Physiological levels of folic acid reveal purine alterations in Lesch-Nyhan disease.

Lesch-Nyhan disease (LND), caused by a deficient salvage purine pathway, is characterized by severe neurological manifestations and uric acid overproduction. However, uric acid is not responsible for brain dysfunction, and it has been suggested that purine nucleotide depletion, or accumulation of other toxic purine intermediates, could be more relevant. Here we show that purine alterations in LND fibroblasts depend on the level of folic acid in the culture media.

Systematic genetic analysis of early-onset gout: ABCG2 is the only associated locus.

Objective: The aim of this study was to examine whether serum urate-associated genetic variants are associated with early-onset gout.

Methods: Participants with gout in the Genetics of Gout in Aotearoa study with available genotyping were included (n = 1648). Early-onset gout was defined as the first presentation of gout <40 years of age.

The genetic etiology in cerebral palsy mimics: The results from a Greek tertiary care center.

Objective: Non-progressive genetic disorders may present with motor dysfunction resembling cerebral palsy (CP). Such patients are often characterized as CP mimics. The purpose of this work was to delineate the clinical manifestations and molecular findings of CP mimic patients, with the ultimate goal to offer specific disease-modifying therapy and genetic counseling.

A novel approach to triple-negative breast cancer molecular classification reveals a luminal immune-positive subgroup with good prognoses.

Triple-negative breast cancer is a heterogeneous disease characterized by a lack of hormonal receptors and HER2 overexpression. It is the only breast cancer subgroup that does not benefit from targeted therapies, and its prognosis is poor. Several studies have developed specific molecular classifications for triple-negative breast cancer.

Serum and blister-fluid elevation and decreased epidermal content of high-mobility group box 1 protein in drug-induced Stevens-Johnson syndrome/toxic epidermal necrolysis.

Background: High-mobility group box 1 (HMGB1) is a damage-associated molecular-pattern protein. Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) are serious, immune-mediated skin-blistering conditions.

Objectives: To determine serum and/or blister-fluid total HMGB1 levels in SJS/TEN cohorts, and HMGB1 expression in formalin-fixed, paraffin-embedded (FFPE) SJS/TEN skin vs.

Increased Risk of Ischemic Stroke in Multiple Myeloma Associated With Lenalidomide Treatment: A Case Report and Review of the Literature.

Objective: The aim of the study was to illustrate the increased risk of ischemic stroke in the context of multiple myeloma (MM) under treatment with lenalidomide combined with dexamethasone.

Methods: This is a case report and literature review.

Results: A 62-year-old woman diagnosed with relapsed MM under treatment with lenalidomide and dexamethasone presented with acute onset disorientation, disturbed behavior, and aphasia.

GLUT9 influences uric acid concentration in patients with Lesch-Nyhan disease.

Background: Patients with deficient hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity present hyperuricemia and/or hyperuricosuria, with a variable degree of neurological manifestations. Hyperuricemia in HPRT deficiency is due to uric acid overproduction and is frequently treated with allopurinol. Renal uric acid excretion is sharply increased in these patients.

Sensitivity and specificity of the lymphocyte transformation test in drug reaction with eosinophilia and systemic symptoms causality assessment.

Background: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe delayed hypersensitivity reaction. The determination of drug causality is complex. The lymphocyte transformation test (LTT) has been reported positive in more than 50% of DRESS cases.

Functional proteomics outlines the complexity of breast cancer molecular subtypes.

Breast cancer is a heterogeneous disease comprising a variety of entities with various genetic backgrounds. Estrogen receptor-positive, human epidermal growth factor receptor 2-negative tumors typically have a favorable outcome; however, some patients eventually relapse, which suggests some heterogeneity within this category. In the present study, we used proteomics and miRNA profiling techniques to characterize a set of 102 either estrogen receptor-positive (ER+)/progesterone receptor-positive (PR+) or triple-negative formalin-fixed, paraffin-embedded breast tumors.

Monocytes inhibit NK activity TGF-β in patients with obstructive sleep apnoea.

Obstructive sleep apnoea (OSA) is associated with cancer incidence and mortality. The contribution of the immune system appears to be crucial; however, the potential role of monocytes and natural killer (NK) cells remains unclear.Quantitative reverse transcriptase PCR, flow cytometry and assays were used to analyse the phenotype and immune response activity in 92 patients with OSA (60 recently diagnosed untreated patients and 32 patients after 6 months of treatment with continuous positive airway pressure (CPAP)) and 29 healthy volunteers (HV).

Functional Rescue of Trafficking-Impaired ABCB4 Mutants by Chemical Chaperones.

Multidrug resistance protein 3 (MDR3, ABCB4) is a hepatocellular membrane protein that mediates biliary secretion of phosphatidylcholine. Null mutations in ABCB4 gene give rise to severe early-onset cholestatic liver disease. We have previously shown that the disease-associated mutations p.

Heterozygous ABCB4 mutations in children with cholestatic liver disease.

Background & Aims: Monoallelic defects in ABCB4, which encodes the canalicular floppase for phosphatidylcholine MDR3, have been encountered in association with a variety of hepatobiliary disorders, particularly in adult subjects. In this study, we examined the presence of heterozygous ABCB4 variants in a cohort of children with chronic cholestasis and assessed the pathogenicity of the missense changes identified.

Methods: Sixty-seven children with chronic liver dysfunction were studied by the sequencing of ABCB4 and multiplex ligation-dependent probe amplification analysis.

Histone deacetylase 4 promotes cholestatic liver injury in the absence of prohibitin-1.

Unlabelled: Prohibitin-1 (PHB1) is an evolutionarily conserved pleiotropic protein that participates in diverse processes depending on its subcellular localization and interactome. Recent data have indicated a diverse role for PHB1 in the pathogenesis of obesity, cancer, and inflammatory bowel disease, among others. Data presented here suggest that PHB1 is also linked to cholestatic liver disease.

Functional analysis of ABCB4 mutations relates clinical outcomes of progressive familial intrahepatic cholestasis type 3 to the degree of MDR3 floppase activity.

Objective: Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a potentially lethal autosomal recessive liver disease associated with mutations in ABCB4, the gene encoding the canalicular translocator of phosphatidylcholine MDR3. While some affected children benefit from ursodeoxycholic acid (UDCA) therapy, others evolve to end-stage liver disease. We aimed to evaluate whether these different outcomes are related to the impact of ABCB4 mutations.

Advanced therapies for the treatment of hemophilia: future perspectives.

Monogenic diseases are ideal candidates for treatment by the emerging advanced therapies, which are capable of correcting alterations in protein expression that result from genetic mutation. In hemophilia A and B such alterations affect the activity of coagulation factors VIII and IX, respectively, and are responsible for the development of the disease. Advanced therapies may involve the replacement of a deficient gene by a healthy gene so that it generates a certain functional, structural or transport protein (gene therapy); the incorporation of a full array of healthy genes and proteins through perfusion or transplantation of healthy cells (cell therapy); or tissue transplantation and formation of healthy organs (tissue engineering).