resistance to insecticides. Partial 16S rRNA gene sequencing identified the isolates as Bacillus cereus (PX-B.C.Or), Enterobacter asburiae (PXE), and Pantoae agglomerans (PX-Pt.ag.Jor). All isolates grew on minimal media (MM) in the presence of acephate at 100 and 200 ppm, with maximum growth at 200 ppm. LC-MS analyses of spent medium showed that E. asburiae degraded acephate to methamidophos and O, O-dimethyl phosporamidate and B. cereus O,S-dimethyl to phosphorothioate but P. agglomerans to an unnamed compound. All three isolates used acephate as a source of carbon and energy for growth; however, P. agglomerans used it also as source of sulphur. Strong evidence revealed that the bacterial communities present in the gut of diamondback moth might aid in acephate degradation and play a role in the development of insecticide resistance.

  7. 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.

  8. Flexibility along the neck of the neogene terror bird Andalgalornis steulleti (Aves Phorusrhacidae.

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    Claudia P Tambussi

    Full Text Available 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.

  9. 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

    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. 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. 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.

  10. 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

  11. 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.

  12. 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