111 research outputs found
Neurofibromatosis type 2 protein co-localizes with elements of the cytoskeleton
The product of the neurofibromatosis type 2 (NF2) tumor suppressor gene is a 595-amino-acid protein bearing resemblance to a family of band-4.1-related proteins. These proteins, including ezrin, radixin, and moesin, probably function as molecular linking proteins, connecting the cytoskeleton to the cell membrane. On the grounds of the homology to the ezrin, radixin, and moesin proteins and on the basis of its predicted secondary structure, the NF2 protein is also thought to act as a cytoskeleton-cell membrane linking protein. Using monoclonal antibodies to amino- and carboxyl-terminal synthetic NF2 peptides we demonstrate the co-localization of the NF2 protein with elements of the cytoskeleton in a COS cell model system and in cultured human cells. Furthermore, the presence of the NF2 protein in tissue sections is shown. The monoclonal antibodies specifically stain smooth muscle cells and the stratum granulosum of the human epidermis. In cultured smooth muscle cells the NF2 protein co-localizes with actin stress fibers. Immunoelectron microscopy demonstrates the presence of the NF2 protein associated with keratohyalin granules and to a lesser extent with intermediate filaments in the human epidermis. We conclude that the NF2 protein is indeed associated with multiple elements of the cytoskeleton.</p
The somatostatin analog Sandostatin (SMS201-995) in treatment of DMBA-induced rat mammary tumors
The effects of treatment with a somatostatin analog (Sandostatin, SMS201-995) were investigated in female rats with dimethylbenzanthracene(DMBA)-induced rat mammary tumors. A 3-week treatment was performed using sandostatin, the LHRH-agonist buserelin alone, or buserelin in combination with sandostatin. Twice daily sandostatin treatment was performed with dosages of 0.05 μg, 0.2 μg, 1 μg, 5 μg, and 20 μg. Buserelin was used in a 2 × 5 μg/day dosage. The combined results from six different experiments show that the various dosages of sandostatin caused no tumor growth inhibition. Somatostatin receptors could not be demonstrated in these mammary tumors. Sandostatin treatment by daily injections did not suppress levels of growth hormone, prolactin, or epidermal growth factor-like activities. Estrogen (ER) and progest
CD4+FOXP3+ regulatory T cells are abundantly present in inflamed muscle of patients with juvenile dermatomyositis
Down syndrome and aberrant right subclavian artery
Down syndrome (DS) may be associated with various organ system disorders. Feeding problems are frequent in children with DS and may be caused by associated defects, including congenital heart defects, gastrointestinal defects, or endocrine disorders. In the absence of these associated conditions, feeding problems are often attributed to general hypotonia. However, an aberrant right subclavian artery (ARSA), a rare vascular anomaly and an unusual cause of problems with the passage of solid food through the esophagus, has recently been suggested to occur more frequently in patients with DS. This knowledge is of importance when evaluating feeding difficulties in patients with DS. Additional investigation for identifying an ARSA may be indicated in selected patients. Diagnostic techniques, such as transthoracic echocardiography, barium contrast esophagram, angiography, or computed tomography–angiography (CT) can be used in a diagnostic flow chart. The presence of ARSA is not synonymous to the cause of feeding problems in patients with DS and corrective surgery of this vascular anomaly should be restricted to selected cases
Complete sequencing of TP53 predicts poor response to systemic therapy of advanced breast cancer
TP53 has been implicated in regulation of the cell cycle, DNA repair, and
apoptosis. We studied, in primary breast tumors through direct cDNA
sequencing of exons 2-11, whether TP53 gene mutations can predict response
in patients with advanced disease to either first-line tamoxifen therapy
(202 patients, of whom 55% responded) or up-front (poly)chemotherapy (41
patients, of whom 46% responded). TP53 mutations were detected in 90 of
243 (37%) tumors, and one-fourth of these mutations resulted in a
premature termination of the protein. The mutations were observed in 32%
(65 of 202) of the primary tumors of tamoxifen-treated patients and in 61%
(25 of 41) of the primary tumors of the chemotherapy patients. TP53
mutation was significantly associated with a poor response to tamoxifen
[31% versu
Interobserver variation in the classification of thymic lesions including biopsies and resection specimens in an international digital microscopy panel
Aims: Thymic tumours are rare in routine pathology
practice. Although the World Health Organization
(WHO) classification describes a number of well-defined categories, the classification remains challenging. The aim of this study was to investigate the
reproducibility of the WHO classification among a
large group of international pathologists with expertise in thymic pathology and by using whole slide
imaging to facilitate rapid diagnostic turnover.
Methods and results: Three hundred and five tumours,
consisting of 90 biopsies and 215 resection specimens,
were reviewed with a panel-based virtual microscopy
approach by a group of 13 pathologists with expertise in
thymic tumours over a period of 6 years. The specimens
were classified according to the WHO 2015 classification.
The data were subjected to statistical analysis, and interobserver concordance (Fleiss kappa) was calculated. All
cases were diagnosed within a time frame of 2 weeks. The
overall level of agreement was substantial (j = 0.6762),
and differed slightly between resection specimens
(j = 0.7281) and biopsies (j = 0.5955). When analysis
was limited to thymomas only, and they were grouped
according to the European Society for Medical Oncology
Clinical Practice Guidelines into B2, B3 versus A, AB, B1
and B3 versus A, AB, B1, B2, the level of agreement
decreased slightly (j = 0.5506 and j = 0.4929, respectively). Difficulties arose in distinguishing thymoma from
thymic carcinoma. Within the thymoma subgroup, difficulties in distinction were seen within the B group.
Conclusions: Agreement in diagnosing thymic lesions
is substantial when they are assessed by pathologists
with experience of these rare tumours. Digital pathology decreases the turnaround time and facilitates
access to what is essentially a multinational resource.
This platform provides a template for de
Smoking cessation and bronchial epithelial remodelling in COPD: a cross-sectional study
<p>Abstract</p> <p>Background</p> <p>Chronic Obstructive Pulmonary Disease (COPD) is associated with bronchial epithelial changes, including squamous cell metaplasia and goblet cell hyperplasia. These features are partially attributed to activation of the epidermal growth factor receptor (EGFR). Whereas smoking cessation reduces respiratory symptoms and lung function decline in COPD, inflammation persists. We determined epithelial proliferation and composition in bronchial biopsies from current and ex-smokers with COPD, and its relation to duration of smoking cessation.</p> <p>Methods</p> <p>114 COPD patients were studied cross-sectionally: 99 males/15 females, age 62 ± 8 years, median 42 pack-years, no corticosteroids, current (n = 72) or ex-smokers (n = 42, median cessation duration 3.5 years), postbronchodilator FEV<sub>1 </sub>63 ± 9% predicted. Squamous cell metaplasia (%), goblet cell (PAS/Alcian Blue<sup>+</sup>) area (%), proliferating (Ki-67<sup>+</sup>) cell numbers (/mm basement membrane), and EGFR expression (%) were measured in intact epithelium of bronchial biopsies.</p> <p>Results</p> <p>Ex-smokers with COPD had significantly less epithelial squamous cell metaplasia, proliferating cell numbers, and a trend towards reduced goblet cell area than current smokers with COPD (p = 0.025, p = 0.001, p = 0.081, respectively), but no significant difference in EGFR expression. Epithelial features were not different between short-term quitters (<3.5 years) and current smokers. Long-term quitters (≥3.5 years) had less goblet cell area than both current smokers and short-term quitters (medians: 7.9% vs. 14.4%, p = 0.005; 7.9% vs. 13.5%, p = 0.008; respectively), and less proliferating cell numbers than current smokers (2.8% vs. 18.6%, p < 0.001).</p> <p>Conclusion</p> <p>Ex-smokers with COPD had less bronchial epithelial remodelling than current smokers, which was only observed after long-term smoking cessation (>3.5 years).</p> <p>Trial registration</p> <p>NCT00158847</p
Multidrug resistance-associated protein-1 (MRP1) genetic variants, MRP1 protein levels and severity of COPD
<p>Abstract</p> <p>Background</p> <p>Multidrug resistance-associated protein-1 (MRP1) protects against oxidative stress and toxic compounds generated by cigarette smoking, which is the main risk factor for chronic obstructive pulmonary disease (COPD). We have previously shown that single nucleotide polymorphisms (SNPs) in <it>MRP1 </it>significantly associate with level of FEV<sub>1 </sub>in two independent population based cohorts. The aim of our study was to assess the associations of <it>MRP1 </it>SNPs with FEV<sub>1 </sub>level, MRP1 protein levels and inflammatory markers in bronchial biopsies and sputum of COPD patients.</p> <p>Methods</p> <p>Five SNPs (rs212093, rs4148382, rs504348, rs4781699, rs35621) in <it>MRP1 </it>were genotyped in 110 COPD patients. The effects of <it>MRP1 </it>SNPs were analyzed using linear regression models.</p> <p>Results</p> <p>One SNP, rs212093 was significantly associated with a higher FEV<sub>1 </sub>level and less airway wall inflammation. Another SNP, rs4148382 was significantly associated with a lower FEV<sub>1 </sub>level, higher number of inflammatory cells in induced sputum and with a higher MRP1 protein level in bronchial biopsies.</p> <p>Conclusions</p> <p>This is the first study linking <it>MRP1 </it>SNPs with lung function and inflammatory markers in COPD patients, suggesting a role of <it>MRP1 </it>SNPs in the severity of COPD in addition to their association with MRP1 protein level in bronchial biopsies.</p
Holmium Nanoparticles: Preparation and In Vitro Characterization of a New Device for Radioablation of Solid Malignancies
# The Author(s) 2010. This article is published with open access at Springerlink.com Purpose The present study introduces the preparation and in vitro characterization of a nanoparticle device comprising holmium acetylacetonate for radioablation of unresectable solid malignancies. Methods HoAcAc nanoparticles were prepared by dissolving holmium acetylacetonate in chloroform, followed by emulsification in an aqueous solution of a surfactant and evaporation of W. Bult: R. Varkevisser: P. R. Luijten: A. D. van het Schip
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