Biochemical characterization of plasma membrane isolated from human skeletal muscle

AbstractSpecific components of ion translocation systems were studied in excitable plasma membranes isolated from normal human muscle. Na+ - K+ ATPase and ouabain-sensitive K+ phosphatase activities were 8.9 ± 1 μmol Pih per mg protein and 96 ± 9 nmolmin per mg protein, respectively. Scatchard analysis of equilibrium binding assays with [3H]ouabain showed non-linear curves consistent with high- and low-affinity sites (estimated Kd 3 nM and 0.22 μM). Two families of receptors with different affinities for a tritiated TTX derivative (estimated Kd 0.4 and 4 nM) were also identified suggesting the existence in human muscle of at least two classes of voltage-dependent Na+ channels. In addition (+)-[methyl-3H]PN200-110, a potent Ca2+ antagonist used for labeling voltage-dependent Ca2+ channels, was observed to bind to a homogeneous population of receptors in the plasma membrane (Kd = 0.2 nM)

How to quantify bilingual experience? Findings from a Delphi consensus survey

While most investigations of bilingualism document participants’ language background, there is an absence of consensus on how to quantify bilingualism. The high number of different language background questionnaires used by researchers and practitioners jeopardises data comparability and cross-pollination between research and practice. Using the Delphi consensus survey method, we asked 132 panellists (researchers, speech and language therapists, teachers) from 29 countries to rate 124 statements on a 5-point agreement scale. Consensus was pre-defined as 75% agreement threshold. After two survey rounds, 79% of statements reached consensus. The need for common measures to quantify bilingualism was acknowledged by 96% of respondents. Agreement was reached to document: language exposure and use, language difficulties, proficiency (when it cannot be assessed directly), education and literacy, input quality, language mixing practices, and attitudes (towards languages and language mixing). We discuss the implications of these findings for the creation of a new tool to quantify bilingual experience

Exploring the patient journey to diagnosis of Gaucher disease from the perspective of 212 patients with Gaucher disease and 16 Gaucher expert physicians

Gaucher disease (GD) is a rare hereditary disorder caused by a deficiency of the lysosomal enzyme β-glucocerebrosidase. Diagnosis is challenging owing to a wide variability in clinical manifestations and severity of symptoms. Many patients may experience marked delays in obtaining a definitive diagnosis. The two surveys reported herein aimed to explore the patient journey to diagnosis of GD from the perspectives of Gaucher expert physicians and patients. Findings from the surveys revealed that many patients experienced diagnostic delays and misdiagnoses, with nearly 1 in 6 patients stating that they were not diagnosed with GD for 7years or more after first consulting a doctor. Physicians and patients both reported multiple referrals to different specialties before a diagnosis of GD was obtained, with primary care, haematology/haematology-oncology and paediatrics the main specialties to which patients first presented. Splenomegaly, thrombocytopenia, anaemia and bone pain were reported as the most common medical problems at first presentation in both surveys. These findings support a clear need for straightforward and easy-to-follow guidance designed to assist non-specialists to identify earlier patients who are at risk of GD

Unusual manifestation of Erdheim-Chester disease

<p>Abstract</p> <p>Background</p> <p>Erdheim-Chester disease (ECD) is a rare multisystem non-Langerhans cell histiocytosis that is characterized histologically by xanthogranulomatous infiltrates and radiologically by symmetrical sclerosis of long bones. The xanthomatous process is characterized by prominent foamy histiocytes staining positive for CD68, occasionally for PS100 and negative for S100 and CD1a. Gastroenterological involvement is exceedingly rare.</p> <p>Case Presentation</p> <p>This case report describes the case of a 69-year-old man who presented otherwise well to the gastroenterology department with unspecific abdominal symptoms, nausea, vomiting and weight loss. ECD involving the gastrointestinal tract was confirmed clinically, radiologically and histologically.</p> <p>Conclusion</p> <p>Gastroenterological manifestation of ECD is rare but should be considered in the differential diagnosis in patients presenting with evidence of multi-organ disease and typical radiological features of Erdheim-Chester disease elsewhere.</p

Anti-hLAMP2-antibodies and dual positivity for anti-GBM and MPO-ANCA in a patient with relapsing pulmonary-renal syndrome

Background Pulmonary-renal syndrome associated with anti-glomerular basement membrane (GBM) antibodies, also known as Goodpasture's syndrome, is a rare but acute and life-threatening condition. One third of patients presenting as anti-GBM antibody positive pulmonary-renal syndrome or rapidly progressive glomerulonephritis are also tested positive for anti-neutrophil cytoplasmic antibodies (ANCA). Whilst anti-GBM disease is considered a non-relapsing condition, the long-term course of double-positive patients is less predictable. Case Presentation We report a patient with such dual positivity, who presented with pulmonary hemorrhage, crescentic glomerulonephritis and membranous nephropathy. Plasmapheresis in combination with immunosuppresive therapy led to a rapid remission but the disease relapsed after two years. The serum of the patient was tested positive for antibodies to human lysosomal membrane protein 2 (hLAMP2), a novel autoantigen in patients with active small-vessel vasculitis (SVV). The anti-hLAMP2 antibody levels correlated positively with clinical disease activity in this patient. Conclusion We hypothesize that this antibody may indicate a clinical course similar to ANCA-associated vasculitis in double-positive patients. However, this needs to be confirmed on comprehensive patient cohorts

Linguistic foundations of heritage language development from the perspective of romance languages in Germany

This paper discusses the role of different factors determining the linguistic competence of heritage speakers (HSs) based on examples from speakers who speak a Romance language (French, Italian, Portuguese, or Spanish) as heritage language (HL) and German as the environmental language. Since the relative amount of contact with the HL and the environmental language may vary during the acquisition process, the role of language dominance (in terms of relative language proficiency) is of particular interest for HL development. In addition to dominance (and related to it), cross-linguistic influence (CLI) may have an influence on the outcome of HL acquisition. Finally, quality and quantity of input also determine HL acquisition and will be discussed in connection with heritage language education.info:eu-repo/semantics/publishedVersio

Management goals for type 1 Gaucher disease: An expert consensus document from the European working group on Gaucher disease

AbstractGaucher Disease type 1 (GD1) is a lysosomal disorder that affects many systems. Therapy improves the principal manifestations of the condition and, as a consequence, many patients show a modified phenotype which reflects manifestations of their disease that are refractory to treatment. More generally, it is increasingly recognised that information as to how a patient feels and functions [obtained by patient- reported outcome measurements (PROMs)] is critical to any comprehensive evaluation of treatment. A new set of management goals for GD1 in which both trends are reflected is needed. To this end, a modified Delphi procedure among 25 experts was performed. Based on a literature review and with input from patients, 65 potential goals were formulated as statements. Consensus was considered to be reached when ≥75% of the participants agreed to include that specific statement in the management goals. There was agreement on 42 statements. In addition to the traditional goals concerning haematological, visceral and bone manifestations, improvement in quality of life, fatigue and social participation, as well as early detection of long-term complications or associated diseases were included. When applying this set of goals in medical practice, the clinical status of the individual patient should be taken into account

Neuromuscular imaging in inherited muscle diseases

Driven by increasing numbers of newly identified genetic defects and new insights into the field of inherited muscle diseases, neuromuscular imaging in general and magnetic resonance imaging (MRI) in particular are increasingly being used to characterise the severity and pattern of muscle involvement. Although muscle biopsy is still the gold standard for the establishment of the definitive diagnosis, muscular imaging is an important diagnostic tool for the detection and quantification of dystrophic changes during the clinical workup of patients with hereditary muscle diseases. MRI is frequently used to describe muscle involvement patterns, which aids in narrowing of the differential diagnosis and distinguishing between dystrophic and non-dystrophic diseases. Recent work has demonstrated the usefulness of muscle imaging for the detection of specific congenital myopathies, mainly for the identification of the underlying genetic defect in core and centronuclear myopathies. Muscle imaging demonstrates characteristic patterns, which can be helpful for the differentiation of individual limb girdle muscular dystrophies. The aim of this review is to give a comprehensive overview of current methods and applications as well as future perspectives in the field of neuromuscular imaging in inherited muscle diseases. We also provide diagnostic algorithms that might guide us through the differential diagnosis in hereditary myopathies