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Central nervous system-specific antinuclear antibodies in patients with multiple sclerosis.

Nuclear antigen released from central nervous system (CNS) cells undergoing destruction may induce production of antinuclear antibodies (ANA). We characterized the CNS-specific production of ANA in multiple sclerosis (MS).

1353 related Products with: Central nervous system-specific antinuclear antibodies in patients with multiple sclerosis.

Multiple organ tumor tiss Chromatin Transcription P Inflammation (Human) Anti IGF-1R Signaling Phospho- NF-kB II Phospho-Specific Angiogenesis (Human) Anti Cytokine (Human) Antibody Cytokine (Rat) Antibody A Apoptosis (Human) Antibod Cytokine (Human) Antibody Multiple organ cancer tis Signal transduction antib

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Assessing localized conformational stability of antibody-drug conjugate by protein conformation assay.

Antibody-drug conjugates (ADCs) are a class of attractive therapeutic agents to fight cancer with conjugation of potent chemical agents on target-selective antibodies. The conceptually elegant approach has encountered mounting practical challenges in combining the mAb and potent drug while maintaining the conformational and physiochemical stability of the bioconjugates. The attachment of hydrophobic drug-linker with antibody could potentially alter the antibody conformational scaffold, locally or globally. Here we propose to use a protein conformation assay (PCA) to measure the higher-order structure of antibodies upon drug-linker conjugation. The PCA analysis provides insights into the formation of partially unfolded ADCs, which may correlate with protein stability and aggregation propensity. To further elucidate the cause of the unfolding events, in-depth peptide mapping combined with the PCA conformational footprints were performed on a commercial ADC trastuzumab emtansine in this study. The locally altered conformational hot-spots observed in PCA matched with conjugation sites with high occupancy rate identified in peptide mapping. In summary, by combining PCA and in-depth peptide mapping, a snapshot of ADC structural conformation and stability profile could be obtained and provide a swift and convenient measurement of the 'fitness' of ADC to facilitate payload selection, conjugation process development and early predictive developability assessment.

1215 related Products with: Assessing localized conformational stability of antibody-drug conjugate by protein conformation assay.

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Selection in the germinal center.

Germinal centers (GCs) are well known for their important role in shaping the secondary B cell repertoire to generate antibodies capable of binding with high-affinity and specificity to foreign antigens. Somatic hypermutation of the Ig variable region genes in GC B cells represents a highly efficient mechanism for generating new antibody variants with increased antigen affinity. To be effective, however, this process needs to be intimately linked with equally efficient processes that positively select high-affinity clones for perpetuation in the GC and, ultimately, for differentiation into plasma cell and memory B cell effector populations. Just as important is the need for mechanisms of negative selection that remove GC B cell clones with unwanted specificities, particularly those that have gained reactivity with self-components. Here, we discuss recent advances in our understanding of the various selective processes that occur within the GC and identify the major questions in this field that remain to be answered.

2980 related Products with: Selection in the germinal center.

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Deep Learning Reveals Cancer Metastasis and Therapeutic Antibody Targeting in the Entire Body.

Reliable detection of disseminated tumor cells and of the biodistribution of tumor-targeting therapeutic antibodies within the entire body has long been needed to better understand and treat cancer metastasis. Here, we developed an integrated pipeline for automated quantification of cancer metastases and therapeutic antibody targeting, named DeepMACT. First, we enhanced the fluorescent signal of cancer cells more than 100-fold by applying the vDISCO method to image metastasis in transparent mice. Second, we developed deep learning algorithms for automated quantification of metastases with an accuracy matching human expert manual annotation. Deep learning-based quantification in 5 different metastatic cancer models including breast, lung, and pancreatic cancer with distinct organotropisms allowed us to systematically analyze features such as size, shape, spatial distribution, and the degree to which metastases are targeted by a therapeutic monoclonal antibody in entire mice. DeepMACT can thus considerably improve the discovery of effective antibody-based therapeutics at the pre-clinical stage. VIDEO ABSTRACT.

2653 related Products with: Deep Learning Reveals Cancer Metastasis and Therapeutic Antibody Targeting in the Entire Body.

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An explorative study identifies miRNA signatures for the diagnosis of non-celiac wheat sensitivity.

Non-celiac wheat sensitivity (NCWS), also referred to as non-celiac gluten sensitivity, is a recently described disorder triggered by wheat/gluten ingestion. NCWS elicits a wide range of symptoms including diarrhoea, intestinal discomfort, and fatigue in analogy with other wheat/gluten-related disorders and celiac disease in particular. From the pathological standpoint, NCWS patients only have a slight increase of intraepithelial lymphocytes, while antibodies to tissue transglutaminase (tTG) and villous atrophy, otherwise diagnostic features of celiac disease, are absent. To date, the diagnosis of NCWS relies on symptoms and exclusion of confounding diseases, since biomarkers are not yet available. Here, the expression levels of selected miRNAs were examined in duodenal biopsies and peripheral blood leukocytes collected from newly diagnosed patients with NCWS and, as controls, from patients with celiac disease and gluten-independent gastrointestinal problems. We identified a few miRNAs whose expression is higher in the intestinal mucosa of patients affected by NCWS in comparison to control patients affect by gluten-independent dyspeptic symptoms (Helicobacter pylori-negative) and celiac disease. The present study provided the first evidence that NCWS patients have a characteristic miRNA expression patterns, such peculiarity could be exploited as a biomarker to the diagnosis of this disease.

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Mother-to-Child Transfer of Reactivated Varicella-Zoster Virus DNA and Varicella-Zoster IgG in Pregnancy.

Stress-induced subclinical reactivation of varicella-zoster virus (VZV) has been studied previously. However, subclinical reactivation of VZV induced by the stress of pregnancy has not been investigated. The objective was to study varicella DNA and varicella antibody levels in mothers and their newborn babies. VZV immunoglobulin G (IgG) levels in 350 mother-newborn dyads were studied using indirect enzyme-linked immunosorbent assay testing. A subset of 73 dyads was selected, DNA was isolated from the serum samples, and quantitative polymerase chain reaction (qPCR) was performed. Nearly 15% (14.6%) mothers tested were positive for varicella antibodies (>100 mIU/dL) and 16% were borderline (<100 and >50 mIU/dL). Approximately 16.9% of the babies were positive, and 18% were in borderline. Among those tested for VZV-DNA, 70% of mothers with low VZ-IgG (<100 mIU/dL) and 11.32% of those with high VZ-IgG (>100 mIU/dL) were positive for DNA. Among the newborns, 60% of those with low VZ-IgG and 15% of those with high VZ-IgG were positive for DNA. Mothers who have had VZV infection in the past can transmit VZV DNA to their babies.

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Rational Design of a Bifunctional AND-Gate Ligand to Modulate Cell-Cell Interactions.

Protein "AND-gate" systems, in which a ligand acts only on cells with two different receptors, direct signaling activity to a particular cell type and avoid action on other cells. In a bifunctional AND-Gate protein, the molecular geometry of the protein domains is crucial. Here we constructed a tissue-targeted erythropoietin (EPO) that stimulates red blood cell (RBC) production without triggering thrombosis. EPO was directed to RBC precursors and mature RBCs by fusion to an anti-glycophorin A antibody V region. Many such constructs activated EPO receptors in vitro and stimulated RBC and not platelet production in mice but nonetheless enhanced thrombosis in mice, and caused adhesion between RBCs and EPO receptor-bearing cells. Based on a protein-structural model of the RBC surface, we rationally designed an anti-glycophorin/EPO fusion that does not induce cell adhesion in vitro or enhance thrombosis in vivo. Thus, meso-scale geometry can inform design of synthetic-biological systems.

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Cell Meter™ Fluorimetri Oral squamous cell cancer Cell Meter™ Fluorimetri Cultrex 24 Well BME Cell CellQuanti-MTT™ Cell Vi Quick Cell Proliferation BAFF (B cell activating f RubyGlowTM Luminescent Cy Cultrex 96 Well Cell Migr Kidney clear cell carcino Human soluble vascular ce Rat anti mouse Pan Endoth

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The Immunopathology of Complement Proteins and Innate Immunity in Autoimmune Disease.

The complement is a powerful cascade of the innate immunity and also acts as a bridge between innate and acquired immune defence. Complement activation can occur via three distinct pathways, the classical, alternative and lectin pathways, each resulting in the common terminal pathway. Complement activation results in the release of a range of biologically active molecules that significantly contribute to immune surveillance and tissue homeostasis. Several soluble and membrane-bound regulatory proteins restrict complement activation in order to prevent complement-mediated autologous damage, consumption and exacerbated inflammation. The crucial role of complement in the host homeostasis is illustrated by association of both complement deficiency and overactivation with severe and life-threatening diseases. Autoantibodies targeting complement components have been described to alter expression and/or function of target protein resulting in a dysregulation of the delicate equilibrium between activation and inhibition of complement. The spectrum of diseases associated with complement autoantibodies depends on which complement protein and activation pathway are targeted, ranging from autoimmune disorders to kidney and vascular diseases. Nevertheless, these autoantibodies have been identified as differential biomarkers for diagnosis or follow-up of disease only in a small number of clinical conditions. For some autoantibodies, a clear relationship with clinical manifestations has been identified, such as anti-C1q, anti-Factor H, anti-C1 Inhibitor antibodies and C3 nephritic factor. For other autoantibodies, the origin and the functional consequences still remain to be elucidated, questioning about the pathophysiological significance of these autoantibodies, such as anti-mannose binding lectin, anti-Factor I, anti-Factor B and anti-C3b antibodies. The detection of autoantibodies targeting complement components is performed in specialized laboratories; however, there is no consensus on detection methods and standardization of the assays is a real challenge. This review summarizes the current panorama of autoantibodies targeting complement recognition proteins of the classical and lectin pathways, associated proteases, convertases, regulators and terminal components, with an emphasis on autoantibodies clearly involved in clinical conditions.

2036 related Products with: The Immunopathology of Complement Proteins and Innate Immunity in Autoimmune Disease.

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Prognostic significance of serum p53 antibody according to KRAS status in metastatic colorectal cancer patients.

Serum anti-p53 antibody is used clinically as a tumor marker of colorectal cancer. However, its prognostic significance in patients with metastatic colorectal cancer (mCRC) remains unclear. KRAS status may influence the host immune response against tumor progression. In the present study, we investigated the prognostic significance of serum anti-p53 in mCRC patients with wild-type KRAS and mutant KRAS treated with systemic chemotherapy.

2215 related Products with: Prognostic significance of serum p53 antibody according to KRAS status in metastatic colorectal cancer patients.

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[Necrotizing fasciitis of the extremities and trunk].

Necrotizing fasciitis (NF) is a disease of a group of entities with an aggressive course summarized under the term necrotizing skin and soft-tissue infections (NSTI). It is a life-threatening and often disabling infection and is primarily clinically diagnosed. Initially, clinical signs of infection can be insidious and confounded by absence of fever and typical cutaneous lesions. The later course is characterized by soft tissue lesions, excessive pain and systemic toxicity. As the infection can spread rapidly, and as a delay in treatment is associated with increased mortality, additional diagnostic imaging should be confined to a minimum. Prompt and radical surgical debridement (including repeated debridement after 24 h) is a prerequisite for survival in NF. Also, prompt administration of high-dose broad-spectrum antibiotics and a differentiated intensive treatment are necessary. The role of immunoglobulins and hyperbaric oxygenation remains controversial, therefore, the routine use of these measures cannot be recommended at the moment. Close interdisciplinary collaboration is required in order to optimize the treatment and to save life and limb of patients suffering from this life-threatening infection.

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