Paraneoplastic Neurological Syndromes associated with anti-Hu antibodies: are T lymphocytes involved or not?

In paraneoplastic neurological syndromes (PNS), ectopic expression of onconeural antigens by the tumor triggers an immune response that not only reacts with the tumor but also with the same antigens expressed in the nervous system. This immune response inhibits tumor growth. However, the price of tumor control is high, as PNS are devastating neurological syndromes leaving most of the patients severely disabled within a few months. One of the most frequently involved tumors is small cell lung cancer (SCLC), and approximately 50% of patients with PNS and SCLC have high-titer antibodies against the onconeural Hu-antigens (anti-Hu). Previous studies have clearly demonstrated that anti-Hu antibodies do not play a pathogenic role in Hu-PNS and tumor control, but rather are a useful diagnostic marker. Therefore, a role for the cellular immune system in the pathogenesis of PNS is hypothesized. In this thesis the role of T cells in PNS was investigated by studying CSF and blood of Hu-PNS patients. This role of T cells was confirmed by (i) 4-fold higher T lymphocyte numbers in CSF of Hu-PNS patients compared to controls; (ii) association of Hu-PNS with HLA-DQ2 and HLA-DR3; and (iii) neurological improvement or stabilization upon treatment with hCG. However, the presence of HuD-specific CD8+ T cells in CSF could not be demonstrated. Therefore, more research is required to either confirm or reject a role for T lymphocytes in Hu-PNS

Quick Scan Streefbeeld Aal

Het gaat slecht met de aal in Europa, de aalpopulatie en aalvangsten zijn sterk teruggelopen. De huidige intrek van glasaal is slechts 1-5% van de intrek in de 60-70-er jaren (ICES 2012). Om herstel van de aalpopulatie mogelijk te maken heeft De Raad van de Europese Unie in 2007 de “EU Regulation for the Recovery of the Eel Stock (EC 1100/2007)” vastgesteld. Deze verordening verplicht de lidstaten om met een eigen nationaal aalbeheerplan te komen en te implementeren. Het doel van deze aalbeheerplannen is daarbij als volgt omschreven: “...het verminderen van de antropogene sterfte, zodat er een grote kans bestaat dat ten minste 40% van de biomassa van schieraal kan ontsnappen naar zee, gerelateerd aan de beste raming betreffende de ontsnapping die plaats zou hebben gevonden indien de mens geen invloed had uitgeoefend op het bestand.” Deze '40% norm' wordt het streefbeeld genoemd. In het Nederlandse aalbeheerplan (2009) is het streefbeeld voor Nederland vastgesteld op 5200 ton

Field-Induced Quantum Criticality of Systems with Ferromagnetically Coupled Structural Spin Units

The field-induced quantum criticality of compounds with ferromagnetically coupled structural spin units (as dimers and ladders) is explored by applying Wilson's renormalization group framework to an appropriate effective action. We determine the low-temperature phase boundary and the behavior of relevant quantities decreasing the temperature with the applied magnetic field fixed at its quantum critical point value. In this context, a plausible interpretation of some recent experimental results is also suggested.Comment: to be published in Physics Letters

Diagnosis of American foulbrood in honey bees: A synthesis and proposed analytical protocols

Worldwide, American foulbrood (AFB) is the most devastating bacterial disease of the honey bee (Apis mellifera). Because the distinction between AFB and powdery scale disease is no longer considered valid, the pathogenic agent has recently been reclassified as one species Paenibacillus larvae, eliminating the subspecies designations Paenibacillus larvae subsp. larvae and Paenibacillus larvae subsp. pulvifaciens. The creamy or dark brown, glue-like larval remains of infected larvae continue to provide the most obvious clinical symptom of AFB, although it is not conclusive. Several sensitive and selective culture media are available for isolation of this spore-forming bacterium, with the type of samples that may be utilized for detection of the organism being further expanded. PCR methods for identification and genotyping of the pathogen have now been extensively developed. Nevertheless, biochemical profiling, bacteriophage sensitivity, immunotechniques and microscopy of suspect bacterial strains are entirely adequate for routine identification purposes.Facultad de Ciencias Agrarias y ForestalesCentro de Investigaciones de Fitopatologí

Diagnosis of American foulbrood in honey bees: A synthesis and proposed analytical protocols

Worldwide, American foulbrood (AFB) is the most devastating bacterial disease of the honey bee (Apis mellifera). Because the distinction between AFB and powdery scale disease is no longer considered valid, the pathogenic agent has recently been reclassified as one species Paenibacillus larvae, eliminating the subspecies designations Paenibacillus larvae subsp. larvae and Paenibacillus larvae subsp. pulvifaciens. The creamy or dark brown, glue-like larval remains of infected larvae continue to provide the most obvious clinical symptom of AFB, although it is not conclusive. Several sensitive and selective culture media are available for isolation of this spore-forming bacterium, with the type of samples that may be utilized for detection of the organism being further expanded. PCR methods for identification and genotyping of the pathogen have now been extensively developed. Nevertheless, biochemical profiling, bacteriophage sensitivity, immunotechniques and microscopy of suspect bacterial strains are entirely adequate for routine identification purposes.Facultad de Ciencias Agrarias y ForestalesCentro de Investigaciones de Fitopatologí

Daily Practice Experience of Baricitinib Treatment for Patients with Difficult-to-Treat Atopic Dermatitis:Results from the BioDay Registry

Clinical trials have shown that baricitinib, an oral selective Janus kinase 1/2 inhibitor, is effective for the treatment of moderate-to-severe atopic dermatitis. However, daily practice data are limited. Therefore, this multicentre prospective study evaluated the effectiveness and safety of 16-weeks' treatment with baricitinib in adult patients with moderate-to-severe atopic dermatitis in daily practice. A total of 51 patients from the BioDay registry treated with baricitinib were included and evaluated at baseline and after 4, 8 and 16 weeks of treatment. Effectiveness was assessed using clinician- and patient-reported outcome measurements. Adverse events and laboratory assessments were evaluated at every visit. At week 16, the probability (95% confidence interval) of achieving Eczema Area and Severity Index ≤ 7 and numerical rating scale pruritus ≤ 4 was 29.4% (13.1-53.5) and 20.5% (8.8-40.9), respectively. No significant difference in effectiveness was found between dupilumab non-responders and responders. Twenty-two (43.2%) patients discontinued baricitinib treatment due to ineffectiveness, adverse events or both (31.4%, 9.8% and 2.0%, respectively). Most frequently reported adverse events were nausea (n = 6, 11.8%), urinary tract infection (n = 5, 9.8%) and herpes simplex infection (n = 4, 7.8%). In conclusion, baricitinib can be an effective treatment option for moderate-to-severe atopic dermatitis, including patients with non-responsiveness on dupilumab. However, effectiveness of baricitinib is heterogeneous, which is reflected by the high discontinuation rate in this difficult-to-treat cohort

Small Hydrophobic Protein of Human Metapneumovirus Does Not Affect Virus Replication and Host Gene Expression In Vitro

Human metapneumovirus (HMPV) encodes a small hydrophobic (SH) protein of unknown function. HMPV from which the SH open reading frame was deleted (HMPVΔSH) was viable and displayed similar replication kinetics, cytopathic effect and plaque size compared with wild type HMPV in several cell-lines. In addition, no differences were observed in infection efficiency or cell-to-cell spreading in human primary bronchial epithelial cells (HPBEC) cultured at an air-liquid interphase. Host gene expression was analyzed in A549 cells infected with HMPV or HMPVΔSH using microarrays and mass spectrometry (MS) based techniques at multiple time points post infection. Only minor differences were observed in mRNA or protein expression levels. A possible function of HMPV SH as apoptosis blocker, as proposed for several members of the family Paramyxoviridae, was rejected based on this analysis. So far, a clear phenotype of HMPV SH deletion mutants in vitro at the virus and host levels is absent