73 results on '"Skin Diseases, Genetic physiopathology"'
Search Results
2. Dermoscopic features of primary cutaneous amyloidosis in skin of colour: A retrospective analysis of 48 patients from South India.
- Author
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Behera B, Kumari R, Mohan Thappa D, Gochhait D, Hanuman Srinivas B, and Ayyanar P
- Subjects
- Adolescent, Adult, Aged, Amyloidosis, Familial pathology, Amyloidosis, Familial physiopathology, Dermoscopy methods, Dermoscopy statistics & numerical data, Female, Humans, India, Male, Middle Aged, Retrospective Studies, Skin Diseases, Genetic pathology, Skin Diseases, Genetic physiopathology, Amyloidosis, Familial diagnosis, Skin Diseases, Genetic diagnosis, Skin Pigmentation
- Published
- 2021
- Full Text
- View/download PDF
3. Plasminogen: an enigmatic zymogen.
- Author
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Keragala CB and Medcalf RL
- Subjects
- Animals, Antifibrinolytic Agents therapeutic use, Brain enzymology, Conjunctivitis physiopathology, Enzyme Activation, Fibrin metabolism, Fibrinolysin physiology, Fibrinolysis physiology, Fibrinolytic Agents therapeutic use, Humans, Immunity physiology, Infections physiopathology, Inflammation, Mice, Plasminogen chemistry, Plasminogen deficiency, Plasminogen pharmacology, Plasminogen therapeutic use, Radiodermatitis drug therapy, Receptors, Cell Surface physiology, Skin Diseases, Genetic physiopathology, Thrombosis diagnosis, Thrombosis drug therapy, Tranexamic Acid pharmacology, Tranexamic Acid therapeutic use, Wound Healing drug effects, Wound Healing physiology, Wounds and Injuries drug therapy, Plasminogen physiology
- Abstract
Plasminogen is an abundant plasma protein that exists in various zymogenic forms. Plasmin, the proteolytically active form of plasminogen, is known for its essential role in fibrinolysis. To date, therapeutic targeting of the fibrinolytic system has been for 2 purposes: to promote plasmin generation for thromboembolic conditions or to stop plasmin to reduce bleeding. However, plasmin and plasminogen serve other important functions, some of which are unrelated to fibrin removal. Indeed, for >40 years, the antifibrinolytic agent tranexamic acid has been administered for its serendipitously discovered skin-whitening properties. Plasmin also plays an important role in the removal of misfolded/aggregated proteins and can trigger other enzymatic cascades, including complement. In addition, plasminogen, via binding to one of its dozen cell surface receptors, can modulate cell behavior and further influence immune and inflammatory processes. Plasminogen administration itself has been reported to improve thrombolysis and to accelerate wound repair. Although many of these more recent findings have been derived from in vitro or animal studies, the use of antifibrinolytic agents to reduce bleeding in humans has revealed additional clinically relevant consequences, particularly in relation to reducing infection risk that is independent of its hemostatic effects. The finding that many viruses harness the host plasminogen to aid infectivity has suggested that antifibrinolytic agents may have antiviral benefits. Here, we review the broadening role of the plasminogen-activating system in physiology and pathophysiology and how manipulation of this system may be harnessed for benefits unrelated to its conventional application in thrombosis and hemostasis., (© 2021 by The American Society of Hematology.)
- Published
- 2021
- Full Text
- View/download PDF
4. Anterior Segment Surgeries Under Topical Fresh Frozen Plasma Treatment in Ligneous Conjunctivitis.
- Author
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Ozbek-Uzman S, Yalniz-Akkaya Z, Nurozler Tabakci B, Singar E, and Burcu A
- Subjects
- Administration, Ophthalmic, Adult, Child, Preschool, Conjunctivitis physiopathology, Female, Follow-Up Studies, Humans, Infant, Male, Middle Aged, Retrospective Studies, Skin Diseases, Genetic physiopathology, Young Adult, Conjunctivitis drug therapy, Lens Implantation, Intraocular, Phacoemulsification, Plasma physiology, Plasminogen deficiency, Skin Diseases, Genetic drug therapy
- Abstract
Purpose: To evaluate the efficacy of topical fresh frozen plasma (FFP) therapy on clinical symptoms, findings, and prognosis after anterior segment surgeries in patients with ligneous conjunctivitis (LC)., Methods: Retrospective case note review., Results: Eleven eyes of 7 cases whose remission was not achieved after medical treatment such as topical corticosteroids, cyclosporine A, and heparin were included in the study. The median age of admission was 19 (1-49) years, median duration of FFP treatment was 48 (15-79) months, median follow-up period was 62 (16-114) months, and median age at symptom onset was 12 (4-252) months. Diagnosis was made according to clinical presentations, plasminogen activities, and response to treatment. Topical FFP that was prepared in our clinic was used in all cases. Surgeries (membrane excision, eyelid surgery, deep anterior lamellar keratoplasty, and cataract surgery) were performed after at least 1 month of FFP treatment. Prosthetic contact lens was applied to one eye. During the follow-up period, recurrences requiring membrane excision and side effects from topical FFP were not observed., Conclusions: LC is a rare membranous conjunctivitis that proceeds with remissions and recurrences. When it was shown that the etiology of LC is plasminogen deficiency, FFP became the only treatment option targeting the etiology. In this study, we observed that the topical FFP is an effective treatment method that prevents recurrence and ensures regression of membranes and safer anterior segment surgeries in LC., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
5. [Stiff skin syndrome in a pediatric patient: a therapeutic challenge. Clinical case].
- Author
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Colombarolli M, Olivera A, Domínguez M, Cirio A, Castro C, and Busso C
- Subjects
- Child, Contracture physiopathology, Female, Humans, Skin Diseases, Genetic physiopathology, Contracture therapy, Quality of Life, Skin Diseases, Genetic therapy
- Abstract
Stiff skin syndrome is a chronic, rare sclerosing disorder that occurs in childhood, characterized by progressive induration of the skin that can cause thoracic restrictions and respiratory distress, limitations in joint mobility and gait difficulties, with significant deterioration of the quality of life. Because their therapeutic options are scarce and ineffective it is essential to start an early physical therapy to prevent these complications and to continue studying this condition to be able to offer patients more and better treatments. We present the case of a 9-year-old patient with indurated skin syndrome and its therapeutic challenge., Competing Interests: None, (Sociedad Argentina de Pediatría.)
- Published
- 2020
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- View/download PDF
6. Visual Diagnosis: A Case of Stretchy Skin and Vascular Abnormalities.
- Author
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Warring SK, Castillo R, Klaas K, Taggart N, and Fischer PR
- Subjects
- Arteries physiopathology, Elasticity, Humans, Infant, Joint Instability physiopathology, Male, Skin Diseases, Genetic physiopathology, Vascular Malformations physiopathology, Arteries abnormalities, Joint Instability diagnosis, Skin physiopathology, Skin Diseases, Genetic diagnosis, Vascular Malformations diagnosis
- Published
- 2020
- Full Text
- View/download PDF
7. Morphological Analysis of Retinal Microvasculature to Improve Understanding of Retinal Hemorrhage Mechanics in Infants.
- Author
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Byrne MP, McMillan KR, and Coats B
- Subjects
- Aging pathology, Aging physiology, Animals, Animals, Newborn, Arteries abnormalities, Arteries pathology, Arteries physiopathology, Biomechanical Phenomena, Female, Humans, Joint Instability pathology, Joint Instability physiopathology, Microscopy, Confocal, Microvessels anatomy & histology, Microvessels physiology, Observer Variation, Retinal Hemorrhage etiology, Retinal Vessels physiology, Sheep, Skin Diseases, Genetic pathology, Skin Diseases, Genetic physiopathology, Vascular Malformations pathology, Vascular Malformations physiopathology, Retinal Hemorrhage pathology, Retinal Vessels anatomy & histology
- Abstract
Purpose: In this experimental study, we quantify retinal microvasculature morphological features with depth, region, and age in immature and mature ovine eyes. These data identify morphological vulnerabilities in young eyes to inform the mechanics of retinal hemorrhage in children., Methods: Retinal specimens from the equator and posterior pole of preterm (n = 4) and adult (n = 9) sheep were imaged using confocal microscopy. Vessel segment length, diameter, angular asymmetry, tortuosity, and branch points were quantified using a custom image segmentation code. Significant differences were identified through two-way ANOVAs and correlation analyses., Results: Vessel segment lengths were significantly shorter in immature eyes compared to adults (P < 0.003) and were significantly shorter at increasing depths in the immature retina (P < 0.04). Tortuosity significantly increased with depth, regardless of age (P < 0.05). These data suggest a potential vulnerability of vasculature in the deeper retinal layers, particularly in immature eyes. Preterm retina had significantly more branch points than adult retina in both the posterior pole and equator, and the number increased significantly with depth (P < 0.001)., Conclusions: The increased branch points and decreased segment lengths in immature microvasculature suggest that infants will experience greater stress and strain during traumatic loading compared to adults. The increased morphological vulnerability of the immature microvasculature in the deeper layers of the retina suggest that intraretinal hemorrhages have a greater likelihood of occurring from trauma compared to preretinal hemorrhages. The morphological features captured in this study lay the foundation to explore the mechanics of retinal hemorrhage in infants and identify vulnerabilities that explain patterns of retinal hemorrhage in infants.
- Published
- 2020
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8. [Arterial tortuosity syndrome in a paediatric patient].
- Author
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Palanca Arias D, Ayerza Casas A, Gutiérrez Alonso C, and Jiménez Montañés L
- Subjects
- Angiography methods, Arteries diagnostic imaging, Arteries physiopathology, Child, Preschool, Female, Humans, Joint Instability physiopathology, Magnetic Resonance Imaging methods, Skin Diseases, Genetic physiopathology, Vascular Malformations physiopathology, Arteries abnormalities, Joint Instability diagnostic imaging, Skin Diseases, Genetic diagnostic imaging, Vascular Malformations diagnostic imaging
- Published
- 2020
- Full Text
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9. A Rare Case of Arterial Tortuosity Syndrome.
- Author
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Pagliariccio G and Macchini M
- Subjects
- Arteries physiopathology, Arthralgia diagnosis, Arthralgia etiology, Female, Glucose Transport Proteins, Facilitative genetics, Humans, Middle Aged, Mutation, Severity of Illness Index, Ultrasonography, Doppler, Duplex methods, Arteries abnormalities, Arteries diagnostic imaging, Carotid Stenosis diagnostic imaging, Computed Tomography Angiography methods, Joint Instability diagnosis, Joint Instability etiology, Joint Instability genetics, Joint Instability physiopathology, Skin Diseases, Genetic diagnosis, Skin Diseases, Genetic genetics, Skin Diseases, Genetic physiopathology, Vascular Malformations diagnosis, Vascular Malformations genetics, Vascular Malformations physiopathology, Watchful Waiting methods
- Published
- 2019
- Full Text
- View/download PDF
10. Prolonged PR Interval and Erythema Marginatum in a Child with Acute Rheumatic Fever.
- Author
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Matsui T, Yamaguchi K, Ikebe T, Aiga S, and Kusakawa I
- Subjects
- Child, Erythema etiology, Female, Humans, Rheumatic Fever complications, Skin Diseases, Genetic etiology, Time Factors, Electrocardiography, Erythema physiopathology, Rheumatic Fever physiopathology, Skin Diseases, Genetic physiopathology
- Published
- 2019
- Full Text
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11. Tortuosity of the superficial femoral artery and its influence on blood flow patterns and risk of atherosclerosis.
- Author
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Li X, Liu X, Li X, Xu L, Chen X, and Liang F
- Subjects
- Adult, Aged, Arteries physiopathology, Female, Hemodynamics physiology, Humans, Male, Middle Aged, Models, Cardiovascular, Risk Factors, Arteries abnormalities, Atherosclerosis physiopathology, Blood Circulation physiology, Femoral Artery physiopathology, Joint Instability physiopathology, Skin Diseases, Genetic physiopathology, Vascular Malformations physiopathology
- Abstract
The superficial femoral artery (SFA) is a typical atherosclerosis-prone site. We aimed to explore whether the tortuosity of the SFA associates with the occurrence of atherosclerosis and investigate how vascular tortuosity influences the characteristics of blood flow. Ten patients diagnosed with atherosclerotic disease in their SFAs while free of systemic atherosclerosis risk factors were enrolled together with ten atherosclerosis-free patients. The tortuosity of each SFA was quantitatively evaluated by calculating the averaged curvature (AC), maximum curvature (MC) and fraction of high curvature (FC) based on the geometrical model reconstructed from medical images. Hemodynamic studies were performed using both geometrically simplified and anatomically realistic models of the SFA to systematically address the hemodynamic effects of vascular tortuosity. Morphological analyses revealed that all curvature indices of the SFA were significantly larger in patients with atherosclerosis than in atherosclerosis-free patients (AC [mm
-1 ]: 0.034 ± 0.016 vs. 0.018 ± 0.006; MC [mm-1 ]: 0.055 ± 0.023 vs. 0.034 ± 0.008; FC [%]: 22.77 ± 10.22 vs. 11.39 ± 6.82; p < 0.001). Simulations of blood flows in the geometrically simplified SFAs showed that increasing vascular curvature caused a progressive increase in the area ratios of low wall shear stress (LWSA) and high oscillatory shear index (HOSA). Hemodynamic studies on the anatomically realistic SFAs further demonstrated that high-curvature SFAs (n = 10) had overall larger LWSA and HOSA compared with low-curvature SFAs (n = 10) (LWSA [%]: 4.13 ± 1.91 vs. 1.79 ± 1.13, p = 0.009; HOSA [%]: 4.95 ± 1.92 vs. 2.37 ± 1.51, p = 0.007). These results suggest that increased vascular tortuosity augments the severity and distribution of atherosclerosis-promoting flow disturbances in the SFA and may be an independent risk factor for atherosclerosis.- Published
- 2019
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12. Association of arterial stiffness with aortic calcification and tortuosity.
- Author
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Moon I, Jin KN, Kim HL, Suh HJ, Lim WH, Seo JB, Kim SH, Zo JH, and Kim MA
- Subjects
- Aged, Ankle Brachial Index, Aorta physiopathology, Arteries pathology, Arteries physiopathology, Body Mass Index, Computed Tomography Angiography, Female, Humans, Joint Instability pathology, Male, Middle Aged, Pulse Wave Analysis, Retrospective Studies, Skin Diseases, Genetic pathology, Vascular Calcification pathology, Vascular Malformations pathology, Aorta pathology, Arteries abnormalities, Joint Instability physiopathology, Skin Diseases, Genetic physiopathology, Vascular Calcification physiopathology, Vascular Malformations physiopathology, Vascular Stiffness physiology
- Abstract
Impact of arterial stiffness on aortic morphology has not been well evaluated. We sought to investigate the association of brachial-ankle pulse wave velocity (baPWV) with aortic calcification and tortuosity.A total of 181 patients (65.4 ± 10.4 years, males 59.7%) who underwent computed tomographic angiography and baPWV measurement within 1 month of study entry were retrospectively reviewed. Aortic calcification was quantified by the calcium scoring software system. Aortic tortuosity was defined as the length of the midline in the aorta divided by the length of linear line from the aortic root to the distal end of the thoraco-abdominal aorta. In simple correlation analyses, baPWV was correlated with aortic calcification (r = 0.36, P < .001) and tortuosity (r = 0.16, P = .030). However, these significances disappeared after controlling for confounders in multivariate analyses. Factors showing an independent association with aortic calcification were age (β = 0.37, P < .001), hypertension (β = 0.19, P = .003), diabetes mellitus (β = 0.12, P = .045), smoking (β = 0.17, P = .016), and estimated glomerular filtration rate (β = -0.25, P = .002). Factors showing an independent association with aortic tortuosity were age (β = 0.34, P < .001), body mass index (β = -0.19, P = .018), and diabetes mellitus (β = -0.21, P = .003).In conclusion, baPWV reflecting arterial stiffness was not associated with aortic calcification and tortuosity. Traditional cardiovascular risk factors were more influential to aortic geometry. Further studies with a larger sample size are needed to confirm our results.
- Published
- 2019
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13. Activography reveals aberrant proteolysis in desquamating diseases of differing backgrounds.
- Author
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Zingkou E, Pampalakis G, Kiritsi D, Valari M, Jonca N, and Sotiropoulou G
- Subjects
- Biopsy, Dermatitis, Seborrheic pathology, Dermatitis, Seborrheic physiopathology, Humans, Skin pathology, Skin Diseases congenital, Skin Diseases pathology, Skin Diseases physiopathology, Skin Diseases, Genetic metabolism, Histocytochemistry methods, Proteolysis, Skin Diseases, Genetic pathology, Skin Diseases, Genetic physiopathology
- Abstract
The role of epidermal proteolysis in overdesquamation was revealed in Netherton syndrome, a rare ichthyosis due to genetic deficiency of the LEKTI inhibitor of serine proteases. Recently, we developed activography, a new histochemical method, to spatially localize and semiquantitatively assess proteolytic activities using activity-based probes. Activography provides specificity and versatility compared to in situ zymography, the only available method to determine enzymatic activities in tissue biopsies. Here, activography was validated in skin biopsies obtained from an array of distinct disorders and compared with in situ zymography. Activography provides a methodological advancement due to its simplicity and specificity and can be readily adapted as a routine diagnostic assay. Interestingly, the levels of epidermal proteolysis correlated with the degree of desquamation independent of skin pathology. Thus, deregulated epidermal proteolysis likely represents a universal mechanism underlying aberrant desquamation., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2019
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14. Hemodynamic investigation of a patient-specific abdominal aortic aneurysm with iliac artery tortuosity.
- Author
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Qiu Y, Yuan D, Wang Y, Wen J, and Zheng T
- Subjects
- Aged, Aortic Aneurysm, Abdominal diagnostic imaging, Arteries diagnostic imaging, Arteries physiopathology, Computer Simulation, Female, Humans, Iliac Artery diagnostic imaging, Imaging, Three-Dimensional, Joint Instability diagnostic imaging, Models, Biological, Pressure, Skin Diseases, Genetic diagnostic imaging, Stress, Mechanical, Tomography, X-Ray Computed, Vascular Malformations diagnostic imaging, Viscosity, Aortic Aneurysm, Abdominal physiopathology, Arteries abnormalities, Hemodynamics physiology, Iliac Artery physiopathology, Joint Instability physiopathology, Skin Diseases, Genetic physiopathology, Vascular Malformations physiopathology
- Abstract
This paper describes a systematic investigation on the hemodynamic environment in a patient-specific AAA with tortuous common iliac artery(CIA) and external iliac artery (EIA). 3D reconstructions from CT scans and subsequent computational simulation are carried out. It is found out that the Newtonian and non-Newtonian models have very similar flow field and WSS distribution. More importantly, it is revealed that the torturous CIA maintained its helical flow. It is concluded that the assumption of Newtonian blood is adequate in capturing the intra-aneurysmal hemodynamics. Moreover, it is speculated that the physiological spiral flow protects the twisted CIA from the thrombosis formation.
- Published
- 2018
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15. Arterial tortuosity syndrome: 40 new families and literature review.
- Author
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Beyens A, Albuisson J, Boel A, Al-Essa M, Al-Manea W, Bonnet D, Bostan O, Boute O, Busa T, Canham N, Cil E, Coucke PJ, Cousin MA, Dasouki M, De Backer J, De Paepe A, De Schepper S, De Silva D, Devriendt K, De Wandele I, Deyle DR, Dietz H, Dupuis-Girod S, Fontenot E, Fischer-Zirnsak B, Gezdirici A, Ghoumid J, Giuliano F, Diéz NB, Haider MZ, Hardin JS, Jeunemaitre X, Klee EW, Kornak U, Landecho MF, Legrand A, Loeys B, Lyonnet S, Michael H, Moceri P, Mohammed S, Muiño-Mosquera L, Nampoothiri S, Pichler K, Prescott K, Rajeb A, Ramos-Arroyo M, Rossi M, Salih M, Seidahmed MZ, Schaefer E, Steichen-Gersdorf E, Temel S, Uysal F, Vanhomwegen M, Van Laer L, Van Maldergem L, Warner D, Willaert A, Collins TR, Taylor A, Davis EC, Zarate Y, and Callewaert B
- Subjects
- Adolescent, Adult, Aorta diagnostic imaging, Aorta physiopathology, Arteries diagnostic imaging, Arteries physiopathology, Biopsy, Child, Child, Preschool, Connective Tissue Growth Factor genetics, Female, Hernia, Diaphragmatic physiopathology, Humans, Infant, Joint Instability epidemiology, Joint Instability physiopathology, Male, Mutation, Pedigree, Respiratory Distress Syndrome, Newborn physiopathology, Skin pathology, Skin Diseases, Genetic epidemiology, Skin Diseases, Genetic physiopathology, Smad2 Protein genetics, Transforming Growth Factor beta genetics, Vascular Malformations epidemiology, Vascular Malformations physiopathology, Arteries abnormalities, Glucose Transport Proteins, Facilitative genetics, Hernia, Diaphragmatic genetics, Joint Instability genetics, Respiratory Distress Syndrome, Newborn genetics, Skin Diseases, Genetic genetics, Vascular Malformations genetics
- Abstract
Purpose: We delineate the clinical spectrum and describe the histology in arterial tortuosity syndrome (ATS), a rare connective tissue disorder characterized by tortuosity of the large and medium-sized arteries, caused by mutations in SLC2A10., Methods: We retrospectively characterized 40 novel ATS families (50 patients) and reviewed the 52 previously reported patients. We performed histology and electron microscopy (EM) on skin and vascular biopsies and evaluated TGF-β signaling with immunohistochemistry for pSMAD2 and CTGF., Results: Stenoses, tortuosity, and aneurysm formation are widespread occurrences. Severe but rare vascular complications include early and aggressive aortic root aneurysms, neonatal intracranial bleeding, ischemic stroke, and gastric perforation. Thus far, no reports unequivocally document vascular dissections or ruptures. Of note, diaphragmatic hernia and infant respiratory distress syndrome (IRDS) are frequently observed. Skin and vascular biopsies show fragmented elastic fibers (EF) and increased collagen deposition. EM of skin EF shows a fragmented elastin core and a peripheral mantle of microfibrils of random directionality. Skin and end-stage diseased vascular tissue do not indicate increased TGF-β signaling., Conclusion: Our findings warrant attention for IRDS and diaphragmatic hernia, close monitoring of the aortic root early in life, and extensive vascular imaging afterwards. EM on skin biopsies shows disease-specific abnormalities.
- Published
- 2018
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16. Annular Lesions: Diagnosis and Treatment.
- Author
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Trayes KP, Savage K, and Studdiford JS
- Subjects
- Diagnosis, Differential, Humans, Erythema diagnosis, Erythema etiology, Erythema physiopathology, Erythema therapy, Patient Care Management methods, Skin Diseases diagnosis, Skin Diseases, Genetic diagnosis, Skin Diseases, Genetic etiology, Skin Diseases, Genetic physiopathology, Skin Diseases, Genetic therapy
- Abstract
Annular lesions can present in a variety of diseases. Knowledge of the physical appearance and history of presentation of these skin findings can help in the diagnosis. A pruritic, annular, erythematous patch that grows centrifugally should prompt evaluation for tinea corporis. Tinea corporis may be diagnosed through potassium hydroxide examination of scrapings. Recognizing erythema migrans is important in making the diagnosis of Lyme disease so that antibiotics can be initiated promptly. Plaque psoriasis generally presents with sharply demarcated, erythematous silver plaques. Erythema multiforme, which is due to a hypersensitivity reaction, presents with annular, raised lesions with central clearing. Lichen planus characteristically appears as planar, purple, polygonal, pruritic papules and plaques. Nummular eczema presents as a rash composed of coin-shaped papulovesicular erythematous lesions. Treatment is aimed at reducing skin dryness. Pityriasis rosea presents with multiple erythematous lesions with raised, scaly borders, and is generally self-limited. Urticaria results from the release of histamines and appears as well-circumscribed, erythematous lesions with raised borders and blanched centers. Annular lesions occur less commonly in persons with fixed drug eruptions, leprosy, immunoglobulin A vasculitis, secondary syphilis, sarcoidosis, subacute cutaneous lupus erythematosus, and granuloma annulare.
- Published
- 2018
17. Acquired and congenital forms of heterotopic ossification: new pathogenic insights and therapeutic opportunities.
- Author
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Pacifici M
- Subjects
- Animals, Anti-Inflammatory Agents, Non-Steroidal therapeutic use, Bone Diseases, Metabolic diagnosis, Bone Diseases, Metabolic genetics, Bone Diseases, Metabolic physiopathology, Bone and Bones pathology, Bone and Bones physiopathology, Bone and Bones radiation effects, Genetic Predisposition to Disease, Humans, Molecular Targeted Therapy, Myositis Ossificans diagnosis, Myositis Ossificans genetics, Myositis Ossificans physiopathology, Ossification, Heterotopic diagnosis, Ossification, Heterotopic genetics, Ossification, Heterotopic physiopathology, Osteogenesis genetics, Osteogenesis radiation effects, Phenotype, Skin Diseases, Genetic diagnosis, Skin Diseases, Genetic genetics, Skin Diseases, Genetic physiopathology, Anti-Inflammatory Agents therapeutic use, Bone Diseases, Metabolic therapy, Bone and Bones drug effects, Drug Discovery methods, Myositis Ossificans therapy, Ossification, Heterotopic therapy, Osteogenesis drug effects, Skin Diseases, Genetic therapy
- Abstract
Heterotopic ossification (HO) involves the formation and accumulation of extraskeletal bone tissue at the expense of local tissues including muscles and connective tissues. There are common forms of HO that are triggered by extensive trauma, burns and other bodily insults, and there are also rare congenital severe forms of HO that occur in children with Fibrodysplasia Ossificans Progressiva or Progressive Osseous Heteroplasia. Given that HO is often preceded by inflammation, current treatments usually involve anti-inflammatory drugs alone or in combination with local irradiation, but are not very effective. Recent studies have provided novel insights into the pathogenesis of acquired and genetic forms of HO and have used the information to conceive and test new and more specific therapies in animal models. In this review, I provide salient examples of these exciting and promising advances that are undoubtedly paving the way toward resolution of this debilitating and at times fatal disease., (Copyright © 2018 Elsevier Ltd. All rights reserved.)
- Published
- 2018
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18. Severe neonatal hypertension revealing arterial tortuosity syndrome.
- Author
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de Marcellus C, Baudouin V, Tanase A, Monet C, Perrin L, Deschenes G, and Hogan J
- Subjects
- Aorta, Abdominal diagnostic imaging, Aorta, Abdominal physiopathology, Aorta, Thoracic diagnostic imaging, Aorta, Thoracic physiopathology, Aortography methods, Arteries diagnostic imaging, Arteries physiopathology, Child, Preschool, Computed Tomography Angiography, Genetic Predisposition to Disease, Genetic Variation, Glucose Transport Proteins, Facilitative genetics, Humans, Hypertension, Renovascular diagnosis, Hypertension, Renovascular physiopathology, Joint Instability diagnostic imaging, Joint Instability genetics, Joint Instability physiopathology, Male, Phenotype, Renal Artery diagnostic imaging, Renal Artery physiopathology, Renal Artery Obstruction diagnostic imaging, Renal Artery Obstruction physiopathology, Severity of Illness Index, Skin Diseases, Genetic diagnostic imaging, Skin Diseases, Genetic genetics, Skin Diseases, Genetic physiopathology, Vascular Malformations diagnostic imaging, Vascular Malformations genetics, Vascular Malformations physiopathology, Aorta, Abdominal abnormalities, Aorta, Thoracic abnormalities, Arteries abnormalities, Blood Pressure, Hypertension, Renovascular etiology, Joint Instability complications, Renal Artery abnormalities, Renal Artery Obstruction etiology, Skin Diseases, Genetic complications, Vascular Malformations complications
- Published
- 2018
- Full Text
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19. Examining tissue composition, whole-bone morphology and mechanical behavior of Gorab Prx1 mice tibiae: A mouse model of premature aging.
- Author
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Yang H, Albiol L, Chan WL, Wulsten D, Seliger A, Thelen M, Thiele T, Spevak L, Boskey A, Kornak U, Checa S, and Willie BM
- Subjects
- Adaptor Proteins, Vesicular Transport, Aging, Premature physiopathology, Animals, Biomechanical Phenomena, Bone Density, Bone Diseases diagnostic imaging, Bone Diseases physiopathology, DNA-Binding Proteins, Disease Models, Animal, Dwarfism physiopathology, Female, Fractures, Bone genetics, Homeodomain Proteins genetics, Mice, Mice, Inbred C57BL, Mice, Transgenic, Protein Kinases genetics, Skin Diseases, Genetic physiopathology, Tibia physiopathology, X-Ray Microtomography, Aging, Premature diagnostic imaging, Bone Diseases congenital, Dwarfism diagnostic imaging, Skin Diseases, Genetic diagnostic imaging, Tibia diagnostic imaging
- Abstract
Gerodermia osteodysplastica (GO) is a segmental progeroid disorder caused by loss-of-function mutations in the GORAB gene, associated with early onset osteoporosis and bone fragility. A conditional mouse model of GO (Gorab
Prx1 ) was generated in which the Gorab gene was deleted in long bones. We examined the biomechanical/functional relevance of the GorabPrx1 mutants as a premature aging model by characterizing bone composition, tissue-level strains, and whole-bone morphology and mechanical properties of the tibia. MicroCT imaging showed that GorabPrx1 tibiae had an increased anterior convex curvature and decreased cortical cross-sectional area, cortical thickness and moments of inertia, compared to littermate control (LC) tibiae. Fourier transform infrared (FTIR) imaging indicated a 34% decrease in mineral/matrix ratio and a 27% increase in acid phosphate content in the posterior metaphyseal cortex of the GorabPrx1 tibiae (p < .05), suggesting delayed mineralization. In vivo strain gauge measurement and finite element analysis showed ∼two times higher tissue-level strains within the GorabPrx1 tibiae relative to LC tibiae when subjected to axial compressive loads of the same magnitude. Three-point bending tests suggested that GorabPrx1 tibiae were weaker and more brittle, as indicated by decreasing whole-bone strength (46%), stiffness (55%), work-to-fracture (61%) and post-yield displacement (47%). Many of these morphological and biomechanical characteristics of the GorabPrx1 tibia recapitulated changes in other animal models of skeletal aging. Future studies are necessary to confirm how our observations might guide the way to a better understanding and treatment of GO., (Copyright © 2017 Elsevier Ltd. All rights reserved.)- Published
- 2017
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20. [Acantholysis].
- Author
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Welfringer-Morin A and Battistella M
- Subjects
- Autoimmune Diseases complications, Humans, Keratosis, Seborrheic complications, Paraneoplastic Syndromes diagnosis, Paraneoplastic Syndromes etiology, Paraneoplastic Syndromes pathology, Paraneoplastic Syndromes physiopathology, Pemphigus complications, Precancerous Conditions pathology, Skin Diseases, Genetic physiopathology, Skin Diseases, Infectious complications, Skin Diseases, Vesiculobullous complications, Skin Neoplasms complications, Acantholysis diagnosis, Acantholysis etiology, Acantholysis pathology, Acantholysis physiopathology
- Published
- 2017
- Full Text
- View/download PDF
21. Risk factors associated with actinic prurigo: a case control study.
- Author
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Cuevas-Gonzalez JC, Vega-Memíje ME, Borges-Yáñez SA, and Rodríguez-Lobato E
- Subjects
- Adolescent, Adult, Age Factors, Aged, Animals, Animals, Domestic, Case-Control Studies, Child, Female, Humans, Hypersensitivity etiology, Hypersensitivity physiopathology, Logistic Models, Male, Middle Aged, Photosensitivity Disorders physiopathology, Risk Factors, Skin Diseases, Genetic physiopathology, Statistics, Nonparametric, Sunlight adverse effects, Time Factors, Young Adult, Environmental Exposure adverse effects, Photosensitivity Disorders etiology, Skin Diseases, Genetic etiology
- Abstract
Background: Actinic prurigo (AP) is an idiopathic photodermatosis. Although its initial manifestations can appear in 6 to 8-year-old children, cases are diagnosed later, between the second and fourth decades of life, when the injuries are exacerbated., Objective: To identify risk factors associated with clinical manifestations of AP such as skin and mucosal lesions., Methods: Thirty patients with AP and 60 controls were included in the study, the dependent variable was the presence of skin or labial mucosal lesions, the independent variables were age, sex, solar exposure, living with pets or farm animals, exposure to wood smoke, smoking habit, years smoking, and hours spent per day and per week in contact with people who smoke., Results: Of the 30 diagnosed AP patients, 66.7% were female. Patients age ranged from 7 to 71 years and the mean age was 35.77 ± 14.55 years. We found significant differences with the age and cohabitation with farm animals. Those who lived with farm animals presented 14.31 times higher probability of developing AP (95% CI 3-78.06)., Study Limitations: This is a case-control study; therefore, a causal relationship cannot be proven, and these results cannot be generalized to every population., Conclusions: The identification of factors related to the development of AP increases our knowledge of its physiopathology. Moreover, identifying antigens that possibly trigger the allergic reaction will have preventive and therapeutic applications in populations at risk of AP.
- Published
- 2017
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22. The prevalence and clinical manifestation of hereditary thrombophilia in Korean patients with unprovoked venous thromboembolisms.
- Author
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Lee SY, Kim EK, Kim MS, Shin SH, Chang H, Jang SY, Kim HJ, and Kim DK
- Subjects
- Adult, Aged, Antithrombin III genetics, Antithrombin III Deficiency complications, Antithrombin III Deficiency diagnosis, Antithrombin III Deficiency genetics, Conjunctivitis complications, Conjunctivitis diagnosis, Conjunctivitis genetics, Female, Gene Expression, Humans, Male, Middle Aged, Plasminogen genetics, Protein C genetics, Protein C Deficiency complications, Protein C Deficiency diagnosis, Protein C Deficiency genetics, Protein S genetics, Protein S Deficiency complications, Protein S Deficiency diagnosis, Protein S Deficiency genetics, Republic of Korea, Retrospective Studies, Sequence Analysis, DNA, Skin Diseases, Genetic complications, Skin Diseases, Genetic diagnosis, Skin Diseases, Genetic genetics, Thrombophilia diagnosis, Thrombophilia etiology, Thrombophilia genetics, Venous Thromboembolism diagnosis, Venous Thromboembolism etiology, Venous Thromboembolism genetics, Antithrombin III Deficiency physiopathology, Conjunctivitis physiopathology, Plasminogen deficiency, Protein C Deficiency physiopathology, Protein S Deficiency physiopathology, Skin Diseases, Genetic physiopathology, Thrombophilia physiopathology, Venous Thromboembolism physiopathology
- Abstract
Background: Hereditary thrombophilia (HT) is a genetic predisposition to thrombosis. Asian mutation spectrum of HT is different from Western ones. We investigated the incidence and clinical characteristics of HT in Korean patients with unprovoked venous thromboembolism (VTE)., Methods: Among 369 consecutive patients with thromboembolic event who underwent thrombophilia tests, we enrolled 222 patients diagnosed with unprovoked VTE. The presence of HT was confirmed by DNA sequencing of the genes that cause deficits in natural anticoagulants (NAs). Median follow-up duration was 40±38 months., Results: Among the 222 patients with unprovoked VTE, 66 (29.7%) demonstrated decreased NA level, and 33 (14.9%) were finally confirmed to have HT in a genetic molecular test. Antithrombin III deficiency (6.3%) was most frequently detected, followed by protein C deficiency (5.4%), protein S deficiency (1.8%), and dysplasminogenemia (1.4%). The HT group was significantly younger (37 [32-50] vs. 52 [43-65] years; P < 0.001) and had a higher proportion of male (69.7% vs. 47%; P = 0.013), more previous VTE events (57.6% vs. 31.7%; P = 0.004), and a greater family history of VTE (43.8% vs. 1.9%; P < 0.001) than the non-HT group. Age <45 years and a family history of VTE were independent predictors for unprovoked VTE with HT (odds ratio, 9.435 [2.45-36.35]; P = 0.001 and 92.667 [14.95-574.29]; P < 0.001)., Conclusions: About 15% of patients with unprovoked VTE had HT. A positive family history of VTE and age <45 years were independent predictors for unprovoked VTE caused by HT.
- Published
- 2017
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23. What's new with common genetic skin disorders?
- Author
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Ma JE and Hand JL
- Subjects
- Animals, Drug Design, Humans, Mutation, Skin Diseases, Genetic diagnosis, Skin Diseases, Genetic therapy, Molecular Diagnostic Techniques, Molecular Targeted Therapy, Skin Diseases, Genetic physiopathology
- Abstract
Familiar genetic disorders such as neurofibromatosis type I (NF1), tuberous sclerosis complex (TSC), oculocutaneous albinism (OCA), basal cell nevus syndrome (BCNS), incontinentia pigmenti, ichthyosis, and epidermolysis bullosa (EB) have prominent, cutaneous manifestations. This review describes recent advances in knowledge concerning the pathophysiology, diagnosis, and treatment of these skin features. Specifically, clinical diagnostic criteria for incontinentia pigmenti, ichthyosis, and tuberous sclerosis have been updated. Additionally, there have been considerable advancements in the technology used in the molecular diagnoses of these conditions. In the case of TSC, the discovery that a portion of TSC mutations are missed due to mosaicism is driving the development of new diagnostic methods. Also, scientists are also seeking minimally invasive methods of genetic diagnosis, as in the case of using hair follicles to diagnose autosomal recessive congenital ichythosis (ARCI). Finally, there are innovative targeted medical therapies being developed that serve as promising tools in the care of patients afflicted with conditions including ichthyosis and EB.
- Published
- 2017
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24. Actinic prurigo as a hypersensitivity reaction type 4.
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Vega Memije ME, Cuevas Gonzalez JC, Hojyo-Tomoka MT, and Rodríguez Lobato E
- Subjects
- Apoptosis, Humans, Hypersensitivity etiology, Hypersensitivity physiopathology, Photosensitivity Disorders etiology, Photosensitivity Disorders physiopathology, Skin Diseases, Genetic etiology, Skin Diseases, Genetic physiopathology, Hypersensitivity immunology, Photosensitivity Disorders immunology, Skin Diseases, Genetic immunology
- Published
- 2017
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- View/download PDF
25. Adult-onset actinic prurigo: report of 19 patients from Taiwan.
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Chen YA, Yang CC, Ting SW, Lee JY, and Chen W
- Subjects
- Adult, Female, Humans, Male, Middle Aged, Photosensitivity Disorders physiopathology, Photosensitivity Disorders prevention & control, Protective Clothing, Skin Diseases, Genetic physiopathology, Skin Diseases, Genetic prevention & control, Sunscreening Agents, Taiwan, Photosensitivity Disorders diagnosis, Skin Diseases, Genetic diagnosis
- Published
- 2016
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26. Arterial tortuosity syndrome.
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Mehrabi E, Khan K, and Malik SA
- Subjects
- Arteries physiopathology, Arteries surgery, DNA Mutational Analysis, Failure to Thrive etiology, Female, Humans, Infant, Infant, Newborn, Joint Instability physiopathology, Joint Instability surgery, Micrognathism physiopathology, Skin Diseases, Genetic physiopathology, Skin Diseases, Genetic surgery, Stents, Treatment Outcome, Vascular Malformations physiopathology, Vascular Malformations surgery, Angioplasty, Balloon, Coronary methods, Arteries abnormalities, Failure to Thrive physiopathology, Joint Instability diagnosis, Micrognathism diagnosis, Skin Diseases, Genetic diagnosis, Vascular Malformations diagnosis
- Published
- 2016
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- View/download PDF
27. Segmental stiff skin syndrome (SSS): A distinct clinical entity.
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Myers KL, Mir A, Schaffer JV, Meehan SA, Orlow SJ, and Brinster NK
- Subjects
- Adolescent, Age Factors, Age of Onset, Child, Child, Preschool, Contracture diagnosis, Female, Humans, Infant, Male, Range of Motion, Articular, Retrospective Studies, Skin Diseases, Genetic diagnosis, Contracture pathology, Contracture physiopathology, Skin Diseases, Genetic pathology, Skin Diseases, Genetic physiopathology
- Abstract
Background: Stiff skin syndrome (SSS) is a noninflammatory, fibrosing condition of the skin, often affecting the limb girdles., Objective: We present 4 new patients with SSS with largely unilateral, segmental distribution. To date, reported cases of SSS have been grouped based on generally accepted clinical and histopathologic findings. The purpose of this study was to analyze differences in clinical and histopathologic findings between previously reported SSS cases., Methods: This is a retrospective review of 4 new cases and 48 previously published cases of SSS obtained from PubMed search., Results: Of 52 total cases, 18 (35%) were segmentally distributed and 34 (65%) were widespread. The average age of onset was 4.1 years versus 1.6 years for segmental versus widespread SSS, respectively. Limitation in joint mobility affected 44% of patients with segmental SSS and 97% of patients with widespread SSS. Histopathologic findings were common between the 2 groups., Limitations: This was a retrospective study of previously published cases limited by the completeness and accuracy of the reviewed cases., Conclusions: We propose a distinct clinical entity, segmental SSS, characterized by a segmental distribution, later age of onset, and less severe functional limitation. Both segmental SSS and widespread SSS share common diagnostic histopathologic features., (Copyright © 2016 American Academy of Dermatology, Inc. All rights reserved.)
- Published
- 2016
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28. Moyamoya disease and artery tortuosity as rare phenotypes in a patient with an elastin mutation.
- Author
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Ishiwata T, Tanabe N, Shigeta A, Yokota H, Tsushima K, Terada J, Sakao S, Morisaki H, Morisaki T, and Tatsumi K
- Subjects
- Adult, Arteries physiopathology, Constriction, Pathologic physiopathology, Female, Humans, Joint Instability physiopathology, Moyamoya Disease physiopathology, Mutation, Phenotype, Skin Diseases, Genetic physiopathology, Vascular Malformations physiopathology, Arteries abnormalities, Constriction, Pathologic genetics, Elastin genetics, Joint Instability genetics, Moyamoya Disease genetics, Skin Diseases, Genetic genetics, Vascular Malformations genetics
- Abstract
Sporadic and familial elastin mutations can occur in large vessel stenosis such as supravalvular aortic stenosis and narrowing of the descending aorta. However, there are very few reports regarding the arteriopathy of cerebral, pulmonary or abdominal arteries in elastin mutations. We herein report the case of a Japanese female patient presenting with multiple arteriopathy including moyamoya disease, a tortuosity of abdominal arteries and pulmonary hypertension due to peripheral pulmonary artery stenosis. This case suggests the possible progression of cerebral arteriopathy including moyamoya disease in patients with elastin mutations. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)
- Published
- 2016
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29. Correlation of serum IgE levels and clinical manifestations in patients with actinic prurigo.
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Cuevas-Gonzalez JC, Lievanos-Estrada Z, Vega-Memije ME, Hojyo-Tomoka MT, and Dominguez-Soto L
- Subjects
- Adolescent, Adult, Case-Control Studies, Child, Female, Humans, Immunoassay, Immunosuppressive Agents therapeutic use, Male, Middle Aged, Photosensitivity Disorders pathology, Reference Values, Severity of Illness Index, Skin Diseases, Genetic pathology, Thalidomide therapeutic use, Young Adult, Immunoglobulin E blood, Photosensitivity Disorders blood, Photosensitivity Disorders physiopathology, Skin Diseases, Genetic blood, Skin Diseases, Genetic physiopathology
- Abstract
Background: Actinic prurigo is an idiopathic photodermatosis, the pathophysiology of which has been hypothesized to involve subtype IV type b (Th2) hypersensitive response, whereby IL4, IL5, and IL13 are secreted and mediate the production of B cells, IgE, and IgG4., Objectives: To examine the association of serum IgE levels and the clinical severity of injuries., Methods: This case-control study comprised patients with a clinical and histopathological diagnosis of actinic prurigo, as well as clinically healthy subjects, from whom 3cc of peripheral blood was taken for immunoassay. Cases were classified by lesion severity as mild, moderate, and severe. Descriptive statistics were analyzed, and chi-square test was performed., Results: We included 21 actinic prurigo patients and 21 subjects without disease; 11 patients with actinic prurigo had elevated serum IgE levels, and 10 had low serum levels. Six actinic prurigo (AP) patients with elevated serum levels of IgE had moderate injuries, 4 had severe injuries, and 1 had minor injuries. Eight out of 10 patients with normal IgE levels presented with minor injuries in the clinical evaluation. The 21 controls did not have increased serum IgE levels., Conclusions: Elevated IgE levels are associated with moderate to severe clinical lesions, suggesting that actinic prurigo entails a type IV subtype b hypersensitivity response in which Th2 cells predominate.
- Published
- 2016
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30. GLUT10 deficiency leads to oxidative stress and non-canonical αvβ3 integrin-mediated TGFβ signalling associated with extracellular matrix disarray in arterial tortuosity syndrome skin fibroblasts.
- Author
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Zoppi N, Chiarelli N, Cinquina V, Ritelli M, and Colombi M
- Subjects
- Arteries metabolism, Arteries physiopathology, Extracellular Matrix physiology, Fibroblasts physiology, Gene Expression Profiling, Glucose Transport Proteins, Facilitative genetics, Homeostasis, Humans, Joint Instability physiopathology, Mutation, Skin metabolism, Skin physiopathology, Skin Diseases, Genetic physiopathology, Vascular Malformations physiopathology, Arteries abnormalities, Fibroblasts metabolism, Glucose Transport Proteins, Facilitative deficiency, Integrin alphaVbeta3 metabolism, Joint Instability metabolism, Oxidative Stress, Signal Transduction, Skin Diseases, Genetic metabolism, Transforming Growth Factor beta physiology, Vascular Malformations metabolism
- Abstract
Arterial tortuosity syndrome (ATS) is an autosomal recessive connective tissue disorder caused by loss-of-function mutations in SLC2A10, which encodes facilitative glucose transporter 10 (GLUT10). The role of GLUT10 in ATS pathogenesis remains an enigma, and the transported metabolite(s), i.e. glucose and/or dehydroascorbic acid, have not been clearly elucidated. To discern the molecular mechanisms underlying the ATS aetiology, we performed gene expression profiling and biochemical studies on skin fibroblasts. Transcriptome analyses revealed the dysregulation of several genes involved in TGFβ signalling and extracellular matrix (ECM) homeostasis as well as the perturbation of specific pathways that control both the cell energy balance and the oxidative stress response. Biochemical and functional studies showed a marked increase in ROS-induced lipid peroxidation sustained by altered PPARγ function, which contributes to the redox imbalance and the compensatory antioxidant activity of ALDH1A1. ATS fibroblasts also showed activation of a non-canonical TGFβ signalling due to TGFBRI disorganization, the upregulation of TGFBRII and connective tissue growth factor, and the activation of the αvβ3 integrin transduction pathway, which involves p125FAK, p60Src and p38 MAPK. Stable GLUT10 expression in patients' fibroblasts normalized redox homeostasis and PPARγ activity, rescued canonical TGFβ signalling and induced partial ECM re-organization. These data add new insights into the ATS dysregulated biological pathways and definition of the pathomechanisms involved in this disorder., (© The Author 2015. Published by Oxford University Press.)
- Published
- 2015
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31. GORAB Missense Mutations Disrupt RAB6 and ARF5 Binding and Golgi Targeting.
- Author
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Egerer J, Emmerich D, Fischer-Zirnsak B, Chan WL, Meierhofer D, Tuysuz B, Marschner K, Sauer S, Barr FA, Mundlos S, and Kornak U
- Subjects
- Bone Diseases congenital, Bone Diseases genetics, Bone Diseases physiopathology, Cells, Cultured, Dwarfism genetics, Dwarfism physiopathology, Fibroblasts metabolism, Golgi Apparatus metabolism, HeLa Cells metabolism, Humans, Sensitivity and Specificity, Skin Diseases, Genetic genetics, Skin Diseases, Genetic physiopathology, Transfection, ADP-Ribosylation Factors genetics, Mutation, Missense, Protein Binding genetics, rab GTP-Binding Proteins genetics
- Abstract
Gerodermia osteodysplastica is a hereditary segmental progeroid disorder affecting skin, connective tissues, and bone that is caused by loss-of-function mutations in GORAB. The golgin, RAB6-interacting (GORAB) protein localizes to the Golgi apparatus and interacts with the small GTPase RAB6. In this study, we used different approaches to shed more light on the recruitment of GORAB to this compartment. We show that GORAB best colocalizes with trans-Golgi markers and is rapidly displaced upon Brefeldin A exposition, indicating a loose association with Golgi membranes. A yeast two-hybrid screening revealed a specific interaction with the small GTPase ADP-ribosylation factor (ARF5) in its active, GTP-bound form. ARF5 and RAB6 bind to GORAB via the same internal Golgi-targeting RAB6 and ARF5 binding (IGRAB) domain. Two GORAB missense mutations identified in gerodermia osteodysplastica patients fall within this IGRAB domain. GORAB carrying the mutation p.Ala220Pro had a cytoplasmic distribution and failed to interact with both RAB6 and ARF5. In contrast, the p.Ser175Phe mutation displaced GORAB from the Golgi compartment to vesicular structures and selectively impaired ARF5 binding. Our findings indicate that the IGRAB domain is crucial for the Golgi localization of GORAB and that loss of this localization impairs its physiological function.
- Published
- 2015
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32. A 7-year-old with indurated skin and unilateral progressive joint immobility: A case of stiff skin syndrome.
- Author
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Ogunmakin K, Vangipuram R, Sturgeon A, and Shimizu I
- Subjects
- Child, Contracture physiopathology, Hip Joint physiopathology, Humans, Male, Range of Motion, Articular, Skin Diseases, Genetic physiopathology, Contracture diagnosis, Contracture therapy, Skin Diseases, Genetic diagnosis, Skin Diseases, Genetic therapy
- Abstract
Stiff skin syndrome is a rare sclerotic condition that presents during infancy or early childhood. It has an insidious chronic course and may lead to significant co-morbidity and reduced quality of life. Often, affected individuals experience impaired ambulation and immobilization related to joint involvement. Clinically, it may resemble other sclerotic diseases, so histopathological evaluation is necessary to establish a diagnosis. As it is a condition with limited treatment options, prompt diagnosis and early initiation of physical therapy is crucial to prevent joint restriction and maintain quality of life. We describe a case of a 7-year-old with stiff skin syndrome, and review the literature to discuss the clinical presentation, histological findings, and management of this condition.
- Published
- 2015
33. The association between retinal microvascular changes, metabolic risk factors, and liver histology in pediatric patients with non-alcoholic fatty liver disease (NAFLD).
- Author
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Liccardo D, Mosca A, Petroni S, Valente P, Giordano U, Mico' AG, Pescosolido S, Buzzonetti L, and Nobili V
- Subjects
- Adolescent, Anthropometry methods, Arteries abnormalities, Arteries pathology, Arteries physiopathology, Biopsy, Blood Pressure Monitoring, Ambulatory methods, Child, Female, Humans, Hypertensive Retinopathy pathology, Hypertensive Retinopathy physiopathology, Joint Instability etiology, Joint Instability pathology, Joint Instability physiopathology, Liver pathology, Male, Non-alcoholic Fatty Liver Disease pathology, Non-alcoholic Fatty Liver Disease physiopathology, Retrospective Studies, Risk Factors, Severity of Illness Index, Skin Diseases, Genetic etiology, Skin Diseases, Genetic pathology, Skin Diseases, Genetic physiopathology, Vascular Malformations etiology, Vascular Malformations pathology, Vascular Malformations physiopathology, Hypertensive Retinopathy etiology, Non-alcoholic Fatty Liver Disease complications, Retinal Vessels pathology
- Abstract
Background: The prevalence of childhood obesity is increasing worldwide. Studies in adult populations show that retinal microvascular changes are associated with obesity and components of the metabolic syndrome. In our study we have assessed the effect of body mass index (BMI), metabolic parameters, and adiposity on the retinal microvasculature in children., Methods: Fifty-four consecutive children with biopsy-proven NAFLD were enrolled in this study. Anthropometric and laboratory parameters were obtained using standardized protocols. Retinal caliber was quantified from digital retinal images using well-known computer-based programs. Twenty-four-hour ambulatory blood pressure monitoring was measured using a standard protocol., Results: In our population, the prevalence of retinopathy was of 53 % (13 males). The 29 patients with retinopathy (mean age 10.91 ± 3.10) showed significantly higher values of triglycerides (mg/day) (105.57 vs. 90.20, p = 0.04), basal insulin (mUI/ml) (17.20 vs. 12.97, p = 0.02), and HOMA-IR (3.37 vs. 2.76, p = 0.04). The patients with a HOMA-IR >2.5 (OR = 3.34, p = 0.02; 95 % IC, 1.07-10.39), and systolic non-dipping (OR 4.16, p = 0.028, 95 % IC, 1.11-13.67), have an increased risk of retinopathy. Moreover, the study of correlation between all stages of liver biopsy (CRN criteria) and the grade of retinopathy showed a positive correlation with fibrosis (r = 0.31) and an NAS score (r = 0.28)., Conclusions: We found an association between metabolic parameters and nocturnal blood pressure on the retinal microvasculature among the obese children with NAFLD. Furthermore, for the first time, we report the positive relationship between hepatic fibrosis in pediatric NAFLD patients and the degree of retinopathy signs.
- Published
- 2015
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34. Actinic Prurigo.
- Author
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Rodríguez-Carreón AA, Rodríguez-Lobato E, Rodríguez-Gutiérrez G, Cuevas-González JC, Mancheno-Valencia A, Solís-Arias MP, Vega-Memije ME, Hojyo-Tomoka MT, and Domínguez-Soto L
- Subjects
- HLA-DR4 Antigen genetics, Humans, Photosensitivity Disorders diagnosis, Photosensitivity Disorders drug therapy, Skin Diseases, Genetic diagnosis, Skin Diseases, Genetic drug therapy, Sunlight adverse effects, Thalidomide adverse effects, Dermatologic Agents therapeutic use, Photosensitivity Disorders physiopathology, Skin Diseases, Genetic physiopathology, Thalidomide therapeutic use
- Abstract
Actinic prurigo is an idiopathic photodermatosis that affects the skin, as well as the labial and conjunctival mucosa in indigenous and mestizo populations of Latin America. It starts predominantly in childhood, has a chronic course, and is exacerbated with solar exposure. Little is known of its pathophysiology, including the known mechanisms of the participation of HLA-DR4 and an abnormal immunologic response with increase of T CD4+ lymphocytes. The presence of IgE, eosinophils, and mast cells suggests that it is a hypersensitivity reaction (likely type IVa or b). The diagnosis is clinical, and the presence of lymphoid follicles in the mucosal histopathologic study of mucosa is pathognomonic. The best available treatment to date is thalidomide, despite its secondary effects.
- Published
- 2015
35. Differential diagnosis and diagnostic flow chart of joint hypermobility syndrome/ehlers-danlos syndrome hypermobility type compared to other heritable connective tissue disorders.
- Author
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Colombi M, Dordoni C, Chiarelli N, and Ritelli M
- Subjects
- Abnormalities, Multiple diagnosis, Abnormalities, Multiple physiopathology, Arteries physiopathology, Connective Tissue Diseases physiopathology, Ehlers-Danlos Syndrome physiopathology, Humans, Joint Instability physiopathology, Loeys-Dietz Syndrome diagnosis, Loeys-Dietz Syndrome physiopathology, Marfan Syndrome diagnosis, Marfan Syndrome physiopathology, Meningocele diagnosis, Meningocele physiopathology, Osteogenesis Imperfecta diagnosis, Osteogenesis Imperfecta physiopathology, Skin Abnormalities diagnosis, Skin Abnormalities physiopathology, Skin Diseases, Genetic physiopathology, Surveys and Questionnaires, Vascular Malformations physiopathology, Arteries abnormalities, Connective Tissue Diseases diagnosis, Diagnosis, Differential, Ehlers-Danlos Syndrome diagnosis, Joint Instability diagnosis, Skin Diseases, Genetic diagnosis, Vascular Malformations diagnosis
- Abstract
Joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type (JHS/EDS-HT) is an evolving and protean disorder mostly recognized by generalized joint hypermobility and without a defined molecular basis. JHS/EDS-HT also presents with other connective tissue features affecting a variety of structures and organs, such as skin, eye, bone, and internal organs. However, most of these signs are present in variable combinations and severity in many other heritable connective tissue disorders. Accordingly, JHS/EDS-HT is an "exclusion" diagnosis which needs the absence of any consistent feature indicative of other partially overlapping connective tissue disorders. While both Villefranche and Brighton criteria include such an exclusion as a mandatory item, a systematic approach for reaching a stringent clinical diagnosis of JHS/EDS-HT is still lacking. The absence of a consensus on the diagnostic approach to JHS/EDS-HT concerning its clinical boundaries with similar conditions contribute to limit our actual understanding of the pathologic and molecular bases of this disorder. In this review, we revise the differential diagnosis of JHS/EDS-HT with those heritable connective tissue disorders which show a significant overlap with the former and mostly include EDS classic, vascular and kyphoscoliotic types, osteogenesis imperfecta, Marfan syndrome, Loeys-Dietz syndrome, arterial tortuosity syndrome, and lateral meningocele syndrome. A diagnostic flow chart is also offered with the attempt to support the less experienced clinician in stringently recognizing JHS/EDS-HT and stimulate the debate in the scientific community for both management and research purposes., (© 2015 Wiley Periodicals, Inc.)
- Published
- 2015
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36. A 2-year-old girl with skin fragility.
- Author
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Mir-Bonafe JF, Baselga-Torres E, and Gonzalez-Sarmiento R
- Subjects
- Biopsy, Child, Preschool, DNA genetics, DNA Mutational Analysis, Dermatitis, Exfoliative genetics, Dermatitis, Exfoliative physiopathology, Diagnosis, Differential, Elasticity, Female, Follow-Up Studies, Glycoproteins genetics, Humans, Intercellular Signaling Peptides and Proteins, Mutation, Skin pathology, Skin Diseases, Genetic genetics, Skin Diseases, Genetic physiopathology, Dermatitis, Exfoliative diagnosis, Skin physiopathology, Skin Diseases, Genetic diagnosis
- Published
- 2015
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37. Desmosomes: regulators of cellular signaling and adhesion in epidermal health and disease.
- Author
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Johnson JL, Najor NA, and Green KJ
- Subjects
- Autoimmune Diseases physiopathology, Desmosomes drug effects, Epidermis growth & development, Gene Expression Regulation physiology, Humans, Signal Transduction physiology, Skin Diseases, Genetic physiopathology, Cell Adhesion physiology, Cell Communication physiology, Desmosomes physiology, Epidermis physiology, Skin Diseases physiopathology
- Abstract
Desmosomes are intercellular junctions that mediate cell-cell adhesion and anchor the intermediate filament network to the plasma membrane, providing mechanical resilience to tissues such as the epidermis and heart. In addition to their critical roles in adhesion, desmosomal proteins are emerging as mediators of cell signaling important for proper cell and tissue functions. In this review we highlight what is known about desmosomal proteins regulating adhesion and signaling in healthy skin-in morphogenesis, differentiation and homeostasis, wound healing, and protection against environmental damage. We also discuss how human diseases that target desmosome molecules directly or interfere indirectly with these mechanical and signaling functions to contribute to pathogenesis., (Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.)
- Published
- 2014
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38. Computation of hemodynamics in tortuous left coronary artery: a morphological parametric study.
- Author
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Xie X, Wang Y, Zhu H, and Zhou J
- Subjects
- Arteries pathology, Arteries physiopathology, Humans, Hydrodynamics, Kinetics, Models, Cardiovascular, Arteries abnormalities, Coronary Vessels pathology, Coronary Vessels physiopathology, Hemodynamics, Joint Instability pathology, Joint Instability physiopathology, Skin Diseases, Genetic pathology, Skin Diseases, Genetic physiopathology, Vascular Malformations pathology, Vascular Malformations physiopathology
- Abstract
Coronary tortuosity (CT) would alter the local wall shear stress (WSS) and may become a risk factor for atherosclerosis. Here we performed a systematic computational study to relate CT morphological parameters to abnormal WSS, which is a predisposing factor to the formation of atherosclerotic lesions. Several idealized left coronary artery (LCA) models were created to conduct a series of morphological parametric studies, in which we concentrate on three specific morphological parameters, the center line radius (CLR), the bend angle (BA), and the length between two adjust bends (LBB). The time averaged WSS (TAWSS), the oscillatory shear index (OSI), and the time averaged WSS gradient (WSSGnd) were explored by using the computational fluid dynamics (CFD) method, in order to determine susceptible sites for the onset of early atherosclerosis. In addition, two realistic LCA models were reconstructed to further validate the finding's credibility. The CLR and LBB had great impact on the distributions of WSS-derived parameters, while the BA had minor impact on the hemodynamic of the tortuous arteries. Abnormal regions with low TAWSS (TAWSS < 0.5 Pa), high OSI (OSI > 0.1) and high WSSGnd (WSSGnd > 8) were observed at the inner wall of bend sections in the models with small CLR or small LBB. These findings were also confirmed in the realistic models. Severe CT with small CLR or LBB would lead to the formation of abnormal WSS regions at the bend sections and providing these regions with favorable conditions for the onset and/or progression of atherosclerosis.
- Published
- 2014
- Full Text
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39. Artery buckling analysis using a four-fiber wall model.
- Author
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Liu Q, Wen Q, Mottahedi M, and Han HC
- Subjects
- Animals, Arteries physiopathology, Biomechanical Phenomena, Blood Pressure, Models, Cardiovascular, Pressure, Stress, Mechanical, Swine, Arteries abnormalities, Carotid Arteries physiology, Extracellular Matrix physiology, Joint Instability physiopathology, Skin Diseases, Genetic physiopathology, Vascular Malformations physiopathology
- Abstract
Artery bent buckling has been suggested as a possible mechanism that leads to artery tortuosity, which is associated with aging, hypertension, atherosclerosis, and other pathological conditions. It is necessary to understand the relationship between microscopic wall structural changes and macroscopic artery buckling behavior. To this end, the objectives of this study were to develop arterial buckling equations using a microstructure-based 4-fiber reinforced wall model, and to simulate the effects of vessel wall microstructural changes on artery buckling. Our results showed that the critical pressure increased nonlinearly with the axial stretch ratio, and the 4-fiber model predicted higher critical buckling pressures than what the Fung model predicted. The buckling equation using the 4-fiber model captured the experimentally observed reduction of critical pressure induced by elastin degradation and collagen fiber orientation changes in the arterial wall. These results improve our understanding of arterial stability and its relationship to microscopic wall remodeling, and the model provides a useful tool for further studies., (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Published
- 2014
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40. An in vivo rat model of artery buckling for studying wall remodeling.
- Author
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Zhang J, Liu Q, and Han HC
- Subjects
- Animals, Arteries metabolism, Arteries physiopathology, Carotid Arteries metabolism, Joint Instability metabolism, Male, Matrix Metalloproteinase 2 metabolism, Matrix Metalloproteinase 9 metabolism, Rats, Sprague-Dawley, Regional Blood Flow, Skin Diseases, Genetic metabolism, Vascular Malformations metabolism, Vascular Remodeling, Arteries abnormalities, Carotid Arteries physiopathology, Disease Models, Animal, Joint Instability physiopathology, Skin Diseases, Genetic physiopathology, Vascular Malformations physiopathology
- Abstract
Theoretical modeling and in vitro experiments have demonstrated that arterial buckling is a possible mechanism for the development of artery tortuosity. However, there has been no report of whether artery buckling develops into tortuosity, partially due to the lack of in vivo models for long-term studies. The objective of this study was to establish an in vivo buckling model in rat carotid arteries for studying arterial wall remodeling after buckling. Rat left carotid arteries were transplanted to the right carotid arteries to generate buckling under in vivo pressure and were maintained for 1 week to examine wall remodeling and adaptation. Our results showed that a significant buckling was achieved in the carotid arterial grafts with altered wall stress. Cell proliferation and matrix metalloprotinease-2 (MMP-2) expression in the buckled arteries increased significantly compared with the controls. The tortuosity level of the grafts also slightly increased 1 week post-surgery, while there was no change in vessel dimensions, blood pressure, and blood flow velocity. The artery buckling model provides a useful tool for further study of the adaptation of arteries into tortuous shapes.
- Published
- 2014
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41. Tranexamic acid-induced ligneous conjunctivitis with renal failure showed reversible hypoplasminogenaemia.
- Author
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Song Y, Izumi N, Potts LB, and Yoshida A
- Subjects
- Administration, Oral, Aged, Conjunctivitis physiopathology, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Follow-Up Studies, Humans, Kidney Failure, Chronic diagnosis, Kidney Failure, Chronic therapy, Remission, Spontaneous, Renal Dialysis methods, Risk Assessment, Severity of Illness Index, Skin Diseases, Genetic physiopathology, Stomach Ulcer diagnosis, Tranexamic Acid therapeutic use, Conjunctivitis chemically induced, Plasminogen deficiency, Plasminogen metabolism, Skin Diseases, Genetic chemically induced, Stomach Ulcer drug therapy, Tranexamic Acid adverse effects
- Abstract
Ligneous conjunctivitis is a rare severe conjunctivitis characterised by fibrin-rich, 'woody', pseudomembranes on the tarsal conjunctiva complicated by congenital hypoplasminogenaemia. A previous report suggested that ligneous conjunctivitis may result from tranexamic acid (TA)-induced 'secondary' hypoplasminogenaemia. However, the serum plasminogen level has not been confirmed in that scenario. We report for the first time a case of TA-induced ligneous conjunctivitis with reversible hypoplasminogenaemia. A 70-year-old woman developed a gastric ulcer that was treated with oral TA. After 5 weeks of treatment, the patient presented with bilateral pale yellow pseudomembranes on the palpebral conjunctivae. Haematological analysis showed hypoplasminogenaemia. We diagnosed ligneous conjunctivitis. TA was discontinued after 14 weeks after the gastric ulcer symptoms resolved. Six weeks after discontinuation of therapy, the pseudomembranes regressed and the serum plasminogen level returned to the normal range. TA should be considered a possible aetiology in the setting of unresolving ligneous conjunctivitis., (2014 BMJ Publishing Group Ltd.)
- Published
- 2014
- Full Text
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42. Whole-exome sequencing identifies ADAM10 mutations as a cause of reticulate acropigmentation of Kitamura, a clinical entity distinct from Dowling-Degos disease.
- Author
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Kono M, Sugiura K, Suganuma M, Hayashi M, Takama H, Suzuki T, Matsunaga K, Tomita Y, and Akiyama M
- Subjects
- ADAM10 Protein, Adult, Aged, Cells, Cultured, Exome, Female, Humans, Hyperpigmentation physiopathology, INDEL Mutation, Keratin-5 genetics, Keratin-5 metabolism, Male, Middle Aged, Mutation, Missense, Pedigree, Phylogeny, Sequence Analysis, DNA, Sequence Analysis, Protein, Skin Diseases, Genetic physiopathology, Skin Diseases, Papulosquamous physiopathology, Young Adult, ADAM Proteins genetics, ADAM Proteins metabolism, Amyloid Precursor Protein Secretases genetics, Amyloid Precursor Protein Secretases metabolism, Hyperpigmentation genetics, Membrane Proteins genetics, Membrane Proteins metabolism, Skin Diseases, Genetic genetics, Skin Diseases, Papulosquamous genetics
- Abstract
Reticulate acropigmentation of Kitamura (RAK) is a rare genetic disorder of cutaneous pigmentation with an autosomal dominant pattern of inheritance and a high penetration rate. The characteristic skin lesions are reticulate, slightly depressed pigmented macules mainly affecting the dorsa of the hands and feet, which first appear before puberty and subsequently expand to the proximal limb and the trunk. To identify mutations that cause RAK, we performed exome sequencing of four family members in a pedigree with RAK. Fifty-three SNV/Indels were considered as candidate mutations after some condition narrowing. We confirmed the mutation status in each candidate gene of four other members in the same pedigree to find the gene that matched the mutation status and phenotype of each member. A mutation in ADAM10 encoding a zinc metalloprotease, a disintegrin and metalloprotease domain-containing protein 10 (ADAM10), was identified in the RAK family. ADAM10 is known to be involved in the ectodomain shedding of various substrates in the skin. Sanger sequencing of four additional unrelated RAK patients revealed four additional ADAM10 mutations. We identified a total of three truncating mutations, a splice site mutation and a missense mutation in ADAM10. We searched for mutations in the KRT5 gene, a causative gene for the similar pigmentation disorder Dowling-Degos disease (DDD), in all the patients and found no KRT5 mutation. These results reveal that mutations in ADAM10 are a cause of RAK and that RAK is an independent clinical entity distinct from DDD.
- Published
- 2013
- Full Text
- View/download PDF
43. [The coronary arterial tortuosity in workers of vibro-noisy professions and its role in the ischemic damage of the myocardium].
- Author
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Sova SH and Lebedieva EO
- Subjects
- Angiography, Arteries physiopathology, Coronary Circulation physiology, Coronary Vessels diagnostic imaging, Echocardiography, Female, Humans, Joint Instability diagnostic imaging, Joint Instability physiopathology, Male, Middle Aged, Myocardial Ischemia diagnostic imaging, Occupational Diseases diagnostic imaging, Occupational Diseases physiopathology, Skin Diseases, Genetic diagnostic imaging, Skin Diseases, Genetic physiopathology, Vascular Malformations diagnostic imaging, Vascular Malformations physiopathology, Arteries abnormalities, Coronary Vessels physiopathology, Joint Instability etiology, Myocardial Ischemia etiology, Noise, Occupational adverse effects, Occupational Diseases etiology, Skin Diseases, Genetic etiology, Vascular Malformations etiology, Vibration adverse effects
- Abstract
The article is devoted the study of role of the phenomenon of coronal arterial tortuosity in pathogeny of ischemic heart disease. For 89% patients with a cardiac pain and coronal arterial tortuosity at which at a conservative cardiologic inspection it was not discovered signs of organic defeat of heart and coronal vessels, by the high-specific functional methods of research and stress-tests the presence of cardial ischemia is set. Accordance localization of ischemic areas of myocardium is also exposed to the areas of vascularization by the coronal tortuosity arteries. Among all inspected persons with the coronal arterial tortuosity 21.7% belonged to the group of workers the profession of which is related to the combined action of local vibration and industrial noise.
- Published
- 2013
44. Impact of coronary tortuosity on coronary blood supply: a patient-specific study.
- Author
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Xie X, Wang Y, Zhu H, Zhou H, and Zhou J
- Subjects
- Arteries physiopathology, Computational Biology methods, Humans, Arteries abnormalities, Coronary Vessels physiopathology, Hydrodynamics, Joint Instability physiopathology, Models, Biological, Regional Blood Flow physiology, Skin Diseases, Genetic physiopathology, Vascular Malformations physiopathology
- Abstract
Background: Tortuous coronary arteries are commonly observed in clinical screenings and it may cause a reduction of the coronary pressure. However, whether this reduction leads to significant decreasing in the coronary blood supply is still unknown. The purpose of this study was to investigate the effect of the coronary tortuosity (CT) on the coronary blood supply., Method: A computational fluid dynamics (CFD) study was conducted to evaluate the impact of tortuosity on the coronary blood supply. Two patient-specific left anterior descending coronary artery (LAD) models and the corresponding non-tortuous models were reconstructed to perform three-dimensional CFD analysis. The lumped parameter model was coupled to the outlet of the simulated branches to represent the absent downstream vasculatures. The rest and exercise conditions were modeled by specifying proper boundary conditions., Result: Under resting condition, the mean flow rate could be maintained by decreasing less than 8% of the downstream vascular bed's resistance for tortuous models. While during exercise (maximal dilatation condition), the maximal coronary blood supply would reduce up to 14.9% due to tortuosity. Assuming that the flow rate can be maintained by the auto-regulation effect under the maximal dilatation condition, the distal resistances for CT models still have to reduce more than 23% to maintain blood perfusion., Conclusions: Coronary tortuosity has minor influence on coronary blood supply at rest; while during exercise, patients with CT may lack the ability to adjust distal resistance sufficiently to compensate for the extra resistances generated by tortuosity and this may further lead to an ineffective regulation of the blood supply.
- Published
- 2013
- Full Text
- View/download PDF
45. MCP-1 as an effector of IL-31 signaling in familial primary cutaneous amyloidosis.
- Author
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Shiao YM, Chung HJ, Chen CC, Chiang KN, Chang YT, Lee DD, Lin MW, Tsai SF, and Matsuura I
- Subjects
- Amyloid metabolism, Amyloidosis, Familial pathology, Amyloidosis, Familial physiopathology, Cell Line, Humans, Interleukins pharmacology, Keratinocytes drug effects, Keratinocytes metabolism, Keratinocytes pathology, STAT3 Transcription Factor metabolism, Signal Transduction drug effects, Skin Diseases, Genetic pathology, Skin Diseases, Genetic physiopathology, Amyloidosis, Familial metabolism, Chemokine CCL2 metabolism, Interleukins metabolism, Signal Transduction physiology, Skin Diseases, Genetic metabolism
- Published
- 2013
- Full Text
- View/download PDF
46. Effects of idebenone on color vision in patients with leber hereditary optic neuropathy.
- Author
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Rudolph G, Dimitriadis K, Büchner B, Heck S, Al-Tamami J, Seidensticker F, Rummey C, Leinonen M, Meier T, and Klopstock T
- Subjects
- Adolescent, Adult, Double-Blind Method, Female, Humans, Male, Middle Aged, Optic Atrophy, Hereditary, Leber complications, Optic Atrophy, Hereditary, Leber physiopathology, Pigmentation Disorders drug therapy, Pigmentation Disorders etiology, Pigmentation Disorders physiopathology, Skin Diseases, Genetic etiology, Skin Diseases, Genetic physiopathology, Treatment Outcome, Ubiquinone therapeutic use, Antioxidants therapeutic use, Color Perception physiology, Optic Atrophy, Hereditary, Leber drug therapy, Pigmentation Disorders congenital, Skin Diseases, Genetic drug therapy, Ubiquinone analogs & derivatives
- Abstract
Background: The authors investigated the correlation of protan and tritan color vision with disease characteristics in Leber hereditary optic neuropathy (LHON). The authors also characterized the therapeutic potential of idebenone in protecting patients from developing dyschromatopsia in LHON., Methods: Color contrast data of 39 LHON patients participating in a randomized, double-blind placebo-controlled intervention study were evaluated. Patients reported disease onset <5 years before enrolment and were genetically confirmed. Protan and tritan color contrast sensitivity was measured using a computer graphics method in patients receiving idebenone (Catena; 900 mg/d; N = 28) or placebo (N = 11) for 6 months., Results: Mean age of patients was 28.1 years, 87.2% were men, 76.9% carried the m11778G>A mutation, and mean duration since onset was 2 years. Assessing protan and tritan color vision at baseline revealed a high degree of color confusion even in young patients (<25 years) and with a short history of disease (<1 year). Treatment with idebenone improved tritan color vision compared with placebo (P = 0.008 at week 24); a similar trend was seen for protan. The effect of idebenone was most prominent in patients with discordant visual acuity (interocular difference of logMAR >0.2). In this subgroup, the treatment effect at week 24 was 20.4% (P = 0.005) in favor of idebenone for the tritan color domain and 13.5% (P = 0.067) for the protan domain., Conclusion: This study confirms that protan and tritan color confusion is an early symptom in LHON. Treatment with idebenone can protect from loss of color vision, particularly in patients who are at imminent risk of further vision loss.
- Published
- 2013
- Full Text
- View/download PDF
47. Unfolded protein response in keratinocytes: impact on normal and abnormal keratinization.
- Author
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Sugiura K
- Subjects
- Animals, Cell Differentiation, Darier Disease physiopathology, Endoplasmic Reticulum Stress, Gene Deletion, Humans, Ichthyosis physiopathology, Keratinocytes physiology, Keratins metabolism, Molecular Chaperones metabolism, Mutation, Photophobia physiopathology, Protein Folding, Signal Transduction, Skin Diseases, Genetic physiopathology, Keratinocytes cytology, Keratins physiology, Unfolded Protein Response physiology
- Abstract
The unfolded protein response (UPR) is a signaling pathway from the endoplasmic reticulum (ER) to the nucleus that protects cells from stress caused by misfolded or unfolded proteins. As such, ER stress is an ongoing challenge for all cells, given the central biologic importance of secretion as part of normal physiologic functions. Mild UPR is activated by mild ER stress, which occurs under normal conditions. Abnormal UPR is activated by severe ER stress, which occurs under pathological conditions. Abnormal UPR activation is associated with a number of diseases, including diabetes mellitus and Alzheimer's disease. Within skin tissues, keratinocytes in the epidermis are especially dependent upon a mild UPR for normal differentiation in the course of their differentiation into secretory cells in the uppermost granular layers. Association between abnormal UPR activation and hereditary keratoses, including Darier's disease, keratosis linearis with ichthyosis congenita and keratoderma syndrome, erythrokeratoderma variabilis, and ichthyosis follicularis with atrichia and photophobia syndrome, have been elucidated recently. This review describes the UPR in normal and abnormal keratinization and discusses the regulation of abnormal UPR activation by chemical chaperones as a potential treatment for one of the hereditary keratoses., (Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2013
- Full Text
- View/download PDF
48. Palms and soles.
- Author
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Stollery N
- Subjects
- Adult, Child, Dermatitis, Exfoliative etiology, Dermatitis, Exfoliative physiopathology, Eczema, Dyshidrotic etiology, Eczema, Dyshidrotic physiopathology, Hand, Foot and Mouth Disease etiology, Hand, Foot and Mouth Disease physiopathology, Humans, Skin Diseases, Genetic etiology, Skin Diseases, Genetic physiopathology, Tinea Pedis etiology, Tinea Pedis physiopathology, Warts etiology, Warts physiopathology, Foot Dermatoses classification, Foot Dermatoses etiology, Foot Dermatoses physiopathology, Hand Dermatoses classification, Hand Dermatoses etiology, Hand Dermatoses physiopathology
- Published
- 2012
49. Impact of coronary tortuosity on coronary pressure: numerical simulation study.
- Author
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Li Y, Shi Z, Cai Y, Feng Y, Ma G, Shen C, Li Z, and Liu N
- Subjects
- Angiography methods, Arteries abnormalities, Arteries physiopathology, Blood Flow Velocity physiology, Blood Pressure, Computer Simulation, Coronary Circulation physiology, Coronary Vessels physiopathology, Hemodynamics, Humans, Models, Cardiovascular, Models, Theoretical, Myocardial Ischemia pathology, Pressure, Arterial Pressure, Coronary Vessels physiology, Heart physiopathology, Joint Instability physiopathology, Skin Diseases, Genetic physiopathology, Vascular Malformations physiopathology
- Abstract
Background: Coronary tortuosity (CT) is a common coronary angiographic finding. Whether CT leads to an apparent reduction in coronary pressure distal to the tortuous segment of the coronary artery is still unknown. The purpose of this study is to determine the impact of CT on coronary pressure distribution by numerical simulation., Methods: 21 idealized models were created to investigate the influence of coronary tortuosity angle (CTA) and coronary tortuosity number (CTN) on coronary pressure distribution. A 2D incompressible Newtonian flow was assumed and the computational simulation was performed using finite volume method. CTA of 30°, 60°, 90°, 120° and CTN of 0, 1, 2, 3, 4, 5 were discussed under both steady and pulsatile conditions, and the changes of outlet pressure and inlet velocity during the cardiac cycle were considered., Results: Coronary pressure distribution was affected both by CTA and CTN. We found that the pressure drop between the start and the end of the CT segment decreased with CTA, and the length of the CT segment also declined with CTA. An increase in CTN resulted in an increase in the pressure drop., Conclusions: Compared to no-CT, CT can results in more decrease of coronary blood pressure in dependence on the severity of tortuosity and severe CT may cause myocardial ischemia.
- Published
- 2012
- Full Text
- View/download PDF
50. Full-thickness human skin models for congenital ichthyosis and related keratinization disorders.
- Author
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Eckl KM, Alef T, Torres S, and Hennies HC
- Subjects
- Adolescent, Adult, Aged, Cells, Cultured, Child, Child, Preschool, Epidermis physiology, Humans, Ichthyosis genetics, Ichthyosis physiopathology, Keratosis genetics, Keratosis physiopathology, Skin Diseases, Genetic genetics, Skin Diseases, Genetic physiopathology, Young Adult, Epidermis pathology, Ichthyosis pathology, Keratosis pathology, Organ Culture Techniques methods, Skin Diseases, Genetic pathology
- Published
- 2011
- Full Text
- View/download PDF
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