Effects of anti-CD20 therapy on circulating and intrathecal follicular helper T cell subsets in multiple sclerosis.

Follicular helper T (Tfh) cells and their interplay with B cells likely contribute to the pathogenesis of relapsing-remitting multiple sclerosis (RRMS). Tfh cells are enriched in cerebrospinal fluid (CSF) in RRMS, but effects of anti-CD20 therapy are unknown. We investigated Tfh cells in controls, untreated and anti-CD20-treated patients with RRMS using flow cytometry.

Neurofilament light chain levels in serum among a large mixed memory clinic cohort: Confounders and diagnostic usefulness.

Introduction: Early and accurate diagnosis of neurocognitive disorders including neurodegenerative dementia remains challenging. This study explores the impact of biological factors on serum neurofilament light chain (NfL) levels and clinical usefulness for the detection of neurocognitive disorders in a mixed memory clinic.

Methods: Serum samples and clinical data were obtained from 1188 patients who underwent diagnostic investigations for memory complaints between January 2018 and September 2019.

Cerebrospinal fluid soluble CD27 is associated with CD8 T cells, B cells and biomarkers of B cell activity in relapsing-remitting multiple sclerosis.

Cerebrospinal fluid (CSF) soluble CD27 (sCD27) is a sensitive biomarker of intrathecal inflammation. Although generally considered a biomarker of T cell activation, CSF sCD27 has been shown to correlate with biomarkers of B cell activity in multiple sclerosis. We analyzed CSF from 40 patients with relapsing-remitting multiple sclerosis (RRMS) and nine symptomatic controls using flow cytometry and multiplex electrochemiluminescence immunoassays.

Cluster headache polygenetic risk and known functional variants of CYP3A4 are not associated with treatment response.

Background And Purpose: The response to cluster headache treatments has a high interindividual variation. To date, treatment response has only been assessed by a candidate gene approach and no investigations into metabolic pathways have been performed. Our aim was to investigate the association between the polygenetic risk of cluster headache and treatment response to first-line cluster headache treatments as well as known functional variants of CYP3A4 and the response to verapamil.

Identification of lysosome-targeting drugs with anti-inflammatory activity as potential invasion inhibitors of treatment resistant HER2 positive cancers.

Purpose: Most HER2 positive invasive cancers are either intrinsic non-responsive or develop resistance when treated with 1st line HER2 targeting drugs. Both 1st and 2nd line treatments of HER2 positive cancers are aimed at targeting the HER2 receptor directly, thereby strongly limiting the treatment options of HER2/ErbB2 inhibition resistant invasive cancers.

Methods: We used phenotypic high throughput microscopy screening to identify efficient inhibitors of ErbB2-induced invasion using 1st line HER2 inhibitor trastuzumab- and pertuzumab-resistant, p95-ErbB2 expressing breast cancer cells in conjunction with the Prestwick Chemical Library®.

Release of transcriptional repression via ErbB2-induced, SUMO-directed phosphorylation of myeloid zinc finger-1 serine 27 activates lysosome redistribution and invasion.

HER2/ErbB2 activation turns on transcriptional processes that induce local invasion and lead to systemic metastasis. The early transcriptional changes needed for ErbB2-induced invasion are poorly understood. Here, we link ErbB2 activation to invasion via ErbB2-induced, SUMO-directed phosphorylation of a single serine residue, S27, of the transcription factor myeloid zinc finger-1 (MZF1).

Let-7 microRNA controls invasion-promoting lysosomal changes via the oncogenic transcription factor myeloid zinc finger-1.

Cancer cells utilize lysosomes for invasion and metastasis. Myeloid Zinc Finger1 (MZF1) is an ErbB2-responsive transcription factor that promotes invasion of breast cancer cells via upregulation of lysosomal cathepsins B and L. Here we identify let-7 microRNA, a well-known tumor suppressor in breast cancer, as a direct negative regulator of MZF1.

The role of GAGE cancer/testis antigen in metastasis: the jury is still out.

Background: GAGE cancer/testis antigens are frequently expressed in various types of malignancies and represent attractive targets for immunotherapy, however their role in cancer initiation and progression has remained elusive. GAGE proteins are expressed in normal cells during early development with migratory and invasive properties and were found to be upregulated in cancer cells with metastasizing potential in a gastric cancer model.

Methods: We have addressed the direct role of GAGE proteins in supporting metastasis using an isogenic metastasis model of human cancer, consisting of 4 isogenic cell lines, which are equally tumorigenic in immunodeficient mice, but differ with their ability to generate metastases in the lungs and lymph nodes.

Cr(III) and Cr(VI) in leather and elicitation of eczema.

The aim of the present study was to investigate the relation between the content of Cr(VI) and soluble Cr(III) in leather and the ability of the leather to elicit eczema in chromium allergic patients. An array of chromium-tanned leather samples was analysed for the content of total Cr(VI) and soluble Cr(III) using the DIN 53314 and the DS/EN 420 methods. Subsequently, a group of 15 patients with a history of foot eczema and leather exposure was exposed to a selection of 14 chromium- and 1 vegetable-tanned leather sample on the upper back for 48 hr.

Cr(III) reactivity and foot dermatitis in Cr(VI) positive patients.

Chromium allergy has become synonymous with Cr(VI) allergy. However, real exposure to chromium from leather products may include both Cr(III) and Cr(VI). In this study, we investigate the reactivity to both Cr(VI) and Cr(III) in consecutive patients to analyse the relation between foot eczema/leather exposure and reactivity to Cr(III).

Gene transcripts as potential diagnostic markers for allergic contact dermatitis.

The standard procedure for diagnosing allergic contact dermatitis is to perform a patch test. Because this has several disadvantages, the development of a new in vitro test system would be of immense value. Gene transcripts that distinguish allergics from non-allergics may have the potential to serve as the molecular basis for such a diagnostic tool.

Quantitative aspects of contact allergy to chromium and exposure to chrome-tanned leather.

The potential of trivalent and hexavalent chromium to induce and elicit allergic contact dermatitis and the degree of chromium exposure from leather products are reviewed. Chromium dermatitis is often due to exposure in the occupational environment, with cement being one of the most common chromium sources. However, consumer products such as chromium(III)-tanned leather products are also an important source of chromium exposure.

Mouse Atf5: molecular cloning of two novel mRNAs, genomic organization, and odorant sensory neuron localization.

The activating transcription factor (ATF) family comprises a group of basic region-leucine zipper (bZIP) proteins, which have roles in the development of species as diverse as insects and mammals. Here we describe two novel mRNAs encoding a single, 30-kDa mouse polypeptide, designated mouse ATF5, which is 58% identical to mouse ATF4 in the carboxy-terminal bZIP region. Both transcripts harbor highly complex 5' untranslated regions that impede translation of the ATF5 open reading frame.