Vedolizumab quantitation using high-resolution accurate mass-mass spectrometry middle-up protein subunit: method validation.

Background While quantitation methods for small-molecule and tryptic peptide bottom-up mass spectrometry (MS) have been well defined, quantitation methods for top-down or middle-up MS approaches have not been as well defined. Therapeutic monoclonal antibodies (t-mAbs) are a group of proteins that can be used to both demonstrate the advantages of top-down or middle-up detection methods over classic tryptic peptide bottom-up along with the growing need for robust quantitation strategies/software for these top-down or middle-up methods. Bottom-up proteolytic digest methods for the t-mAbs tend to suffer from challenges such as limited peptide selection due to potential interference from the polyclonal immunoglobulin background, complicated workflows, and inadequate sensitivity and specificity without laborious purification steps, and therefore have prompted the search for new detection and quantitation methods.

Prevalence of Clinically Significant Differences in Sodium Measurements Due to Abnormal Protein Concentrations Using an Indirect Ion-Selective Electrode Method.

Background: Indirect ion-selective electrode (ISE) is the primary method used to measure sodium in automated clinical laboratories and is susceptible to the electrolyte exclusion effect. Pseudohyponatremia due to hyperproteinemia can affect patient management. The aims of this study were to () establish the relationship between serum total protein (TP) concentration and the magnitude of the electrolyte exclusion effect on indirect ISE-measured sodium values () estimate the frequency at which TP concentrations outside the reference interval may impact indirect-ISE measured sodium values, and () determine whether clinical decision support (middleware) rules in the laboratory would be effective for detecting cases of pseudohyponatremia.

Analytical and clinical performance of thyroglobulin autoantibody assays in thyroid cancer follow-up.

Background: While thyroglobulin autoantibodies (TgAb) can result in false low serum thyroglobulin (Tg) immunoassay (IA) measurements, they might also be indicators of disease persistence/recurrence. Hence, accurate TgAb measurement, in addition to Tg quantification, is crucial for thyroid cancer monitoring. We compared the analytical and clinical performance of four commonly used TgAb IAs.

Interactions of linoleic and alpha-linolenic acids in the development of fatty acid alterations in cystic fibrosis.

Patients with cystic fibrosis (CF) exhibit characteristic polyunsaturated fatty acid abnormalities, including low linoleic acid and high arachidonic acid levels that are thought to contribute to the pathophysiology of this disease. Recent studies indicate that changes in fatty acid metabolism are responsible for these abnormalities. This study examines the role of fatty acid substrate concentrations in the development of these alterations in a cultured cell model of CF.

DHA and EPA reverse cystic fibrosis-related FA abnormalities by suppressing FA desaturase expression and activity.

Patients and models of cystic fibrosis (CF) exhibit consistent abnormalities of polyunsaturated fatty acid composition, including decreased linoleate (LA) and docosahexaenoate (DHA) and variably increased arachidonate (AA), related in part to increased expression and activity of fatty acid desaturases. These abnormalities and the consequent CF-related pathologic manifestations can be reversed in CF mouse models by dietary supplementation with DHA. However, the mechanism is unknown.

Increased Δ5- and Δ6-desaturase, cyclooxygenase-2, and lipoxygenase-5 expression and activity are associated with fatty acid and eicosanoid changes in cystic fibrosis.

Patients with cystic fibrosis consistently demonstrate selective abnormalities in essential fatty acid concentrations, including decreased linoleate (LA) and docosahexaenoate (DHA), with variably increased arachidonate (AA). These changes appear important for the pathophysiology of the disease. However, the mechanisms of these changes are not clearly understood.

Increased elongase 6 and Δ9-desaturase activity are associated with n-7 and n-9 fatty acid changes in cystic fibrosis.

Patients with cystic fibrosis, caused by mutations in CFTR, exhibit specific and consistent alterations in the levels of particular unsaturated fatty acids compared with healthy controls. Evidence suggests that these changes may play a role in the pathogenesis of this disease. Among these abnormalities are increases in the levels of n-7 and n-9 fatty acids, particularly palmitoleate (16:1n-7), oleate (18:1n-9), and eicosatrienoate or mead acid (20:3n-9).

A mechanism accounting for the low cellular level of linoleic acid in cystic fibrosis and its reversal by DHA.

Specific fatty acid alterations have been described in the blood and tissues of cystic fibrosis (CF) patients. The principal alterations include decreased levels of linoleic acid (LA) and docosahexaenoic acid (DHA). We investigated the potential mechanisms of these alterations by studying the cellular uptake of LA and DHA, their distribution among lipid classes, and the metabolism of LA in a human bronchial epithelial cell model of CF.

Cell culture models demonstrate that CFTR dysfunction leads to defective fatty acid composition and metabolism.

Cystic fibrosis (CF) is associated with fatty acid alterations characterized by low linoleic and docosahexaenoic acid. It is not clear whether these fatty acid alterations are directly linked to cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction or result from nutrient malabsorption. We hypothesized that if fatty acid alterations are a result of CFTR dysfunction, those alterations should be demonstrable in CF cell culture models.