Biomedical subjects

A J Bailey

Publications and source records attributed to A J Bailey.

At least 55 records · Page 3Linked to original sources

PubMed1999

The effect of advanced glycation end-product formation upon cell-matrix interactions.

The formation of advanced glycation end-products plays a central role in the progressive deterioration of tissues with age, a process that is accelerated in diabetes. Collagen in addition to providing structure and tensile strength to tissues also provides a dynamic matrix for cells to interact with, and due to its long-lived nature is particularly susceptible to modification with age and disease. We have recently identified methylglyoxal as a key intermediate in this process, reacting predominantly with arginine residues to form imidazolone compounds. We therefore postulated that modification of RGD sequences in collagen with methylglyoxal would interfere with crucial cell-matrix interactions. To investigate this concept we studied the interaction of two cell lines, MG63 and HT1080, with collagen modified to varying degrees with respect to arginine. Adhesion and subsequent spreading of both cell lines was significantly decreased by minimal methylglyoxal modification leading to the conclusion that such modification of collagen severely inhibits cell matrix interactions, most likely via the loss of specific arginine residues involved in integrin mediated cell attachment. This is the first demonstration that methylglyoxal modification of collagen can affect cell-matrix interactions and introduces a possible mechanism by which some of the deleterious changes in tissues with age and disease are occurring.

Antibodies, Monoclonal↗

PubMed1999

Physical and psychological symptoms of quality of life in the CHART randomized trial in head and neck cancer: short-term and long-term patient reported symptoms. CHART Steering Committee. Continuous hyperfractionated accelerated radiotherapy.

The randomized multicentre trial of continuous hyperfractionated accelerated radiotherapy (CHART) versus conventional radiotherapy in patients with advanced head and neck cancer showed no good evidence of a difference in any of the major clinical outcomes of survival, freedom from metastases, loco-regional control and disease-free survival. Therefore an assessment of the effect of treatment on physical and psychological symptoms is vital to balance the costs and benefits of the two treatments. A total of 615 patients were asked to complete a Rotterdam Symptom Checklist and the Hospital Anxiety and Depression Scale, which cover a variety of physical and psychological symptoms, at a total of ten time points. The data consisted of short-term data (the initial 3 months) and long-term data (1 and 2 years). The short-term data was split into an exploratory data set and a confirmatory data set, and analysed using subject-specific and group-based methods. Differences were only claimed if hypotheses generated in the exploratory data set were confirmed in the confirmatory data set. The long-term data was not split into two data sets and was analysed using a group-based approach. There was evidence of significantly worse symptoms of pain at day 21 in those treated with CHART and significantly worse symptoms of cough and hoarseness at 6 weeks in those treated conventionally. There was also evidence to suggest a higher degree of decreased sexual interest at 1 year and sore muscles at 2 years in those treated with conventional radiotherapy. There is no clear indication that one regimen is superior to the other in terms of 'quality of life', generally the initially more severe reaction in the CHART group being offset by the longer duration of symptoms in the conventionally treated group.

Anxiety↗

PubMed1999

Collagen biochemistry of avian bone: comparison of bone type and skeletal site.

1. Skeletal disorders in poultry are of considerable welfare and economic importance. The collagenous matrix in bone is involved in many human skeletal disorders, however little is known about the nature of the collagenous matrix in avian bone. 2. This paper describes an investigation of the collagen and mineral biochemistry together with the biomechanics of bone from different sites (humerus and tibiotarsus) and with differing functions (medullary and cortical bone). In vivo and in vitro studies of immature bone assessed the changes in collagen biochemistry during bone maturation. 3. The material strength of the humerus was greater than the tibiotarsus; this difference in strength was reflected in both the collagen and mineral matrix biochemistry. 4. The bone matrix of the humerus was more mature than that of the tibiotarsus, suggesting a higher level of matrix turnover in the tibiotarsus. The pyrrole collagen cross-link concentrations were positively correlated with breaking stress, in contrast to the pyridinoline cross-link concentrations, neither of which showed any correlation with bone strength. 5. The in vivo and in vitro maturation studies underline the importance of the pyrrole cross-link in avian bone and support the mechanism postulated by Kuypers et al. (1992) for the formation of the pyrrole cross-link from a lysine aldehyde and the immature cross-links HLKNL or LKNL. 6. Medullary bone had no biomechanical influence on the breaking stress of the bone. The biochemistry of the matrix was dramatically different. The high level of collagen lysine hydroxylation affected the cross-link profile and may be responsible for the narrow fibrils and disorganised matrix of this bone. 7. Avian bone matrix varies greatly with skeletal site and reflects the differing functions of bone. Further investigation of the collagenous matrix of both normal and diseased avian bone has the potential to aid our understanding of the aetiology of avian skeletal disease.

Animals↗

PubMed1999

Combining summaries of binary outcomes with those of continuous outcomes in a meta-analysis.

We present a methodology for combining trials some of which report continuous outcome measures and others binary outcomes created by a dichotomy of the continuous measurement. This was motivated by a series of controlled clinical trials investigating the effect of prophylactic use of oxytocics on postpartum blood loss during labor. Data were available in the form of summary statistics from published papers. The log-odds ratio is used as a common measure of treatment difference across all trials. We discuss the general applicability of this approach.

Female↗

PubMed1999

Age-related changes to the molecular and cellular components of equine flexor tendons.

Specific tendons show a high incidence of partial central core rupture which is preceded by degeneration. In the performance horse, the superficial digital flexor tendon (SDFT) is most often affected. We have described previously the molecular changes that are associated with degeneration in the central core region of the equine SDFT. The pathophysiological mechanism leading to change in synthetic activity of central zone cells in degenerated tendons is not known. In this study, we test the hypothesis that ageing results in matrix composition changes within the central zone of the SDFT. Extracellular matrix composition and cellularity were analysed in equine SDFTs collected from Thoroughbred horses and compared with a flexor tendon which rarely shows degenerative change and subsequent injury (deep digital flexor tendon, DDFT). Data were examined for age-related changes to central and peripheral zone tissue of the SDFT and DDFT. Ageing in both tendons (SDFT and DDFT) resulted in a significant increase in collagen-linked fluorescence and a decrease in cellularity in the DDFT but not the SDFT. The central zone tissue from the SDFT had a significantly higher proportion of type III collagen than the peripheral zone of the tendon. The highest level of type III collagen was found in the central zone tissue of the SDFT from the older group of horses and this may represent the early stages of a degenerative change. Collagen content did not differ between the 2 flexor tendons; however, there were differences in collagen type and organisation. The SDFT had a higher type III collagen content, higher levels of the mature trifunctional collagen crosslink hydroxylysylpyridinoline, lower total chondroitin sulphate equivalent glycosaminoglycan content, smaller diameter collagen fibrils and a higher cellularity than the DDFT. In conclusion, differences in macromolecular composition exist between the flexor tendons and ageing contributes to a tendon specific change in composition.

Aging↗

PubMed1998

Mechanisms of maturation and ageing of collagen.

The deleterious age-related changes in collagen that manifest in the stiffening of the joints, the vascular system and the renal and retinal capillaries are primarily due to the intermolecular cross-linking of the collagen molecules within the tissues. The formation of cross-links was elegantly demonstrated by Verzar over 40 years ago but the nature and mechanisms are only now being unravelled. Cross-linking involves two different mechanisms, one a precise enzymically controlled cross-linking during development and maturation and the other an adventitious non-enzymic mechanism following maturation of the tissue. It is this additional non-enzymic cross-linking, known as glycation, involving reaction with glucose and subsequent oxidation products of the complex, that is the major cause of dysfunction of collagenous tissues in old age. The process is accelerated in diabetic subjects due to the higher levels of glucose. The effect of glycation on cell-matrix interactions is now being studied and may be shown to be an equally important aspect of ageing of collagen. An understanding of these mechanisms is now leading to the development of inhibitors of glycation and compounds capable of cleaving the cross-links, thus alleviating the devastating effects of ageing.

Aging↗

PubMed1998

Abnormal cancellous bone collagen metabolism in osteoarthritis.

Biochemical investigations into the pathogenesis of osteoarthritis have, for the last two decades, concentrated on the mechanisms involved in the destruction of the articular cartilage. Although bone changes are known to occur, the biochemistry of the collagenous matrix within osteoarthritic bone has received scant attention. We report that bone collagen metabolism is increased within osteoarthritic femoral heads, with the greatest changes occurring within the subchondral zone. Collagen synthesis and its potential to mineralize were determined by the carboxy-terminal propeptide content and alkaline phosphatase activity, respectively. These data supported elevated new matrix formation. Our finding of a three- to fourfold increase in TGF-beta in osteoarthritic bone indicates that this might represent a stimulus for the increased collagen synthesis observed. Of additional significance is the hypomineralization of deposited collagen in the subchondral zone of osteoarthritic femoral heads, supporting a greater proportion of osteoid in the diseased tissue. The cross-linking of collagen was similar to that observed for controls. In addition, the degradative potential of osteoarthritic bone was considerably higher as demonstrated by increased matrix metalloproteinase 2 activity, and again the greater activity was associated with the subchondral bone tissue. The polarization exhibited in the metabolism of bone collagen from osteoarthritic hips might exacerbate the processes involved in joint deterioration by altering joint morphology. This in turn may alter the distribution of mechanical forces to the various tissues, to which bone is a sensitive responder. Bone collagen metabolism is clearly an important factor in the pathogenesis of osteoarthritis and certainly warrants further biochemical study.

Aged↗

PubMed1998

Differences between the thermal stabilities of the three triple-helical domains of type IX collagen.

Fibre-forming collagens in dilute solution show highly co-operative helix-coil transitions at temperatures that are remarkably close to the body temperature of the animal from which the collagen was extracted. This close correlation holds across animal Phyla and the transition temperatures, which range from 5 degrees C to 40 degrees C, are adjusted to suit by changing the primary structure, especially the concentration of the water-bridge-enhancing hydroxyproline residue. Fibril-forming collagens are thermally stabilised by fibrillogenesis, which causes a loss of random coil configurational entropy by intermolecular and intramolecular cross-linking and by spacial confinement of the molecule within the lattice of the fibre. But this mechanism cannot apply to the full length of the type IX collagen molecule, since its COL3 arm, according to current models, projects out from the stabilising influence of the type II fibre. In this paper we examine the thermal stability of the type IX collagen molecule and its three triple-helical domains, thereby demonstrating that the COL3 arm is much more stable than the rest of the molecule. At a scanning rate of 60 deg. C/h COL3 exhibited an unfolding endotherm with a tmax at 49.0 degrees C, well above body temperature. Corresponding peak maxima for COL1 and COL2 were seen at 40.6 degrees C and 39.6 degrees C, respectively. The sizes of the thermally labile units of COL1, COL2 and COL3, calculated from the measured activation enthalpies, were 24, 28 and 28 residues, respectively, much smaller than type I (65 residues) because of the relatively short lengths of triple helix to be unfolded. However, unlike type I collagen, no regions of the required size were found completely devoid of hydroxyproline. Consequently, the intrinsic stabilities of these thermally labile units were higher than that of type I with DeltaH updownarrow DeltaS updownarrow for COL1, COL2 and COL3 being, respectively, 385 K, 371 K and 384 K, contrasting with the much lower 349 K of type I collagen. We therefore speculate that the increased thermal stability of the thermally labile units was caused by the presence of the water-bridge-enhancing residue, hydroxyproline. Finally the stabilisation of type IX collagen tissue is considered and an alternative structural organisation of the type IX molecule on the type II fibre is proposed.

Animals↗

PubMed1998

Isolation and characterization of advanced glycation end products derived from the in vitro reaction of ribose and collagen.

An amino acid component, NFC-1, when formed in vitro by the reaction of ribose and protein was shown to comprise a complex mixture of high and low molecular AGE compounds. Two low-molecular-weight components have been successfully isolated and their structure determined. These were alphaNFC-1 [Ndelta-(4-oxo-5-dihydroimidazol-2-yl)-l-ornithine] and betaNFC-1 a 4-imidazolon-2-yl derivative existing in three tautomeric forms. These imidazolone compounds have been shown to originate from the reaction of arginine with glyoxal and methylglyoxal, respectively. A third ninhydrin-positive AGE, gammaNFC-1, was shown to be composed of a number of chromatographically similar compounds which have not yet been characterized.

Animals↗

PubMed1998

Formation of a dihydropyridine derivative as a potential cross-link derived from malondialdehyde in physiological systems.

Malondialdehyde is a major oxidation product of lipids which is capable of cross-linking the collagen of the cardiovascular system. Identification of cross-links usually involves degradative procedures. In this paper, we use a novel, direct, approach using nuclear magnetic resonance to identify early and labile products. Initial model studies show that malondialdehyde reacts with lysine to form a dihydropyridine derivative rather than the unstable imidopropene Schiff base previously reported. The aldehydes on the pyridine ring could react further to cross-link collagen and stiffen the aorta, thereby promoting further glycation, a process that would be accelerated in diabetes.

Cross-Linking Reagents↗

PubMed1998

Neural processing of human faces: a magnetoencephalographic study.

This is a whole head magnetoencephalographic (MEG) study of the neural processing of briefly presented images of human faces in 14 normal subjects. The experiments involved three tasks of increasing complexity, involving image categorisation, image comparison and the identification of emotion. The analyses were based on average responses to repeated stimuli in the different image categories. These averages were processed to give numerical measures of the power within defined regions and latency spans. The only statistically significant difference in these data between the response to faces and other images is in the right occipito-temporal channels at a latency of 140 ms. The face-specific response is largely independent of the task. Source modelling suggests an extended source in the ventral occipito-temporal region. The analysis supports the notions of both face-specificity and right hemisphere dominance for all image types at early latencies.

Adult↗

PubMed1998

Biomechanical characterization of tissues in Dupuytren's disease.

The aim of this study was to characterize mechanical properties of tissues of Dupuytren's disease and to attempt to identify changes due to cellular activity. Tensile tests confirmed the heterogeneity of Dupuytren's disease tissue with distinct stress-strain curves for the three tissue types normally present, namely, cord, transition zone and nodule. The tensile strength for cord tissue was nearly twice that of nodule tissue, but the latter was nearly twice as stretchable as cord. In contrast, the transition tissue had the tensile strength of cord with the stretchability of nodule. It was found that tensile loading stimulated a cellular response as demonstrated by an increase in the creep strain rate of the tissue at 37 degrees C compared with that at 4 degrees C using Dupuytren's tissue in an in vitro culture test. The creep strain rate for nodule at 37 degrees C was more than seven times that for cord at a nominal creep stress of 0.75 MPa.

Biomechanical Phenomena↗

PubMed1998

Mechanical stress in vitro induces increased expression of MMPs 2 and 9 in excised Dupuytren's disease tissue.

We have previously shown that the ability to mechanically extend Dupuytren's contractures in vivo by the Continuous Elongation Technique before surgery resulted in increased metalloproteinase activity. However, under these conditions it was not possible to show whether the response was proportional to the mechanical stimulus or was inflammatory cell mediated. Using an in vitro system of controlled extensions in which inflammatory involvement is absent, we have now shown that there is a clear correlation between the load applied to the tissue and the release of matrix metalloproteinase-2. The subsequent degradation of the collagen results in a loss of mechanical strength reported in the preceding paper.

Aged↗

PubMed1998

Collagen cross-links in mineralizing tissues: a review of their chemistry, function, and clinical relevance.

Bone collagen cross-links are now widely used to assess bone resorption levels in many metabolic bone diseases. The post-translational modifications of bone and other mineralizing collagens are significantly different from those of other type I collagen matrices, a fact that has been exploited during recent advances in the development of biochemical markers of bone resorption. The enzymatic collagen cross-linking mechanism is based upon aldehyde formation from specific telopeptide lysine or hydroxylysine residues. The immature ketoimine cross-links in bone form via the condensation of a telopeptide aldehyde with a helical lysine or hydroxylysine. Subsequent maturation to the pyridinoline and pyrrole cross-links occur by further reaction of the ketoimines with telopeptide aldehydes. In mineralizing tissues, a relatively low level of lysyl hydroxylation results in low levels of hydroxylysyl pyridinoline, and the occurrence of the largely bone specific lysyl pyridinoline and pyrrolic cross-links. The collagen post-translational modifications appear to play an integral role in matrix mineralization. The matrix of the turkey tendon only mineralizes after a remodeling of the collagen and the subsequent formation of a modified matrix more typical of bone than tendon. Further, disturbances in the post-translational modification of collagen can also affect the mineralization density and crystal structure of the tissue. In addition to their use as a convenient measure of matrix degradation, collagen cross-links are of significant importance for the biomechanical integrity of bone. Recent studies of osteoporotic bone, for example, have demonstrated that subtle perturbations in the pattern of lysine hydroxylation result in changes in the cross-link profile. These alterations, specifically changes in the level of the pyrrolic cross-link, also correlate with the strength of the bone. Further research into the biochemistry of bone collagen cross-links may expand current understanding and their clinical application in metabolic bone disease. This review also demonstrates the potential for further study into this area to provide more subtle information into the mechanisms and etiology of disease and aging of mineralizing tissues.

Aging↗

PubMed1998

Macroscopic 'degeneration' of equine superficial digital flexor tendon is accompanied by a change in extracellular matrix composition.

Injuries to the superficial digital flexor tendon are common in horses required to gallop and jump at speed. Partial rupture of this tendon usually occurs in the central core of the midmetacarpal region and may be preceded by localised degenerative changes. Post mortem examination of apparently normal equine flexor tendons has revealed an abnormal macroscopic appearance in the central core, characterised by a reddish discolouration. We have previously shown that there is also physical damage to the collagen fibres. In the present study we tested the hypothesis that the abnormal appearance is accompanied by changes in the composition of the extracellular matrix of the tendon. Biochemical analysis of the extracellular matrix demonstrated an increase in total sulphated glycosaminoglycan content, increase in the proportion of type III collagen and decrease in collagen linked fluorescence in the central core of 'degenerated' tendons relative to tissue from the peripheral region of the same tendon. Dry matter content and total collagen content were not significantly different between tendon zones or normal and 'degenerated' tendons. These changes suggest a change in cell metabolism and matrix turnover in the central core of the tendon and are likely to contribute to a decrease in mechanical properties in this part of the tendon, predisposing to the characteristic partial rupture of the tendon.

Animals↗

PubMed1998

Family migration and employment: the importance of migration history and gender.

"This article uses event history data to specify a model of employment returns to initial migration, onward migration, and return migration among newly married persons in the U.S. Husbands are more likely to be full-time employed than wives, and being a parent reduces the employment odds among married women. Employment returns to repeated migration differ by gender, with more husbands full-time employed after onward migration and more wives full-time employed after return migration events. We interpret these empirical findings in the context of family migration theory, segmented labor market theory, and gender-based responsibilities." Data are from the National Longitudinal Survey of Youth from 1979 to 1991.

Americas↗

PubMed1998

Patient-reported short-term and long-term physical and psychologic symptoms: results of the continuous hyperfractionated accelerated [correction of acclerated] radiotherapy (CHART) randomized trial in non-small-cell lung cancer. CHART Steering Committee.

PURPOSE: The randomized multicenter trial of continuous hyperfractionated accelerated radiotherapy (CHART) versus conventional radiotherapy for patients with non-small-cell lung cancer (NSCLC) showed a significant survival benefit to CHART (29% v 20% at 2 years, P=.004). However, an assessment of the effect on physical and psychologic symptoms is vital to balance the costs and benefits of the two treatments. METHODS: A total of 356 patients in the United Kingdom completed the Rotterdam Symptom Checklist (RSCL) and the Hospital Anxiety and Depression Scale (HADS) at 10 time points. The principal aim of the analyses was to keep the methods simple, so as to allow the presentation and interpretation of the results to be as clear as possible. This was achieved by (1) considering individual symptoms rather than symptom subscales or domains, (2) assessing short-term effects (up to 3 months) and long-term effects (at 1 and 2 years) separately, and (3) for the short-term analyses, (a) splitting the data randomly into an exploratory data set and a confirmatory data set, and (b) using two different methods of analysis: a subject-specific approach, which used the area under the curve (AUC) as a summary measure, and a group-based method, which plotted the percent of patients with moderate or severe symptoms over time. RESULTS: The results indicate that apart from CHART causing transient pain on swallowing and heartburn, there was little difference between the regimens in the short or long-term. CONCLUSION: Combining the results of the patient-assessed symptom comparisons with the clinical results indicates that CHART confers a major benefit without serious morbidity.

Anxiety↗

PubMed1997

Chemistry of collagen cross-linking: biochemical changes in collagen during the partial mineralization of turkey leg tendon.

With age, the proximal sections of turkey leg tendons become calcified, and this phenomenon has led to their use as a model for collagen mineralization. Mineralizing turkey leg tendon was used in this study to characterize further the composition and cross-linking of collagen in calcified tissues. The cross-link profiles of mineralizing collagen are significantly different from those of other collagenous matrices with characteristically low amounts of hydroxylysyl-pyridinoline and the presence of lysyl-pyridinoline and pyrrolic cross-links. However, the presence of the immature cross-link precursors previously reported in calcifying tissues was not supported in the present study, and was found to be due to the decalcification procedure using EDTA. Analysis of tendons from young birds demonstrated differences in the cross-link profile which indicated a higher level of hydroxylation of specific triple-helical lysines involved in cross-linking of the proximal tendon. This may be related to later calcification, suggesting that this part of the tendon is predestined to be calcified. The minimal changes in lysyl hydroxylation in both regions of the tendon with age were in contrast with the large changes in the cross-link profile, indicating differential hydroxylation of the helical and telopeptide lysine residues. Changes with age in the collagen matrix, its turnover and thermal properties in both the proximal and distal sections of the tendon clearly demonstrate that a new and modified matrix is formed throughout the tendon, and that a different type of matrix is formed at each site.

Age Factors↗