Search results for " type II"
showing 10 items of 542 documents
Effects of enzyme replacement therapy on growth in patients with mucopolysaccharidosis type II
2010
Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is an X-linked, recessive, lysosomal storage disorder caused by deficiency of iduronate-2-sulfatase. It has multisystemic involvement, with manifestations in the brain, upper respiratory tract, heart, abdomen, joints and bones. Bone involvement leads to decreased growth velocity and short stature in nearly all patients. A therapeutic option for patients with MPS II is enzyme replacement therapy (ERT) with idursulfase (Elaprase®). We compared annual growth rates before and during ERT in 18 patients from Mainz, Germany, and Manchester, UK. Group 1 included nine patients who started ERT before 10 years of age; group 2 contained nine patie…
Nitric oxide production and endothelium-dependent vasorelaxation ameliorated by N1-methylnicotinamide in human blood vessels.
2012
N 1 -methylnicotinamide (MNA + ) has until recently been thought to be a biologically inactive product of nicotinamide metabolism in the pyridine nucleotides pathway. However, the latest observations imply that MNA + may exert antithrombotic and anti-inflammatory effects through direct action on the endothelium. We examined both in vivo and in vitro whether the compound might induce vasorelaxation in human blood vessels through the improvement of nitric oxide (NO) bioavailability and a reduction of oxidative stress mediated by endothelial NO synthase (eNOS) function. MNA + treatment (100 mg/m 2 orally) in healthy normocholesterolemic and hypercholesterolemic subjects increased the l-argini…
Six novel mutations of the LDL receptor gene in FH kindred of Sicilian and Paraguayan descent
2006
Familial hypercholesterolemia (FH) is an autosomal dominant inherited disease caused by mutations in the gene coding for the low density lipoprotein receptor (LDL-R). It is characterized by a high concentration of low density lipoprotein (LDL), which frequently gives rise to premature coronary artery disease. We studied the probands of five FH Sicilian families with 'definite' FH and one proband of Paraguayan descent with homozygous FH who has been treated with an effective living-donor liver transplantation. In order to seek the molecular defect in these six families, we used direct sequencing to define the molecular defects of the LDL-R gene responsible for the disease. We described three…
Cell Death and Oxidative Damage in Inflammatory Myopathies
1998
There is evidence that muscle fibers in denervating disorders and muscular dystrophies undergo apoptosis. In 21 patients with autoimmune inflammatory myopathies, we found no features of muscle fiber apoptosis such as DNA fragmentation or expression of apoptosis-related proteins. However, muscle fibers in myositis displayed distinct up-regulation of inducible and neuronal nitric oxide synthase (NOS). While inducible NOS was distinctly up-regulated on the sarcolemma of all kinds of muscle fibers neuronal NOS displayed increased expression in the sarcoplasm of damaged as well as atrophic muscle fibers. There were no disease-specific patterns in the different myositis subtypes. Enhanced express…
NO Reduces PMN Adhesion to Human Vascular Endothelial Cells Due to Downregulation of ICAM-1 mRNA and Surface Expression
2000
Reperfusion damage is largely due to the adherence of polymorphonuclear leukocytes to the endothelium initiated by adhesion molecule upregulation. The reduced endothelial nitric oxide release during ischemia may be involved in the upregulation of intercellular adhesion molecule 1. In this study, we tested if nitric oxide donors suppress polymorphonuclear leukocyte adherence to activated endothelial cells by inhibition of the intercellular adhesion molecule 1 surface expression. Confluent human umbilical vein endothelial cells were stimulated with tumor necrosis factor alpha (300 U/mL) after preincubation with increasing concentrations of the nitric oxide donors CAS 1609 (0.005-5 mM/L) and 3…
Development and Aging Are Oxygen-Dependent and Correlate with VEGF and NOS along Life Span
2012
During development and aging, vascular remodeling represents a critical adaptive response to modifications in oxygen supply to tissues. Hypoxia inducible factor (HIF) has a crucial role and is modulated by oxygen levels, with an age-dependent response in neonates, adult, and aged people. ROS are generated under hypoxic conditions and the accumulation of free radicals during life reduces the ability of tissues to their removal. In this immunohistochemical study we investigated the presence and localization of VEGF and iNOS in human carotid bodies (CB) sampled at autopsy from three children (mean age – 2 years), four adult young subjects (mean age – 44.3 years), and four old subjects (mean ag…
Hereditary angioedema caused by missense mutations in the factor XII gene: clinical features, trigger factors, and therapy.
2009
Background Hereditary angioedema caused by mutations in the factor XII gene is a recently described disease entity that occurs mainly in women. It differs from hereditary angioedema caused by C1 inhibitor deficiency. Objective To assess the clinical symptoms, factors triggering acute attacks, and treatments of this disease. Methods Thirty-five female patients with hereditary angioedema and the factor XII mutations p.Thr309Lys and p.Thr309Arg who came from 13 unrelated families were studied. The observation period was 8.4 years on average (range, 2-26 years). Results Patients had on average 12.7 ± 7.9 angioedema attacks per year. Recurrent facial swellings occurred in all patients; skin swel…
A new PCSK9 gene promoter variant affects gene expression and causes autosomal dominant hypercholesterolemia.
2008
Autosomal dominant hypercholesterolemia (ADH) is a genetic disorder characterized by increased low-density lipoprotein (LDL)-cholesterol levels, leading to high risk of premature cardiovascular disease. More than 900 mutations in LDL receptor, six in APOB and 10 in PCSK9 have been identified as a cause of the disease in different populations. All known mutations in PCSK9 causing hypercholesterolemia produce an increase in the enzymatic activity of this protease. Up to now, there are data about the implication of PCSK9 in ADH in a low number of populations, not including a Spanish population.The objective of the study was to study the prevalence of PCSK9 mutations in ADH Spanish population.W…
Expanding the clinical spectrum of late-onset Pompe disease: Dilated arteriopathy involving the thoracic aorta, a novel vascular phenotype uncovered
2011
Abstract Purpose Cerebro-vascular arteriopathy has been reported in late-onset Pompe disease (LOPD). Evidence of increased aortic stiffness in some patients and smooth muscle involvement in LOPD raises the possibility of aortic involvement. Our aim was to determine if aortic arteriopathy may be a complication of LOPD. Methods One patient with LOPD was diagnosed with aortic dilatation at Duke Metabolic clinic, 4 others were diagnosed at University of Mainz, Germany, where chest X-ray and echocardiography are routinely done for patients. Other causes of aortic vascular disease were assessed. Results We report evidence of dilated arteriopathy involving primarily the ascending thoracic aorta in…
Extracorporeal circuit heparinization in selective low density lipoprotein apheresis: changes in patient hemostasis and low molecular weight heparin …
1993
Treatment by low density lipoprotein (LDL) apheresis using dextran sulfate columns (DSC) leads to hemostasis alterations with prolonged activated partial thromboplastin time (APTT) of more than 120 seconds. In order to explain this hypocoagulability, we studied hemostasis parameters both in patients and in the extracorporeal circulation (ECC). Hemostasis changes are first related to unfractionated heparin (UFH)—needed to avoid circuit coagulation—which leads to high residual heparinemia in the patient (more than 3 times the recommended level for therapeutic use). Second, the hypocoagulability is induced by a coagulation factor decrease (primarily factors V, VIH, and X) mainly due to an adso…