ABSTRACT
To identify the binding motifs of peptides which bind to the celiac disease and insulin-dependent-diabetes-mellitus (IDDM)-associated DQ2 molecule, peptides were eluted from affinity-purified DQ2 molecules. The eluted peptides were separated by reverse-phase HPLC. Prominent peptide peaks and the remaining pool of peptides were sequenced by Edman degradation. Truncated variants of eight different peptides with a length of 9-19 amino acids were identified; among them class II-associated invariant chain peptides (CLIP) and peptides that stem from HLA class I alpha, HLA-DQ alpha 1*0501, Ig and CD20 molecules. Data from the pool sequencing and the biochemical binding analyses of synthetic variants of an eluted high-affinity ligand (HLA class I alpha 46-60), indicate that the side chains of amino acid residues at relative position P1 (bulky hydrophobic), P4 (negatively charged or aliphatic), P6 (Pro or negatively charged), P7 (negatively charged) and P9 (bulky hydrophobic) are important for binding of peptides to DQ2. Computer modeling of the DQ2 with variants of the high-affinity ligand in the groove suggests that peptides bind to DQ2 through the primary anchors P1, P7 and P9 and making additional advantageous interactions using the P4 and P6 positions.
Subject(s)
Alleles , Celiac Disease/genetics , Celiac Disease/immunology , Diabetes Mellitus, Type 1/genetics , Diabetes Mellitus, Type 1/immunology , HLA-DQ Antigens/genetics , HLA-DQ Antigens/metabolism , Peptide Fragments/genetics , Peptide Fragments/immunology , Amino Acid Sequence , HLA-DQ Antigens/isolation & purification , Humans , Ligands , Molecular Sequence Data , Peptide Fragments/metabolism , Protein Binding/immunology , Sequence AlignmentABSTRACT
Autoregulation of blood flow in response to changes in perfusion pressure is known to occur in a number of tissues including the human retina. Defective autoregulation may play a part in the pathophysiology of several retinal diseases. Laser Doppler velocimetry has been used to study retinal blood flow. Technically superior measurements are obtained from veins by this method but arterial measurements might provide additional information. The response of the normal human retina to an acute elevation of systemic blood pressure induced by isometric exercise was investigated in nine normal volunteers using laser Doppler velocimetry and computer-assisted image analysis. Measurements were taken from retinal veins and arteries. Autoregulation was demonstrated by an 8.4% rise in flow in response to a 34% rise in perfusion pressure (P = 0.0007) using data derived from veins and a 4.8% rise in flow in response to a 33% rise in perfusion pressure (P = 0.01) using data derived from arteries. Arteries constricted by 3.4% (P = 0.002) and veins dilated by 1.6% (P = 0.02). Red cell velocity rose in veins by 5.0% (P = 0.008) and in arteries by 12.2% (P = 0.02). The variability in velocity change derived from veins (SD 3.4%) was lower than that from arteries (SD 12.1%). A similar pattern of flow change was found in both sets of data. This makes venous measurements more useful for obtaining statistically reliable results from these techniques.
Subject(s)
Retinal Vessels/physiology , Adult , Arteries/physiology , Blood Flow Velocity , Female , Humans , Image Processing, Computer-Assisted , Isometric Contraction , Laser-Doppler Flowmetry , Male , Microcirculation , Veins/physiologyABSTRACT
The concentrations of glycosylated haemoglobin (HbA1c) were determined in eight patients with acute haemolytic anaemia and were found to be significantly lower than in a control group of 16 patients. A case history is presented in which HbA1c was employed as longitudinal parameter of haemolysis. It is concluded that in haemolytic anaemia in non-diabetic patients, HbA1c is a specific parameter of haemolysis which may be employed as a supplement to the traditional parameters of haemolysis.
