High expression of 5-lipoxygenase in normal and malignant mantle zone B lymphocytes

<p>Abstract</p> <p>Background</p> <p>Human B lymphocytes can produce leukotriene B₄but the biological function of the 5-lipoxygenase (5-LO) pathway in B cells is unclear. In order to better understand and define the role of 5-LO in B cells, we investigated the expression of 5-LO mRNA and protein in subsets of B cells from human tonsils and different types of B cell lymphoma.</p> <p>Results</p> <p>Based on RT-PCR and western blot/immunohistochemical staining, with a polyclonal antibody raised against 5-LO, high expression of 5-LO was found in mantle zone B cells from tonsils. By contrast, only a weak expression of 5-LO was detected in germinal centre cells and no expression in plasma cells from tonsils. This pattern of 5-LO expression was preserved in malignant lymphoma with high expression in mantle B cell lymphoma (MCL) and weak or no expression in follicular lymphoma. Primary leukemized MCL, so called B-prolymphocytic leukaemia cells, and MCL cell lines also expressed 5-LO and readily produced LTB₄after activation.</p> <p>Conclusion</p> <p>The present report demonstrates the expression of 5-LO mainly in normal and malignant mantle zone B cells while the expression is low or absent in germinal centre B cells and plasma cells, indicating a role of the 5-LO pathway in B cells before the cells finally differentiate to plasma cells.</p

Adapted cognitive behavior therapy for obsessive compulsive disorder with co-occurring autism spectrum disorder: A clinical effectiveness study

Obsessive-compulsive disorder (OCD) and autism spectrum disorder (ASD) commonly co-occur. Adapted CBT for OCD in adults with ASD has not previously been evaluated outside the United Kingdom. In this study, 19 adults with OCD and ASD were treated using an adapted CBT protocol that consisted of 20 sessions focused on exposure with response prevention. The primary outcome was the clinician-rated Yale-Brown Obsessive-Compulsive Scale (YBOCS). Participants were assessed up to 3 months after treatment. There were significant reductions on the YBOCS at post-treatment (d=1.5), and improvements were sustained at follow-up (d=1.2). Self-rated OCD symptoms and depressive symptoms showed statistically significant reductions. Improvements in general functioning and quality of life were statistically non-significant. Three participants (16%) were responders at post-treatment and four (21%) were in remission from OCD. At follow-up, three participants (16%) were responders and one (5%) was in full remission. Adapted CBT for OCD in adults with co-occurring ASD is associated with reductions in obsessive-compulsive symptoms and depressive symptoms. However, outcomes are modest; few patients were completely symptom free, and treatment engagement was low with few completed exposures and low adherence to homework assignments. We identify and discuss the need for further treatment refinement for this vulnerable group

Detailed analysis of metastatic colorectal cancer patients who developed cardiotoxicity on another fluoropyrimidine and switched to S-1 treatment (subgroup analysis of the CardioSwitch-study)

BACKGROUND AND PURPOSE: The CardioSwitch-study demonstrated that patients with solid tumors who develop cardiotoxicity on capecitabine or 5-fluorouracil (5-FU) treatment can be safely switched to S-1, an alternative fluoropyrimidine (FP). In light of the European Medicines Agency approval of S-1 in metastatic colorectal cancer (mCRC), this analysis provides more detailed safety and efficacy information, and data regarding metastasectomy and/or local ablative therapy (LAT), on the mCRC patients from the original study. MATERIALS AND METHODS: This retrospective cohort study was conducted at 12 European centers. The primary endpoint was recurrence of cardiotoxicity after switch. For this analysis, safety data are reported for 78 mCRC patients from the CardioSwitch cohort (N = 200). Detailed efficacy and outcomes data were available for 66 mCRC patients. RESULTS: Data for the safety of S-1 in mCRC patients were similar to the original CardioSwitch cohort and that expected for FP-based treatment, with no new concerns. Recurrent cardiotoxicity (all grade 1) with S-1-based treatment occurred in 4/78 (5%) mCRC patients; all were able to complete FP treatment. Median progression-free survival from initiation of S-1-based treatment was 9.0 months and median overall survival 26.7 months. Metastasectomy and/or LAT was performed in 33/66 (50%) patients, and S-1 was successfully used in recommended neoadjuvant/conversion or adjuvant-like combination regimens and schedules as for standard FPs. INTERPRETATION: S-1 is a safe and effective FP alternative when mCRC patients are forced to discontinue 5-FU or capecitabine due to cardiotoxicity and can be safely used in the standard recommended regimens, settings, and schedules

Bryggan : En processutvärdering av en social investering med fokus på elever med destruktivt normbrytande beteende och problematisk skolfrånvaro

Editors: Björn Johansson and Daniel Uhnoo</p