Monoclonal gammopathy of undetermined significance and COVID-19: a population-based cohort study.

Multiple myeloma (MM) patients have increased risk of severe coronavirus disease 2019 (COVID-19) when infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Monoclonal gammopathy of undetermined significance (MGUS), the precursor of MM has been associated with immune dysfunction which may lead to severe COVID-19. No systematic data have been published on COVID-19 in individuals with MGUS.

Iceland screens, treats, or prevents multiple myeloma (iStopMM): a population-based screening study for monoclonal gammopathy of undetermined significance and randomized controlled trial of follow-up strategies.

Monoclonal gammopathy of undetermined significance (MGUS) precedes multiple myeloma (MM). Population-based screening for MGUS could identify candidates for early treatment in MM. Here we describe the Iceland Screens, Treats, or Prevents Multiple Myeloma study (iStopMM), the first population-based screening study for MGUS including a randomized trial of follow-up strategies.

Association between non-malignant monoclonal gammopathy and adverse outcomes in chronic kidney disease: A cohort study.

Background: In studies including the general population, the presence of non-malignant monoclonal gammopathy (MG) can be causally associated with kidney damage and shorter survival. We assessed whether the presence of an MG is associated with a higher risk of kidney failure or death in individuals with chronic kidney disease (CKD).

Methods And Findings: Data were used from 3 prospective cohorts of individuals with CKD (not on dialysis or with a kidney transplant): (1) Renal Impairment in Secondary Care (RIISC, Queen Elizabeth Hospital and Heartlands Hospital, Birmingham, UK, N = 878), (2) Salford Kidney Study (SKS, Salford Royal Hospital, Salford, UK, N = 861), and (3) Renal Risk in Derby (RRID, Derby, UK, N = 1,739).

Serum free light chain assays not total light chain assays are the standard of care to assess Monoclonal Gammopathies.

The diagnosis of Multiple Myeloma is a challenge to the physician due to the non-specific symptoms (anemia, bone pain and recurrent infections) that are commonplace in the elderly population. However, early diagnosis is associated with less severe disease, including fewer patients presenting with acute renal injury, pathological fractures and severe anemia. Since 2006, the serum free light chain test Freelite(®) has been included alongside standard laboratory tests (serum and urine protein electrophoresis, and serum and urine immunofixation) as an aid in the identification of monoclonal proteins, which are a cornerstone for the diagnosis of Multiple Myeloma.

FKBP25, a novel regulator of the p53 pathway, induces the degradation of MDM2 and activation of p53.

The p53 tumour suppressor protein is tightly controlled by the E3 ubiquitin ligase, mouse double minute 2 (MDM2), but maintains MDM2 expression as part of a negative feedback loop. We have identified the immunophilin, 25kDa FK506-binding protein (FKBP25), previously shown to be regulated by p53-mediated repression, as an MDM2-interacting partner. We show that FKBP25 stimulates auto-ubiquitylation and proteasomal degradation of MDM2, leading to the induction of p53.

Thiopurine S-methyltransferase genotype-phenotype concordance: used as a quality assurance tool to help control the phenotype assay.

Background: As part of the quality control system for our TPMT phenotyping service we monitor the genotype-phenotype concordance for patient samples with deficient and low TPMT activity. We have studied the genotype-phenotype concordance over the last year to demonstrate its effectiveness as a quality assurance tool.

Methods: From July 2007 to July 2008 TPMT genotyping was performed on all routine samples analysed using our phenotypic assay with an activity of View Article and Find Full Text PDF

Development and validation of an improved test for the measurement of human faecal elastase-1.

Background: Human faecal elastase-1 (FE-1) is an established biochemical test for the investigation of pancreatic exocrine insufficiency. Conventional extraction methods for FE-1 analysis can give false-positive results with watery stools. This is a major limitation as patients investigated for pancreatic disease commonly produce such stools.

A novel site of AKT-mediated phosphorylation in the human MDM2 onco-protein.

MDM2 is an E3 ubiquitin ligase which mediates ubiquitylation and proteasome-dependent degradation of the p53 tumor suppressor protein. Phosphorylation of MDM2 by the protein kinase AKT is thought to regulate MDM2 function in response to survival signals, but there has been uncertainty concerning the identity of the sites phosphorylated by AKT. In the present study, we identify Ser-166, a site previously reported as an AKT target, and Ser-188, a novel site which is the major site of phosphorylation of MDM2 by AKT in vitro.