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Biomedical subjects

Andrew W Lyon

Publications and source records attributed to Andrew W Lyon.

9 recordsLinked to original sources
PubMed2005

Abnormal proinsulin congeners as autoantigens that initiate the pathogenesis of Type 1 diabetes.

Exposure of concentrated and purified monomeric insulin solutions to inorganic oxidants as iodine and chlorine lead to the appearance of a minor peak on gel chromatography that was disulfide cross-linked. It exhibited a 20-fold reduction in bioactivity, a markedly decreased immunoreactivity and a different electrophoretic pattern as compared to the starting material. The covalent dimer was formed by way of aggregation. These findings were reproduced by incubating monomeric insulin in normal blood spiked to hyperglycemic levels. In contrast, normoglycemic blood used as incubating medium failed to induce dimerization. Since the conformation of proinsulin is similar to that of insulin, involving the exposure of the anterior A7-B7 disulfide bridge, the authors hypothesize that proinsulin dimers rather than insulin dimers might be formed in Type 1 diabetes (TD1), leading to the autoimmune destruction of pancreatic B-cells. Proinsulin is present in a soluble aggregate state in the coated granule and may further accumulate allowing disulfide exchange due to abnormalities of the processing enzymes. This might be caused by inborn errors in genetically susceptible children or perhaps secondary to viral infection, whereas crystallization of insulin in mature granules is unlikely to be conducive to dimerization. Dimeric proinsulin would then migrate to pancreatic B-cell membranes to be taken up by surface immunoglobulins on B-lymphocytes that would in turn present it to cytotoxic T lymphocytes. The abnormal configuration of this congener would not be recognized as self by the immune system, triggering a selective destruction of pancreatic B-cells in the early pre-clinical development of TD1, resulting eventually in clinical disease. Since proinsulin is continuously converted to insulin in the coated granules of Type 2 diabetics, dimerization is unlikely in this condition. As pointed out by earlier investigators, TD1 is not a homogeneous disease, since several of its clinical features are different in children up to 6 years of age as compared to older patients. It is thus conceivable that there are subsets of TD1 triggered by dissimilar autoantigens and we propose in the present hypothesis that a conformationally altered congener of native proinsulin might play such a role.

Animals↗
PubMed2004

Effect of hemolysis on cardiac troponin T determination by the Elecsys 2010 immunoanalyzer.

OBJECTIVE: To evaluate the effect of hemolysis on the measurement of cardiac troponin T (cTnT) using the Elecsys 2010 immunoanalyzer. METHODS: cTnT concentrations were measured using the Elecsys 2010. Interference studies were conducted by mixing serum of known cTnT concentration with either hemolysates or serum to which purified hemoglobin (Hgb) had been added. Hemolysates were prepared by mechanical disruption. PROBIT analysis was conducted to determine the probability of a cTnT result of >0.1 microg/l being decreased to <0.1 microg/l due to hemoglobin interference. RESULTS: Purified hemoglobin as well as serum-hemolysates mediated a concentration-dependent inhibition of cTnT determination with the Elecsys 2010. With every 1 g/l increase in hemoglobin, the probability of cTnT >0.1 is decreased by 2.5%. CONCLUSIONS: A concentration-dependent negative bias in the measurement of cTnT is associated with increasing hemoglobin concentrations in serum.

Chemistry, Clinical↗
PubMed2004

Analytic evaluation and application of a novel spectrophotometric serum lithium method to a rapid response laboratory.

The authors present an evaluation of the Lithium DST spectrophotometric method developed by Thermotrace (Victoria, Australia) on a Hitachi 917 analyzer. Accuracy was assessed by method comparison with an ion-selective electrode (ISE; Roche Integra 700) (n = 80). Linearity, within-run and between-run precision, and susceptibility to interference by hemolysis, icterus, lipemia, and sodium were assessed. The method was linear to 3.0 mM/L, and analyzer auto-dilution extended the reportable range to 7.2 mmol/L. Within-run coefficient of variation was 1.5% at 0.68 mmol/L and 0.7% at 2.06 mM/L. Between-run precision for the same lithium concentrations assayed daily for 20 days were 3.1% and 1.9%, respectively. Method agreement with ISE was excellent, with an intercept of 0.000 and slope of 1.000 by Passing Bablock regression analysis. Hemolysis, icterus, lipemia, and high and low sodium levels did not significantly interfere. The manufacturer's recommended calibration stability of 1 week was confirmed. The authors conclude that this method is reliable, accurate, and precise. The Thermotrace serum lithium spectrophotometric method provides a useful alternative to ISE or flame photometry, facilitates workstation consolidation on the Hitachi 917 multiple-channel analyzer, and is well adapted for use in a rapid response laboratory.

Antimanic Agents↗
PubMed2003

A preliminary evaluation of the interaction between urine specific gravity and leukocyte esterase results using Bayer Multistix and the Clinitek 500.

OBJECTIVES: To determine the sensitivity of the leukocyte esterase (LE) pad to predict microscopically quantified white blood cells in urine sediment and to assess the interaction of urine specific gravity (SG) on leukocyte esterase sensitivity. METHODS: Microscopic quantification of white blood cells in urine sediment was performed manually and automated chemical urinalysis was performed using the Bayer Clinitek 500 and Multistix 8 SG strips on 422 random urine specimens. RESULTS: The sensitivity of the leukocyte esterase pad to predict white blood cells in centrifuged urine was 58% (61/106). There was a weak but statistically significant negative correlation between SG and LE pad performance, r = -0.12, p < 0.05. CONCLUSIONS: The 58% sensitivity of the Multistix leukocyte esterase detection of white blood cells in urine sediment was consistent with previous reports. The negative correlation of specific gravity and leukocyte esterase provides partial explanation for the lack of sensitivity of the leukocyte esterase test.

Adolescent↗
PubMed2003

Structural analysis, fatty acid and thyroxine binding properties of Vancouver and Naskapi variants of human serum albumin.

OBJECTIVES: To purify and structurally identify two albumin variants found in the Canadian population of native Amerindian origin. To assess the ability of variant albumins to bind lauric acid and L-thyroxine. METHODS: The structural characterization of the alloalbumins was performed by conventional protein chemistry methods and by mass spectrometric analysis. Lauric acid and L-thyroxine affinities to variant albumins were assessed by kinetic dialysis and equilibrium dialysis techniques, respectively. RESULTS: The sequence investigations proved the two variants to be albumin Naskapi [372Lys --> Glu] and albumin Vancouver [501Glu --> Lys], respectively. Among the carriers of albumin Naskapi, we found a rare case of homozygosity. Furthermore, this is the first reported case of the 501Glu-->Lys mutation in the native North American population. Scatchard plot analysis revealed that the association constants for lauric acid and L-thyroxine to the two variants were indistinguishable from the endogenous form of albumin. CONCLUSION: We show that albumin variants Vancouver and Naskapi have normal fatty acid and L-thyroxine binding capabilities. These findings support the assumption that bisalbuminemias associated with these albumin variants are benign conditions.

British Columbia↗
PubMed2003

Cesium toxicity: a case of self-treatment by alternate therapy gone awry.

Cesium salts have been used in animal models to induce cardiac arrhythmias for several decades, but the sequelae of human cesium toxicity have seldom been described. The authors describe a case of cesium toxicity manifested by syncope, polymorphic ventricular tachycardia, hypokalemia, and a QT interval prolonged to 650 milliseconds that resolved over 4 days following withdrawal of cesium. The patient had a 2-year history of colon cancer and had self-treated with cesium chloride, 3 g/d, for several weeks, using cesium as a form of alternate therapy for cancer. The authors describe the pathophysiologic correlates and risks of cesium consumption and conclude that cesium toxicity should be considered among the differential diagnoses of prolonged QT interval.

Cesium↗
PubMed2002

Molecular diagnosis of analbuminemia: a novel mutation identified in two Amerindian and two Turkish families.

BACKGROUND: Analbuminemia is a rare autosomal recessive disorder in which individuals have little or no circulating albumin, usually the most abundant plasma protein. We describe a new mutation associated with analbuminemia. METHODS: We studied four apparently unrelated patients who had congenital analbuminemia: two of Amerindian and two of Turkish origin. The 14 exons and the flanking intron sequences of the albumin gene were amplified by PCR and screened for mutations by single-strand conformational polymorphism and heteroduplex analysis. The mutated DNA fragments were sequenced directly. RESULTS: In all four cases, analbuminemia was caused by the same mutation, an AT deletion at nucleotides 2430-2431, the 91st and 92nd bases of exon 3. This novel defect, named Kayseri, produces a frameshift leading to a premature stop two codons downstream. The predicted translation product would consist of 54 amino acid residues. CONCLUSIONS: The AT deletion at nucleotides 2430-2431 is a novel mutation associated with analbuminemia.

Albumins↗