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Biomedical subjects

A Tardieu

Publications and source records attributed to A Tardieu.

At least 19 recordsLinked to original sources
PubMed1992

Protein interactions in the calf eye lens: interactions between beta-crystallins are repulsive whereas in gamma-crystallins they are attractive.

Non-specific interactions in beta- and gamma-crystallins have been studied by solution X-ray scattering and osmotic pressure experiments. Measurements were carried out as a function of protein concentration at two ionic strengths. The effect of temperature was tested between 7 degrees C and 31 degrees C. Two types of interactions were observed. With beta-crystallin solutions, a repulsive coulombic interaction could be inferred from the decrease of the normalized X-ray scattering intensity near the origin with increasing protein concentration and from the fact that the osmotic pressure increases much more rapidly than in the ideal case. As was previously observed with alpha-crystallins, such behaviour is dependent upon ionic strength but is hardly affected by temperature. In contrast, with gamma-crystallin solutions, the normalized X-ray scattering intensity near the origin increases with increasing protein concentration and the osmotic pressure increases less rapidly than in the ideal case. Such behaviour indicates that attractive forces are predominant, although we do not yet know their molecular origin. Under our experimental conditions, the effect of temperature was striking whereas no obvious contribution of the ionic strength could be seen, perhaps owing to masking by the large temperature effect. The relevance of the different types of non-specific interactions for lens function is discussed.

Animals↗
PubMed1989

Image processing of proteinase- and methylamine-transformed human alpha 2-macroglobulin. Localization of the proteinases.

Comparative x-ray scattering experiments and electron microscopic observations have been performed on native S-form, and on different F-forms of human plasma alpha 2-macroglobulin (alpha 2M), obtained by proteinase (chymotrypsin, plasmin, and thrombin) or methylamine treatment. Image processing of electron micrographs of the alpha 2M molecules transformed by chymotrypsin, plasmin, and methylamine displayed average images which could be compared. The proteinase-complex alpha 2M molecules exhibited the usual H-like structure, but the methylamine-inactivated ones showed a different organization, with almost no stain-excluding material in the central region of the molecule, which therefore presented a central cavity filled with stain. By subtracting average images of alpha 2M-methylamine from alpha 2M-chymotrypsin or alpha 2M-plasmin, a putative localization of the proteinases inside the alpha 2M molecule, very close to its center was revealed. The values of the radii of gyration for the S- and F-forms obtained by x-ray scattering were very different (78 and 67.7 A, respectively). All four scattering curves of the F-forms were comparable in shape and showed maxima and minima different from that of the S-form alpha 2M. Image processing of electron micrographs and x-ray scattering have provided independent results which indicate that a large cavity exists in the alpha 2M-methylamine molecule and that the proteinases might be located in a very central position inside the alpha 2M-proteinase molecules.

Chymotrypsin↗
PubMed1989

Molecular basis of eye lens transparency. Osmotic pressure and X-ray analysis of alpha-crystallin solutions.

Short range, liquid-like order of the crystallin proteins accounts for eye lens transparency. The relationship between structural and thermodynamic properties of eye lens was further investigated using osmotic pressure and small-angle X-ray scattering measurements of calf lens alpha-crystallins. The consistency of both data sets confirms that the macroscopic thermodynamic properties are determined by the structural properties accessible to X-ray scattering. In addition, the experimental data were correctly accounted for using a model developed in liquid-state physics: the rescaled mean spherical approximation combined with a Verwey-Overbeek potential. This model provides as best fit parameters the excluded volume, the charge and the diameter of an "equivalent" particle that compare well with the corresponding values found in the literature for alpha-crystallins. As a result, transparency may now be expressed as a function of a few structural parameters, the role of which is discussed. The approach presented here may be extended to studies of the thermodynamic-structural relationships of other protein solutions.

Animals↗
PubMed1989

The protein concentration gradient within eye lens might originate from constant osmotic pressure coupled to differential interactive properties of crystallins.

A protein concentration gradient exists from the center to the periphery of most lenses, the origin of which is still a matter of debate. The gradient, which contributes to the lens optical quality, seems to be accompanied by an uneven distribution of the crystallin classes, with the nucleus usually enriched in gamma- and the cortex in alpha-crystallins. Since the osmotic pressure within the lens seems to be constant and since a rather different interaction behaviour of alpha- and gamma-crystallins was demonstrated in previous studies, we propose that the maintenance of a constant osmotic pressure through the lens is sufficient to induce and stabilize a protein concentration gradient. The theoretical treatment has been worked out and the validity of the hypothesis has been demonstrated with colloidal osmotic pressure measurements of lens cortical and nuclear cytoplasmic extracts as a function of protein concentration. To account for the observed lens concentration gradient, however, a small additional concentration gradient in the opposite direction, involving an ion or small molecule, might be required.

Animals↗
PubMed1987

Lac repressor-Lac operator complexes. Solution X-ray scattering and electrophoretic studies.

Complexes between the Lac repressor and a small DNA operator fragment (29 base pairs) were investigated using polyacrylamide gel electrophoresis and solution X-ray scattering. Titration of the DNA fragment with the repressor, followed by gel electrophoresis showed that only two types of complexes are formed with repressor/operator ratios of 0.5 and 2. Radii of gyration and forward scattered intensities were obtained from Guinier plots for repressor/operator ratios ranging from 0.3 to 2. They demonstrated that the first complex contains one repressor and two operators, whereas the second one contains four repressors and two operators. Mixing operator and repressor in equimolar concentrations leads to a mixture of both complexes. A possible model for the four repressor/two operator complex is proposed.

Base Sequence↗
PubMed1987

Effect of calcium on the calf lens cytoplasm.

Opacification was induced in calf lens cytoplasmic extracts by addition of calcium. The sample turbidity was shown to increase with calcium molarity, incubation time and temperature and to decrease with the protein cytoplasmic concentration. Although this turbidity was enhanced when membrane fragments were left over in the cytoplasmic extracts, it did show up in the absence of any detectable vesicular fragment. Scattering techniques (X-ray and light) showed that the calcium-induced opacification is linked to enhanced light scattering, which results from the formation of additional scatterers, a few tens of nm in diameter. Additional structures were indeed visualized by freeze-fracture electron microscopy (FFEM): they appear as molecular clusters with diameters ranging from 20 to 90 nm, made of densely packed particles, with heterogeneous sizes. The turbidity expected from these clusters, as well as the expected variation of turbidity with cytoplasmic concentration, was calculated to be in agreement with the measurements. When compared with cold cataract, these results illustrate that similar opacities may result from completely different biophysical mechanisms.

Animals↗
PubMed1987

The crystal lattice of Paramecium trichocysts before and after exocytosis by X-ray diffraction and freeze-fracture electron microscopy.

Paramecium trichocysts are unusual secretory organelles in that: (a) their crystalline contents are built up from a family of low molecular mass acidic proteins; (b) they have a precise, genetically determined shape; and (c) the crystalline trichocyst contents expand rapidly upon exocytosis to give a second, extracellular form which is also an ordered array. We report here the first step of our study of trichocyst structure. We have used a combination of x-ray powder diffraction, freeze-etching, and freeze-fracture electron microscopy of isolated, untreated trichocysts, and density measurements to show that trichocyst contents are indeed protein crystals and to determine the elementary unit cell of both the compact intracellular and the extended extracellular form.

Animals↗
PubMed1987

[Automatic quantitative analysis of myocardial tomography thallium-201 scintigraphy].

An automatic and quantitative analysis method for tomographic scintigraphy was applied to 104 patients with myocardial infarction (anterior 37, inferior 67, lateral 20, involving 2 territories in some cases). All patients underwent exercise and redistribution scintigraphy and coronary arteriography which served as reference. Two types of tomographic sections were used: 2 short axis sections exploring the left ventricle at different levels, and 1 apical section at a right angle with the first ones. A circumferential analysis program studied the isotopic activity of each section and drew an activity profile curve which was compared with those obtained in normal subjects. Exercise curves proved superior to redistribution and wash-out curves and were therefore used exclusively. Two sectoring methods for territories with infarcts were defined: conventional sectoring, which gives a 90 degrees angle to the anterior region and a 180 degrees angle to the inferior lateral region, and real sectoring established from the scintigraphic abnormalities observed in patients whose infarction was not accompanied by significant lesions in other territories. Real sectoring divides the territory into two regions (anterior and infero-lateral) and determines the extension territory and the territories specific to each necrotic region. The sensitivity and specificity of these two methods for the diagnosis of necrosis and the detection of a significant abnormality (greater than 70% stenosis, or necrosis) in a territory other than the one with infarct were compared. In the diagnosis of infarction: conventional sectoring sensitivity 92%, specificity 46% for anterior infarcts, 94% and 25% for inferior and lateral infarcts; real sectoring 94% and 63% respectively for anterior infarcts, 92% and 68% for inferior infarcts.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Calf lens alpha-crystallin quaternary structure. A three-layer tetrahedral model.

Calf lens alpha-crystallins are polydisperse globular particles made of a large number of two types of subunits, A and B, both of molecular weight congruent to 20,000. alpha-Crystallin populations consisting on average of 40 subunits or more were subjected to various changes in pH, ionic strength, temperature and urea concentration. Modifications in quaternary structure induced by variation of these physicochemical parameters were followed by means of X-ray and quasi-elastic light-scattering and quantified in terms of weight average molecular weight (M), radius of gyration (Rg) and hydrodynamic radius (Rh). High-pressure liquid chromatography was used as a control of polydispersity. Increasing the pH, decreasing the ionic strength and incubating at temperatures from 20 degrees C to 45 degrees C all resulted in the formation of particles of decreasing M, Rg and Rh values. These effects are cumulative. All monomodal alpha-crystallin populations encountered in this study, which covers a wide range of sizes and molecular weights, may be accounted for by a three-layer model with partial filling up of the layers. Applying basic principles of symmetry and postulating specific contacts between protein subunits to construct this three-layer model leads to tetrahedral symmetry, with 12, 24 and 24 sites in the first, second and third layers, respectively. Variations in probabilities of site occupancy account for both the observed quaternary structure modifications and the intrinsic polydispersity of alpha-crystallins

Animals↗
PubMed1986

[Short and intermediate-term hemodynamic study at rest and during exercise of cardiac insufficiency treated by captopril].

Administration of 25 mg of captopril to 10 patients with heart failure (NYHA II, III) produces at rest after 60 min bradycardia (-7 per cent, p less than 0.01), hypotension (-8 per cent) and improvement of the preload (-30 per cent, p less than 0.01). This effect is still apparent after two months of treatment where PAP is decreased by 20 per cent (p less than 0.05). A prolonged effect of captopril is present in these 10 patients. The capacity to perform a muscular exercise on an ergometric bicycle is prolonged by 10 per cent (p less than 0.01) on the first day and by 18 per cent (p less than 0.01) after two months of treatment. This improvement seems to be related to improvement of the hemodynamic parameters, especially of preload indices. In 5 patients, lactacidemia, the arterio-venous difference and the extraction coefficient of O2 were studied at rest and during exercise. No significant difference are noted after the treatment with the inhibitors of conversion enzymes.

Adult↗
PubMed1986

Effects of captopril on myocardial perfusion in patients with coronary insufficiency: evaluation by the exercise test and quantitative myocardial tomoscintigraphy using thallium-201.

Nine patients with coronary insufficiency were investigated using an exercise test coupled with quantitative myocardial tomoscintigraphy with thallium-201 before and after 48 hours' treatment with captopril. After captopril treatment, an improvement in ST segment depression was noted during exercise. The quantitative tomoscintigraphy showed a reduction in the ischaemic zone with captopril during exercise. However, in three patients, although there was an overall improvement in myocardial perfusion during exercise, aggravation of wash-out was observed in some regions, reminiscent of a coronary steal effect.

Adult↗
PubMed1985

[Late chronic constrictive pericarditis following aortic valve replacement].

The authors report a case of chronic constrictive pericarditis in a 54 year old patient who had undergone aortic valve replacement 6 years previously. The valve was replaced with a Starr-Edwards prosthesis because of aortic regurgitation due to infective endocarditis. The outcome after pericardectomy was favourable with a 3 year follow-up. This complication of cardiac surgery, of which there are now 45 reported cases, should not be overlooked because it can be cured surgically. The diagnosis is based on phonomechanographic, echocardiographic and, above all, haemodynamic investigations to distinguish the condition from irreversible myocardial dysfunction.

Aortic Valve↗
PubMed1985

[A case of electrically and mechanically stunned myocardium].

The authors report the case of a 72 year old patient with ECG changes of anterior myocardial infarction complicated by left ventricular failure and shock which has a favourable outcome with regression of the pathological Q waves on the 7th day. Radionuclide investigation and coronary angiography showed no myocardial sequellae and the coronary arteries appeared normal. This case, an example of stunned myocardium, confirms that severe myocardial ischaemia, even of short duration, may induce reversible but prolonged metabolic disturbances. The practical implications of this concept are discussed.

Aged↗
PubMed1985

[Outcome of patients with inoperable multivessel coronary disease].

The authors studied the clinical course of 100 patients with two or three vessel coronary artery disease who were unsuitable for surgery because of the poor quality of the distal vascular bed or excessively depressed left ventricular function. The 6 year actuarial survival was 58 per cent; 43 of the 100 patients did not present any serious cardiac events causing death or requiring further admission to hospital, over this follow-up period. The severity of the clinical course in women and the presence of heart failure prior to coronary angiography were considered to be among the most important clinical prognostic factors. On the basis of the haemodynamic survey, the probability of survival or the risk of a further coronary accident appears to depend more on the extent of the left ventricular kinetic abnormalities than on the ejection fraction or the severity of the coronary lesions.

Adult↗