Plasmablastic myeloma transformation of light-chain multiple myeloma.

Plasmablastic myeloma (PBM) is an uncommon and aggressive morphologic variant of multiple myeloma (MM). The neoplastic immature cells exhibit diverse morphology, posing a diagnostic challenge. The diagnostic criteria for PBM include the identification of ≥ 2% plasmablasts in the bone marrow aspirate.

Elevated vitamin B₁₂ levels in autoimmune lymphoproliferative syndrome attributable to elevated haptocorrin in lymphocytes.

Objective: Identify the etiology of elevated B(12) in autoimmune lymphoproliferative syndrome (ALPS).

Design: Peripheral blood of ALPS patients with elevated B(12) and controls were evaluated.

Results: Total and holo-haptocorrin (HC) levels were 26- and 23-fold higher in ALPS patients, respectively.

Taking a new biomarker into routine use--a perspective from the routine clinical biochemistry laboratory.

There is increasing pressure to provide cost-effective healthcare based on "best practice." Consequently, new biomarkers are only likely to be introduced into routine clinical biochemistry departments if they are supported by a strong evidence base and if the results will improve patient management and outcome. This requires convincing evidence of the benefits of introducing the new test, ideally reflected in fewer hospital admissions, fewer additional investigations and/or fewer clinic visits.

Introduction to urinalysis: historical perspectives and clinical application.

Urinalysis was the first laboratory test performed in medicine and has been used for several thousand years. Today urinalysis continues to be a powerful tool in obtaining crucial information for diagnostic purposes in medicine. Urine is an unstable fluid, and changes to its composition begin to take place as soon as it is voided.

Improved detection of intact tyrosine sulfate-containing peptides by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry in linear negative ion mode.

Sulfation of tyrosine residues is a common post-translational modification, but detecting and quantitating this modification poses challenges due to lability of the sulfate group. The goal of our studies was to determine how best to detect and to assess the stoichiometry of this modification using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI TOF MS). Sulfated and nonsulfated forms of peptides-hirudin(55-65), caerulein, and cholecystokinin octapeptide and phosphorylated and nonphosphorylated pp60-c-src (521-533)-were analyzed using several matrices: sinapinic acid (SA), 2,5-dihydroxybenzoic acid (DBA), and cyano-4-hydroxycinnamic acid (CHCA).

Impact of blood collection devices on clinical chemistry assays.

Blood collection devices interact with blood to alter blood composition, serum, or plasma fractions and in some cases adversely affect laboratory tests. Vascular access devices may release coating substances and exert shear forces that lyse cells. Blood-dissolving tube additives can affect blood constituent stability and analytical systems.

Comparison of urinary albumin quantification by immunoturbidimetry, competitive immunoassay, and protein-cleavage liquid chromatography-tandem mass spectrometry.

Background: Increased urinary albumin excretion is a well-documented diagnostic and prognostic biomarker for renal disease. Urinary albumin is typically measured in clinical settings by immunoassay methods. However, neither a reference method nor a urine albumin calibration reference material is currently available.

The dynamic range problem in the analysis of the plasma proteome.

One of the greatest challenges in analyzing the plasma proteome is the wide range of concentration of different proteins. The current study examines the range of protein concentration for 18 proteins measured over a year in a clinical laboratory to provide data on pathological extremes in protein concentrations. The complete measured range, from upper limits for albumin to lowest values for thyroid-stimulating hormone (TSH), represented more than 10 logs of molar abundance.

Proteinuria without albuminuria: urinary protein excretion by a subset of patients with burn injuries.

Background: There is disagreement regarding the utility of urinary albumin excretion as a marker for capillary injury in patients with severe burn injuries. We examined protein components in urine specimens from patients with burn injury.

Methods: Detailed analysis was performed for a set of 5 urine specimens selected based on a high ratio of albumin-sized molecules by size-exclusion HPLC (Accumin) versus albumin by immunoassay methods.

Urine albumin measurement: effects of urine matrix constituents.

Background: There is increasing clinical interest in accurate measurement of urine albumin as an early indicator of kidney disease. However, urine is a highly variable sample matrix that may exert matrix effects on assays for urine albumin.

Methods: Variation in urine composition was assessed for components routinely measured in the clinical laboratory over 1 year.

Current issues in measurement and reporting of urinary albumin excretion.

Background: Urinary excretion of albumin indicates kidney damage and is recognized as a risk factor for progression of kidney disease and cardiovascular disease. The role of urinary albumin measurements has focused attention on the clinical need for accurate and clearly reported results. The National Kidney Disease Education Program and the IFCC convened a conference to assess the current state of preanalytical, analytical, and postanalytical issues affecting urine albumin measurements and to identify areas needing improvement.

High-abundance polypeptides of the human plasma proteome comprising the top 4 logs of polypeptide abundance.

Background: Plasma contains thousands of proteins, but a small number of these proteins comprise the majority of protein molecules and mass.

Content: We surveyed proteomic studies to identify candidates for high-abundance polypeptide chains. We searched the literature for information on the plasma concentrations of the most abundant components in healthy adults and for the molecular mass of the mature polypeptide chains in plasma.

Analysis of molecular forms of albumin in urine.

Albumin is not only one of the most abundant urinary protein components and one of the most widely used clinical markers for kidney disease, it also is a significant source of molecular complexity of the urinary proteome and peptidome. Urine contains multiple fragments and modified forms of albumin. Analysis of molecular forms of albumin in urine is of fundamental importance for understanding clinical assays for albumin quantification, specimen stability, and proteomic and peptidomic analysis of urine.

Reactivity of urinary albumin (microalbumin) assays with fragmented or modified albumin.

Background: Controversy exists regarding occurrence and measurement of structural variants of albumin in urine. In this study, we examined cross-reactivity of in vitro modified albumins in assays for urine albumin (microalbumin).

Methods: We analyzed albumin modified by reagents, trypsin, or physical treatments or differing in primary sequence (animal albumins) with an immunoturbidimetric assay (Beckman LX20) using goat antiserum and a competitive immunoassay (Siemens Immulite) using a monoclonal antibody.

Ant colony optimization for biomarker identification from MALDI-TOF mass spectra.

We present a novel method that combines ant colony optimization with support vector machines (ACO-SVM) to select candidate biomarkers from MALDI-TOF serum profiles of hepatocellular carcinoma (HCC) patients and matched controls. The method identified relevant mass points that achieve high sensitivity and specificity in distinguishing HCC patients from healthy individuals. The results indicate that the MALDI-TOF technology could provide the means to discover novel biomarkers for HCC.

Pseudohyperphosphatemia associated with high-dose liposomal amphotericin B therapy.

Background: Acute increases in serum inorganic phosphorus (Pi) up to 4.75 mmol/l in the absence of hypocalcemia and tissue deposition of calcium phosphate were noted in 3 patients receiving liposomal amphotericin B (L-AMB). We investigated L-AMB as a possible cause of pseudohyperphosphatemia.

Quality control of serum albumin depletion for proteomic analysis.

Background: Prefractionation techniques such as serum albumin depletion are useful precursors to proteomic analysis, but they may introduce preanalytical bias if the depletion is not reproducible. We examined the reproducibility of albumin immunodepletion and describe a method of QC for this process.

Methods: Depletion of albumin from pooled serum, performed using IgY immunoaffinity spin columns, was assessed for 21 runs on each of 4 columns.