Search results for "Asthenia"

Gpibα Engagement Induces Activation of Human Platelet TF and Association with Constitutively Platelet Surface-Bound FVIIa

2019

The membranes of activated platelets assemble clotting protein complexes and enzymatic reactions needed for hemostasis and causing pathological thrombosis. Several reports have shown that human platelets contain TF, but controversies remain on the functional contributions of platelet TF to coagulation initiation. Here, we delineate the mechanism that converts platelet-associated TF to a procoagulant molecule. By combining specific inhibitors with human platelets from normal probands or patients with Glanzmann thrombasthenia or homozygous GPVI deficiency, we analyzed the procoagulant activation of platelet TF by biochemical methods, confocal microscopy, platelet adhesion under flow on VWF an…

A Phase Ib Dose-Escalation Study of the Safety, Tolerability, and Pharmacokinetics of Cobimetinib and Duligotuzumab in Patients with Previously Treat…

2017

Abstract Lessons Learned Cobimetinib and duligotuzumab were well tolerated as single agents and in combination with other agents. The cobimetinib and duligotuzumab combination was associated with increased toxicity, most notably gastrointestinal, and limited efficacy in the patient population tested. Background KRAS-mutant tumors possess abnormal mitogen-activated protein kinases (MAPK) pathway signaling, leading to dysregulated cell proliferation. Cobimetinib blocks MAPK signaling. The dual-action antibody duligotuzumab (MEHD7945A) inhibits ligand binding to both epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 3 (HER3). Blockade of EGFR/HER3 and inhibitio…

Late-onset myasthenia gravis - CTLA4(low) genotype association and low-for-age thymic output of naïve T cells.

2014

Abstract Late-onset myasthenia gravis (LOMG) has become the largest MG subgroup, but the underlying pathogenetic mechanisms remain mysterious. Among the few etiological clues are the almost unique serologic parallels between LOMG and thymoma-associated MG (TAMG), notably autoantibodies against acetylcholine receptors, titin, ryanodine receptor, type I interferons or IL-12. This is why we checked LOMG patients for two further peculiar features of TAMG – its associations with the CTLA4 high/gain-of-function  +49A/A genotype and with increased thymic export of naive T cells into the blood, possibly after defective negative selection in AIRE-deficient thymomas. We analyzed genomic DNA from 116 …

Myasthenia-like syndrome induced by cardiovascular agents. Report of a case

1987

The case of a myasthenia-like syndrome induced by cardiovascular drugs is reported. The clinical and electrophysiological features of the case are discussed. © 1987 Masson Italia Periodici S.r.l.

Minimal manifestation status and prednisone withdrawal in the MGTX trial

2020

ObjectiveTo examine whether sustained minimal manifestation status (MMS) with complete withdrawal of prednisone is better achieved in thymectomized patients with myasthenia gravis (MG).MethodsThis study is a post hoc analysis of data from a randomized trial of thymectomy in MG (Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone Therapy [MGTX]). MGTX was a multicenter, randomized, rater-blinded 3-year trial that was followed by a voluntary 2-year extension for patients with acetylcholine receptor (AChR) antibody–positive MG without thymoma. Patients were randomized 1:1 to thymectomy plus prednisone vs prednisone alone. Participants were age 18–65 years at enr…

Drug‐refractory myasthenia gravis: Clinical characteristics, treatments, and outcome

2022

[Objective] To describe the clinical characteristics and outcomes in patients with refractory myasthenia gravis (MG) and to determine the effectiveness and side effects of the drugs used for their treatment.

Comparative analysis of biochip mosaic-based indirect immunofluorescence with enzyme-linked immunosorbent assay for diagnosing myasthenia gravis

2021

Background: The detection of anti-acetylcholine receptor (AChR) and anti-muscle-specific tyrosine kinase (MuSK) antibodies is useful in myasthenia gravis (MG) diagnosis and management. BIOCHIP mosaic-based indirect immunofluorescence is a novel analytical method, which employs the simultaneous detection of anti-AChR and anti-MuSK antibodies in a single miniature incubation field. In this study, we compare, for the first time, the BIOCHIP MG mosaic with conventional enzyme-linked immunosorbent assay (ELISA) in the diagnosis of MG. Methods: A total of 71 patients with MG diagnosis were included in the study. Anti-AChR and anti-MuSK antibodies were measured separately by two different ELISA an…

The Molecular Anatomy of Human Hsp60 and its Similarity with that of Bacterial Orthologs and Acetylcholine Receptor Reveal a Potential Pathogenetic R…

2012

Heat-shock protein 60 (Hsp60) is ubiquitous and highly conserved being present in eukaryotes and prokaryotes, including pathogens. This chaperonin, although typically a mitochondrial protein, can also be found in other intracellular sites, extracellularly, and in circulation. Thus, it can signal the immune system and participate in the development of inflammation and immune reactions. Both phenomena can be elicited by human and foreign Hsp60 (e.g., bacterial GroEL), when released into the blood by infectious agents. Consequently, all these Hsp60 proteins become part of a complex autoimmune response characterized by multiple cross reactions because of their structural similarities. In this s…

Severe congenital myasthenic syndrome due to homozygosity of the 1293insG ε-acetylcholine receptor subunit mutation

2000

Recently, a congenital myasthenic syndrome (CMS) with end-plate acetylcholine receptor (AChR) deficiency due to missense mutations in the genes for the AChR subunit was described. The first observed patient with this CMS was heteroallelic for the two epsilon-AChR subunit mutations epsilon1101insT and epsilon1293insG. This patient had only a moderate phenotype with mild muscle weakness and abnormal fatigue. We have now found homozygosity for the epsilon1293insG mutation in a severely affected CMS patient, who lost the ability to walk in midchildhood and shows profound weakness and muscle wasting. Our observation allows a genotype-phenotype correlation illustrating how differences in the AChR…

METHOTREXATE AS STEROID SPARING AGENT IN MYASTHENIA GRAVIS: A RETROSPECTIVE STUDY IN A SMALL COHORT OF PATIENTS

Introduction Myasthenia gravis (MG) is an autoimmune disorder of neuromuscular junction. Therapy for MG is still debated and controversial: corticosteroids alone or in combination with immunosuppressive agents are the most used drugs. Azathioprine (AZA) has been shown to be effective for MG in randomized placebo-controlled studies with a significant steroid-sparing activity after 15 months administration although several side effects1. Recently, some studies on Methotrexate (MTX) activity in MG have evidenced controversial results on efficacy, tolerability and steroid-sparing activity. Patients and Methods We have retrospectively evaluated in our MG cohort of (over 850 pts), a number of pat…