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Biomedical subjects

A J Bailey

Publications and source records attributed to A J Bailey.

At least 109 records · Page 6Linked to original sources
PubMed1992

Restrictive dermopathy: a disorder of fibroblasts.

Restrictive dermopathy is a rare, lethal genodermatosis, characterized by a thin, tightly adherent skin which causes a dysmorphic facies, arthrogryposis and respiratory insufficiency. The recorded cases to date show a remarkable phenotypic similarity. Thinning of the dermis and the arrangement of collagen in parallel bundles appear to be constant findings. We have found many dead and degenerating fibroblasts in the dermis on ultrastructural examination, and have demonstrated their poor growth in vitro. Studies of collagen from a skin sample showed a marked increase in mature cross-links, indicating a decrease in skin collagen turnover. These findings suggest a primary disorder of fibroblasts, and may explain the apparent arrest in growth and differentiation of the skin which appears to be important in the pathogenesis of this rare condition.

Bone and Bones↗
PubMed1991

Autism.

Autism is a severe disorder of development characterized by abnormalities in communication, social relationships and patterns of behaviour. This paper reviews the concepts of autism as they have developed over time in relation to research findings showing it to be an organic disorder, involving cognitive deficits, and which is largely genetically determined. Current research is focusing on the ways in which underlying brain abnormalities, genetic factors, neuropsychological deficits and behavioural manifestations are interconnected.

Autistic Disorder↗
PubMed1990

Characterization of temperature-sensitive cytidine triphosphate synthase mutations in bacteria by high-performance liquid chromatography.

Cytidine triphosphate (CTP) synthase catalyzes the last step in pyrimidine ribonucleotide synthesis, namely the formation of CTP from UTP, ATP, and glutamine. Mutants devoid of CTP synthase activity require cytidine for growth and have been designated pyrG in an obligate cdd background. Using a ts mutation blocked in the conversion of UTP to CTP at 43 degrees C, it was demonstrated that the conversion occurs by growing cells at 33 degrees C or below where UTP and CTP pools are normal. Growth at 43 degrees C shuts off the enzyme, while UTP accumulates and CTP is decreased significantly. By now feeding exogenous cytidine the CTP pool can be restored to the level found at the permissive temperature. Intracellular nucleoside triphosphates (CTP and UTP) were separated on a Partisil SAX10 cartridge, using a linear gradient of low buffer (7 mM ammonium dihydrogenphosphate, pH 3.8) to high buffer (250 mM ammonium dihydrogenphosphate, pH 4.5 with 500 mM potassium chloride). Nucleoside triphosphates were also separated after enzymatic conversion of UTP to CTP in solution by cell extracts using ion-pair reversed-phase chromatography on a C18 cartridge eluted with a mixture of 95% buffer A (25 mM ammonium dihydrogenphosphate with 1 mM tetrabutylammonium phosphate, pH 7.0) and 5% buffer B (15% aqueous acetonitrile). Using the two different separation techniques, it was possible to monitor the level of UTP and CTP inside cells as well as the enzymatic conversion of UTP to CTP by the enzyme CTP synthase.

Bacteria↗
PubMed1989

Getting on your bike: what difference does a migration history make?

"This research is an investigation of the relationship between individuals' histories of migration and their durations of residential sojourns. The use of longitudinal data makes it possible to directly verify the hypothesis that previous migrants will migrate sooner than individuals with no history of migration. The research also provides a random utility justification for a model of residential sojourns." The model is applied to data from the U.S. National Longitudinal Survey of Youth.

Americas↗
PubMed1989

Non-enzymatic glycosylation of fibrous and basement membrane collagens.

Physical and biochemical techniques have clearly demonstrated that a second stage of reaction of the hexosyl-lysines initially formed on non-enzymatic glycosylation of collagen involves the formation of intermolecular crosslinking of the collagen molecules. We have identified an early product of this crosslinking reaction as a putative crosslink and its structure is currently being elucidated. Similar changes occurred with both the tightly packed fibrous collagen and the open network of the basement membrane collagen. The effect of these crosslinks on the optimal functioning of basement membrane is likely to be more dramatic than on fibrous collagen, particularly in regard to flexibility and permeability of capillaries.

Animals↗
PubMed1988

Natural taxonomy of collagen based on amino acid composition.

Hierarchical cluster analysis and principal components have been used to provide a more detailed separation of the collagens into natural taxonomic groupings than previously obtained. These groups strongly reflect the evolutionary development of collagen. The first component separates land- from sea-based animals, primarily based on the hydroxylation of lysine and proline, indicating that control of hydroxylation, a post-translational event, has exerted a dominant influence during evolutionary adaptation. The power of the technique is illustrated by the ability to partially separate the evolutionarily closely related main homothermic species. Furthermore, the genetically different fibrous collagens, Types I and III, are well separated from basement membrane Type IV collagen and the filamentous collagens. The technique could, therefore, in addition to providing a taxonomic grouping, classify any new collagen and provide clues to its evolutionary development.

Amino Acids↗
PubMed1987

Chemistry of the collagen cross-links. Origin and partial characterization of a putative mature cross-link of collagen.

The conversion of the reducible divalent cross-links in collagen to non-reducible multivalent cross-links in mature collagen has resulted in the identification of several new amino acids as the putative mature cross-link. None of these compounds has completely satisfied the necessary criteria. We have now isolated an amino acid of high Mr, derived from lysine, that is only present in high-Mr peptides derived from mature collagen. Its increase with age of the tissue correlates with the decrease in the reducible cross-links, and it is present both in mature skin and bone, which are initially cross-linked through the aldimine and oxo-imine divalent cross-link respectively. We propose that this amino acid, as yet incompletely characterized and designated compound M, is a major cross-link of mature collagen.

Aging↗
PubMed1987

Basement membrane collagen--evidence for a novel molecular packing.

Type IV collagen is the major structural protein of basement membranes but very little is known about its molecular organisation in vivo. We have used X-ray diffraction of a thick basement membrane, bovine lens capsule, to provide information. Under constant load, lens capsule gave a collagen diffraction pattern of a similar quality to unstretched rat rail tendon. In addition there were clear meridional reflections which indexed as orders of 10 nm, and equatorial reflections at 2.1 and 3.8 nm. These results suggest the ordering of type IV collagen molecules in fibrils, with a 10 nm periodicity along the length of the fibrils.

Animals↗
PubMed1987

Polypeptide composition of the mammalian tectorial membrane.

The effects of the enzymes collagenase, pepsin, chondroitinase ABC and keratanase on the polypeptide composition of the mammalian tectorial membrane have been analysed using one dimensional SDS-polyacrylamide gel electrophoresis (SDS-PAGE). After reduction at least ten polypeptides can be consistently and clearly recognized in SDS gels with molecular weights relative to globular protein standards of 245, 235, 190, 165, 155, 145, 100, 93, 60-73 and 35-49 kDa. With the exception of the 60-73 and 35-49 kDa bands all these polypeptides are sensitive to digestion with bacterial collagenase. The 235, 165, 155, 145 and 93 kDa bands also resist degradation by cold, acidic pepsin. Amino acid analysis of whole tectorial membranes demonstrates that glycine accounts for nearly 25% of the total amino acid content, that proline, hydroxyproline and hydroxylysine are present and that amine sugars can be detected in fairly high concentrations. Estimates based on hydroxyproline content suggest that collagens account for 25-50% of the total tectorial membrane protein. Immunoblotting techniques demonstrate the presence of polypeptides cross reacting with antisera to Type II collagen, Type IX collagen and Type V collagen. Results from immunohistochemical studies confirm that these polypeptides are present in the tectorial membrane and are not contaminants of the isolation procedure. Collagenase treatment of tectorial membranes reveals the presence of an additional non-collagenous polypeptide with an apparent molecular weight of 173 kDa on 7.5% polyacrylamide gels, and polydisperse high molecular weight material spreading over a broad range at the top of the gels. This high molecular weight material and the 173, 60-73 and 35-49 kDa non-collagenous polypeptides are pepsin sensitive and all bind wheat germ agglutinin (WGA) suggesting that they contain N-acetyl glucosamine. The 173 kDa band also binds soybean agglutinin (SBA) suggesting the presence of N-acetyl galactosamine. In the absence of reducing agent the 173 and 60-73 kDa bands are no longer observed and high molecular weight material forming a broad band at the top of the separating gel is seen. The electrophoretic behaviour of this non-collagenous, glycosylated, disulphide bonded, high molecular weight material is altered by treatment with keratanase but not by chondroitinase ABC. The results of this study indicate the tectorial membrane contains at least three different collagen types and, in addition to these collagenous proteins, several non-collagenous, glycosylated polypeptides that may account for as much as 50% of the total tectorial membrane protein.

Acetylgalactosamine↗
PubMed1985

Collagen cross-links: location of pyridinoline in type I collagen.

Collagen from bone, dentine and tendon (type I), all of which contain the pyridinoline cross-link at varying levels, were each digested with CNBr. The resulting peptide mixtures were resolved by gel filtration on A1.5m agarose and assayed for pyridinoline. The polymeric cross-linked peptide complex, poly alpha 1CB6 [(1980) Biochem. J. 189, 111] isolated from each of these tissues did not contain pyridinoline. Only one peptide fraction contained the pyridinoline cross-link; that identified as alpha 2CB3,5. However, this peptide showed only a small increase in Mr in its cross-linked form (approx. 2000-5000) demonstrating that pyridinoline is not involved in the formation of polymeric structures like poly alpha 1CB6. These data, considered in the light of the recent finding that pyridinoline is present in type I collagens from different sources in widely varying amounts, cast doubt on its role in collagen maturation.

Amino Acids↗
PubMed1985

Evidence for glucose-mediated covalent cross-linking of collagen after glycosylation in vitro.

Rabbit forelimb tendons incubated for 15 or 21 days at 35 degrees C in the presence of 8 or 24 mg of glucose/ml were shown to change their chemical, biochemical and mechanical characteristics. The tendons treated with glucose contained up to three times as much hexosyl-lysine and hexosylhydroxylysine as did control tendons as judged by assay of NaB3H4-reduced samples. Measurement of the force generated on thermal contraction showed significant increases in glycosylated tendons compared with controls, indicating the formation of new covalent stabilizing bonds. This conclusion was supported by the decreased solubility of intact tendons and re-formed fibres glycosylated in vitro, and by the evidence from peptide maps of CNBr-digested glucose-incubated tendons. The latter, when compared with peptide maps of control tendons, revealed the presence of additional high-Mr peptide material. These peptides appear to be cross-linked by a new type of covalent bond stable to mild thermal and chemical treatment. This system in vitro provides a readily controlled model for the study of the chemistry of changes brought about in collagen by non-enzymic glycosylation in diabetes.

Animals↗
PubMed1985

Intermolecular cross-linking in fibrotic collagen.

The extent, nature and location of the cross-links involved in the stabilization of collagen in fibrotic lesions are crucial to its subsequent removal, naturally or induced by treatment. Stabilization is achieved initially by divalent aldimine and keto-imine intermolecular cross-links located at the end-overlap region in the quarter-stagger alignment of the molecules in the fibre. Elucidation of the location of the cross-links also provides chemical evidence for the organization of the collagen molecule in the fibre. All the fibrous collagens are stabilized by these cross-links, the more stable keto-imine cross-link predominating in the types I and II collagens present in the initial stages of fibrosis. Further stabilization of the lesion usually follows, increasing the resistance to degradative enzymes, thus rendering the fibrosis irreversible. This maturation process, which also occurs in normal ageing, involves the formation of multivalent cross-links derived from the initial aldimine and keto-imine cross-links to form a three-dimensional network through a polymeric peptide (poly-alpha 1CB6 in type I collagen). The nature of these cross-links has not yet been elucidated. The so-called mature cross-link, 3-hydroxypyridinoline, could not be identified in this polymeric network. A secondary process involving non-enzymic glycosylation of lysine residues and subsequent intermolecular cross-linking has also been demonstrated, although the nature and extent of this type of cross-link remain to be determined.

Aging↗
PubMed1985

Skeletal muscle injury--molecular changes in the collagen during healing.

Changes in the collagen types and cross-linking of granulation and scar tissue in the injured site of partially ruptured gastrocnemius muscle were studied after a reproducible contusion injury to the left calf of a rat. In normal i.m. collagen the proportion of Type I collagen was considerably higher than Type III. Following injury there was a rapid increase in the proportion of Type III collagen reaching a maximum at 5 days after injury. After a further 2 days the proportion of Type I had increased significantly resulting in a decrease of the Type III/I ratio to below that of the control. However, as healing progressed there was a gradual shift back to the Type III/I ratio for normal i.m. collagen. The collagen produced in response to an injury was initially stabilized by the stable keto-imine cross-link hydroxylysino-5-keto-norleucine, characteristic of embryonic collagenous tissues. The proportion of the stable keto-imine cross-link gradually decreased, and a reversion to the cross-link pattern of normal uninjured i.m. collagenous connective tissue occurred towards the end of the 42-day follow-up period. The present biochemical study demonstrates that during the early phases of the repair process there is a reversion to the collagens typically present in high proportions in embryonic dermal connective tissue. This suggests that the fibroblasts have the ability to modify their product expression under varying circumstances. The study also demonstrates the importance of collagen cross-linking in determining the tensile strength of collagen fibre during the repair process.

Animals↗
PubMed1984

Isolation and characterization of the precursor of type M collagen.

A 225000-Mr peptide has been purified from rat chondrosarcoma which is immunologically and biochemically related to type M collagen. Rotary shadowing shows this molecule to be twice the length of the type M molecule and has a prominent kink close to one end. We believe this molecule represents parent type M, the form of the molecule in vivo.

Animals↗
PubMed1984

Cross-linking in type IV collagen.

Type IV collagen could not be extracted from human placenta using 6M-urea containing 10mM-dithiothreitol, indicating that the type IV molecule is stabilized within the basement membrane by covalent cross-links. However, various forms of type IV collagen molecule were extractable by means of increasingly severe proteolytic conditions. Type IV collagen tetramers ('spiders') lacking only the C-terminal globular region (NC1) were further digested to the 'long-form' 7S fragment and an assortment of helical rod-like molecules derived from the 'leg' region. These molecules were separated by salt fractionation and examined by rotary-shadowing electron microscopy. Isolation of these fractions from placenta which had been reduced with NaB3H4 revealed that both the 7S (N-terminal) and C-terminal regions contained significant proportions of reducible lysine-derived cross-links. These cross-links were shown to be exclusively the stable oxo-imine hydroxylysino-5-oxonorleucine. The number of the cross-links per molecule was significantly lower than might be expected in order to fully stabilize the molecule. These results suggest that the keto-imine cross-links in type IV collagen have been stabilized in part by conversion into an unknown non-reducible form, although a sensitive immunoassay failed to show the presence of any pyridinoline. Comparison with the fibrous collagen from placenta suggested that the rate of this conversion is much greater in basement-membrane collagen.

Basement Membrane↗