Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Language
Publication year range
1.
Clin Chem ; 62(12): 1570-1578, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27679433

ABSTRACT

BACKGROUND: Several hematological alterations are associated with altered hemoglobin A1c (Hb A1c). However, there have been no reports of their influence on the rates of exceeding standard Hb A1c thresholds by patients for whom Hb A1c determination is requested in clinical practice. METHODS: The initial data set included the first profiles (complete blood counts, Hb A1c, fasting glucose, and renal and hepatic parameters) of all adult patients for whom such a profile was requested between 2008 and 2013 inclusive. After appropriate exclusions, 21844 patients remained in the study. Linear and logistic regression models were adjusted for demographic, hematological, and biochemical variables excluded from the predictors. RESULTS: Mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV) correlated negatively with Hb A1c. Fasting glucose, MCH, and age emerged as predictors of Hb A1c in a stepwise regression that discarded sex, hemoglobin, MCV, mean corpuscular hemoglobin concentration (MCHC), serum creatinine, and liver disease. Mean Hb A1c in MCH interdecile intervals fell from 6.8% (51 mmol/mol) in the lowest (≤27.5 pg) to 6.0% (43 mmol/mol) in the highest (>32.5 pg), with similar results for MCV. After adjustment for fasting glucose and other correlates of Hb A1c, a 1 pg increase in MCH reduced the odds of Hb A1c-defined dysglycemia, diabetes and poor glycemia control by 10%-14%. CONCLUSIONS: For at least 25% of patients, low or high MCH or MCV levels are associated with increased risk of an erroneous Hb A1c-based identification of glycemia status. Although causality has not been demonstrated, these parameters should be taken into account in interpreting Hb A1c levels in clinical practice.


Subject(s)
Blood Glucose/analysis , Diabetes Mellitus/blood , Diabetes Mellitus/diagnosis , Erythrocytes/chemistry , Glycated Hemoglobin/analysis , Hemoglobins/analysis , Adult , Aged , Aged, 80 and over , Fasting , Female , Humans , Linear Models , Logistic Models , Male , Middle Aged
2.
Biochemistry ; 44(30): 10100-9, 2005 Aug 02.
Article in English | MEDLINE | ID: mdl-16042387

ABSTRACT

Elucidation of the structure of PrP(Sc) continues to be one of the most important and difficult challenges in prion research. This task, essential for gaining an understanding of the basis of prion infectivity, has been hampered by the insoluble, aggregated nature of this molecule. We used a combination of chemical cross-linking, proteolytic digestion, and mass spectrometry (MALDI-TOF and nanoLC-ESI-QqTOF), in an attempt to gain structural information about PrP 27-30 purified from the brains of Syrian hamsters infected with scrapie. The rationale of this approach is to identify pairs of specific amino acid residues that are close enough to each other to react with a bifunctional reagent of a given chain length. We cross-linked PrP 27-30 with the amino-specific reagent bis(sulfosuccinimidyl) suberate (BS(3)), obtaining dimers, trimers, and higher-order oligomers that were separated by SDS-PAGE. In-gel digestion followed by mass spectrometric analysis showed that BS(3) reacted preferentially with Gly90. A cross-link involving two Gly90 amino termini was found in cross-linked PrP 27-30 dimers, but not in intramolecularly cross-linked monomers or control samples. This observation indicates the spatial proximity of Gly90 amino termini in PrP 27-30 fibrils. The Gly90-Gly90 cross-link is consistent with a recent model of PrP 27-30, based on electron crystallographic data, featuring a fiber composed of stacked trimers of PrP monomers; specifically, it is compatible with cross-linking of monomers stacked vertically along the fiber axis but not those adjacent to each other horizontally in the trimeric building block. Our results constitute the first measured distance constraint in PrP(Sc).


Subject(s)
Cross-Linking Reagents , Glycine/chemistry , Peptide Fragments/chemistry , PrP 27-30 Protein/chemistry , Amino Acid Sequence , Animals , Cricetinae , Cross-Linking Reagents/metabolism , Dimerization , Endopeptidase K/metabolism , Hydrolysis , Lysine/chemistry , Mesocricetus , Nanotechnology , Peptide Fragments/metabolism , PrP 27-30 Protein/metabolism , Serine Endopeptidases/metabolism , Spectrometry, Mass, Electrospray Ionization , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Succinimides , Trypsin/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL
...