Decreased expression of miR-29 family associated with autoimmune myasthenia gravis.

Background: Myasthenia gravis (MG) is a rare autoimmune disease mainly mediated by autoantibodies against the acetylcholine receptor (AChR) at the neuromuscular junction. The thymus is the effector organ, and its removal alleviates the symptoms of the disease. In the early-onset form of MG, the thymus displays functional and morphological abnormalities such as B cell infiltration leading to follicular hyperplasia, and the production of AChR antibodies.

Role of miRNAs in Normal and Myasthenia Gravis Thymus.

The thymus, a primary lymphoid organ, provides a complex environment essential for the generation of the T-cell repertoire. Thymic alterations occur during life either in the context of thymic involution upon aging or the pathophysiological context of Myasthenia Gravis (MG). These changes involve complicated regulatory networks, in which microRNAs (miRNAs) are key players.

Causes and Consequences of miR-150-5p Dysregulation in Myasthenia Gravis.

Autoimmune Myasthenia gravis (MG) is a chronic neuromuscular disease mainly due to antibodies against the acetylcholine receptor (AChR) at the neuromuscular junction that induce invalidating muscle weaknesses. In early-onset MG, the thymus is the effector organ and is often characterized by B-cell infiltrations leading to ectopic germinal center (GC) development. The microRNA miR-150-5p has been previously characterized as a biomarker in MG due to its increase in the serum of patients and its decrease after thymectomy, correlated with an improvement of symptoms.

Analysis of microRNA expression in the thymus of Myasthenia Gravis patients opens new research avenues.

In early-onset Myasthenia Gravis (MG) with anti-acetylcholine receptor antibodies, thymic abnormalities associated with ectopic germinal centers are frequent. miRNAs by acting as post-transcriptional regulators are involved in autoimmunity. To investigate the implication of miRNAs in thymic changes associated with early-onset MG, we performed a miRnome study and data were analyzed with different approaches.

Thymus involvement in early-onset myasthenia gravis.

It has long been established that the thymus plays a central role in autoimmune myasthenia gravis (MG) because of either thymoma or thymic hyperplasia of lymphoproliferative origin. In this review, we discuss thymic changes associated with thymic hyperplasia and their implications in the development of an autoimmune response against the acetylcholine receptor (AChR).The hyperplastic MG thymus displays all the characteristics of tertiary lymphoid organs (TLOs): neoangiogenic processes with high endothelial venule and lymphatic vessel development, chemokine overexpression favoring peripheral cell recruitment, and ectopic germinal center development.

Use of Toll-Like Receptor Agonists to Induce Ectopic Lymphoid Structures in Myasthenia Gravis Mouse Models.

Myasthenia gravis (MG) is an autoimmune disease mediated by autoantibodies against the acetylcholine receptor (AChR) at the neuromuscular junction. MG symptoms are characterized by muscle weaknesses. The thymus of MG patients is very often abnormal and possesses all the characteristics of tertiary lymphoid organs such as neoangiogenesis processes, overexpression of inflammatory cytokines and chemokines, and infiltration of B lymphocytes leading to ectopic germinal center (GC) development.

Salmonella FraE, an Asparaginase Homolog, Contributes to Fructose-Asparagine but Not Asparagine Utilization.

can utilize fructose-asparagine (F-Asn) as a source of carbon and nitrogen. This capability has been attributed to five genes in the locus. Previously, we determined that mutations in (deglycase), (kinase), or (transporter) eliminated the ability of to grow on F-Asn, while a mutation in allowed partial growth.

Review on Toll-Like Receptor Activation in Myasthenia Gravis: Application to the Development of New Experimental Models.

Abnormal toll-like receptor (TLR) activation and uncontrolled resolution of inflammation are suspected to play a key role in the development of autoimmune diseases. Acquired myasthenia gravis (MG) is an invalidating neuromuscular disease leading to muscle weaknesses. MG is mainly mediated by anti-acetylcholine receptor (AChR) autoantibodies, and thymic hyperplasia characterized by ectopic germinal centers is a common feature in MG.

Palatability evaluation study of a new oral formulation of marbofloxacin in cats.

At a time when antimicrobial resistance is a global concern in human and animal health, it is of primary importance to draw attention to the problem of compliance with antibiotic therapy in animals hard to medicate such as cats. Resistance may develop because of poor patient compliance with the prescribed course of antibiotic therapy. Increasing palatability might enhance administration compliance.

Common occurrence of a positive δ53Cr shift in Central European waters contaminated by geogenic/industrial chromium relative to source values.

Carcinogenic effects of hexavalent chromium in waters are of concern in many countries worldwide. We explored Cr isotope systematics at 11 sites in the Czech Republic and Poland. Geogenic Cr pollution was associated with serpentinite bodies at former convergent plate margins, while anthropogenic Cr pollution resulted from electroplating, tanning, and the chemical industry.

Anti-inflammatory activity of topical THC in DNFB-mediated mouse allergic contact dermatitis independent of CB1 and CB2 receptors.

Background: ∆(9) -Tetrahydrocannabinol (THC), the active constituent of Cannabis sativa, exerts its biological effects in part through the G-protein-coupled CB1 and CB2 receptors, which were initially discovered in brain and spleen tissue, respectively. However, THC also has CB1/2 receptor-independent effects. Because of its immune-inhibitory potential, THC and related cannabinoids are being considered for the treatment of inflammatory skin diseases.

Cannabinoid 1 receptors in keratinocytes modulate proinflammatory chemokine secretion and attenuate contact allergic inflammation.

Epidermal keratinocytes (KCs) and cannabinoid (CB) receptors both participate in the regulation of inflammatory responses in a mouse model for allergic contact dermatitis, the contact hypersensitivity (CHS) response to the obligate sensitizer 2,4-dinitrofluorobenzene. In this study, we investigated the cellular and molecular mechanisms how CB1 receptors attenuate CHS responses to 2,4-dinitrofluorobenzene. We used a conditional gene-targeting approach to identify the relative contribution of CB1 receptors on epidermal KCs for the control of CHS responses.

Melanomas resist T-cell therapy through inflammation-induced reversible dedifferentiation.

Adoptive cell transfer therapies (ACTs) with cytotoxic T cells that target melanocytic antigens can achieve remissions in patients with metastatic melanomas, but tumours frequently relapse. Hypotheses explaining the acquired resistance to ACTs include the selection of antigen-deficient tumour cell variants and the induction of T-cell tolerance. However, the lack of appropriate experimental melanoma models has so far impeded clear insights into the underlying mechanisms.

Autochthonous primary and metastatic melanomas in Hgf-Cdk4 R24C mice evade T-cell-mediated immune surveillance.

Genetically engineered mouse models offer new opportunities to investigate the role of cell-mediated immunity in the natural progression of melanoma in an immunocompetent host. Here we report that Hgf-Cdk4(R24C) mice spontaneously develop a spectrum of primary melanomas with high penetrance during their first year of life. Malignant transformation proceeds in a stepwise manner from multiple melanocytic nevi to single nodular melanomas and disseminated metastases in most mice.

Complete regression of advanced primary and metastatic mouse melanomas following combination chemoimmunotherapy.

The development of therapeutic strategies which induce effective cellular antitumor immunity represents an important goal in cancer immunology. Here, we used the unique features of the genetically engineered Hgf-Cdk4(R24C) mouse model to identify a combination chemoimmunotherapy for melanoma. These mice develop primary cutaneous melanomas which grow progressively and metastasize in the absence of immunogenic foreign proteins such as oncogenes or antigens.

Safety and efficacy of overnight orthokeratology in myopic children.

Background: This prospective case series was conducted to describe the safety and efficacy of orthokeratology with the Emerald Contact Lens for Overnight Orthokeratology (Oprifocon A; Euclid Systems Corporation, Herndon, Virginia) among young myopes.

Methods: Twenty subjects (ages 10 to 16) were enrolled in the 6-month pilot study. Subjects were fit empirically with overnight orthokeratology lenses and evaluated at 1 day, 1 week, 1 month, 2 months, 3 months, and 6 months.

Evaluation of the Parsons Visual Acuity Test in screening exceptional children.

The Parsons Visual Acuity Test (PVAT) is a non-verbal picture based visual acuity test designed for the difficult-to-test preschool child, school age child and adult with handicapping conditions. It is designed primarily for vision screening of the exceptional child and adult with special needs. Since visual acuity measures are quite important in these populations, a comparative study between the PVAT and standard Snellen acuity were designed and completed.

Broken wheel acuity test: a new and valid test for preschool and exceptional children.

This study describes a new visual acuity test for preschool and exceptional children. It is independent of verbal responses, uses a forced-choice testing procedure, incorporates the psychometric design advantages of the Landolt ring, and can be administered at 3m (10 ft) in 5 to 7 minutes. The results support its construct validity in accurately measuring visual acuity levels and its clinical applicability for preschool and exceptional children.