| 1. |
- Terhal, Paulien A., et al.
(författare)
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A Study of the Clinical and Radiological Features in a Cohort of 93 Patients with a COL2A1 Mutation Causing Spondyloepiphyseal Dysplasia Congenita or a Related Phenotype
- 2015
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Ingår i: American Journal of Medical Genetics. Part A. - : Wiley. - 1552-4825 .- 1552-4833. ; 167A:3, s. 461-475
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Tidskriftsartikel (refereegranskat)abstract
- Type 2 collagen disorders encompass a diverse group of skeletal dysplasias that are commonly associated with orthopedic, ocular, and hearing problems. However, the frequency of many clinical features has never been determined. We retrospectively investigated the clinical, radiological, and genotypic data in a group of 93 patients with molecularly confirmed SEDC or a related disorder. The majority of the patients (80/93) had short stature, with radiological features of SEDC (n=64), others having SEMD (n=5), Kniest dysplasia (n=7), spondyloperipheral dysplasia (n=2), or Torrance-like dysplasia (n=2). The remaining 13 patients had normal stature with mild SED, Stickler-like syndrome or multiple epiphyseal dysplasia. Over 50% of the patients had undergone orthopedic surgery, usually for scoliosis, femoral osteotomy or hip replacement. Odontoid hypoplasia was present in 56% (95% CI 38-74) and a correlation between odontoid hypoplasia and short stature was observed. Atlanto-axial instability, was observed in 5 of the 18 patients (28%, 95% CI 10-54) in whom flexion-extension films of the cervical spine were available; however, it was rarely accompanied by myelopathy. Myopia was found in 45% (95% CI 35-56), and retinal detachment had occurred in 12% (95% CI 6-21; median age 14 years; youngest age 3.5 years). Thirty-two patients complained of hearing loss (37%, 95% CI 27-48) of whom 17 required hearing aids. The ophthalmological features and possibly also hearing loss are often relatively frequent and severe in patients with splicing mutations. Based on clinical findings, age at onset and genotype-phenotype correlations in this cohort, we propose guidelines for the management and follow-up in this group of disorders.
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| 2. |
- Eckhardt, CL, et al.
(författare)
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Factor VIII gene (F8) mutation and risk of inhibitor development in nonsevere hemophilia A
- 2013
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 122:11, s. 1954-1962
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Tidskriftsartikel (refereegranskat)abstract
- The inhibitor incidence in nonsevere hemophilia A patients with certain F8 mutations approaches the inhibitor incidence in severe patients. These findings are highly relevant for clinical practice, as they facilitate identification of high-risk patients based on F8 genotype.
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| 3. |
- Van de Bovenkamp, Jeroen H, et al.
(författare)
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The MUC5AC glycoprotein is the primary receptor for Helicobacter pylori in the human stomach
- 2003
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Ingår i: Helicobacter. - : Wiley. - 1083-4389 .- 1523-5378. ; 8:5, s. 521-532
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Tidskriftsartikel (refereegranskat)abstract
- Background and objectives. Helicobacter pylori shows a characteristic tropism for the mucusproducing gastric epithelium. In infected patients, H. pylori colocalizes in situ with the gastric secretory mucin MUC5AC. The carbohydrate blood-group antigen Lewis B (LeB) was deemed responsible for the adherence of H. pylori to the gastric surface epithelium. We sought to determine if MUC5AC is the carrier of LeB, and thus if MUC5AC is the underlying gene product functioning as the main receptor for H. pylori in the stomach. Methods. We studied three types of human tissue producing MUC5AC: Barrett’s esophagus (BE), normal gastric tissue, and gastric metaplasia of the duodenum (GMD). Tissue sections were immunofluorescently stained for MUC5AC or LeB, and subsequently incubated with one of three strains of Texas red-labeled H. pylori , one of which was unable to bind to LeB. We determined the colocalization of MUC5AC or LeB with adherent H. pylori. Results. The binding patterns for the two LeBbinding strains to all tissues were similar, whereas the strain unable to bind to LeB did not bind to any of the tissues. In normal gastric tissue, the LeBbinding strains always bound to MUC5AC- and LeBpositive epithelial cells. In four nonsecretor patients, colocalization of the LeB-binding strains was found to MUC5AC-positive gastric epithelial cells. In BE, the LeB-binding H. pylori strains colocalized very specifically to MUC5AC-positive cells. MUC5ACproducing cells in GMD contained LeB. Yet, LeBbinding H. pylori not only colocalized to MUC5AC or LeB present in GMD, but also bound to the LeBpositive brush border of normal duodenal epithelium. Conclusions. Mucin MUC5AC is the most important carrier of the LeB carbohydrate structure in normal gastric tissue and forms the major receptor for H. pylori.
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| 4. |
- Lützenkirchen, Johannes, et al.
(författare)
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Comparison of various models to describe the charge−pH dependence of Poly(acrylic acid)
- 2011
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Ingår i: Journal of Chemical and Engineering Data. - : American Chemical Society. - 0021-9568 .- 1520-5134. ; 56:4, s. 1602-1612
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Tidskriftsartikel (refereegranskat)abstract
- The charge of poly(acrylic acid) (PAA) in dilute aqueous solutions depends on pH and ionic strength. We report new experimental data and test various models to describe the deprotonation of PAA in three different NaCl concentrations. A simple surface complexation approach is found to be very successful: the constant capacitance model requires one pKa value and one capacitance for excellent fits to the data, with both parameters depending on ionic strength. The use of a self-consistent set of diffuse double layer parameters with one pKa for flat, spherical, and cylindrical geometry does not result in a satisfactory description of the data, and a number of adjustments to that model were tested to improve the fit. The basic Stern model (BSM) was tested with both plate and cylinder geometry. The cylinder geometry along with strong electrolyte binding was found to be superior to a similar approach involving weak electrolyte binding both in terms of goodness of fit and self-consistency of the parameters. The third approach, the non-ideal competitive consistent adsorption-Donnan (NICCA-Donnan) model, involving one functional group, allows an excellent description of the experimental data. Finally, the polyacid chain was modeled using a mechanistically more realistic self-consistent field (SCF) approach, which allows for radially inhomogeneous distributions of the charges and radial variations in the polymer density and electrostatic potential, while the functional groups can be in protonated, deprotonated, or complexed states. One functional group was insufficient for a satisfactory description of the data. With two segments (one monoprotic, the other diprotic) a reasonable description of the data, including the ionic strength dependence, is achieved, and the tendency of the size of the macro-ion with pH and ionic strength is as expected. This model has the fewest adjustable parameters and is considered the most realistic and comprehensive among the models tested.
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