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S Lees

Publications and source records attributed to S Lees.

At least 19 recordsLinked to original sources

Comparison of dosage-dependent effects of beta-aminopropionitrile, sodium fluoride, and hydrocortisone on selected physical properties of cortical bone.

BAPN, sodium fluoride, and hydrocortisone are reported to induce altered mineralization states. Three separate sets of experiments, one set for each agent, were performed using male New Zealand white rabbits. In each experiment the rabbits were segregated into groups, each fed a specified weight-determined dose for 13 weeks and then sacrificed. Compact bone from the left femur and tibia were tested for density, composition, sonic velocity, longitudinal elastic modulus, equatorial diffraction spacing of mineralized collagen, diaphyseal cross-sectional area, and relative load stress. beta-Aminopropionitrile (BAPN) induced monotonic degradation of all properties at all dose levels, corresponding to the decreasing density with dosage level. The elastic moduli show a decrease; the equatorial diffraction spacing of the collagen increases. The cross-sectioned diaphysis resembled woven bone. The variability in properties increased with dosage. The total cross-sectional area for a given weight increased, implying that the decreased elastic properties were compensated for by a larger area to support the weight. There was a slight increase in average density and other properties for fluoride-treated rabbits, peaking at 20 mg/kg BW/day. For higher dosages the properties are degraded and the values were much lower at high fluoride dosages than for BAPN. There was no peak for the equatorial diffraction spacing, which increased with dosage. It is inferred that the fluorosed apatite is denser than normal apatitic mineral and therefore has a smaller specific volume. A greater weight fraction of fluorosed mineral has a smaller volume fraction than the equivalent normal apatitic mineral. The bone sections look more normal, except for the porosis. The total cross-sectional area decreases when the bone density increases and then increases as the density falls, again implying that the area required to support body weight depends on the magnitude of the elastic moduli. There was a small change in some of the properties of the bones of the hydrocortisone-treated rabbits, but the effects on others were undetectable within the uncertainty of the procedures. There was no change in the cross-sectional areas of the diaphyses.

Aminopropionitrile

The loci of mineral in turkey leg tendon as seen by atomic force microscope and electron microscopy.

Transmission electron micrographs of fully mineralized turkey leg tendon in cross-section show the ultrastructure to be more complex than has been previously described. The mineral is divided into two regions. Needlelike-appearing crystallites fill the extrafibrillar volume whereas only platelike crystallites are found within the fibrils. When the specimen is tilted through a large angle, some of the needlelike-appearing crystallites are replaced by platelets, suggesting that the needlelike crystallites are platelets viewed on edge. If so, these platelets have their broad face roughly parallel to the fibril surface and thereby the fibril axis, where the intrafibrillar platelets are steeply inclined to the fibril axis. The projection of the intrafibrillar platelets is perpendicular to the fibril axis. The extrafibrillar volume is at least 60% of the total, the fibrils occupying 40%. More of the mineral appears to be extrafibrillar than within the fibrils. Micrographs of the mineralized tendon in thickness show both needlelike-appearing and platelet crystallites. Stereoscopic views show that the needlelike-appearing crystallites do not have a preferred orientation. From the two-dimensional Fourier transform of a selected area of the cross-sectional image, the platelike crystallites have an average dimension of 58 nm. The needlelike-appearing crystallites have an average thickness of 7 nm. The maximum length is at least 90 nm. Atomic force microscopy (AFM) of unstained, unmineralized turkey leg tendon shows collagen fibrils very much like shadow replicas of collagen in electron micrographs. AFM images of the mineralized tendon show only an occasional fibril. Mineral crystallites are not visible. Because the collagen is within the fibrils, the extrafibrillar mineral must be embedded in noncollagenous organic matter. When the tissue is demineralized, the collagen fibrils are exposed. The structure as revealed by the two modalities is a composite material in which each component is itself a composite. Determination of the properties of the mineralized tendon from the properties of its elements is more difficult than considering the tendon to be just mineral-filled collagen.

Animals

Effect of fluoride dosage on bone density, sonic velocity, and longitudinal modulus of rabbit femurs.

Relationships between the fluoride dosage administered to weanling New Zealand white male rabbits and some mechanical properties of the compact bone were investigated for a wide range of dosages. The measured quantities were density, longitudinal sonic velocity in the radial direction, and fluoride ion concentration in compact bone. The longitudinal elastic modulus was estimated from the product of the density and the square of the sonic velocity. The relative static load stress was estimated from the ratio of the final body weight to the cross-sectional area of the femur. These measurements and derived quantities provide quantitative measures of bone quality. A slight peak (2% greater than reference) was determined for the density and a slightly larger peak (5% above reference) for the longitudinal sonic velocity at a dosage of approximately 20 mg/kg/day. The longitudinal elastic modulus exhibited a substantial peak, 14% greater than reference. The relative static load stress showed a very slight peak as a function of dosage and also as a function of fluoride concentration in the bone. When plotted against the elastic modulus, a nonlinear monotonic increase was observed with modulus, showing that the cross-sectional area of the bone is responsive to the stiffness of the tissue. Stiffer tissue produces a smaller cross section, whereas a more compliant tissue requires a marked increase in the area.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

X-ray diffraction by collagen in the fully mineralized cortical bone of cow tibia.

X-ray diffraction patterns were recorded from fully mineralized and demineralized sections of the cortical bone from cow tibia. The results were used to obtain a measure, d, of the mean side-to-side spacing (equatorial diffraction spacing) of the molecules in the type I collagen fibrils of bone. Mineralized bone yielded a d value of 1.23 nm; for the demineralized tissue this value increased to 1.52 nm. Thus it appears that mineralization of bone compacts its collagen molecules within the fibrils.

Animals

Sonic velocity and attenuation in wet compact cow femur for the frequency range 5 to 100 MHz.

Ultrasonic studies on bone have not been done as intensively as other tissues, probably because there is less opportunity to examine bone in vivo by this modality. There is considerable interest in using ultrasonics to learn about the material properties of bone for which purpose the sonic spectrum may be useful. The longitudinal sonic velocity and attenuation have been found for several sections from one sample of wet cow femur for both the axial and radial directions over the frequency range of 5 to 100 MHz. The basic technique was solid-to-solid contact using a fused quartz buffer rod coupled to the bone specimen. There is clear evidence of velocity dispersion which Lakes et al. (1986) did not find over a frequency range up to 16 MHz. While there seems to be a peak in both velocity and attenuation at 70 MHz, it is necessary to obtain measurements at higher frequencies to make sure this is not an artifact. The axial sonic velocity varied from 4.29 km/s at 5 MHz to 4.447 km/s at 50 MHz, while the radial velocity was 3.45 km/s at 5 MHz and increased to 3.62 km/s at 50 MHz. The attenuation coefficient axially started at a mean value of 3.5 db/mm at 5 MHz and increased to a mean of 19 db/mm at 100 MHz. The corresponding radial attenuation coefficients are 5.2 and 26, respectively.

Animals

Measuring the microelastic properties of biological material.

We have used the atomic force microscope (AFM) to measure the local rigidity modulus at points on the surface of a section of hydrated cow tibia. These data are obtained either from contrast changes that occur as the contact force is altered, or from force versus distance curves obtained at fixed points. These two methods yield the same values for rigidity modulus (at a given point). At low resolution, the elastic morphology and topography mirror the features seen in optical and electron micrographs. At high resolution we see dramatic variations in elastic properties across distances as small as 50 nm.

Animals

A study of some properties of mineralized turkey leg tendon.

Several macroscopic physical properties of mineralized turkey leg tendon were measured including wet density, composition, volume fractions of the major components, sonic velocity in three axes, longitudinal modulus and dimensional changes on drying. Where possible the properties were related to density. Typically the wet density of unmineralized tissue is 1.09 g/cc, where for fully mineralized tissue it is 1.6 g/cc (compared with 2.06 to 2.10 g/cc for compact cow bone). Longitudinal sonic velocity axially is 3.22 km/sec, 2.57 km/sec transversely and 2.21 km/sec in thickness. The axial longitudinal modulus is 16.7 GPa compared to the axial Young's modulus of 8.53 GPa. MTLT shrinks 0.5% axially, 4.75% transversely and 4.15% in thickness. The anisotropy is equally exhibited in its microscopic structure when observed optically. Least squares second order curves were fitted to the water, mineral and organic component experimental values. Apparently the water in MTLT is replaced by mineral, unlike the process in bone where there is less organic matter as the mineral content increases and the water fraction changes much less. The generalized packing model for collagen was used to relate the data to the ultrastructure. The distribution of the major components between the intrafibrillar and extrafibrillar volumes as a function of the density was calculated. The results show the intrafibrillar volume fraction increases with density, the water content of the intrafibrillar volume remains almost constant, but the water fraction of the extrafibrillar volume decreases from 51 to 8% of the water in the tissue. It is concluded that the mineralization process in MTLT differs from that in bone.

Animals

The design of a stress-management programme for nursing personnel.

This study identifies the stressors and coping strategies of nursing staff (students, trained staff and those who had left the profession before qualification) in a variety of ward specialisms. The research instruments included an open-ended interview concerning pre-nursing experience, perceived stressors and satisfactions, and ways of coping, and psychometric tests of self-esteem, assertion, ways of coping and personality. The five most frequently cited stressors were understaffing, conflict with nurses, dealing with death and dying, overwork and conflict with doctors. Experience of stressors was related to role and seniority of respondents, with different aspects of the same stressor differentially affecting nurses at different levels of experience. Coping strategies also depended on experience. Trained staff showed more use of problem-focused ways of coping, whilst students and leavers relied more on emotion-focused strategies to deal with stressful situations. These differences were related to personality characteristics of respondents and to self-esteem as well as to situational characteristics of the stressful episode. Social support was important in times of work-related stress, with students in particular making good use of peer group support. Respondents were generally lacking in assertiveness and high in anxiety. Although self-esteem was generally high, leavers scored markedly less than other subject groups in the areas of personal and social self-esteem. Leavers had little prior knowledge or experience of nursing before entering training and knew few nurses or doctors: consequently, nursing failed to meet their expectations. Stress was identified as the major cause of attrition and the sources of stress are identified. This study informed a major programme of stress-management training for student nurses which began in 1988 at the North Wales School of Nursing and which is currently under evaluation. It includes relaxation therapy, assertiveness training, and on-going group discussions which foster peer-group support and which explore the stressors and coping strategies relevant to different stages of training and ward specialisms.

Adaptation, Psychological

Studies of compact hard tissues and collagen by means of Brillouin light scattering.

A measure of the elastic properties of tissue can be found from the propagation of sound in the tissue. Longitudinal sonic velocities were measured for mineralized turkey leg tendon (density 1.50 g/cc), deer antler (1.77 g/cc) and cow tibia (2.05 g/cc) in the 10 GHz frequency regime by means of Brillouin light scattering using a nine pass Fabry-Perot interferometer. Wet, air dried, mineralized and demineralized specimens were tested. Sonic velocity in each tissue increased with mineral content and decreased when the tissue was wet. All wet values are higher than for wet rat tail tendon collagen, axially and radially, but with considerably less anisotropy. The results are interpreted to indicate that bone matrix collagen is more highly crosslinked than tail tendon collagen. The loss of anisotropy is taken to correspond to a much higher crosslinking density between adjacent collagen molecules in mineralized tissue compared to rat tail tendon. The axial sonic velocity of dried rat tail tendon is almost that for low density dried mineralized tissue and greater than the radial sonic velocity of these tissues, but the radial sonic velocity for dried rat tail tendon is much lower, again corresponding to less crosslinking in this tissue. Longitudinal modulus, K, is defined as the tissue density times the square of the velocity. The compliance, 1/K, was found to be a linear function of density for each of the four conditions. It suggests that a Reuss formalism describes the elastic properties. Since the difference between the compliance for wet and dry tissue is also a linear function of density, the effect of water on the compliance is additive. The axial sonic velocity for cow bone is essentially constant over a frequency range spanning 10 orders. Presumably the axial sonic velocity is controlled by the continuity of the collagen fibers lying along the bone axis. The radial velocity decreases by 30% over this frequency range, probably due to the many levels of structure observed in long bone like osteons, Haversian canals and blood vessels, as well as internal surfaces like cement lines and between lamellae. The sonic anisotropy of hard tissues decreases considerably with increasing frequency. While rat tail tendon collagen is very anisotropic both sonically and optically, hard tissues whether wet, dry, mineralized or demineralized show much less anisotropy. The optical index of refraction, both axially and radially, was found by Brillouin scattering for the air dried demineralized tissues. A close match was found between optical and sonic anisotropy for all the demineralized tissues.

Animals

BAPN dose dependence of mature crosslinking in bone matrix collagen of rabbit compact bone: corresponding variation of sonic velocity and equatorial diffraction spacing.

Crosslinking density in demineralized bone matrix collagen was found to depend on the beta-aminopropionitrile (BAPN) dose level for compact bone from rabbit femurs. The dependence was demonstrated for the hydroxypyridinium (HP) concentration, a mature crosslink. A more consistent dependence on BAPN dosage was observed for the fraction of the demineralized bone matrix insoluble in 0.5 M acetic acid (AIF) corresponding to the remaining crosslinked collagen. The average HP concentration in 21 week old controls was 0.24 moles HP/mole collagen which decreased to 0.13 +/- 0.04 for the same age rabbits dosed with 1 gm BAPN/kg/day for 13 wks. The comparable mean AIF values were 0.91 for controls and 0.75 for maximum dose level. Most of the effect of BAPN on crosslinking was observed at the lower dosages below 0.2 g/kg/day. On the other hand, overt osteolathyritic symptoms are seen only for BAPN dosages greater than 0.2 g/kg/day. The mean sonic plesio-velocity was previously found to decrease from 3.4 to 3.03 km/sec as the BAPN dosage was increased. A similar close relationship was discovered for the equatorial diffraction spacing in fully mineralized bone which increased from 1.235 for normal rabbit bone to 1.28 nm for maximum dose. Most of the effect on these physical properties is exhibited at the highest BAPN dosage after much of the decrease in mature crosslinking density has been observed and when the further decrease in mature crosslinking density proceeds very slowly with increased drug dosage. These observations suggest that osteolathyrism does not become manifest until practically all mature crosslinking that can be affected has been inhibited. The mineralization process apparently can be maintained in the newly laid collagen even in the presence of severe osteolathyritic conditions. Intermolecular crosslinking in bone collagen appears to play an important role in the development of bone properties whether by direct or indirect processes. Much of the effects on bone properties occur at the higher BAPN dosages where overt osteolathyrism is observed and where there seem to be only small changes in crosslinking density.

Acetates

The locus of mineral crystallites in bone.

The organic content of mineralized tissues has been found to decrease with increasing tissue density, from about 60% of the mineral weight in light bone like deer antler to 1 to 2% in hyperdense bone like porpoise petrosal. The ratio of the weight of mineral that can fill the collagen hole zones to the total mineral content can be no greater than 20% for deer antler and decreases to less than 5% for hyperdense bone. Moreover, the dimensions of hydroxyapatite crystallites have been determined by various investigators to be larger than the intermolecular spacing of collagen molecules. Such crystallites can only be fitted within the collagen fibril if collagen molecules are packed differently from the accepted models. Electron micrographs of fish dentin, at a very early stage of mineralization, show the needle-like crystallites lying in dense strips between collagen fibrils and practically no crystallites within the fibrils. A similar pattern of dense strips of crystallites between fibrils can be identified in examples from more advanced stages of mineralization, taken from fish dentin, cat dentin and cow tibia, even though some of the needle-like crystallites are superimposed on the fibril banded pattern. In every instance there are regions of the fibrils where there are no visible needle-like crystallites. Examination of the work of others shows a similar distribution of the mineral component, except that none exactly resemble the micrograph of the earliest stage of fish dentin provided in this report. The collagen banding is observed to be in spatial phase over many fibrils. The needle-like crystallites may be observed to be bunched in phase with the collagen banding and with the same spatial periodicity. The bunching is most obvious in the least densely mineralized specimens. This observation can account for the x-ray and neutron diffraction patterns which shown the axial period of the mineral to be like that of the collagen axial macroperiod and to be in phase with the hole zones of collagen fibrils. These prior studies were interpreted to show that the crystallites must be within the hole zones. Our images are interpreted to show that most of the mineral is outside of the collagen fibrils in the extrafibrillar volume. The interpretation is in agreement with neutron diffraction studies of various mineralized tissues as well as with earlier diffraction studies of mineralized turkey leg tendon and with the calculations of the amount of mineral that can be contained within the collagen of mineralized tissue.

Animals

The variation of sonic plesio-velocity in dose dependent lathyritic rabbit femurs.

It has been hypothesized that the origin of the increased elastic modulus of mineralized bone compared with the demineralized bone matrix is in the higher crosslinking density of the collagen in bone. Osteolathyrism is ascribed to an inhibition of crosslinking of the collagen by the lathyrogen and should be accompanied by a decrease in the elastic modulus of the bone. Dose dependent osteolathyrism was induced by varying the amount of BAPN ingested per day by young New Zealand white rabbits until they were mature. The femurs exhibited dose dependent properties, including wet bone density and sonic plesio-velocity in the radial direction. It was found that there is no minimum critical dose. Even though no overt osteolathyritic stigmata could be observed, both the sonic properties and the wet bone density could be affected at any dose level. The sonic plesio-velocity and the longitudinal elastic modulus decreased with BAPN dose level, most rapidly at the lower dose levels and then less so at higher dosages. Since BAPN acts to inhibit the crosslinking density, it appears that the elastic moduli of bone are dependent on the crosslinking density.

Aminopropionitrile

Considerations regarding the structure of the mammalian mineralized osteoid from viewpoint of the generalized packing model.

The relative magnitudes of mineral, organic and water contents of dense mammalian bone are calculated by a new theory based on recent findings: (1) The neutron diffraction studies of mineralized tissues with different densities demonstrated an inverse relationship between wet density and the equatorial diffraction spacing of the collagen. (2) The neutron studies showed there was very little mineral within the collagen fibrils. (3) A generalized packing model for collagen has been advanced to show how the equatorial spacing can be varied depending on tissue type, water content, and mineral content. (4) The water content of collagen fibrils when calculated from the generalized packing model matches the experimentally determined values for rat tail tendon fibers, bone matrix, and fully mineralized bone. A computational model was developed based on the generalized packing model. It provides a unifying approach to explain many features of mineralized fibrous collagenous tissues. The results are presented as estimates of the mineralized collagen fibril density, the volume fraction of collagen in bone, the density of the extrafibrillar space, the fraction of the e.f. space occupied by mineral and the ratio of mineral within collagen to total mineral content, each expressed as a function of wet bone density. A useful data base, available from previous studies, related mineral, organic and water weight fractions to wet bone density, for a density range from 1.7 g/cc for deer antler to 2.7 g/cc for porpoise petrosal. A second order polynomial was found for each weight fraction component, with bone density as the input variable, with a standard deviation less than 2% of total bone weight. This permits the bone properties to be related to a single variable, the wet bone density. It is seen that compacting the collagen fibrils as well as reducing the organic component weight fraction are two important factors determining the structure of the mineralized osteoid. It was concluded that voids and pore spaces may occupy at least 5% of the bone volume.

Animals

Vapor pressure isotherms, composition and density of hyperdense bones of horse, whale and porpoise.

Water adsorption studies of three types of hyperdense bone show vapor pressure isotherms and enthalpy to be different from that for pure apatitic mineral. The mineral content of these bones varied from 80 to 98%, much greater than for the better known cortical bone. The high mineral content of all these bones and the variation of mineral content from one type of bone to the next make it possible to evaluate the contribution of the mineral component in bone to water adsorption. Both water content and the fractional shrinkage when dried decrease with increasing mineral content of the bone and increase with the organic component. The total water content of hyperdense bone is much less than the maximum water adsorbed by the equivalent pure mineral powder or by anorganic bone. It was concluded that: (1) Very little water appears to be adsorbed by the mineral in hyperdense bone; (2) It is likely that the mineral crystallites are coated with noncollagenous organic matter; (3) Water is taken up by organic matter both intra- and extrafibrillar; and (4) the enthalpy associated with the adsorption of water by HAP is higher than for hyperdense bone at all corresponding vapor pressures.

Adsorption

Equatorial diffraction spacing as a function of water content in fully mineralized cow bone determined by neutron diffraction.

Variation of the equatorial diffraction spacing of soft type I collagen tissues with water content using X-rays has been known for many years. Recently, a generalized model for collagen molecule packing within fibrils was deduced from this information for different collagenous tissues. It is now known that the eq. diff. sp. of mineralized tissues can be less than for soft tissues and is inversely dependent on the wet density. A determination of the eq. dif. sp. dependence on water content using neutron diffraction of fully mineralized cow bone was undertaken for comparison. Specimens with various partial water content between 0 and 100% were tested. Data show collagen molecules pack more closely together as water content decreases, just as for soft tissues.

Animals

Major histocompatibility complex restriction fragment length polymorphisms define three diabetogenic haplotypes in BB and BBN rats.

Class I and II major histocompatibility complex (MHC) probes can be used to subdivide diabetes-prone BB rats and their BBN control strain, coderived from the same outbred colony by selection against diabetes. Class II probes (A-alpha in particular) distinguish four restriction fragment length polymorphisms (RFLP), termed 1a, 1b, 2a, and 2b, in the BBN population, only one of which (2a) is found in BB rats. The degree of class II RFLP in the population studied is RT1.B-alpha greater than or equal to RT1.B-beta greater than RT1.D-alpha greater than or equal to RT1.D-beta, suggesting that intra-class II region dynamics may be different in rats compared with mice. A class I probe (S16) absolutely distinguished BB from BBN rats, since all BB rats exhibit an RFLP pattern termed 2a0, while 2a BBN rats can be subdivided into 2a1 and 2a2 forms. Serologic evaluation has shown that 2a0, 2a1, and 2a2 rats express RT1.AuBu, 1a rats express RT1.AaDa, and 1b rats express neither RT1a nor RT1u at the loci tested. A breeding study was carried out to determine the diabetogenicity of the MHC-defined RFLP's. As expected, the BB-derived 2a0 is diabetogenic. The BBN-derived 2a1 and 2a2 RFLPs are also diabetogenic, while 1a and 1b rats do not carry MHC-linked diabetogenic genes. The MHC-linked diabetes gene acts in a functionally recessive manner, since there is a 10-fold higher incidence in homozygotes than in heterozygotes. Analysis of the RFLP patterns leads us to hypothesize that the 2a1 RFLP results from a crossover between 1a and 2a0 MHCs and that the diabetogenic MHC-linked gene is on the class II side of Qa and T1. The availability of three diabetogenic MHC haplotypes should help localize the MHC-linked diabetogenic gene of rats.

Animals

Neutron diffraction studies of collagen in fully mineralized bone.

Neutron diffraction measurements have been made of the equatorial and meridional spacings of collagen in fully mineralized mature bovine bone and demineralized bone collagen, in both wet and dry conditions. The collagen equatorial spacing in wet mineralized bovine bone is 1.24 nm, substantially lower than the 1.53 nm value observed in wet demineralized bovine bone collagen. Corresponding spacings for dry bone and demineralized bone collagen are 1.16 nm and 1.12 nm, respectively. The collagen meridional long spacing in mineralized bovine bone is 63.6 nm wet and 63.4 nm dry. These data indicate that collagen in fully mineralized bovine bone is considerably more closely packed than had been assumed previously, with a packing density similar to that of the relatively crystalline collagens such as wet rat tail tendon. The data also suggest that less space is available for mineral within the collagen fibrils in bovine bone than had previously been assumed, and that the major portion of the mineral in this bone must be located outside the fibrils.

Achilles Tendon