Search results for "cytoskeletal proteins"
showing 10 items of 119 documents
5th generation vs 4th generation troponin T in predicting major adverse cardiovascular events and all-cause mortality in patients hospitalized for no…
2020
Objective The frequency and implications of an elevated cardiac troponin (4th or 5th generation TnT) in patients outside of the emergency department or presenting with non-cardiac conditions is unclear. Methods Consecutive patients aged 18 years or older admitted for a primary non-cardiac condition who had the 4th generation TnT drawn had the 5th generation TnT run on the residual blood sample. Primary and secondary outcomes were all-cause mortality (ACM) and major adverse cardiovascular events (MACE) respectively at 1 year. Results 918 patients were included (mean age 59.8 years, 55% male) in the cohort. 69% had elevated 5th generation TnT while 46% had elevated 4th generation TnT. 5th ge…
Expanding the clinical spectrum of COL1A1 mutations in different forms of glaucoma
2016
Background Primary congenital glaucoma (PCG) and early onset glaucomas are one of the major causes of children and young adult blindness worldwide. Both autosomal recessive and dominant inheritance have been described with involvement of several genes including CYP1B1, FOXC1, PITX2, MYOC and PAX6. However, mutations in these genes explain only a small fraction of cases suggesting the presence of further candidate genes. Methods To elucidate further genetic causes of these conditions whole exome sequencing (WES) was performed in an Italian patient, diagnosed with PCG and retinal detachment, and his unaffected parents. Sanger sequencing of the complete coding region of COL1A1 was performed in…
Loss of desmoglein 2 suggests essential functions for early embryonic development and proliferation of embryonal stem cells.
2002
Summary Desmoglein 2 (Dsg2) is a Ca 2+ -dependent adhesion molecule of desmosomes and is synthesized in all desmosome-bearing tissues from their earliest appearance onward. To examine the function of Dsg2, its gene was inactivated by homologous recombination in embryonal stem (ES) cells for the generation of knockout mice. DSG2 −/− mice and a considerable number of DSG2 +/− mice died at or shortly after implantation. On the other hand, DSG2 −/− blastocysts developed an apparently normal trophectoderm layer, the first tissue known to produce desmosomes, and hatched properly. Immunofluorescence analyses of these blastocysts showed, however, that the distribution of the desmosomal plaque prote…
Rare variants in the genetic background modulate cognitive and developmental phenotypes in individuals carrying disease-associated variants
2019
Purpose: To assess the contribution of rare variants in the genetic background toward variability of neurodevelopmental phenotypes in individuals with rare copy-number variants (CNVs) and gene-disruptive variants. Methods: We analyzed quantitative clinical information, exome sequencing, and microarray data from 757 probands and 233 parents and siblings who carry disease-associated variants. Results: The number of rare likely deleterious variants in functionally intolerant genes (“other hits”) correlated with expression of neurodevelopmental phenotypes in probands with 16p12.1 deletion (n=23, p=0.004) and in autism probands carrying gene-disruptive variants (n=184, p=0.03) compared with thei…
Establishment and Characterization of Two Merkel Cell Tumor Cultures
1994
Two Merkel cell tumor cultures (MC-MA1, MC-MA2) have been established from metastases of typical Merkel cell tumors. The mestastases in vivo were characterized by co-expression of cytokeratins 8, 18, 19, 20 and neurofilaments, presence of intermediate filament whirls, expression of synaptophysin, neuron-specific enolase, and chromogranin A, rare and weak immunostaining for plakoglobin but absence of cadherins and desmoplakins. Both cultures grow, using supplemented RPMI medium on human irradiated fibroblast feeder layers, as loosely arranged floating small aggregates. Their karyotypes are mostly hyperdiploid. The mean doubling times were about 84 h in the first 8 months and later increased.…
GDF-15 predicts cardiovascular events in acute chest pain patients
2017
Background Treatment of patients presenting with possible acute myocardial infarction (AMI) is based on timely diagnosis and proper risk stratification aided by biomarkers. We aimed at evaluating the predictive value of GDF-15 in patients presenting with symptoms suggestive of AMI. Methods Consecutive patients presenting with suspected AMI were enrolled in three study centers. Cardiovascular events were assessed during a follow-up period of 6 months with a combined endpoint of death or MI. Results From the 1818 enrolled patients (m/f = 1208/610), 413 (22.7%) had an acute MI and 63 patients reached the combined endpoint. Patients with MI and patients with adverse outcome had higher GDF-15 le…
A comparative evaluation of NB30, NB54 and PTC124 in translational read-through efficacy for treatment of an USH1C nonsense mutation
2012
Translational read-through-inducing drugs (TRIDs) promote read-through of nonsense mutations, placing them in the spotlight of current gene-based therapeutic research. Here, we compare for the first time the relative efficacies of new-generation aminoglycosides NB30, NB54 and the chemical compound PTC124 on retinal toxicity and read-through efficacy of a nonsense mutation in the USH1C gene, which encodes the scaffold protein harmonin. This mutation causes the human Usher syndrome, the most common form of inherited deaf-blindness. We quantify read-through efficacy of the TRIDs in cell culture and show the restoration of harmonin function. We do not observe significant differences in the read…
Proteomic Analysis of Protein Components in Periodontal Ligament Fibroblasts
2005
BACKGROUND: Characterization of periodontal ligament (PDL) fibroblast proteome is an important tool for understanding PDL physiology and regulation and for identifying disease-related protein markers. PDL fibroblast protein expression has been studied using immunological methods, although limited to previously identified proteins for which specific antibodies are available. METHODS: We applied proteomic analysis coupled with mass spectrometry and database knowledge to human PDL fibroblasts. RESULTS: We detected 900 spots and identified 117 protein spots originating in 74 different genes. In addition to scaffold cytoskeletal proteins, e.g., actin, tubulin, and vimentin, we identified protein…
Effect of mountain ultramarathon distance competition on biochemical variables, respiratory and lower-limb fatigue
2020
The study aimed at assessing the acute physiological effects of running a 65-km vs a 107- km mountain ultramarathon. Nineteen athletes (15 males and 4 females) from the shorter race and forty three athletes (26 males and 17 females) from the longer race were enrolled. Body weight, respiratory and lower limb strength were assessed before and after the race. Blood samples were obtained before, after and 24-h post-race. Body weight loss did not differ between races. A decrease in squat jump height (p<0.01; d = 1.4), forced vital capacity (p<0.01; d = 0.5), forced expiratory volume in 1 s (p<0.01; d = 0.6), peak inspiratory flow (p<0.01; d = 0.6) and maximal inspiratory pressure (p<0.01; d = 0.…
Specific release of membrane-bound annexin II and cortical cytoskeletal elements by sequestration of membrane cholesterol
1997
Annexin II is an abundant protein which is present in the cytosol and on the cytoplasmic face of plasma membrane and early endosomes. It is generally believed that this association occurs via Ca(2+)-dependent binding to lipids, a mechanism typical for the annexin protein family. Although previous studies have shown that annexin II is involved in early endosome dynamics and organization, the precise biological role of the protein is unknown. In this study, we found that approximately 50% of the total cellular annexin was associated with membranes in a Ca(2+)-independent manner. This binding was extremely tight, since it resisted high salt and, to some extent, high pH treatments. We found, h…