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J K Sheehan

Publications and source records attributed to J K Sheehan.

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Hyaluronates: relation between molecular conformations.

The discovery that both potassium and sodium salts of hyaluronic acid can exist in a double-strand helical conformation that will convert to the already known single-strand helical structures illustrates the remarkable conformational versatility of this biopolymer. X-ray diffraction was used to monitor variations in molecular conformation as a function of several independent, controllable variables, such as relative humidity, temperature, and applied tension. A scheme is presented for the interrelation of a range of hyaluronate conformations.

Humidity↗

The conformation of the mucopolysaccharides. Hyaluronates.

X-ray-diffraction patterns of hyaluronate fibres from a variety of sources were obtained. Sodium hyaluronate gives well-defined patterns which index on a hexagonal unit cell with dimensions a=1.17+/-nm and a fibre repeat-distance of 2.85+/-0.03nm. A further form of sodium hyaluronate is produced by annealing at 60 degrees C in 75% relative humidity. This stable state indexes on a hexagonal unit cell of unchanged fibre repeat-distance but with a=1.87nm. The chain conformation is a threefold helix. Analysis of these diffraction patterns led to two tentative structures for sodium hyaluronate, involving different packing of the polysaccharide chains. The significance of side-chain interaction is discussed. Hyaluronic acid produces an X-ray pattern different from that obtained with the sodium salt. The fibre repeat-distance is 1.96+/-0.02nm and the unit cell appears to be monoclinic. The chain conformation is a twofold helix and conformational change between free acid and monovalent salt is discussed. These findings, together with model-building experiments, are interpreted as indicating a highly ordered structure, and the physical properties of hyaluronate solutions with regard to molecular shape and polyelectrolyte behaviour are rationalized.

Hyaluronic Acid↗

Interaction between mycobacteria and mucus on a human respiratory tissue organ culture model with an air interface.

Mycobacteria adhere specifically to extracellular matrix (ECM) and mucus with a fibrous, but not globular, appearance, in organ cultures of human respiratory mucosa examined by scanning electron microscopy. Previously, light microscopy sections made of tissue infected for 7 days demonstrated mycobacteria associated with mucus on the organ culture surface, and within submucosal glands in areas of damaged epithelium. The authors have now investigated the interactions between Mycobacterium avium complex (MAC), Mycobacterium tuberculosis (MTB), and Mycobacterium smegmatis (MS) and mucus by preincubating bacteria with purified mucins MUC5AC and MUC5B prior to inoculation onto the organ culture mucosal surface. They have also measured mucin production by the organ culture after mycobacterial infection. Mucus did not cause clumping of mycobacteria. There was a significant (P=.03) increase in the amount of fibrous mucus, but not globular mucus, observed on tissue inoculated with mucins compared to controls. The number of bacteria adhering to ECM was markedly reduced after incubation with mucins, which could indicate a protective effect. Mycobacterial infection did not increase mucin production by the organ culture. Mycobacterial adherence to mucins may play a role in the pathogenicity of mycobacteria in diseases such as cystic fibrosis, bronchiectasis, and chronic obstructive pulmonary disease (COPD), in which there are changes in mucus composition and clearance.

Air↗