Applying realistic medicine to intrathecal opioid utilisation in Scotland: do we have a standardised approach?

Intrathecal opioids (ITOs) are commonly administered as part of a multimodal anaesthetic strategy for a variety of surgical procedures. The evolution of laparoscopic surgical techniques has seen the popularity of ITOs increase as they are effective, well tolerated and lack the cardiovascular side effects associated with epidural infusions. The risk of delayed respiratory depression remains a concern; therefore, high-quality post-operative monitoring is vital.

FAT1 cadherin is multiply phosphorylated on its ectodomain but phosphorylation is not catalysed by the four-jointed homologue.

The interaction between the Drosophila cadherins fat and dachsous is regulated by phosphorylation of their respective ectodomains, a process catalysed by the atypical kinase four-jointed. Given that many signalling functions are conserved between Drosophila and vertebrate Fat cadherins, we sought to determine whether ectodomain phosphorylation is conserved in FAT1 cadherin, and also whether FJX1, the vertebrate orthologue of four-jointed, was involved in such phosphorylation events. Potential Fj consensus phosphorylation motifs were identified in FAT1 and biochemical experiments revealed the presence of phosphoserine and phosphothreonine residues in its extracellular domain.

Fat1 cadherin provides a novel minimal residual disease marker in acute lymphoblastic leukemia.

Measurement of minimal residual disease (MRD) maintains an important role in the clinical management of acute lymphoblastic leukemia (ALL). Recently, we identified Fat1 cadherin as a unique and independent prognostic factor for relapse-free and overall survival in pediatric pre-B-ALL. Here, we analyzed Fat1 mRNA for its potential as a novel marker of MRD in cases of pre-B- and T-ALL.

Dual processing of FAT1 cadherin protein by human melanoma cells generates distinct protein products.

The giant cadherin FAT1 is one of four vertebrate orthologues of the Drosophila tumor suppressor fat. It engages in several functions, including cell polarity and migration, and in Hippo signaling during development. Homozygous deletions in oral cancer suggest that FAT1 may play a tumor suppressor role, although overexpression of FAT1 has been reported in some other cancers.

Palmitoylation of CD36/FAT regulates the rate of its post-transcriptional processing in the endoplasmic reticulum.

CD36/FAT is a transmembrane glycoprotein that functions in the cellular uptake of long-chain fatty acids and also as a scavenger receptor. As such it plays an important role in lipid homeostasis and, pathophysiologically, in the progression of type 2 diabetes and atherosclerosis. CD36 expression is tightly regulated at the levels of both transcription and translation.

Shed gangliosides provide detergent-independent evidence for type-3 glycosynapses.

Membrane microdomains, or rafts, at the plasma membrane have been invoked to explain many cellular processes. Protein-protein interactions within such microdomains including, for example, the tetraspanin web are reported to provide a scaffold for signal transduction. However, the nature of such protein-protein interactions is not fully elucidated.

CD36 is a receptor for oxidized high density lipoprotein: implications for the development of atherosclerosis.

Atherosclerotic plaques result from the excessive deposition of cholesterol esters derived from lipoproteins and lipoprotein fragments. Tissue macrophage within the intimal space of major arterial vessels have been shown to play an important role in this process. We demonstrate in a transfection system using two human cell lines that the macrophage scavenger receptor CD36 selectively elicited lipid uptake from Cu(2+)-oxidized high density lipoprotein (HDL) but not from native HDL or low density lipoprotein (LDL).

The association between CD36 and Lyn protein tyrosine kinase is mediated by lipid.

CD36 is a transmembrane glycoprotein receptor that engages in signal transduction implicated in important physiological and pathophysiological events. CD36 in platelets has been shown physically and functionally to associate with members of the Src family of protein tyrosine kinases, Fyn, Lyn, and Yes, but the nature of this important association has never been rigorously examined. Here, we show that CD36 does not associate with Lyn through a protein-mediated interaction.

Novel immunoblotting monoclonal antibodies against human and rat CD36/fat used to identify an isoform of CD36 in rat muscle.

CD36, a surface membrane glycoprotein, functions as a class B scavenger receptor that binds to several distinct ligands. Included among these is oxidized low-density lipoprotein (Ox-LDL), a major trigger of atherosclerotic lesions, and the levels of CD36 activity and Ox-LDL uptake may have an impact on coronary artery disease. In addition, recent studies in rodents have shown that CD36, also known as FAT, controls the levels of free fatty acids and triglycerides in plasma, and is an important regulator of the metabolic pathways involved in insulin resistance.

Immunohistological localisation of human FAT1 (hFAT) protein in 326 breast cancers. Does this adhesion molecule have a role in pathogenesis?

Aims: To examine the immunohistological expression in human breast cancers of human FAT1 (hFAT) protein, a recently described member of the cadherin superfamily, and its correlation with histological type and grade.

Methods: A total of 326 cases of invasive and in situ breast cancer representing a broad spectrum of histological subtypes were immunostained with affinity-purified rabbit antibodies produced to the cytoplasmic region of hFAT using a standard avidin-biotin system. Staining intensity was arbitrarily graded on a scale of 0 to 3.

Cloning and expression of the large zebrafish protocadherin gene, Fat.

The cadherin superfamily members play an important role in mediating cell-cell contact and adhesion (Takeichi, M., 1991. Cadherin cell adhesion receptors as a morphogenetic regulator.

The LFA-1-associated molecule PTA-1 (CD226) on T cells forms a dynamic molecular complex with protein 4.1G and human discs large.

Clustering of the T cell integrin, LFA-1, at specialized regions of intercellular contact initiates integrin-mediated adhesion and downstream signaling, events that are necessary for a successful immunological response. But how clustering is achieved and sustained is not known. Here we establish that an LFA-1-associated molecule, PTA-1, is localized to membrane rafts and binds the carboxyl-terminal domain of isoforms of the actin-binding protein 4.

The role of the Eph-ephrin signalling system in the regulation of developmental patterning.

The Eph and ephrin system, consisting of fourteen Eph receptor tyrosine kinase proteins and nine ephrin membrane proteins in vertebrates, has been implicated in the regulation of many critical events during development. Binding of cell surface Eph and ephrin proteins results in bi-directional signals, which regulate the cytoskeletal, adhesive and motile properties of the interacting cells. Through these signals Eph and ephrin proteins are involved in early embryonic cell movements, which establish the germ layers, cell movements involved in formation of tissue boundaries and the pathfinding of axons.