Linoleic acid increases monocyte chemotaxis and adhesion to human aortic endothelial cells through protein kinase C- and cyclooxygenase-2-dependent mechanisms

The effects of polyunsaturated n-6 linoleic acid on monocyte-endothelial interactions were investigated with particular emphasis on the expression of platelet/endothelial cell adhesion molecule (PECAM)-1 and the role of protein kinase C (PKC) and cyclooxygenase-2 (COX-2). As a diet rich in polyunsaturated fatty acids may favour atherosclerosis in hyperglycaemia, this study was performed in both normal and high-glucose media using human aortic endothelial cells (HAEC). The HAEC were preincubated with normal (5 mM) or high (25 mM) d-glucose for 3 days before addition of fatty acids (0.2 mM) for 3 days. Linoleic acid enhanced PECAM-1 expression independently of tumor necrosis factor (TNF)-a and significantly increased TNF-a-induced monocyte adhesion to HAEC in comparison to the monounsaturated n-9 oleic acid. Chronic glucose treatment (25 mM, 6 days) did not modify the TNF-a-induced or fatty acid-induced changes in monocyte binding. The increase in monocyte binding was accompanied by a significant increase in E-selectin and vascular cell adhesion molecule (VCAM)-1 expression and could be abrogated by an interleukin (IL)-8 neutralising antibody and by the PKC and COX inhibitors. Inhibition of PKC-d reduced VCAM-1 expression regardless of experimental condition and was accompanied by a significant decrease in monocyte binding. Conditioned medium from linoleic acid-treated HAEC grown in normal glucose conditions significantly increased THP-1 chemotaxis. These results suggest that linoleic acid-induced changes in monocyte chemotaxis and subsequent binding are not solely mediated by changes in adhesion molecule expression but may be due to secreted factors such as IL-8, monocyte chemoattractant protein-1 or prostaglandins (PGs) such as PGE2, as IL-8 neutralisation and COX-2 inhibition reduced monocyte binding without changes in adhesion molecule expression.

PIM-1 kinase expression in adipocytic neoplasms: diagnostic and biological implications

The differential diagnosis of soft tissue tumours poses a considerable challenge for pathologists, especially adipocytic tumours, as these may show considerable overlap in clinical presentation and morphological features with many other mesenchymal neoplasms. Hence, a specific and reliable marker that identifies adipocytic differentiation is much sought. We investigated the immunohistochemical expression of PIM-1 kinase in 35 samples of soft tissue tumours using tissue microarray technology and 49 full sections of adipocytic (n = 26) and non-adipocytic tumours (n = 23). Benign and malignant adipocytic tumours showed strong expression of PIM-1 while the non-adipocytic tumours were either negative or showed only weak staining for the protein. In myxoid liposarcomas, PIM-1 showed a distinct, unique vacuolar staining pattern, clearly outlining fine cytoplasmic lipid vacuoles. By contrast, non-adipocytic myxoid tumours (myxoma, chordoma and myxoid chondrosarcoma) did not show this vacuolar pattern of PIM-1 staining, although vacuolated cells were present on H&E. This differential expression was confirmed at a gene expression level in selected cases. Our results indicate that the expression of PIM-1 in adipose tissue may be a useful marker of adipocytic differentiation, in particular if the staining is both of high intensity and present in a unique, vacuolar pattern.

Potential roles for the PIM1 kinase in human cancer - A molecular and therapeutic appraisal

In vitro experiments have shown the PIM1 kinase to have diverse biological roles in cell survival, proliferation and differentiation. In humans, PIM1 is often expressed in both normal and transformed cells. The PIM1 kinase is a true oncogene implicated in early transformation and tumour progression in haematopoietic malignancies and prostate carcinomas. it is associated with aggressive subgroups of lymphoma, is a marker of poor prognosis in prostate carcinomas and has been suggested to have a role in hormone insensitivity of prostate malignancies. PIM1 has a possible role in other carcinomas with 6p21 genomic alterations. On one hand, PIM1 (due to its role in malignancy) appears to be a promising target for drug development programmes but, on the other hand, the complexity of its molecular structure has posed challenges in the development of PIM1 inhibitors. In this review we discuss PIM1 expression in human tissues (including some new data from our laboratory), its role in human malignancies, as well as the possibilities and challenges in the development of target therapy for PIM1. (c) 2008 Elsevier Ltd. All rights reserved.

N1, P2 and T-complex of the auditory brain event-related potentials to tones with varying rise times in adults with and without dyslexia

Dyslexia is a learning difficulty affecting the acquisition of fluent reading and spelling skills due to poor phonological processing. Underlying deficits in processing sound rise time have also been found in children and adults with dyslexia. However, the neural basis for these deficits is unknown. In the present study event-related potentials were used to index neural processing and examine the effect of rise time manipulation on the obligatory N1. T-complex and P2 responses in English speaking adults with and without dyslexia. The Tb wave of the T-complex showed differences between groups, with the amplitudes for Tb becoming less negative with increased rise time for the participants with dyslexia only. Frontocentral N1 and P2 did not show group effects. Enhanced Tb amplitude that is modulated by rise time could indicate altered neural networks at the lateral surface of the superior temporal gyrus in adults with dyslexia. (C) 2011 Elsevier B.V. All rights reserved.

The causal attributions of nursing students towards adolescent survivors of brain injury

Background: The hidden nature of brain injury means that it is often difficult for people to understand the sometimes challenging behaviors that individuals exhibit. The misattribution of these behaviors may lead to a lack of consideration and public censure if the individual is seen as simply misbehaving.

Objective: The aim of this study was to explore the impact of visual cues indicating the presence or absence of brain injury on prejudice, desire for social interaction, and causal attributions of nursing and computing science students.

Method: An independent-groups design was employed in this research, which recruited 190 first-year nursing students and 194 first-year computing science students from a major university in Belfast, UK. A short passage describing an adolescent’s behavior after a brain injury, together with one of three images portraying a young adolescent with a scar, a head dressing, or neither of these, was given to participants. They were then asked to answer questions relating to prejudice, social interaction, locus of control, and causal attributions. The attributional statements suggested that the character’s behavior could be the result of brain injury or adolescence.

Results: Analysis of variance demonstrated a statistically significant difference between the student groups, where nursing students (M = 45.17, SD = 4.69) desired more social interaction with the fictional adolescent than their computer science peers (M = 38.64, SD = 7.69). Further, analysis of variance showed a main effect of image on the attributional statement that described adolescence as a suitable explanation for the character’s lack of self-confidence.

Discussion: Attributions of brain injury were influenced by the presence of a visible but potentially specious indicator of injury. This suggests that survivors of brain injury who do not display any outward indicator may receive less care and face expectations to behave in a manner consistent with the norms of society. If their injury does not allow them to meet with these expectations, they may face public censure and discrimination.