The Use of a Patency Capsule in Pediatric Crohn’s Disease: A Prospective Evaluation

Background  

Capsule endoscopy (CE) retention remains a concern in patients with suspected or known Crohn’s Disease (CD).     

Primary hepatic lymphoma: a case report and review of the literature

We report here a case of an older woman, 90 years old on admission, who presented with general deterioration, fever, abdominal pain, large hepatic mass, and was found to have an extra-nodal large B-cell lymphoma of the liver. The patient was successfully treated with multi-agent chemotherapy and followed up for 2 years with no recurrence of the disease. To the best of our knowledge this is the oldest patient reported with such a primary extra-nodal hepatic lymphoma and a remarkably favourable response to chemotherapy.     

Refractory coeliac disease

A small proportion of coeliac disease (CD) patients fail to improve after a gluten-free diet (GFD) and may be considered as atypical regarding their outcome (refractory coeliac disease). The aim of this study is to diagnose and manage patients with CD who fail to improve after a GFD. Refractory coeliac disease (RCD) is a malabsorption syndrome defined by persisting villous atrophy with, usually, an increase of intraepithelial lymphocytes (IELs) in the small bowel in spite of a strict GFD and comprises a heterogenous group of diseases. Some of these diseases have to be excluded and can be treated by specific therapies like antibiotics in tropical sprue and giardiasis and immune globulin substitution in common variable immunodeficiency, while other malabsorption syndromes are less well defined and may require immunosuppressive therapy. Standardized treatment, however, has not been evaluated in such patients so far. In a subgroup of patients with RCD, an abnormal intraepithelial lymphocyte (IEL) population may be observed with the lack of surface expression of usual T-cell markers (CD3-CD8 and/or the T-cell receptor (TCR)) on IELs associated with T-cell clonality pattern suggest the presence of an early enteropathy-associated T-cell lymphoma (EATL) in a subgroup of patients with RCD. This hypothesis has been supported by studies, which revealed progression into overt intestinal T-cell lymphomas in a subgroup of RCD. Steroid treatment has been reported effective even in patients with underlying early EATL. However, long-term results are unsatisfactory in most of these patients with RCD and parenteral nutrition has to be applied in some of these cases. First results with more aggressive chemotherapies and use of cytokines are under way. Due to the difficulty of diagnostic and therapeutic regimens patients should be referred to tertiary centres for coeliac disease.     

The interaction of TIGIT with PVR and PVRL2 inhibits human NK cell cytotoxicity

NK cell cytotoxicity is controlled by numerous NK inhibitory and activating receptors. Most of the inhibitory receptors bind MHC class I proteins and are expressed in a variegated fashion. It was recently shown that TIGIT, a new protein expressed by T and NK cells binds to PVR and PVR-like receptors and inhibits T cell activity indirectly through the manipulation of DC activity. Here, we show that TIGIT is expressed by all human NK cells, that it binds PVR and PVRL2 but not PVRL3 and that it inhibits NK cytotoxicity directly through its ITIM. Finally, we show that TIGIT counter inhibits the NK-mediated killing of tumor cells and protects normal cells from NK-mediated cytoxicity thus providing an “alternative self” mechanism for MHC class I inhibition.     

Capsule endoscopy: comparison of two different reading modes

Purpose  

Capsule endoscopy (CE) is a very useful tool for the evaluation of the small intestine, but it is time consuming. The aim of this study was to compare evaluation times and detection rates in two different reading modes (single view at a speed of 10 frames per second (fps) and four images simultaneously, i.e., quadview mode at a speed of 20 fps) to find the optimum setting mode for evaluation of CE videos.     

Angiostatin diminishes activation of the mitogen-activated protein kinases ERK-1 and ERK-2 in human dermal microvascular endothelial cells

Angiostatin is an endogenous inhibitor of angiogenesis that was isolated from tumor-bearing mice. It has been established that angiostatin inhibits endothelial cell proliferation; however, the underlying mechanisms remain to be elucidated. Here we report that angiostatin reduces transiently the phosphorylation of the mitogen-activated protein kinases ERK-1 and ERK-2 in human dermal microvascular cells, but not in human vascular smooth muscle cells or human dermal fibroblasts. We demonstrate that angiostatin diminishes ERK activation by basic fibroblast growth factor and vascular endothelial growth factor. Dephosphorylation of ERK and other tyrosine-phosphorylated proteins was blocked by pretreatment of the cells with sodium meta-vanadate, an inhibitor of protein tyrosine phosphatases, indicating that angiostatin signaling may require the activity of a tyrosine phosphatase. Concentrations of angiostatin that inhibited ERK activation also inhibited basic fibroblast growth factor-stimulated collagen gel invasion by endothelial cells, but did not affect endothelial cell proliferation. We thus show that angiostatin inhibits primarily the invasion of endothelial cells and exerts minimal (if any) effects on their proliferation. Invasion is a process that involves proteolysis, adhesion and migration, all of which have been linked to ERK signaling.     

Regulation of thylakoid protein phosphorylation at the substrate level: Reversible light-induced conformational changes expose the phosphorylation site of the light-harvesting complex II

Light-dependent activation of thylakoid protein phosphorylation regulates the energy distribution between photosystems I and II of oxygen-evolving photosynthetic eukaryotes as well as the turnover of photosystem II proteins. So far the only known effect of light on the phosphorylation process is the redox-dependent regulation of the membrane-bound protein kinase(s) activity via plastoquinol bound to the cytochrome bf complex and the redox state of thylakoid dithiols. By using a partially purified thylakoid protein kinase and isolated native chlorophyll (chl) a/b light-harvesting complex II (LHCII), as well as recombinant LHCII, we find that illumination of the chl-protein substrate exposes the phosphorylation site to the kinase. Light does not activate the phosphorylation of the LHCII apoprotein nor the recombinant pigment-reconstituted complex lacking the N-terminal domain that contains the phosphothreonine site. The suggested light-induced conformational change exposing the N-terminal domain of LHCII to the kinase is evidenced also by an increase in its accessibility to tryptic cleavage after light exposure. Light activates preferentially the trimeric form of LHCII, and the process is paralleled by chl fluorescence quenching. Both phenomena are slowly reversible in darkness. Light-induced exposure of the LHCII N-terminal domain to the endogenous protein kinase(s) and tryptic cleavage occurs also in thylakoid membranes. These results demonstrate that light may regulate thylakoid protein phosphorylation not only via the signal transduction chain connecting redox reactions to the protein kinase activation, but also by affecting the conformation of the chl-protein substrate.     

Mechanisms of Disease: genetics of fibromyalgia

Fibromyalgia is characterized by widespread pain and tenderness, and has a significant familial component. The etiology of fibromyalgia remains unclear, but genetic factors seem to have a significant role, and are influenced by environmental factors. Research over the past two decades has demonstrated that genetic polymorphisms in the serotoninergic, dopaminergic and catecholaminergic systems of pain transmission and processing are involved in the etiology of fibromyalgia, but additional candidates continue to emerge. Fibromyalgia is thought to belong to the group of affective spectrum disorders, which include related psychiatric and medical disorders. As the concept of affective spectrum disorders continues to evolve, progress in the understanding of the genetic basis of related functional disorders, such as irritable bowel syndrome and post-traumatic-stress disorder, is aiding our understanding of the genetic basis of fibromyalgia.     

The Maudsley Mentation test: a method for extended monitoring of mental status after aneurysmal subarachnoid hemorrhage.

A new scale for the repeated, rapid assessment of mental function in patients with subarachnoid hemorrhage is described. Its reproducibility is evaluated and early experience with its use in the intended clinical setting is reported. The test (Maudsley Mentation Test) proved to be more sensitive to fluctuations in cerebral functioning than existing measures of conscious level, and the results were reproducible among observers with different backgrounds (surgeons, nurses, and psychologists). The results suggest a relationship between performance on mentation testing and quality of outcome. The Maudsley Mentation Test is thought to offer a suitable measure with which to monitor patients during the acute phase of their illness to supplement clinical assessment and provide evidence of deterioration at an early stage. It is also potentially useful as an end point in acute protection and treatment studies.