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Biomedical subjects

J M Snowden

Publications and source records attributed to J M Snowden.

At least 19 recordsLinked to original sources

Analysis of the inhibition of tumour metastasis by sulphated polysaccharides.

Lung metastases resulting from the intravenous (i.v.) injection of cells from the rat mammary adenocarcinoma 13762 MAT were significantly reduced by a variety of sulphated polysaccharides, the most effective being heparin, fucoidan and Carrageenan lambda. Although all the inhibitory polysaccharides were anticoagulants, it is unlikely that anticoagulation is the total explanation of their antimetastatic effect because: (i) heparin preparations from 2 different suppliers, although exhibiting comparable anticoagulant activities, differed 10-fold in their antimetastatic capability; (ii) certain sulphated polysaccharides consistently gave a 30% difference in the number of metastatic lesions, yet exhibited identical anticoagulant activity; and (iii) the entrapment of 13762 MAT cells in the lung was not impaired by heparin or fucoidan. It was more probable that the sulphated polysaccharides were interfering with the passaging of tumour cells across the capillary wall as heparin significantly inhibited metastasis when injected up to 3 hr after lodgement, and heparin and fucoidan caused a gradual loss of tumour cells from the lung which only became apparent greater than 1 hr following cell lodgement. The data did not eliminate the possibility that tumour cell adhesion to the endothelium occurred via sulphated polysaccharide recognition. A negative correlation existed between the sulphated polysaccharides that bound to the surface of the tumour cells and those that inhibited metastasis.

Animals

Lymphocytes express a diverse array of specific receptors for sulfated polysaccharides.

Lymphocyte receptors for sulfated polysaccharides were detected in two ways, namely, by the ability of lymphocytes to form rosettes with sheep red blood cells (SRBC) coupled with one of fourteen different sulfated polysaccharides, and by the ability of cholate extracts of lymphocytes to hemagglutinate the same sulfated polysaccharide-coupled SRBC. It was found that murine lymphocytes lacked receptors for a number of glycosaminoglycans, such as hyaluronic acid, chondroitin-4-sulfate, chondroitin-6-sulfate, and dermatan sulfate, but reacted strongly with heparin, arteparon, and a number of sulfated polysaccharides of plant and bacterial origin. In each case receptor activity was demonstrated by rosetting and by the ability of lymphocyte lysates to strongly agglutinate sulfated polysaccharide-coupled SRBC. The receptors exhibited a high degree of diversity as evidenced by (a) only subpopulations of lymphocytes, particularly splenic B cells, expressing receptors for some of the sulfated polysaccharides and (b) hemagglutination-inhibition analyses revealing numerous subsets of receptors with different binding specificities. Receptor diversity was further highlighted by a 48% difference in the hemagglutination-inhibiton results between thymus and spleen. It is proposed that these receptors are involved in cell-cell communication and lymphocyte homing and recirculation. The likely target structures for the receptors in vivo are the heparan sulfates, a ubiquitous and structurally diverse family of sulfated glycosaminoglycans.

Animals

Wound contraction. Correlations between the tension generated by granulation tissue, cellular content and rate of contraction.

The tension generated in vitro by samples of granulation tissue taken from wounds at various times after wounding has been measured. Throughout the period when in vivo contraction was occurring with a constant linear rate of movement of the wound margins the in vitro tension produced by samples of the granulation tissue remained constant at approximately 80 mg/mm2. With cessation of contraction in vivo, the tension generated by the granulation tissue fell to 40 mg/mm2. Morphometric studies demonstrated that total cellularity paralleled the tension developed. However, the decrease in cellularity preceded by approximately 4 d the decrease in the tension developed. Strong correlation between the rate of contraction and the maximum thickness of the granulation tissue was demonstrated.

Animals

The contractile properties of wound granulation tissue.

A systematic examination of the contractile properties of wound granulation tissue is presented. Shortening of and tension generated by granulation tissue in the presence of 30 mM diphenhydramine HCl have been measured. Analysis of the stress (load per unit area)/strain (extent of shortening) results from isotonic shortening studies showed that over the range of 0 to 2.5% shortening there was an approximately linear relationship between stress and strain with a high modulus of elasticity. At lower stresses, wide variations in the amount of shortening occurred with little change in stress. Our interpretation of these findings is that diphenhydramine HCl caused an active shortening of the granulation tissue by 2.5% of its length and contractions greater than this were the result of secondary effects such as coiling and bending of the strips. It is shown that the granulation tissue would have to shorten by 2% once every 3 days to account for observed in vivo rates of contraction for large human wounds and once every 13 hr for rapidly contracting experimental rabbit wounds. The time course of the development of isometric tension by the granulation tissue is shown to be consistent with the proposal that each contractile cell contributes equally to the overall tension developed and that each cell is individually activated by a critical concentration of diphenhydramine HCl which is transported through the tissue by diffusion.

Animals

Wound closure: an analysis of the relative contributions of contraction and epithelialization.

The behavior of excisional wounds in rat and man has been analyzed. The rate of change in wound area due to contraction has been shown to be consistent with a constant linear rate of movement of the wound margins. The rate of change of area due to epithelialization has been shown to be consistent with a constant linear rate of growth of the epithelium. These rates together with the relevant delay times are shown to be the appropriate parameters for the comparison of the behaviors of excisional wounds. These parameters can be calculated from the change in wound area with time. An unexpected finding was that in both rat and man, the values obtained for the rates of contraction and epithelialization varied widely but the combined rates of these two processes varied little.

Animals

Demonstration of lymphocyte surface lectins that recognize sulphated polysaccharides.

Cholate extracts of murine lymphocytes were shown to contain haemagglutinating activity against autologous erythrocytes. The species specificity and sugar inhibition pattern of the haemagglutinin closely paralleled the specificity of autorosetting, an interaction that had been shown previously to involve the recognition by lymphocytes of carbohydrate structures on autologous erythrocytes. The probable identity of the haemagglutinin and autorosetting receptors was confirmed by experiments utilizing the unique plasma protein autorosette inhibition factor, which appears to block both interactions by masking carbohydrate acceptor sites on erythrocytes. Detailed sugar inhibition studies revealed that the haemagglutinin and autorosetting receptors have a high affinity for certain sulphated polysaccharides, such as heparin and dextran sulphate. Since similar sulphated polysaccharides have been shown previously to inhibit lymphocyte recirculation, a possible role for these receptors in lymphocyte homing and recirculation is discussed.

Agglutinins

Comparison of the thermal stabilities and solubilities of human hypertrophic scar, normal scar and normal skin collagens.

The thermal stability and solubility profiles of human hypertrophic scar collagen have been measured and compared with those of the collagens present in human normal scar, human normal skin and a lathyritic dermal tissue. The thermal stability profiles of the hypertrophic scar collagens were found to be very similar to each other and to closely resemble that of lathyritic collagen but differ significantly from those obtained with the other dermal collagens. The hydrothermal solubility profiles did not, however, show a clear distinction between normal and hypertrophic scars.

Adolescent

The effects of polymers on the shrinkage temperature of tendon.

The shrinkage temperature of tendon increases in the presence of a variety of polymers, both charged and uncharged. Using poly(ethylene glycol)s and carbohydrates of varying size, an effective radius of approx. 0.6 nm was found to be the minimum size required to achieve maximum stabilization. Above this minimum size, variations in solute size had little effect. Smaller solutes lowered the shrinkage temperature of tendon by disrupting the fibrillar structure. The study demonstrates that stabilization occurs when the solute is excluded from the fibrils and does not appear to require binding of the solute and collagen.

Animals

The stabilization of in vivo assembled collagen fibrils by proteoglycans/glycosaminoglycans.

The effects of proteoglycans/glycosaminoglycans on the thermal stability of in vivo assembled collagen fibrils have been examined. The shrinkage temperature of tendon collagen was found to be linearly dependent on the concentration of chondroitin sulphate in the surrounding fluid. Enzymic pretreatment of articular cartilage, to reduce its glycosaminoglycan content, resulted in decreased stability of the collagen present. The stability of the collagen in hyaluronidase-treated cartilage was found to be higher when measured in a solution of chondroitin sulphate (30 g/dl) than in buffer alone. The results of this study demonstrate that the proteoglycans stabilize collagen fibrils in tissues such as articular cartilage.

Animals

Wound contraction. The effects of scab formation and the nature of the wound bed.

The effects of scab formation and the nature of the wound bed on the contraction of wounds have been investigated. Rabbit paraffin gauze dressed flank wounds with the panniculus carnosus intact and rat paraffin gauze dressed full skin thickness back wounds had constant linear rates of movement of the wound margins throughout the time of contraction. Rabbit undressed wounds with the panniculus carnosus retained or excised and rat undressed wounds showed phases of rapid movement, no movement and normal movement of the wound margins during the course of contraction. These were effects of scab formation, they were transient and had little or no effect on the overall rate of wound contraction. The behaviour of rabbit undressed wounds with the panniculus excised was similar to that of comparable wounds with the panniculus intact, except that healing was delayed by approximately 3 days. Very variable behaviour was observed with rabbit paraffin gauze dressed wounds with the panniculus excised.

Animals

Wound contraction. A quantitative interpretation.

The behavior of dressed excisional wounds in a number of species (man, rabbit, rat and mouse) has been analysed. The change in wound area with time due to contraction was found to be consistent with a constant linear rate of movement of the wound margins. The linear rate of movement of the wound margins is shown to be an appropriate parameter for the quantitative comparison of rates of contraction. This parameter can be calculated from the slope of the (area)1/2 versus time plots.

Animals

The formation and thermal stability of in vitro assembled fibrils from acid-soluble and pepsin-treated collagens.

The role of the non-helical regions of the collagen molecule in fibrillogenesis has been investigated by comparing the kinetics of fibril formation of pepsin-treated acid-soluble collagen, acid-soluble collagen and mixtures of the two and by comparison of the thermal stabilities of the fibrils formed. The acid-soluble collagen was found to aggregate more rapidly than the pepsin-treated collagen under physiological conditions of pH and ionic strength. Variations in ionic strength, at physiological pH, were found to have differing effects on the aggregation of these two forms of soluble collagen. Fibrils formed from the pepsinized-collagen had a lower thermal stability tha n those formed from the intact collagen. The behavior observed with mixtures of acid-soluble and pepsin-treated collagens was found to be quantitatively consistent with the pepsinized collagen being able to utilize the nuclei formed by the acid-soluble collagen for subsequent growth. However, the use of the acid-soluble nuclei by the pepsinized collagen for growth did not enhance its rate of precipitation during the growth phase, nor did it enhance the thermal stability of the fibrils formed from the pepsinized collagen.

Animals

The distribution of serum albumin in human normal and degenerate articular cartilage.

A method for studying the distribution of a high molecular weight solute (serum albumin) between physiological saline and human articular cartilage is described. Samples of normal and fibrillated articular cartilage from both femoral condyles and femoral heads have been studied. Limited studies have also been performed where the glycosaminoglycan content of normal cartilage has been reduced by chemical or enzymic methods. With naturally occurring cartilage a wide range of partition coefficients (0.3 to less than 0.002) was obtained. The partition coefficients are very dependent upon proteoglycan concentration, with the partition coefficient decreasing with increasing fixed charge density. An attempt is made to interpret the observed partitioning in terms of the steric exclusion by the proteoglycans.

Binding Sites