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Biomedical subjects

A J Bailey

Publications and source records attributed to A J Bailey.

At least 37 records · Page 2Linked to original sources
PubMed2001

Anabolic effect of long-term estrogen replacement on bone collagen in elderly postmenopausal women with osteoporosis.

Estrogen has been shown to stimulate osteoblasts in cell culture and increase bone formation in animal models. Such an anabolic effect of estrogen replacement therapy (ERT) would be beneficial to postmenopausal women with osteoporosis. Hence, we assessed the total collagen content and collagen crosslink maturity in iliac crest bone biopsy from 18 such women before and after 6 years of higher-dose ERT. These results were compared with the serum estradiol level and bone mineral density (BMD). Total collagen content of both cortical and cancellous bone increased, showing a median (95% CI) percent change of 6.7 (0.3-14.2) and 25.6 (13.5-33.8), respectively. Increase in collagen synthesis was supported by a rise in intermediate crosslinks in both cortical and cancellous bone, and mature crosslinks in cortical bone only. At the same time, BMD showed a substantial rise both at the lumbar spine and proximal femur with a median (95% CI) percent change of 28.6 (19.8-37.3) and 14.5 (8.4-20.7), respectively. Serum estradiol and BMD results correlated with cortical bone collagen levels. Our results suggest that long-term higher-dose ERT has a therapeutic role due to its anabolic effect on bone in postmenopausal women with osteoporosis.

Absorptiometry, Photon↗
PubMed2001

Changes in collagen metabolism in prostate cancer: a host response that may alter progression.

PURPOSE: The interaction of cancer cells and the extracellular matrix is essential for cancer progression. However, little is known about the influence of cancer on the metabolism of collagen, which is the major constituent of the extracellular matrix. We studied changes in collagen metabolism in prostate cancer with increasing Gleason score and correlated them with clinical parameters and patient survival. MATERIALS AND METHODS: Collagen content and clinical parameters in 3 types of prostatic tissue were compared, including the foci of prostatic cancer, unaffected tissue from the same cancerous prostates and prostatic tissue from patients with no evidence of cancer. In addition, to assess collagen metabolism tissue obtained prospectively from 45 patients undergoing prostatic biopsy was assessed for collagen content, the type and extent of collagen cross-linking, serine proteinase, matrix metalloproteinase and the C-terminal propeptide of type I collagen. RESULTS: With increasing Gleason sum of the cancer collagen content at the focus decreased, while that of surrounding unaffected tissue from the same prostate increased to levels significantly above that from controls with no cancer. Markers of collagen synthesis in the prostate biopsy material were significantly increased in the presence of prostate cancer. CONCLUSIONS: In prostate cancer there are changes in collagen metabolism not only in the cancer focus but also in nearby histologically benign prostatic tissue. These observed changes are related to the Gleason score of the tumor and may represent a host response. Collagen content in the surrounding unaffected tissue may be a predictor of patient survival.

Cell Transformation, Neoplastic↗
PubMed2001

Phase-locked gamma band responses to semantic violation stimuli.

This paper addresses the role of gamma-band activity in semantic networks associated with the processing of words and sentences in humans. Magnetoencephalography (MEG) was used to compare the responses of eleven normal volunteers to semantically congruous and incongruous words at the end of syntactically correct sentences. The averaged low frequency responses evoked by the two word classes were clearly different within the latency range associated with N400 components. The oscillatory characteristics of the evoked responses were analysed using Gabor transform techniques in conjunction with statistical re-sampling. This revealed transient gamma-oscillations ( approximately 35 Hz) that were significantly phase-locked to both types of stimuli but preferentially present at intermediate ( approximately 300 ms) and long (>500 ms) latencies for incongruous words. This stimulus dependent phase locked gamma-activity occurred at latencies that were distinct from the short latency and evoked N400 components. The findings suggest that synchronised oscillations provide independent information about brain dynamics and that some semantic processes may dissociate into distinct functional stages.

Adult↗
PubMed2001

Thermally labile domains in the collagen molecule.

We have proposed that the denaturation kinetics of the characteristic sharp melting point of the collagen molecules is an irreversible rate rather than an equilibrium process as previously believed. This leads to the concept of domains of variable thermal stability along the length of the molecule. We have identified the major thermally labile domains from which the denaturation process is initiated as hydroxyproline deficient sequences of 65, 65 and 59 residues near the carboxy terminus in fibrillar collagen types I, II and III, respectively. These domains differ in that there is a single hydroxyproline in the type II domain and two hydroxyprolines in the type III domain. Similar sized domains are conserved in these collagen types across species including amphibians and invertebrates. The effective size of the domain is reduced in the fibrillar aggregates to 26 residues due to the interaction with adjacent molecules and because of the precise quarter-staggered alignment of the molecules the domains are located in the gap region. This spatial confinement within the lattice of the fibre leads to the significant increase in denaturation temperature of the fibre compared to the molecule. These labile domains have also been located in molecules that form the non-fibrillar type IV basement membrane collagens and the fibril-associated aggregates such as type IX. Based on the location of the different domains in type IX we have proposed a different arrangement of the type IX on the type II fibril. The model stresses the importance of hydroxyproline in stabilising the triple helix and supports the concept of hydrogen-bonded water-bridges originally proposed from X-ray diffraction studies in contrast to other studies indicating water-bridges do not play a role in stabilising the collagen molecule.

Amino Acid Sequence↗
PubMed2000

Identification of an intermediate state in the helix-coil degradation of collagen by ultraviolet light.

Differential scanning calorimetry has revealed the presence of a new denaturation endotherm at 32 degrees C following UV irradiation of collagen, compared with 39 degrees C for the native triple helix. Kinetic analyses showed that the new peak was a previously unknown intermediate state in the collagen helix-coil transition induced by UV light, and at least 80% of the total collagen was transformed to random chains via this state. Its rate of formation was increased by hydrogen peroxide and inhibited by free radical scavengers. SDS-polyacrylamide gels showed evidence of competing reactions of cross-linking and random primary chain scission. The cross-linking was evident from initial gelling of the collagen solution, but there was no evidence for a dityrosine cross-link. Primary chain scission was confirmed by end group analysis using fluorescamine. Electron microscopy showed that the segment long spacing crystallites formed from the intermediate state were identical to the native molecules. Clearly, collagen can undergo quite extensive damage by cleavage of peptide bonds without disorganizing the triple helical structure. This leads to the formation of a damaged intermediate state prior to degradation of the molecules to short random chains.

Animals↗
PubMed2000

Isinglass/collagen: denaturation and functionality.

Isinglass is widely used commercially to clarify alcoholic beverages by aggregation of the yeast and other insoluble particles. It is derived from swim bladders of tropical fish by solubilisation in organic acids and consists predominantly of the protein collagen. The low content of intermolecular cross-links allows ready dissolution of swim bladder compared to bovine hide which is cross-linked by a high proportion of stable bonds and requires enzymic digestion to solubilise. Isinglass is no longer effective as a clarifying agent if thermally denatured hence the collagenous triple helical structure must be maintained. Thermal denaturation of isinglass occurs at 29 degrees C, compared to 40-41 degrees C for mammalian collagens, primarily due to the lower hydroxyproline content. The hydroxyproline is essential for the formation of H-bonded water-bridges through the hydroxyl group and the peptide chain thereby stabilising the triple helix. Based on the lower enthalpy determined by differential scanning calorimetry we have calculated that the thermally labile domain of the isinglass molecule was 41 residues compared to 66 for mammalian collagen. The fining efficiency was unaffected by pH, chelating agents, detergents and removal of surface proteins from yeast cells. Studies on the mechanism of action of isinglass have shown that higher molecular weight aggregates that increase the length of the collagen molecules (trimers, tetramers, etc.) increase efficiency and that their surface charge are important in the clarification process. By chemical modification, we have shown that blocking positively charged groups had no effect on the fining process, whilst negative charges are clearly essential and that increasing the negative charge by succinylation increases its efficacy. Solutions of bovine hide collagen were shown to be equally effective in refining beers and standard yeast preparations. The higher thermal denaturation temperature, ready availability and reproducibility of bovine collagen preparations gives it considerable advantages over isinglass.

Air Sacs↗
PubMed2000

The importance of lipid-derived malondialdehyde in diabetes mellitus.

Malondialdehyde (MDA) is a highly toxic by-product formed in part by lipid oxidation derived free radicals. Many studies have shown that its concentration is increased considerably in diabetes mellitus. Malondialdehyde reacts both irreversibly and reversibly with proteins and phospholipids with profound effects. In particular, the collagen of the cardiovascular system is not only stiffened by cross-links mediated by malondialdehyde but then becomes increasingly resistant to remodelling. It is important in diabetes mellitus because the initial modification of collagen by sugar adducts forms a series of glycation products which then stimulate breakdown of the lipids to malondialdehyde and hence further cross-linking by malondialdehyde of the already modified collagen. Some progress is being made into the mechanisms of formation and the nature of the intermolecular cross-links induced by malondialdehyde which result in the stiffening of the collagenous tissues. Our recent studies indicate the formation of pyridyl cross-links. Malondialdehyde has been shown to react several orders of magnitude faster with the pre-existing collagen enzymic cross-links than the amino acid side-chains. Malondialdehyde modification of basic amino-acid side-chains also results in a change in properties, for example, in the charge profile of the molecule resulting in modified cell-matrix interactions. Although aspects of the biochemistry of malondialdehyde are still not fully understood its complex chemistry is being unravelled and this should lead to ways of preventing its damaging reactions, for example, through antioxidant therapy.

Amino Acids↗
PubMed2000

Distance and health care utilization among the rural elderly.

This paper explores the relationship between distance and the utilization of health care by a group of elderly residents in rural Vermont. By drawing on recent work on the geography of health we frame the decision to visit a primary care physician in the context of the experience of place. The paper devises a test of this broader reading of the role of distance for utilization, and operationalizes this test using a custom designed survey. Using a randomized mail survey of elderly residents of Vermont's North East Kingdom we explore how grocery shopping, travel to work, home location relative to local services, access to private transportation, and living arrangements are associated with the number of doctor visits made to primary health care providers. Although the results confirm the idea that increased distance from provider does reduce utilization, they strongly suggest that distance to provider is a surrogate for location in a richer web of relations between residents and their local communities. We conclude by calling for further research that establishes links between place and the use of health facilities.

Aged↗
PubMed2000

Alterations in the organisation, ultrastructure and biochemistry of the myocardial collagen matrix in doberman pinschers with dilated cardiomyopathy.

Remodelling of the collagen matrix of the myocardium has been implicated in the pathogenesis of dilated cardiomyopathy, a major cause of heart failure in Doberman pinschers. The aim of this study was to characterise the myocardial collagen matrix of Dobermans. In clinically normal Dobermans there was evidence of focal fibrosis. Collagen cross-links were altered in both diseased and clinically normal Doberman myocardium as compared with myocardium from control dogs. Extensive remodelling, in the form of a loss of collagen tethers, increased collagen synthesis and alterations in the collagen cross-links, occurs in diseased Doberman myocardium. Changes in the collagenous matrix are also present in apparently normal Dobermans. These changes are likely to be involved in the progression of the disease and may explain the predisposition of this breed to dilated cardiomyopathy.

Animals↗
PubMed1999

Reactions of lipid-derived malondialdehyde with collagen.

Malondialdehyde is a product of fatty acid oxidation (e.g. from low density lipoprotein) implicated in the damage of proteins such as collagen in the cardiovascular system (Chio, K. J., and Tappel, A. L. (1969) Biochemistry 8, 2821-2827). Its concentration is raised in diabetic subjects probably as a side effect of increased protein glycation. Collagen has enzyme-catalyzed cross-links formed between its individual molecules that are essential for maintaining the structure and flexibility of the collagen fiber. The cross-link dehydro-hydroxylysinonorleucine reacts irreversibly with 10 mM malondialdehyde at least 3 orders of magnitude faster than glucose reactions with lysine or arginine, such that there is little cross-link left after 1 h at 37 degrees C. Other cross-links and glycated elements of collagen are also vulnerable. Several possible products of malondialdehyde with collagen cross-links are proposed, and the potential involvement of collagenous histidine in these reactions is discussed. We have also isolated Ndelta-(2-pyrimidyl)-L-ornithine from collagenous arginine reacted with malondialdehyde. The yields of this product were considerably higher than those from model reactions, being approximately 2 molecules/collagen molecule after 1 day at 37 degrees C in 10 mM malondialdehyde. Collagenous lysine-derived malondialdehyde products may have been present but were not protected from protein acid hydrolysis by standard reduction techniques, thus resulting in a multitude of fragmented products.

Animals↗
PubMed1999

Collagen remodeling in the anterior cruciate ligament associated with developing spontaneous murine osteoarthritis.

The initiating factors in primary, idiopathic osteoarthritis are unknown, the characteristic bone and cartilage changes being late features of the disease. We have proposed that biochemical cruciate ligament alteration may be important in early osteoarthritis by mediating loading consequences on the bone and cartilage. Using the widely accepted STR/ORT mouse model of spontaneous osteoarthritis we have found biochemical evidence that, before radiological signs of osteoarthritis develop, cruciate ligament collagen metabolism is upregulated in the STR/ORT mouse when compared to controls. Also, importantly, at this time the anterior cruciate ligament is weaker in STR/ORT mice than in controls. This is the first biochemical evidence to show that alterations in cruciate ligament metabolism occur early in the etiopathogenesis of idiopathic, primary osteoarthritis.

Animals↗
PubMed1999

Age-related changes in the biochemical properties of human cancellous bone collagen: relationship to bone strength.

The metabolism of bone collagen has received little attention in relation to age-related loss of bone mass and strength. The aim of the present study was to analyze bone collagen content and metabolism in human bone with respect to age. The material consisted of iliac crest bone biopsies from 94 individuals: 46 women (ages 18-96, mean age 60.8 years) and 48 men (ages 23-92, mean age 59.5 years). Excluded from the study were all individuals with known osteoporotic lumbar vertebral fractures and renal, hepatic, or malignant diseases. Prior to collagen analysis the biopsies were scanned in a pQCT scanner for density assessment and then tested biomechanically. The results showed a decline in apparent bone density with age (P < 0.0001), a decline in maximum stress, Young's modulus, and energy absorption with age (P < 0.001). Concomittantly, there was an age-related decline in the intrinsic collagen content with age (P < 0.001). However, there were no biochemical modifications of the bone collagen during aging. There were no significant differences between women and men in the slopes of the regressions-curves. When multiple regression analyses were performed, only apparent bone density came out as a significant contributor in the correlation to biomechanical properties. Nevertheless, the decrease in bone collagen content with age might indicate an increase in the mineralization degree (probably due to decreased bone turnover) and thereby a change in material properties of bone. In conclusion, the present study has shown that loss of bone mass plays the major role in loss of bone strength. However, there is also a change in bone composition during normal aging, leading to a decrease in collagen content and an increase in the degree of mineralization. At this skeletal site, in a normal population there was no change in the biochemical properties of bone collagen.

Adolescent↗