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Biomedical subjects

A Tardieu

Publications and source records attributed to A Tardieu.

66 records · Page 4Linked to original sources

alpha-Crystallin quaternary structure and interactive properties control eye lens transparency.

The eye lens is the foremost biological system where function is directly under control of the physico-chemical properties of the cytoplasmic macromolecular solution. Indeed, lens transparency and opacity, lens refractive index gradient and viscosity, are the result of the structural and interactive properties of the crystallins, of their stability, of the fine tuning of their interaction potentials and associations at different levels of organization. Among the different crystallin classes, alpha-crystallins have represented a major challenge for a long time. The alpha-crystallin secondary, tertiary and quaternary structures are still unknown. On the functional side, however, it is established that alpha-crystallin quaternary structure and repulsive interactions determine lens transparency, whereas the alpha-crystallin chaperone effect most probably plays a role in the aging process. In the present paper, we recall the physico-chemical properties and the quaternary structure features of alpha-crystallins that were demonstrated to control light scattering and transparency. The interest of a crystallin mixture for lens function is discussed. Then, a formal approach is proposed to design models for the alpha-crystallin quaternary structure, including the question of whether alpha-crystallins assemble with symmetry. An hypothesis relevant to the fold of the alpha-crystallin C-terminal domain is presented in another paper in this issue.

Animals↗

alpha-Crystallin C-terminal domain: on the track of an Ig fold.

New results obtained from a two-dimensional sequence analysis of the small heat shock protein (shsp) family are described. It is confirmed that the conserved C-terminal alpha-crystallin domain is essentially made of beta-strands, most probably two groups of beta-strands separated by a large loop. A direct correspondence between the putative beta-strands that have been identified in shsps and the seven beta-strands of a classical immunoglobulin-like fold is proposed. The hypothesis that the shsp family could belong to the immunoglobulin superfamily (IgSF) is consistent with the ubiquitous distribution and the multifunctional properties of the crystallins that are now emerging.

Amino Acid Sequence↗

Short-range order of crystallin proteins accounts for eye lens transparency.

In its normal state, the eye lens is transparent despite the presence in the cell cytoplasm of high concentrations of proteins, the crystallins, which, a priori, could be expected to scatter an important part of the incident light. Early on, an explanation was sought in the spatial correlations between individual scatterers. Trokel first proposed that the "high concentration of proteins in the lens must be accompanied by a degree of local order approaching a paracrystalline state"; Benedek subsequently suggested that a dense, noncrystalline packing of the proteins would sufficiently reduce the scattered intensity. However, in spite of an improved understanding of the molecular structure of crystallins, their spatial order remained unknown. We present here a small-angle X-ray scattering study of the problem, performed with calf lens cytoplasm both in intact lenses and in cytoplasmic extracts where the crystallin concentration was varied from 3 to 510 mg ml-1. All our experimental data are consistent with short-range spatial order, as in dense liquids or glasses, and this provides a simple explanation for lens transparency. In addition, we detected no conformational change or reorganization of the crystallin proteins throughout the investigated concentration range.

Animals↗

[Coronary angiography after the age of 70 years].

100 patients over the age of 70 years underwent coronary angiography. The indications for this examination at this age were different from those in younger patients. After the age of 70 years, 58 per cent of coronary angiographies are performed as part of the haemodynamic survey of valvular disease. The risk of the examination appears to be higher, as two deaths occurred in this small series, while the mortality is estimated to be 2 per thousand in younger patients. Coronary angiography is very useful at this age in patients with valvular disease to determine the need for an associated coronary graft and also to determine contraindications for operation because of the severity of the lesions. A surgical indication was confirmed in 50 patients, but surgery was only performed in 36 of them. The follow-up of these patients demonstrates that patients operated for valvular disease had a longer survival that those considered to be inoperable or who refused operation. On the other hand, there was no difference in survival between grafted and non-operated patients over the age of 70 years.

Aged↗

[Coronary stenoses and surgical possibilities according to the coronarographic indication. Evaluation of 1000 studies].

The degree of severity of coronary artery lesions and the quality of the distal vessels which justify revascularisation by by-pass grafting were studied in 1,000 consecutive cases of coronary angiography. The results are presented in terms of the clinical indication for coronary angiography and in terms of the patients' age and sex. 47% of patients were investigated because of unstable angina and 53% of them had surgical lesions. 16% of the angiographies were performed three weeks after myocardial necrosis. 45% of these patients had a surgical lesion in a coronary territory other than that of the necrotic area. In 20% of cases, the coronary angiography was performed as part of the pre-operative work-up for valvular heart disease. 17% of these operations combined a by-pass graft with the valve replacement. Independent of the indication for coronary angiography, 20% of cases had major coronary artery stenoses which reduced the lumen by more than 70% and which were inoperable.

Constriction, Pathologic↗

[Preliminary report on the demonstration of resistance to coumafene in Rattus rattus in Marseilles].

An abnormal proliferation of Rattus rattus in an important food-products warehouse in Marseille's periportuary zone has been recorded in spite of preventative measures put in place and aimed at testing these rodents resistance to basic anticoagulants, especially to coumafene. The laboratory experiments on animals taken from the invaded area have enabled us to prove for the first time on metropolitan ground a Rattus rattus resistance to coumafene. The colony of rodents responsible is giving proof of its resistance in already large proportions, since the survival beyond 10 days of treatment is established in 74% of the tested subjects, whereas 30% of them survive treatments prolonged by 4 to 10 weeks. The recorded results allow us to confirm the variable degrees of the state of resistance which appear to be developed locally, the origin of which cannot be defined. Taking into account the size of the affected zone and the numerous food-products storage establishments found there and usually infected with Rattus rattus, one is forced to fear a rapid progress of the territorial resistance. It is therefore opportune to take the necessary measures to destroy the resistant colony on the spot, to follow the ultimate progress in the area and to follow up in the laboratory the methods of evaluation of the efficiency of new rodenticides.

Animals↗

[Supplementary report on the study of resistance to coumafene in Rattus ratus observed at Marseilles].

A resistance to coumafene has previously been observed among Rattus rattus in a foodstuffs warehouse in the port of Marseille. New tests are here reported. They concern rats captured in two warehouses situated at a distance of 1,000 m. from one another, and separated by a distance approximately similar to that of the first warehouse explored. The experiments which were carried out, although limited in number, have clearly shown a resistance to coumafene administered in high doses in a rat of the first group and in three rats of the second group. There is every reason to fear a resistance extended to all the territories where Rattus rattus are found in the harbour and in the neighbouring regions.

Animals↗