Canine mitral valve size as measured by computed tomography.

Objective: To measure the mitral annulus in dogs. Our hypothesis was that mitral measurement would be possible and consistent among observers using CT.

Sample: Thoracic CT scans of dogs without known heart disease.

Energy cost for the proper ionization of active site residues in 6-phosphogluconate dehydrogenase from T. brucei.

The catalytic mechanism of 6-phosphogluconate dehydrogenase requires the inversion of a Lys/Glu couple from its natural ionization state. The pKa of these residues in free and substrate bound enzymes has been determined measuring by ITC the proton release/uptake induced by substrate binding at different pH values. Wt 6-phosphogluconate dehydrogenase from Trypanosoma brucei and two active site enzyme mutants, K185H and E192Q were investigated.

HIV-1 tat promotes integrin-mediated HIV transmission to dendritic cells by binding Env spikes and competes neutralization by anti-HIV antibodies.

Use of Env in HIV vaccine development has been disappointing. Here we show that, in the presence of a biologically active Tat subunit vaccine, a trimeric Env protein prevents in monkeys virus spread from the portal of entry to regional lymph nodes. This appears to be due to specific interactions between Tat and Env spikes that form a novel virus entry complex favoring R5 or X4 virus entry and productive infection of dendritic cells (DCs) via an integrin-mediated pathway.

Effects of the regulatory ligands calcium and GTP on the thermal stability of tissue transglutaminase.

Tissue transglutaminase undergoes thermal inactivation with first-order kinetics at moderate temperatures, in a process which is affected in opposite way by the regulatory ligands calcium and GTP, which stabilize different conformations. We have explored the processes of inactivation and of unfolding of transglutaminase and the effects of ligands thereon, combining approaches of differential scanning calorimetry (DSC) and of thermal analysis coupled to fluorescence spectroscopy and small angle scattering. At low temperature (38-45°C), calcium promotes and GTP protects from inactivation, which occurs without detectable disruption of the protein structure but only local perturbations at the active site.

6-Phosphogluconate dehydrogenase mechanism: evidence for allosteric modulation by substrate.

The reductive carboxylation of ribulose-5-phosphate (Ru5P) by 6-phosphogluconate dehydrogenase (6PGDH) from Candida utilis was investigated using kinetic isotope effects. The intrinsic isotope effect for proton abstraction from Ru5P was found at 4.9 from deuterium isotope effects on V and V/K and from tritium isotope effects on V/K.

Thermodynamics of binding of regulatory ligands to tissue transglutaminase.

The transamidating activity of tissue transglutaminase is regulated by the ligands calcium and GTP, via conformational changes which facilitate or interfere with interaction with the peptidyl-glutamine substrate. We have analysed binding of these ligands by calorimetric and computational approaches. In the case of GTP we have detected a single high affinity site (K (D) approximately 1 microM), with moderate thermal effects suggestive that binding GTP involves replacement of GDP, normally bound to the protein.

Thermodynamic characterization of substrate and inhibitor binding to Trypanosoma brucei 6-phosphogluconate dehydrogenase.

6-Phosphogluconate dehydrogenase is a potential target for new drugs against African trypanosomiasis. Phosphorylated aldonic acids are strong inhibitors of 6-phosphogluconate dehydrogenase, and 4-phospho-d-erythronate (4PE) and 4-phospho-d-erythronohydroxamate are two of the strongest inhibitors of the Trypanosoma brucei enzyme. Binding of the substrate 6-phospho-d-gluconate (6PG), the inhibitors 5-phospho-d-ribonate (5PR) and 4PE, and the coenzymes NADP, NADPH and NADP analogue 3-amino-pyridine adenine dinucleotide phosphate to 6-phospho-d-gluconate dehydrogenase from T.

Coping with a chronic disease.

Interviews were conducted with 55 experienced patients with insulin-dependent diabetes with the aim of identifying strategies for coping with diabetes. This study was based on a health-oriented approach known as Antonovsky's salutogenic model, which conceptualizes the person as being actively involved in maintaining biological, psychological, and social homeostasis. All patients had developed some strategy for maintaining biological balance.

Health and unhealth in chronic disease.

When health is defined from a holistic view, traditional measures of control in diabetes, such as analysis of blood glucose or HbA1c, are of limited use as indicators of health and unhealth. On the other hand, evaluation of attitudes and certain personality variables might provide guidance both in discovering unhealth and in creating individual self-care programmes for its treatment. In the present study the subjective experience of health and unhealth was studied in a defined population of patients with insulin dependent diabetes mellitus (IDDM).

Metabolic control, residual insulin secretion and self-care behaviours in a defined group of patients with type 1 diabetes.

A population of 185 type 1 diabetes patients (insulin-dependent, IDDM), 25-45 years old, was studied retro- and prospectively over a 9-year period with the aim of analysing background factors of importance for the ability to perform adequate self-care. Expressed as mean HbA1c, the metabolic control was slightly improved at the end of the study, when the insulin schedule had been changed in 60% of the patients to multidose treatment. The degree of metabolic control remained constant over the years.

The patient's experience of diabetes and its treatment: construction of an attitude scale by a semantic differential technique.

An instrument for measuring attitudes towards diabetes and self-care was constructed by a semantic differential technique. The instrument contained nine adjective pairs. Factor analysis classified these into four factors: self-esteem/autonomy, object evaluation, quality of life supporting factor and self-strength/vulnerability.