Succinate cytochrome c reductase in schistosomiasis: in vitro inhibition by some schistosomicidal drugs.

Enzymes in mitochondria play an important role in biological oxidation and energy production. To understand the effect of schistosomiasis on these important processes, succinate cytochrome c reductase (SCR) from control and Schistosoma-infected mice was subjected for investigation. In this article, we report that SCR from Schistosoma-infected mouse showed a significant decrease in its Vmax and Km compared to control using both cytochrome c and 2,6-dichlorophenolindophenol as substrates.

ENT manifestations in patients with primary ciliary dyskinesia: prevalence and significance of otorhinolaryngologic co-morbidities.

Primary ciliary dyskinesia (PCD) is a rare inherited disease with a prevalence of about 1:20,000. The underlying pathogenesis is disrupted ciliary function, which results in delayed mucus transportation leading to chronic inflammation, mainly in the upper and lower respiratory tract. Although the pathogenesis of the disease and its clinical presentation is somewhat understood, data regarding the prevalence of accompanying symptoms is limited, especially in the field of otorhinolaryngology.

PLAATO (Percutaneous Left Atrial Appendage Transcatheter Occlusion) for prevention of cardioembolic stroke in non-anticoagulation eligible atrial fibrillation patients: results from the European PLAATO study.

Aims: The European PLAATO (Percutaneous Left Atrial Appendage Transcatheter Occlusion) study was performed to determine the safety and efficacy of left atrial appendage occlusion by catheter technique. Embolic stroke due to atrial fibrillation is a common observation, especially in the elderly. Most thrombi in atrial fibrillation form in the left atrial appendage (LAA), its occlusion may therefore reduce the incidence of stroke in these patients.

Factors influencing age at diagnosis of primary ciliary dyskinesia in European children.

Primary ciliary dyskinesia (PCD) is a hereditary disorder of mucociliary clearance causing chronic upper and lower airways disease. We determined the number of patients with diagnosed PCD across Europe, described age at diagnosis and determined risk factors for late diagnosis. Centres treating children with PCD in Europe answered questionnaires and provided anonymous patient lists.

Aminoacylase 1 deficiency associated with autistic behavior.

Aminoacylase 1 (ACY1) deficiency is a recently described inborn error of metabolism. Most of the patients reported so far have presented with rather heterogeneous neurologic symptoms. At this moment, it is not clear whether ACY1 deficiency represents a true metabolic disease with a causal relationship between the enzyme defect and the clinical phenotype or merely a biochemical abnormality.

Mucopolysaccharidosis type IIID: 12 new patients and 15 novel mutations.

Mucopolysaccharidosis III D (Sanfilippo disease type D, MPS IIID) is a rare autosomal recessive lysosomal storage disorder previously described in only 20 patients. MPS IIID is caused by a deficiency of N-acetylglucosamine-6-sulphate sulphatase (GNS), one of the enzymes required for the degradation of heparan sulphate. So far only seven mutations in the GNS gene have been reported.

Novel integrin-dependent platelet malfunction in siblings with leukocyte adhesion deficiency-III (LAD-III) caused by a point mutation in FERMT3.

Leukocyte adhesion deficiency-III (LAD-III) also called leukocyte adhesion deficiency-1/variant (LAD1v) is a rare congenital disease caused by defective integrin activation of leukocytes and platelets. Patients with LAD-III present with non-purulent infections and increased bleeding symptoms. We report on a novel integrin-dependent platelet dysfunction in two brothers with LAD-III syndrome caused by a homozygous mutation 1717C>T in the FERMT3 gene leading to a premature stop codon R573X in the focal adhesion protein kindlin-3.

Primary ciliary dyskinesia: a consensus statement on diagnostic and treatment approaches in children.

Primary ciliary dyskinesia (PCD) is associated with abnormal ciliary structure and function, which results in retention of mucus and bacteria in the respiratory tract, leading to chronic oto-sino-pulmonary disease, situs abnormalities and abnormal sperm motility. The diagnosis of PCD requires the presence of the characteristic clinical phenotype and either specific ultrastructural ciliary defects identified by transmission electron microscopy or evidence of abnormal ciliary function. Although the management of children affected with PCD remains uncertain and evidence is limited, it remains important to follow-up these patients with an adequate and shared care system in order to prevent future lung damage.

Deletions and point mutations of LRRC50 cause primary ciliary dyskinesia due to dynein arm defects.

Genetic defects affecting motility of cilia and flagella cause chronic destructive airway disease, randomization of left-right body asymmetry, and, frequently, male infertility in primary ciliary dyskinesia (PCD). The most frequent defects involve outer and inner dynein arms (ODAs and IDAs) that are large multiprotein complexes responsible for cilia-beat generation and regulation, respectively. Here, we demonstrate that large genomic deletions, as well as point mutations involving LRRC50, are responsible for a distinct PCD variant that is characterized by a combined defect involving assembly of the ODAs and IDAs.

Bridging of chronic oral anticoagulation with enoxaparin in patients with atrial fibrillation: results from the prospective BRAVE registry.

Current American College of Chest Physicians (ACCP) guidelines on the perioperative management of oral anticoagulation (OAC) suggest bridging therapy with therapeutic doses of low-molecular-weight heparin (LMWH) in patients with atrial fibrillation (AF) if at high or moderate thromboembolic (TE) risk, and with reduced doses in patients with low TE risk. Our objective was to assess the efficacy and safety of bridging OAC with enoxaparin in AF patients. These are the results of an open, prospective monocenter register.

Myocardial contrast echocardiography enhances long-term prognostic value of supine bicycle stress two-dimensional echocardiography.

Background: The aim of this study was to determine the incremental prognostic value of myocardial contrast echocardiography (MCE) over two-dimensional echocardiography (2DE) in patients undergoing supine bicycle stress.

Methods: Eighty-four patients with known or suspected coronary artery disease who underwent supine bicycle stress with 2DE and MCE (mean age, 58.5 +/- 9.

Novel ALG8 mutations expand the clinical spectrum of congenital disorder of glycosylation type Ih.

Congenital disorders of glycosylation (CDG) are an expanding group of inherited disorders caused by defects in the N- or O-Glycosylation of proteins and lipids. Several CDG subtypes have been described so far, including CDG type Ih which is caused by a deficiency of the dolichyl-P-Glc:Glc(1)Man(9)GlcNAc(2)-PP-dolichyl alpha1,3-glucosyltransferase (hALG8). The defect leads to an accumulation of Dol-PP-GlcNAc(2)Man(9) and Dol-PP-GlcNAc(2)Man(9)Glc(1) in the endoplasmic reticulum of patients' fibroblasts that can be detected by analyzing the lipid-linked oligosaccharyl intermediates.

Bridging of oral anticoagulation with low-molecular-weight heparin: experience in 373 patients with renal insufficiency undergoing invasive procedures.

If surgery or another intervention is planned, current guidelines recommend bridging oral anticoagulation (OAC) with heparins in patients at elevated thromboembolic (TE) risk. While patients with renal impairment have a higher risk of bleeding and dosing of heparins is more difficult, there are no specific recommendations for bridging the latter patients. Hence, we aimed to investigate the efficacy and tolerability of using reduced low-molecular-weight heparin (enoxaparin) dosages for bridging of OAC.

Doxycycline accelerates renal cyst growth and fibrosis in the pcy/pcy mouse model of type 3 nephronophthisis, a form of recessive polycystic kidney disease.

Nephronophthisis belongs to a family of recessive cystic kidney diseases and may arise from mutations in multiple genes. In this report we have used a spontaneous mouse mutant of type 3 nephronophthisis to examine whether the doxycycline-inducible synthesis of Timp-2, a natural inhibitor of matrix metalloproteinases, can influence renal cyst growth in transgenic mice. Metalloproteinases may exert either a negative or a positive effect on the progression of cystic kidney disease, and we reasoned that this may be most effectively examined by using a natural inhibitor.

Initiation and maturation of cilia-generated flow in newborn and postnatal mouse airway.

Mucociliary clearance in the adult trachea is well characterized, but there are limited data in newborns. Cilia-generated flow was quantified across longitudinal sections of mouse trachea from birth through postnatal day (PND) 28 by tracking fluorescent microsphere speed and directionality. The percentage of ciliated tracheal epithelial cells, as determined by immunohistochemistry, was shown to increase linearly between PND 0 and PND 21 (R(2) = 0.

How useful is determination of anti-factor Xa activity to guide bridging therapy with enoxaparin? A pilot study.

Low-molecular-weight heparins (LMWH) are commonly used as peri-procedural bridging anticoagulants. The usefulness of measurement of anti-factor Xa activity (anti-Xa) to guide bridging therapy with LMWH is unknown. It was the objective of this study to determine levels of anti-Xa during standard bridging therapy with enoxaparin, and to examine predictors for residual anti-Xa.

Immunofluorescence staining of ciliated respiratory epithelial cells.

Respiratory epithelial cells carry multiple motile cilia. Defective ciliary motility results in reduced mucociliary airway clearance in a destructive chronic airway disease referred to as primary ciliary dyskinesia. Immunofluorescence (IF) microscopy of respiratory cells allows visualization of proteins along the length of the ciliary axoneme and distinct compartments such as the transition zone and the basal body region at the ciliary base.

Ktu/PF13 is required for cytoplasmic pre-assembly of axonemal dyneins.

Cilia and flagella are highly conserved organelles that have diverse roles in cell motility and sensing extracellular signals. Motility defects in cilia and flagella often result in primary ciliary dyskinesia. However, the mechanisms underlying cilia formation and function, and in particular the cytoplasmic assembly of dyneins that power ciliary motility, are only poorly understood.

Refining the phenotype of alpha-1a Tubulin (TUBA1A) mutation in patients with classical lissencephaly.

Mutations in the alpha-1a Tubulin (TUBA1A) gene have recently been found to cause cortical malformations resemblant of classical lissencephaly but with a specific combination of features. To date, TUBA1A mutations have been described in five patients and three foetuses. Our aims were to establish how common TUBA1A mutations are in patients with lissencephaly and to contribute to defining the phenotype associated with TUBA1A mutation.

DNAI2 mutations cause primary ciliary dyskinesia with defects in the outer dynein arm.

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder characterized by chronic destructive airway disease and randomization of left/right body asymmetry. Males often have reduced fertility due to impaired sperm tail function. The complex PCD phenotype results from dysfunction of cilia of the airways and the embryonic node and the structurally related motile sperm flagella.

Impact of previous myocardial infarction on the incremental value of myocardial contrast to two-dimensional supine bicycle stress echocardiography in evaluation of coronary artery disease.

Background: If compared to two-dimensional echocardiography (2DE), myocardial contrast echocardiography (MCE) improves detection of coronary artery disease (CAD) during pharmacological stress, but data on MCE vs. 2DE during supine bicycle stress is limited. Although previous myocardial infarction (MI) influences sensitivity of 2DE, its effect on MCE has not been evaluated.

L-2-hydroxyglutaric aciduria: identification of ten novel mutations in the L2HGDH gene.

L-2-hydroxyglutaric aciduria (L-2-HGA) is a metabolic disease with an autosomal recessive mode of inheritance. It was first reported in 1980. Patients with this disease have mutations in both alleles of the L2HDGH gene.

BRAF gene duplication constitutes a mechanism of MAPK pathway activation in low-grade astrocytomas.

The molecular pathogenesis of pediatric astrocytomas is still poorly understood. To further understand the genetic abnormalities associated with these tumors, we performed a genome-wide analysis of DNA copy number aberrations in pediatric low-grade astrocytomas by using array-based comparative genomic hybridization. Duplication of the BRAF protooncogene was the most frequent genomic aberration, and tumors with BRAF duplication showed significantly increased mRNA levels of BRAF and a downstream target, CCND1, as compared with tumors without duplication.

Loss of nephrocystin-3 function can cause embryonic lethality, Meckel-Gruber-like syndrome, situs inversus, and renal-hepatic-pancreatic dysplasia.

Many genetic diseases have been linked to the dysfunction of primary cilia, which occur nearly ubiquitously in the body and act as solitary cellular mechanosensory organelles. The list of clinical manifestations and affected tissues in cilia-related disorders (ciliopathies) such as nephronophthisis is broad and has been attributed to the wide expression pattern of ciliary proteins. However, little is known about the molecular mechanisms leading to this dramatic diversity of phenotypes.