Publications by authors named "Simone Thomas"

Background And Aims: Peripheral neuropathy (PN) is a common neurological condition in elderly adults. Vitamin D deficiency has been associated with diabetic and chemotherapy-induced neuropathy, but its role in idiopathic PN, in which no underlying cause of neuropathy can be identified, has not been investigated.

Methods: Two hundred thirty patients with idiopathic PN enrolled in the Peripheral Neuropathy Research Registry (PNRR) at Johns Hopkins University School of Medicine had vitamin D testing information on record.

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Dominant mutations in the calcium-permeable ion channel TRPV4 (transient receptor potential vanilloid 4) cause diverse and largely distinct channelopathies, including inherited forms of neuromuscular disease, skeletal dysplasias, and arthropathy. Pathogenic TRPV4 mutations cause gain of ion channel function and toxicity that can be rescued by small molecule TRPV4 antagonists in cellular and animal models, suggesting that TRPV4 antagonism could be therapeutic for patients. Numerous variants in TRPV4 have been detected with targeted and whole exome/genome sequencing, but for the vast majority, their pathogenicity remains unclear.

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Dominant missense mutations of the calcium-permeable cation channel TRPV4 cause Charcot-Marie-Tooth disease (CMT) type 2C and two forms of distal spinal muscular atrophy. These conditions are collectively referred to as TRPV4-related neuromuscular disease and share features of motor greater than sensory dysfunction and frequent vocal fold weakness. Pathogenic variants lead to gain of ion channel function that can be rescued by TRPV4 antagonists in cellular and animal models.

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Article Synopsis
  • This paper gives tips on how to work together internationally to do research on nerve damage caused by chemotherapy (CIPN).
  • A team of experts from different fields shared their knowledge to help make these collaborations successful across countries.
  • Their recommendations cover many areas, like research methods, communication, funding, and training, to ensure better research that includes diverse participants and helps cancer survivors everywhere.
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D-2-hydroxyglutarate (D-2-HG) accumulates in patients with acute myeloid leukemia (AML) with mutated isocitrate dehydrogenase (IDH) and in other malignancies. D-2-HG suppresses antitumor T-cell immunity but little is known about potential effects on non-malignant myeloid cells. Here we show that D-2-HG impairs human but not murine dendritic cell differentiation, resulting in a tolerogenic phenotype with low major histocompatibility class II expression.

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Norovirus is the leading cause of viral gastroenteritis worldwide, and there are no approved vaccines or therapeutic treatments for chronic or severe norovirus infections. The structural characterisation of the norovirus protease and drug development has predominantly focused upon GI.1 noroviruses, despite most global outbreaks being caused by GII.

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Article Synopsis
  • A study aimed to understand why only some patients with idiopathic peripheral neuropathy (IPN) experience neuropathic pain by analyzing proteins in their blood.
  • Researchers compared blood plasma from 31 painful IPN patients with 29 non-painful ones using mass-spectrometry to identify potential protein biomarkers.
  • The findings highlight a possible connection between the complement system and neuropathic pain, identifying specific proteins that could serve as indicators for pain severity in IPN patients.
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Chimeric antigen receptors (CARs) in the canonical "second generation" format provide two signals for inducing T cell effector functions; the primary "signal-1" is provided through the TCR CD3ζ chain and the "signal-2" through a linked costimulatory domain to augment activation. While therapy with second generation CAR T cells can induce remissions of leukemia/lymphoma in a spectacular fashion, CAR T cell persistence is frequently limited which is thought to be due to timely limited activation. Following the "three-signal" dogma for inducing a sustained T cell response, cytokines were supplemented to provide "signal-3" to CAR T cells.

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Human cytomegalovirus (HCMV) infection is associated with severe disease conditions either following congenital transmission of the virus or viral reactivation in immunosuppressed individuals. Consequently, the establishment of a protective vaccine is of high medical need. Several candidates have been tested in preclinical and clinical studies, yet no vaccine has been licensed.

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Polycystic ovary syndrome (PCOS) is associated with elevated androgen and luteinizing hormone (LH) secretion and with oligo/anovulation. Evidence indicates that elevated androgens impair sex steroid hormone feedback regulation of pulsatile LH secretion. Hyperandrogenemia in PCOS may also disrupt the preovulatory LH surge.

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Background: To date, in-depth analysis of leukapheresis products as starting material for CAR T-cell manufacturing, specifically Tisagenlecleucel production, are scarce. In this study, we report on lymphapheresis data for production of Tisagenlecleucel for elderly and pretreated lymphoma patients.

Study Design And Methods: Spectra Optia from Terumo BCT, Lakewood, CO, was employed for apheresis using the cMNC program.

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Accelerated glycolysis leads to secretion and accumulation of lactate and protons in the tumor environment and determines the efficacy of adoptive T cell and checkpoint inhibition therapy. Here, we analyzed effects of lactic acid on different human CD4 T cell subsets and aimed to increase CD4 T cell resistance towards lactic acid. In all CD4 T cell subsets analyzed, lactic acid inhibited metabolic activity (glycolysis and respiration), cytokine secretion, and cell proliferation.

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CD19-directed chimeric antigen receptor (CAR) T cells have evolved as a new standard-of-care (SOC) treatment in patients with relapsed/refractory (r/r) large B-cell lymphoma (LBCL). Here, we report the first German real-world data on SOC CAR T-cell therapies with the aim to explore risk factors associated with outcomes. Patients who received SOC axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) for LBCL and were registered with the German Registry for Stem Cell Transplantation (DRST) were eligible.

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Pyridoxine (vitamin B6) toxicity is known to cause a length-dependent, sensory predominant axonal polyneuropathy. There is debate regarding the threshold at which intake levels can cause neurological symptoms through pyridoxine toxicity. We asked if elevated plasma vitamin B6 levels were related to outcome measures in a well-characterized cohort of patients with chronic idiopathic axonal polyneuropathy (CIAP).

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Acute myeloid leukemia (AML) is an attractive entity for the development of chimeric antigen receptor (CAR) T-cell immunotherapy because AML blasts are susceptible to T-cell-mediated elimination. Here, we introduce sialic acid-binding immunoglobulin-like lectin 6 (Siglec-6) as a novel target for CAR T cells in AML. We designed a Siglec-6-specific CAR with a targeting domain derived from the human monoclonal antibody JML-1.

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In recent years, onco-metabolites like D-2-hydroxyglutarate, which is produced in isocitrate dehydrogenase-mutated tumors, have gained increasing interest. Here, we report a metabolite in human specimens that is closely related to 2-hydroxyglutarate: the intramolecular ester of 2-hydroxyglutarate, 2-hydroxyglutarate-γ-lactone. Using C-L-glutamine tracer analysis, we showed that 2-hydroxyglutarate is the endogenous precursor of 2-hydroxyglutarate-lactone and that there is a high exchange between these two metabolites.

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Background: Electromechanical- and robot-assisted gait-training devices are used in rehabilitation and might help to improve walking after stroke. This is an update of a Cochrane Review first published in 2007 and previously updated in 2017.

Objectives: Primary • To determine whether electromechanical- and robot-assisted gait training versus normal care improves walking after stroke Secondary • To determine whether electromechanical- and robot-assisted gait training versus normal care after stroke improves walking velocity, walking capacity, acceptability, and death from all causes until the end of the intervention phase SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (last searched 6 January 2020); the Cochrane Central Register of Controlled Trials (CENTRAL; 2020 Issue 1), in the Cochrane Library; MEDLINE in Ovid (1950 to 6 January 2020); Embase (1980 to 6 January 2020); the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 20 November 2019); the Allied and Complementary Medicine Database (AMED; 1985 to 6 January 2020); Web of Science (1899 to 7 January 2020); SPORTDiscus (1949 to 6 January 2020); the Physiotherapy Evidence Database (PEDro; searched 7 January 2020); and the engineering databases COMPENDEX (1972 to 16 January 2020) and Inspec (1969 to 6 January 2020).

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Although exercise is associated with better outcomes in patients with some peripheral neuropathies, data in idiopathic peripheral neuropathies is lacking. This study was completed to do a comprehensive data analysis about the benefits of regular exercise in a well-characterized cohort of patients with idiopathic distal, symmetrical, axonal polyneuropathy enrolled in the Peripheral Neuropathy Research Registry (PNRR) at Johns Hopkins University School of Medicine. From the patient-reported exercise habits, metabolic equivalents (METs) were calculated and the patient information was grouped into four categories.

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HLA-DPB1 antigens are mismatched in about 80% of allogeneic hematopoietic stem cell transplantations from HLA 10/10 matched unrelated donors and were shown to be associated with a decreased risk of leukemia relapse. We recently developed a reliable in vitro method to generate HLA-DPB1 mismatch-reactive CD4 T-cell clones from allogeneic donors. Here, we isolated HLA-DPB1 specific T cell receptors (TCR DP) and used them either as wild-type or genetically optimized receptors to analyze in detail the reactivity of transduced CD4 and CD8 T cells toward primary AML blasts.

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Objectives: To describe physiotherapeutic interventions used in the post-acute inpatient rehabilitation of chronic critically ill patients with intensive-care-unit-acquired muscle weakness, and to determine the influence of such interventions on patients' ability to walk.

Methods: Chronic critically ill patients with intensive-care-unit-acquired muscle weakness who were in post-acute and rehabilitation units were included in a cohort study. During post-acute rehabilitation, the patients' functional status at baseline, all daily physiotherapeutic interventions, and ability to walk were documented.

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