Conceivable difference in the anti-inflammatory mechanisms of lipocortins 1 and 5

Human recombinant lipocortins (LCT) 1 and 5 have been expressed in a yeast secretion vector and purified by ion exchange chromatography. The action of the proteins has been investigated in two models of experimental acute inflammation in the rat: carrageenin induced paw oedema and zymosan induced pleurisy. The effects of the proteins on PGE2 release in vitro by rat macrophages stimulated with zymosan and on rat neutrophil chemotaxis induced by FMLP have also been assessed. LCT-1 significantly inhibited both paw swelling in carrageenin oedema and leukocyte migration in zymosan pleurisy. Moreover it showed a dose dependent, inhibitory effect on PGE2 release. Neutrophil chemotaxis was only weakly affected by LCT-1. Conversely LCT-5 did not reduce carrageenin oedema and slightly inhibited PGE2 release, but showed profound, dose dependent inhibitory activity on leukocyte migration in zymosan pleurisy and on neutrophil chemotaxis. These data suggest that LCT-1 acts mainly by interfering with arachidonic acid metabolism via the inhibition of phospholipase A2. The anti-inflammatory activity of LCT-5, at variance with LCT-1, may be due to a direct effect on cell motility in addition to the interference with arachidonic acid metabolism

Induction of annexin-1 at transcriptional and posttranscriptional level in rat brain by methylprednisolone and the 21-aminosteroid U74389F

Jan Kornelis de Cock-Foundation

MV-MS-FETE: Multi-view multi-scale feature extractor and transformer encoder for stenosis recognition in echocardiograms

Background: aortic stenosis is a common heart valve disease that mainly affects older people in developed countries. Its early detection is crucial to prevent the irreversible disease progression and, eventually, death. A typical screening technique to detect stenosis uses echocardiograms; however, variations introduced by other tissues, camera movements, and uneven lighting can hamper the visual inspection, leading to misdiagnosis. To address these issues, effective solutions involve employing deep learning algorithms to assist clinicians in detecting and classifying stenosis by developing models that can predict this pathology from single heart views. Although promising, the visual information conveyed by a single image may not be sufficient for an accurate diagnosis, especially when using an automatic system; thus, this indicates that different solutions should be explored. Methodology: following this rationale, this paper proposes a novel deep learning architecture, composed of a multi-view, multi-scale feature extractor, and a transformer encoder (MV-MS-FETE) to predict stenosis from parasternal long and short-axis views. In particular, starting from the latter, the designed model extracts relevant features at multiple scales along its feature extractor component and takes advantage of a transformer encoder to perform the final classification. Results: experiments were performed on the recently released Tufts medical echocardiogram public dataset, which comprises 27,788 images split into training, validation, and test sets. Due to the recent release of this collection, tests were also conducted on several state-of-the-art models to create multi-view and single-view benchmarks. For all models, standard classification metrics were computed (e.g., precision, F1-score). The obtained results show that the proposed approach outperforms other multi-view methods in terms of accuracy and F1-score and has more stable performance throughout the training procedure. Furthermore, the experiments also highlight that multi-view methods generally perform better than their single-view counterparts. Conclusion: this paper introduces a novel multi-view and multi-scale model for aortic stenosis recognition, as well as three benchmarks to evaluate it, effectively providing multi-view and single-view comparisons that fully highlight the model's effectiveness in aiding clinicians in performing diagnoses while also producing several baselines for the aortic stenosis recognition task

Induction of annexin-1 during TRAIL-induced apoptosis in thyroid carcinoma cells

We investigated the expression of annexin-1 (ANXA1) in thyroid carcinoma cell lines and in thyroid cancers with a different degree of differentiation. The highest level of ANXA1 expression examined by Western blotting was detected in the papillary carcinoma cells (NPA) and in the follicular cells (WRO). On the other hand, the most undifferentiated thyroid carcinoma cells (ARO and FRO) presented the lowest level of ANXA1 expression. In surgical tissue specimens from 32 patients with thyroid cancers, we found high immunoreactivity for ANXA1 in papillary (PTC) and follicular (FTC) thyroid cancers while in undifferentiated thyroid cancers (UTC) the expression of the protein was barely detectable. Control thyroid tissue resulted positive for ANXA1. In summary, 70% of UTC examined weakly expressed ANXA1, whereas 65% of PTC or FTC specimens tested showed high expression of the protein. Thus ANXA1 expression may correlate with the tumorigenesis suggesting that the protein may represent an effective differentiation marker in thyroid cancer

The Effect of Steroid Treatment on Lipocortin Immunoreactivity of Rat Brain

Lipocortin-1, lipocortin-2 and lipocortin-5 were immunohistochemically assessed in rats. Apart from animals receiving no treatment, other animals received pretreatment with methylprednisolone, or the 21-aminosteroid U-74389F. Whereas Hpocortin immunoreactivity was absent in the greater part of the brain in animals not pretreated with steroid (except in sporadic microglial cells and choroid plexus), there was obvious immunostaining of parenchymatous elements in steroid pretreated animals. In the steroid pretreated animals lipocortin immunoreactivity of the brain tissue may indicate local formation of lipocortin under the influence of steroids that had entered the tissue. The cellular elements which showed immunostaining included meningeal cells, neurones, ependyma, oligodendroglia and capillary endotheHum

Induction of annexin-1 at transcriptional and post-transcriptional level in rat brain by methylprednisolone and the 21-aminosteroid U74389F

Brain tissue of rats pretreated with methylprednisolone or with the 21-aminosteroid U74389F, and that of untreated control rats, was assessed for the expression of annexin-1 (Anx-1) and the transcription of its mRNA. For this purpose Anx-1 cDNA was amplified and simultaneously a T7-RNA-polymerase promoter was incorporated into the cDNA using a polymerase chain reaction (PCR). Then digoxigenin-11-UTP was incorporated into the transcribed cRNA with T7-RNA-polymerase. With this probe in situ hybridization was carried out on sections of the brain. The probe was visualized by an immunoassay using an antidigoxigenin antibody conjugate. Anx-1 protein was assessed by means of immunohistochemistry using a polyclonal antibody. The various brain areas of the control animals showed an appreciable amount of Anx-1 at mRNA or protein level; on the other hand, the animals which had been pretreated with either steroid, showed a more intense Anx-1 mRNA signal than the controls in many areas. In the pretreated animals Anx-1 immunostaining was unchanged in cortex, basal ganglia, amygdala and septum, but more intense in hippocampus, hypothalamus and thalamus. In ependyma, choroid plexus, meninges, and vascular walls there was no Anx-1 mRNA transcription detectable. An opposite profile was shown by the Anx-1 immunoreactivity, the protein was present in control animals as well as the steroid-pretreated animals, suggesting that here the protein was either from systemic origin, or has diffused from adjacent structures. The results indicated that Anx-1 mRNA transcription is upregulated by either steroid, and that in the untreated animals there is a resting level of Anx-1 mRNA transcription, presumably reflecting physiological influences on Anx-1 expression