Publications by authors named "Tim Plant"

Objectives: Patients with Systemic Lupus Erythematosus are known to have dysregulated immune responses and may have reduced response to vaccination against COVID-19 while being at risk of severe COVID-19 disease. The aim of this study was to identify whether vaccine responses were attenuated in SLE and to assess disease- and treatment-specific associations.

Methods: Patients with SLE were matched by age, sex and ethnic background to healthcare worker healthy controls (HC).

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Genome sequencing is a powerful tool for identifying SARS-CoV-2 variant lineages; however, there can be limitations due to sequence dropout when used to identify specific key mutations. Recently, ThermoFisher Scientific has developed genotyping assays to help bridge the gap between testing capacity and sequencing capability to generate real-time genotyping results based on specific variants. Over a 6-week period during the months of April and May 2021, we set out to assess the ThermoFisher TaqMan mutation panel genotyping assay, initially for three mutations of concern and then for an additional two mutations of concern, against SARS-CoV-2-positive clinical samples and the corresponding COVID-19 Genomics UK Consortium (COG-UK) sequencing data.

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Article Synopsis
  • * A study developed an improved ELISA test that focuses on trimeric spike glycoprotein, leading to better detection of low antibody levels in serum and saliva from non-hospitalized subjects.
  • * Results showed that while hospitalized patients had detectable antibody responses using various antigens, saliva tests were effective for only some symptomatic individuals, indicating that combining saliva and serum testing can enhance understanding of immune responses post-infection.
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Lateral flow devices (LFDs) are quickly being implemented for use in large-scale population surveillance programs for SARS-CoV-2 infection in the United Kingdom. These programs have been piloted in city-wide screening in the city of Liverpool and are now being rolled out to support care home visits and the return home of University students for the Christmas break. Here, we present data on the performance of LFDs to test almost 8,000 students at the University of Birmingham between December 2 and December 9, 2020.

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A SARS-CoV-2 variant B1.1.7 containing mutation Δ69/70 has spread rapidly in the United Kingdom and shows an identifiable profile in ThermoFisher TaqPath RT-qPCR, S gene target failure (SGTF).

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Background And Aims: A variety of auto-antibody assays are available as part of the clinical care of patients with liver disease. We sought to better understand the clinical utility of immune serological testing in patients with primary biliary cholangitis (PBC).

Methods: We retrospectively analysed data from 2846 patients investigated for liver disease at a UK liver centre between 2001 and 2017.

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Article Synopsis
  • Detecting antibody responses to SARS-CoV-2 is crucial for understanding the virus's spread and the immune response, especially since assessing responses in mild or asymptomatic cases is challenging.
  • An optimized ELISA assay was developed to measure antibody responses in serum and saliva from both symptomatic and asymptomatic COVID-19 patients, revealing that anti-spike antibodies were more effective than nucleocapsid antibodies in low responders.
  • The study found that antibody responses in saliva were independent of symptom severity, suggesting that testing both saliva and serum is the best way to assess exposure to the virus and immune responses following infection.
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Background: In January 2020 reports of unidentified severe respiratory illness were described in Wuhan, China. A rapid expansion in cases affecting most countries around the globe led to major changes in the way people live their daily lives. In the United Kingdom, the Department of Health and Social Care directed healthcare providers to establish additional resources to manage the anticipated surge in cases that could overwhelm the health services.

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The cation channel subunit TRPC1 is strongly expressed in central neurons including neurons in the CA1 region of the hippocampus where it forms complexes with TRPC4 and TRPC5. To investigate the functional role of TRPC1 in these neurons and in channel function, we compared current responses to group I metabotropic glutamate receptor (mGluR I) activation and looked for major differences in dendritic morphology in neurons from and mice. mGluR I stimulation resulted in the activation of a voltage-dependent nonselective cation current in both genotypes.

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Background: Polyclonal FLCs can be used as a biomarker of inflammation and immune activation in a range of diseases. This study evaluated the performance of new FLC ELISAs (Seralite FLC ELISA) for the quantitation of polyclonal κ and λ FLC, including comparisons to existing assays.

Methods: Technical performance was assessed for the ELISA and reference ranges were generated using healthy donor serum (N = 91).

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 It is widely believed that patients bearing auto-antibodies to histidyl tRNA synthetase (anti-Jo-1) very likely have a connective tissue disease including myositis and interstitial lung disease.  The value of positive tests in low disease prevalence settings such as those tested in routine care is unknown.  We sought to determine the value of anti-Jo-1 auto-antibodies in routine practice.

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Background: Mast cell activation can lead to nonclassical activation of the Renin-Angiotensin-Aldosterone System. However, the relevance of this to human chronic kidney disease is unknown. We assessed the association between serum tryptase, a product of mast cell activation, and progression to end-stage renal disease or mortality in patients with advanced chronic kidney disease.

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Mechanosensitive channels allow cells to respond to changes in membrane stretch that occur due to external stimuli like pressure or flow or that occur because of osmotically induced cell swelling or shrinkage. Ion fluxes through the channels change the membrane potential and ion concentrations and link the stretch to cellular signalling. Changes in cellular activity evoked by mechanical stimuli can be used to elicit local tissue responses or can be transmitted further to generate more widespread responses.

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The measurement of antibody responses to vaccination is useful in the assessment of immune status in suspected immune deficiency. Previous reliance on enzyme-linked immunoabsorbent assays (ELISA) has been cumbersome, time-consuming and expensive. The availability of flow cytometry systems has led to the development of multiplexed assays enabling simultaneous measurement of antibodies to several antigens.

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The dynamic expression of AMPA-type glutamate receptors (AMPA-R) at synapses is a key determinant of synaptic plasticity, including neuroadaptations to drugs of abuse. Recently, microRNAs (miRNAs) have emerged as important posttranscriptional regulators of synaptic plasticity, but whether they target glutamate receptors to mediate this effect is not known. Here we used microarray screening to identify miRNAs that regulate synaptic plasticity within the nucleus accumbens, a brain region critical to forming drug-seeking habits.

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Several Ca(2+)-permeable channels, including the non-selective cation channel TRPV4, are subject to Ca(2+)-dependent facilitation. Although it has been clearly demonstrated in functional experiments that calmodulin (CaM) binding to intracellular domains of TRP channels is involved in this process, the molecular mechanism remains elusive. In this study, we provide experimental evidence for a comprehensive molecular model that explains Ca(2+)-dependent facilitation of TRPV4.

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Background: Monoclonal free light chains (FLCs) frequently cause rapidly progressive renal failure in patients with multiple myeloma. Immunoassays which provide quantitative measurement of FLCs in serum, have now been adopted into screening algorithms for multiple myeloma and other lymphoproliferative disorders. The assays indicate monoclonal FLC production by the presence of an abnormal kappa to lambda FLC ratio (reference range 0.

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Background: Endothelin-1 (ET-1) both stimulates nociceptors and sensitizes them to noxious stimuli, an effect probably mediated by the ETA receptor (ETAR) expressed in sensory neurons. The cellular mechanisms of this ET-1-mediated effect are only poorly understood. TRPV1, the heat-, pH- and capsaicin-sensitive cation channel already known to be modulated by a number of cellular mediators released in response to noxious stimuli and during inflammation, is a potential target for the action of ET-1.

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Mammalian members of the classical transient receptor potential channel subfamily (TRPC) are Ca(2+)-permeable cation channels involved in receptor-mediated increases in intracellular Ca(2+). TRPC4 and TRPC5 form a group within the TRPC subfamily and are activated in a phospholipase C-dependent manner by an unidentified messenger. Unlike most other Ca(2+)-permeable channels, TRPC4 and -5 are potentiated by micromolar concentrations of La(3+) and Gd(3+).

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