Structure of the Kunitz-type soybean trypsin inhibitor (STI): implication for the interactions between members of the STI family and tissue-plasminogen activator.

The Kunitz-type soybean trypsin inhibitor (STI) has played a key role in the early study of proteinases, having been used as the main substrate in the biochemical and kinetic work that led to the definition of the standard mechanism of action of proteinase inhibitors. A partial structure of STI complexed with porcine trypsin has previously been reported, in which the first 93 residues of the inhibitor, including the region of contact with trypsin, were relatively well defined, whereas for the remaining part of the peptide chain only some Calpha atoms were located. The structure of the inhibitor in its free form has now been determined by molecular replacement to 2.5 A, using the coordinates of the homologous Erythrina trypsin inhibitor as a search model. When the refined atomic coordinates of STI are compared with the partial model previously available, the conformation of the reactive-site loop and its position with respect to the main body of the molecule does not change when the inhibitor interacts with trypsin. There are instead, despite the high similarity in the overall tertiary structure, significant differences between STI and Erythrina trypsin inhibitor (ETI) in the region which is in contact with the enzyme in the STI:trypsin crystal structure. Some of these differences can explain the unique specificity of ETI and its ability to inhibit the fibrinolytic enzyme tissue-type plasminogen activator.

The monetary value of the person-Sievert: a practical approach in case of occupational exposures.

This paper gives some practical advice on the determination of the value of the person-Sievert, this figure being of primary importance when cost-benefit analysis is used to optimize (ALARA-principle) routine occupational exposures of professionals to external radiation. After a brief introduction on the use of cost-benefit analysis in a radioprotection context, more attention will be paid to the theoretical guidelines that exist on the monetary value of the person-Sievert. By combining these insights with the practical problems that occur in daily task preparations and evaluations, a more workable proposal for the determination of the value of the person-Sievert will be presented.

The influence of internal stone structure upon the fracture behaviour of urinary calculi.

In vitro extracoporeal shock wave lithotripsy (ESWL) on different types of urinary calculi, in combination with microfocus x-ray and microphotography, illustrates the importance of the internal stone structure. Calculi with a rough surface layered structure (calcium oxalate monohydrate) and untextured calculi (cystine) are characterized by a low stone fragility, whereas coarse-grain calculi (calcium oxalate dihydrate, struvite), and calculi with a smooth surface layered structure (uric acid), are very fragile. Shell-like fragmentation in layered calculi, with smooth surface of the crystalline laminations, suggests that the stone matrix influenced the propagation of the shock wave energy inside the stone.

Mechanical behaviour of femoral bones in bending loading.

A series of 33 human femoral bones have been subjected to a four point bending test at high strain rates. Two different failure modes were recognized. A Y shaped fracture at the middle region induced by a pure bending moment yielded a zone of non-linearity at the load vs deformation curve and a higher bending force, more deformation of the structure and higher strain energy to fracture compared with the less frequently occurring oblique fracture at the distal third of the structure resulting in a failure without a 'plastic' portion at the load-deformation curve. Estimated values of bending modulus and maximum bending moment based upon a simple uniform beam model showed high correlation coefficients with the experimentally determined values. Scanning electron microscopic examination of the Y fracture showed distortion and void formation of the material at the structural level. This could explain the extensive non-elastic deformation prior to failure.

Bioglass composites: a potential material for dental application.

Bioglass, a promising material for dental applications, can be reinforced with ductile stainless steel fibres. Three aspects of the fibre-reinforced bioglass composites are discussed. They are the interface between the glass and the metal fibres, the mechanical properties of the composites and their in vivo bonding behaviour. The importance of a good interfacial bond between the glass and the metal fibres is outlined. The improvement in strength and toughness, due to the fibres, is explained. The in vivo bonding behaviour of the bioglass composite is checked under statically loaded conditions.

Fatigue properties of implant materials in hip prosthesis form: a standardized test.

The determination of the fatigue properties on small specimens is not accurate. It does not take into account the considerable scatter in fatigue properties which may arise in the implants. Therefore, testing of the properties on the actual implant is needed. The working hypothesis of the present article is that four-point bending fatigue tests allow determination of the fatigue limit of the femoral component material in total hip prostheses. It eliminates the disadvantages of the previously proposed load on head test because (1) the reproducibility of the stress pattern is easy; (2) the fatigue testing is over the whole critical part of the stem; and (3) the stresses do not change during the test. Testing of a series of hip prostheses shows that (1) the measured fatigue limit is typical for the material tested; (2) the location of the fatigue fractures is over the critical medial third of the stem; and (3) the fractographic aspects correspond to those of in vivo failed prostheses. The four-point bending procedure is proposed as a standard method.

The mechanical characteristics of cancellous bone at the upper femoral region.

Mechanical behaviour of trabecular bone at the upper femoral region of human bones has been studied by compression tests on trabecular bone specimens removed from normal femora obtained at autopsy. Compression tests were performed along three different axes of loading on wet specimens and high loading rates. Femoral head specimens proved to be the strongest for any axis of loading. Large variation in compressive strength and modulus of elasticity is seen within and between femoral bone samples. Anisotropy and differences in anisotropy for the different regions have been observed. A significant correlation between mechanical properties (sigma max - E) and bone mineral content of the specimen was found. Tests on whole bone structures demonstrate that removal of the central part of the trabecular bone at the proximal femur reduces the strength for impact loading considerably (+/- 50%).

The geometrical properties of human femur and tibia and their importance for the mechanical behaviour of these bone structures.

A series of non pathological human tibial and femoral bones have been tested in torsional loading at high strain rates. Elastic (torsional stiffness) and ultimate properties (Tmax) have been determined. A geometrical description of the individual bone structures has been performed by determination of the polar moment of inertia (assuming axial symmetry), variation of this parameter along the long axis of the bone and length of the specimen between the grips. A fairly accurate prediction of mechanical behaviour of bone structures could be obtained using these geometrical parameters. The high variation of elastic and ultimate properties of whole bone structures in torsional loading is primarily the result of the high variation of polar moment of inertia for the different bone specimens.

Performance analysis of total hip prostheses: some particular metallurgical observations.

Metallurgical observations of phenomena which influence the clinically successful performance of permanent implants and implant materials are reported. The effect of casting voids in cast cobalt chromium femoral stems of total hip replacements is discussed first. Pitting corrosion occurred in a retrieved stainless-steel implant type AISI 316 containing 2.7% Mo. The fractographic pattern of this device retrieved for fatigue failure shows typical characteristics of corrosion-enhanced fatigue.

Skeletal fixation of implants by bone ingrowth into surface pores.

An alternative skeletal fixation by bone ingrowth into porous coatings has been studied. Stainless steel fiber coatings using different fiber diameters (50-100 micrometer) and different pore sizes have been tested. Plugs, intramedullary rods and various types of knee prostheses have been implanted in dogs in non functional and also in functional loading conditions. Histological and mechanical evaluation of the bone implant interface has been performed. Consistent bone ingrowth was observed for implants in non functional conditions if the pore size exceeded 70 micrometer. Ingrowth in functional loading conditions requires rigid initial stability of the implant and intimate contact of implantcoating and surrounding bone tissue.

Microscopic fracture aspects of impact tested human bones.

The fracture aspects of impact twisted human femurs and tibias have been studied in their wet condition. The main tool used to correlate fracture behaviour with bone structure was the scanning electron microscope. Supplementary data were obtained from macroscopic fracture pattern analyses and stress coat experiments on slowly tested dried bone. The interest of the data reported concerns two major points. Firstly the analysis of the fractographic results leads to the conclusion that the fracture has presumably been initiated by shearing parallel with the torsion axis. The fracture propagates along so called spiral and oblique fracture lines. Secondly, the correlation of the macroscopic fracture pattern with microscopic fracture aspects indicates that the fracture is initiated along the cement lines, which can be considered as the weak matrix in an osteon-cement lining composite. The fracture propagates along the cement lines as well as through osteons and lamellae. Throughout the impact fracture surfaces ductile and brittle fracture aspects were observed, although the brittle fracture mode was predominant during propagation.