Biomedical subjects

A J Bailey

Publications and source records attributed to A J Bailey.

At least 19 recordsLinked to original sources

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↗

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↗

PubMed1997

Increased expression of promatrix metalloproteinase-9 and neutrophil elastase in canine dilated cardiomyopathy.

OBJECTIVE: Canine dilated cardiomyopathy, commonly affecting Doberman pinschers, results in extracellular matrix remodelling within the myocardium. The aim of this study was to examine the proteolytic activity in myocardium from Doberman pinschers with dilated cardiomyopathy. METHODS: Samples of myocardium, obtained rapidly post mortem from the left ventricular free wall of Dobermans with dilated cardiomyopathy, clinically normal Dobermans and control dogs (non-Dobermans), were examined for proteolytic activity using substrate gel zymography. Gels were analysed by scanning densitometry. RESULTS: Promatrix metalloproteinase-9 activity was significantly increased in all Doberman myocardium when compared to controls. A significant increase in an enzyme, identified to be neutrophil elastase by inhibition of its activity by Elastatinal and Western blotting, was also detected in all Dobermans when compared to controls. CONCLUSIONS: The results indicate that promatrix metalloproteinase-9 and neutrophil elastase, both of which are implicated in inflammatory responses, are present in significantly elevated levels in Doberman dilated cardiomyopathy and are raised in clinically normal Dobermans. Both proteolytic enzymes degrade a wide variety of connective tissue components and thus the increased levels found may play an important role in the structural remodelling seen in the myocardium and subsequent heart failure. Increased proteolytic enzyme levels in clinically normal Dobermans may be indicative of the predisposition of the breed to dilated cardiomyopathy.

Animals↗

PubMed1997

Biomechanical and biochemical study of a standardized wound healing model.

Standardized protocols were developed for use in a detailed investigation into the biomechanical and biochemical properties of a dermal wound healing model in the rat. The use of a rapid freezing method at -80 degrees C minimized the detrimental effects of freezing on the biomechanical properties of the tissue and also allowed for convenient inter-laboratory collaboration to be performed. The methodology described allowed for the simultaneous and reproducible measurement of tensile strength, collagen cross-linking and proteolytic enzyme activity. Increases in the tensile properties of the tissue with time were consistent with an active process of remodelling process as indicated by changes in the cross-link and enzyme profiles. Initially the granulation tissue was comparatively rich in the keto-imine cross-link hydroxylysino-keto-norleucine, which was later replaced by the aldimine cross-link dehydro-hydroxy-lysinonorleucine. The mature cross-link histidino-hydroxy-lysinonorleucine was not observed within the granulation tissue at any stage and was also absent in aged control skin. A peak of matrix metalloproteinase-9 activity was observed at early timepoints (48 hr) and then decreased rapidly to normal levels and is consistent with an acute inflammatory response. In contrast matrix metalloproteinase-2 activity peaked later (3 days) and then decreased gradually, consistent with its role as one of the predominant enzymes involved in the remodelling process. The results described validate the animal model used and emphasize its potential for use in combined biomechanical and biochemical studies of acute wound healing.

Animals↗

PubMed1997

Expression of gelatinases within the trabecular bone compartment of ovariectomized and parathyroidectomized adult female rats.

Ovariectomized (ovx) and parathyroidectomized (ptx) rat models of disturbed bone metabolism have been widely used in evaluating bone changes resulting from hormonal depletion, and are characterized by elevated and depressed bone turnover, respectively. We report here the expression of gelatinases extracted from native trabecular bone in these models. Nine-month-old female Sprague-Dawley rats were sacrificed after 3 weeks following ovx or 10 days post ptx to determine the influence of these procedures on the levels of proximal tibial bone tissue gelatinases. Identification and quantitation of these enzymes were performed via gelatin gel zymography of native tissue extracts and laser densitometry of developed gels, respectively. In the ptx model, a reduction in tissue levels of pro- and active-MMP-2 and a 45 kDa activated fragment was seen, whereas ovx exhibited significant increases in these enzymes. The MMPs are therefore clearly under the influence of factors known to modulate bone remodeling in vivo. The study of MMP levels directly extracted from bone using these experimental models may assist in developing management regimes for metabolic bone diseases through the use of drugs aimed at controlling turnover.

Animals↗

PubMed1997

Biochemical evidence for altered subchondral bone collagen metabolism in osteoarthritis of the hip.

Osteoarthritis (OA) of the hip is invariably viewed as a disease primarily affecting the articular cartilage. Data presented in this report, however, demonstrate changes in the metabolic activity of the underlying trabecular bone tissue, the processes of which may represent a significant factor in the pathogenesis of hip OA. Trabecular bone tissue from OA subjects expressed significantly more matrix metalloproteinase (MMP)-2 (gelatinase A, 72 kDa type IV collagenase) when compared to age-matched osteoporotic (OP) and normal bone tissue. Alkaline phosphatase was also significantly elevated in OA bone tissue. The combination of increased MMP-2 and alkaline phosphatase indicates heightened collagen turnover in the subchondral bone compartment of osteoarthritic hips. The data obtained from this study warrant a closer investigation into the significance of these changes in OA and emphasize the multifactorial elements of the whole joint in the whole joint in the overall disease process.

Age Factors↗

PubMed1997

Postsurgical wound progression monitored by temporal changes in the expression of matrix metalloproteinase-9.

It is important to monitor the early stages of postoperative wound repair in order to identify those problems associated with impaired healing. Many of the crucial cellular responses of early wound healing, such as inflammatory infiltration, angiogenesis and re-epithelialization, are made possible through the action of matrix metalloproteinases (MMPs). Expression of MMP-2 and MMP-9 is elevated in acute wounds, and still greater levels are found in chronic wounds, indicating that uncontrolled proteolysis is a characteristic of retarded healing. Therefore, comparative measurements of MMPs may be used to monitor the progression of early wound healing. To investigate this, wound fluids and sera were collected from mastectomy and colectomy patients throughout early stages of repair, and the temporal expression profile established. Wounds which were healing were expressed maximal levels of MMP-9 at 24 h, followed by a significant decline by 48 h. Persistent elevation of MMP-9 expression was associated with infected and chronic wounds, and was identified in postoperative wounds by the absence of the significant decline between 24 and 48 h. Measurement of MMP-9 in postoperative wound fluids, therefore, provides an early indicator of impaired healing, which may be evaluated non-invasively within 48 h of closure.

Biomarkers↗

PubMed1997

Analysis of collagen status in premenopausal nulliparous women with genuine stress incontinence.

OBJECTIVE: To determine if differences exist in the collagen status of premenopausal nulliparous women with genuine stress incontinence compared with continent controls. DESIGN: Thirty-six premenopausal nulliparous women with urodynamically-proven genuine stress incontinence were compared with 25 controls. All the women studied had a periurethral vaginal biopsy taken of approximately 30-50 mg in wet weight. This biopsy was then analysed to determine the collagen content, the type I:III collagen ratio and the collagen cross-link content. SETTING: A tertiary referral urodynamic unit. RESULTS: The nulliparous women with genuine stress incontinence had significantly less collagen in their tissues (P < 0.0001) compared with the continent controls. In addition, there was a decreased ratio of type I to type III collagen (P = 0.0008), and the cross-link content was also significantly reduced in the women with genuine stress incontinence (P < 0.0001). CONCLUSION: Genuine stress incontinence is present in a significant number of women before childbirth. The aetiology of their incontinence appears to be due to a defect in their connective tissue, with both a quantitative and qualitative reduction in their collagen.

Adolescent↗

PubMed1997

Do subchondral bone changes exacerbate or precede articular cartilage destruction in osteoarthritis of the elderly?

Research into the aetiology of osteoarthritis has for several decades been concentrated on the destruction of the articular cartilage, the initiating events being believed to be changes in the proteoglycans and subsequently in the supporting collagenous framework, whereafter the disease is irreversible. Recent evidence has supported an old contention that the underlying bone may be involved, namely, increased technetium scintigraphy correlated with increased severity of the osteoarthritis as demonstrated by joint narrowing, and a demonstration of increased metabolism of cancellous bone collagen compared to age-matched controls. These studies have not been able to answer the question of the primary initiating event: does increased bone metabolism initiate cartilage destruction or vice versa? However, recent detailed studies on animal models, particularly the macaque, have demonstrated that in this case thickening of the subchondral bone precedes fibrillation of the cartilage, which is possibly due to increased resistance of the bone to compression. Further, MRI studies on the guinea pig suggest that the initial site of activity is at the ligament bone insertion site, prior to endochondral bone sclerosis. We propose that the biomechanics of the joint are perturbed by the loss of tension from the ligament following trauma, leading to remodelling of the subchondral bone. Certainly in humans damage to the cruciate ligament often results in osteoarthritis. It may be that subclinical damage also ultimately results in osteoarthritis. Although the results from animal models will need to be treated with caution, the concept that bone ligament changes precede articular cartilage destruction should lead to a redirection of research, and perhaps therapy, for this important and cruelly disabling disease.

Aged↗

PubMed1996

Changes in metabolism of collagen in genitourinary prolapse.

BACKGROUND: Genitourinary prolapse is a common problem, the pathophysiology of which is unknown. METHODS: We analysed vaginal-epithelial tissue from premenopausal women with genitourinary prolapse and compared them with controls. FINDINGS: We found that genitourinary prolapse is associated with a reduction in total collagen content and a decrease in collagen solubility. Both intermediate intermolecular cross-links and advanced glycation cross-links were increased in prolapse tissue. Collagen turnover, as indicated by matrix metalloproteinase activity, was up to four times higher in prolapse tissue. Collagen-type ratios, mature cross-link pyridinoline and total elastin content were similar in both prolapse and control tissues. Increased collagenolytic activity causes loss of collagen from prolapse tissue. INTERPRETATION: Based on these findings, we have identified a probable mechanism for genitourinary prolapse. Development of agents to inhibit collagenolytic activity may help in the treatment of this condition.

Adult↗

PubMed1996

The role of glycation cross-links in diabetic vascular stiffening.

Previous studies have shown that biomechanical analysis of aorta from diabetic subjects reveals a marked increase in stiffness compared to aorta from age-matched control subjects. In the present paper we have proposed that this increased stiffness can be attributed to glycation-induced inter-molecular cross-links based on a direct analysis of the two known glycation cross-links, the fluorescent pentosidine and the non-fluorescent NFC-1. There was a significant difference in the increase in concentration of both cross-links with increasing age for both the intima (p < 0.0025) and the media (p < 0.0005) from the diabetic compared to the control subjects, but no correlation with the mature enzymic cross-link hy droxylysyl-pyridinoline. Finally, we have obtained a significant correlation of stiffness with both glycation cross-links (NFC-1, r = 0.86; p < 0.005 and pentosidine r = 0.75, p < 0.05), but the concentration of NFC-1 is about 50 times greater than that of pentosidine, indicating that it is the major glycation cross-link responsible for the stiffening of the aorta.

Adult↗