Introduction: Real-world data are required to provide a greater understanding of the impact of ofatumumab on the ability to mount an effective immune response following the receipt of approved COVID-19 vaccinations. This retrospective real-world analysis aimed to describe the humoral immune response to COVID-19 vaccination during ofatumumab treatment in patients with multiple sclerosis (MS).
Methods: Data from patients with MS treated with ofatumumab who were fully vaccinated against COVID-19 infection were abstracted from medical charts at four clinical sites in the USA.
Purpose: To characterize brain MR imaging findings in a cohort of 58 patients with ECD and to evaluate relationship between these findings and the BRAF pathogenic variant.
Methods: ECD patients of any gender and ethnicity, aged 2-80 years, with biopsy-confirmed ECD were eligible to enroll in this study. Two radiologists experienced in evaluating ECD CNS disease activity reviewed MRI studies.
Erdheim-Chester disease (ECD) is a rare histiocytic disease that affects multiple systems in the body. While it typically targets long bones, cardiovascular structures, the retroperitoneum, and the central nervous system, reports of tendon and skeletal muscle involvement are scarce. This review presents 2 cases: a case of ECD involving the left Achilles tendon and left abductor hallucis, as well as an unusual manifestation of ECD in the thigh musculature.
View Article and Find Full Text PDFJ Natl Compr Canc Netw
November 2021
Adult-onset histiocytoses (AOH), primarily Rosai-Dorfman disease (RDD), Erdheim-Chester Disease (ECD), and adult Langerhans cell histiocytosis (ALCH), are a group of related histiocytic neoplastic disorders featuring multisystemic manifestations. The disorders are largely incurable, and are essentially chronic neoplastic diseases with a variable prognosis. Prompt diagnosis and treatment is important to prevent debilitating and even life-threatening complications.
View Article and Find Full Text PDFPurpose: We examined abnormal pituitary imaging (API) and associated endocrine dysfunction in subjects with ECD.
Methods: A cross-sectional descriptive examination of a natural history cohort study diagnosed with ECD was conducted at a clinical research center. Subjects underwent baseline endocrine tests of anterior and posterior pituitary function and dedicated pituitary gland MRI scans.
Importance: Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis affecting multiple organs and commonly caused by somatic pathogenic variants in BRAF V600E and mitogen-activated protein kinase genes. Clinical features of ECD result from histiocytic involvement of various tissues; while endocrine involvement in ECD occurs frequently, the prevalence of central or primary hypothyroidism has not been thoroughly investigated.
Objective: To assess hypothalamus-pituitary-thyroid (HPT) dysfunction in patients with ECD.
Intractable epilepsy remains a significant medical challenge, resulting in recurrent and prolonged intensive care unit (ICU) admissions. Autoimmune encephalitis is emerging as a treatable cause of intractable epilepsy. It is characterized by antibodies against cerebral antigens, such as potassium channels such as leucine-rich, glioma inactivated 1 (LGI1) and contactin-associated protein 2 (CASPR2), calcium channels such as the voltage-gated calcium channel (VGCC), or neurotransmitter receptors such as the -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), gamma aminobutyric acid receptor (GABAR), and -methyl-D-aspartate receptor (NMDAR).
View Article and Find Full Text PDFObjective: To characterize the spectrum of neurologic involvement in Erdheim-Chester Disease (ECD), a treatable inflammatory neoplasm of histiocytes.
Methods: Sixty-two patients with ECD were prospectively enrolled in a natural history study that facilitated collection of clinical, imaging, laboratory, neurophysiologic, and pathologic data.
Results: Ninety-four percent of the patients had neurologic abnormalities on examination or imaging, and 22% had neurologic symptoms as the initial presentation of ECD.
Erdheim-Chester Disease (ECD) is a rare, potentially fatal, multi-organ myeloid neoplasm occurring mainly in adults. The diagnosis is established by clinical, radiologic, and histologic findings; ECD tumors contain foamy macrophages that are CD68+, CD163+, CD1a-, and frequently S100-. The purpose of this report is to describe the clinical and molecular variability of ECD.
View Article and Find Full Text PDFThe heterotrimeric, G protein-coupled receptor-associated G protein, Gα(s), binds tubulin with nanomolar affinity and disrupts microtubules in cells and in vitro. Here we determine that the activated form of Gα(s) binds tubulin with a K(D) of 100 nm, stimulates tubulin GTPase, and promotes microtubule dynamic instability. Moreover, the data reveal that the α3-β5 region of Gα(s) is a functionally important motif in the Gα(s)-mediated microtubule destabilization.
View Article and Find Full Text PDFNow days, breast cancer is the most frequently diagnosed life-threatening cancer in women and the leading cause of cancer death among women. Since last two decades, researches related to the breast cancer has lead to extraordinary progress in our understanding of the disease, resulting in more efficient and less toxic treatments. Increased public awareness and improved screening have led to earlier diagnosis at stages amenable to complete surgical resection and curative therapies.
View Article and Find Full Text PDFLipid rafts and caveolae are specialized membrane microdomains implicated in regulating G protein-coupled receptor signaling cascades. Previous studies have suggested that rafts/caveolae may regulate beta-adrenergic receptor/Galpha(s) signaling, but underlying molecular mechanisms are largely undefined. Using a simplified model system in C6 glioma cells, this study disrupts rafts/caveolae using both pharmacological and genetic approaches to test whether caveolin-1 and lipid microdomains regulate G(s) trafficking and signaling.
View Article and Find Full Text PDFIt is now evident that Galpha(s) traffics into cytosol following G protein-coupled receptor activation, and alpha subunits of some heterotrimeric G-proteins, including Galpha(s) bind to tubulin in vitro. Nevertheless, many features of G-protein-microtubule interaction and possible intracellular effects of G protein alpha subunits remain unclear. In this study, several biochemical approaches demonstrated that activated Galpha(s) directly bound to tubulin and cellular microtubules, and fluorescence microscopy showed that cholera toxin-activated Galpha(s) colocalized with microtubules.
View Article and Find Full Text PDFA large percentage of current drugs target G-protein-coupled receptors, which couple to well-known signaling pathways involving cAMP or calcium. G-proteins themselves may subserve a second messenger function. Here, we review the role of tubulin and microtubules in directly mediating effects of heterotrimeric G-proteins on neuronal outgrowth, shape and differentiation.
View Article and Find Full Text PDF