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Biomedical subjects

A H Gordon

Publications and source records attributed to A H Gordon.

At least 37 records · Page 2Linked to original sources
PubMed1981

Acute turpentine inflammation and kinin release in rat-paw thermic oedema.

Livers from rats at 2-3 days after s.c. injection of turpentine, when perfused, synthesized prekallikrein nearly 3 times faster than did livers from normal rats. On the other hand paw oedema, produced by heating to 46 degrees, in rats injured in this way was less marked. Likewise in such rats the amount of bradykinin release by 50 min. of coaxial perfusion of the paw was only 13.6 +/- 4.6 compared with 63.1 +/- 13.4 ng in normal rats. A possible explanation for the observed reduction in production of bradykinin may be inhibition of kallikrein due to an increased concentration of alpha 2-macroglobulin.

Animals↗
PubMed1980

Ammonia inhibits phagosome-lysosome fusion in macrophages.

When foreign bodies, including many microorganisms, are ingested by cultured macrophages, they become enclosed in phagosomes, with which lysosomes usually fuse and then discharge their enzymes and other contents into the resulting phagolysosomes. Such fusion is, however, diminished or absent after the phagocytosis of some pathogens, notably Mycobacterium tuberculosis and Toxoplasma gondii. Assuming that the nonfusion is due to active inhibition by the intrapoagosomal microbe, identification of an inhibitor should clarify the lysosomal control mechanism. It has been suggested that strongly acidic sulphatides present in virulent tuberculosis, which, like other substances with polyanionic structural features, can themselves block phagosome-lysosome fusion (P-LF), may contribute to the negative lysosome response to ingested tubercle bacilli. We report here another possibility, based on inhibition of fusion of yeast-containing phagosomes by filtrates from cultures of tubercle bacilli on traditional-type defined media; we show that the ammonia content of such filtrates is sufficient to account for their effect. This inhibition of fusion seems to be an hitherto unrecognized intracellular consequence of added ammonia, in striking contrast to the enhancement produced by some lipophilic amines.

Amines↗
PubMed1980

A pyrogen derived from human white cells which is active in mice.

An endogenous pyrogen smaller in molecular size than that previously obtained from human white cells has been found in supernatants of these cells after uptake of zymosan and incubation for 18 h. The new pyrogen after separation from other pyrogens which are produced at the same time has been found to produce fever in mice but not in rabbits. Because it is not formed if cycloheximide is present and is inactivated by leucine aminopeptidase, it is believed to be a peptide.

Animals↗
PubMed1979

Effects of bacterial endotoxin and corticosteroids on plasma concentrations of alpha 2 macroglobulin, haptoglobin and fibrinogen in rats.

Bacterial endotoxin injected into rats resulted in increased plasma concentration of alpha 2 macroglobulin, haptoglobin and fibrinogen. Cortisone acetate injected i.m. by itself was sufficient to increase the plasma concentration of haptoglobin by 54% and to a lesser extent the concentrations of the other two proteins. When cortisone acetate and/or cortisol succinate were injected simultaneously with varying doses of endotoxin, the effects of the corticosteroid differed for each plasma protein. Doubtless because of the effect of cortisone by itself the slope of the dose-response relationship for haptoglobin was greatly reduced. In contrast to this the slope for alpha 2 macroglobulin was reduced and that for fibrinogen was unaffected. These findings suggest that, if effects due to endogenous corticosteroids are to be avoided, increases in plasma fibrinogen will serve best as indicators of stimulation of the acute-phase response. Since, however, the relative increase of alpha 2 macroglobulin due to the lowest dose of endotoxin was much greater than that of fibrinogen, increases in concentration of the former protein represent the most sensitive indication of the acute-phase response. Consideration of the responses in individual rats has made possible division into those with more or less than average increases for all 3 plasma proteins and those showing irregular responses. Especially in the group which had received the lowest dose of endotoxin, a much larger number than would be expected on a random basis was found to respond regularly with either more or less than average increases for all 3 proteins.

Animals↗
PubMed1979

Human blood and rabbit peritoneal leucocytes as sources of endogenous mediators.

"Buffy-coat" residues from human blood have been investigated as a source of leucocytic endogenous mediator (LEM). After separation from most of the erythrocytes and uptake of opsonized zymosan by the polymorphonuclear leucocytes (PML) and macrophages, the cells were incubated in Hanks' medium. To demonstrate the presence of LEM the supernatant thus produced was injected into rats and then after 24 h increases in the plasma concentrations of haptoglobin, alpha 2 macroglobulin and fibrinogen were estimated. For comparison rats were also injected with LEM prepared from rabbit peritoneal cells. Because these cells were obtained from rabbits which had been stimulated by i.p. injection of glycogen, addition of zymosan in vitro was not required. Despite the different species from which the leucocytes were obtained and the different method of preparation of LEM, similar increases in concentration of haptoglobin, fibrinogen and alpha 2 macroglobulin in the plasma of the recipient rats were obtained. Because injection of LEM resulted in very varied increases in concentration of each of the 3 plasma proteins, an attempt was made to ascertain whether positive responses for all 3 proteins occurred in the same rats or whether the rats responded randomly. The presence of endogenous pyrogen as a constituent of the LEM produced from both sources was confirmed using both rabbits and prewarmed mice (Bodel and Miller, 1976).

Animals↗
PubMed1976

The alpha macroglobulins of rat serum.

A three-stage method for isolation of alpha1 macroglobulin and alpha2 macroglobulin from the serum of normal and injured rats is described. The methods successively used, namely gel filtration, ultracentrifugation and chromatography on DEAE-cellulose, were chosen to minimize loss of tryptic esterase-protecting activity. The two proteins differed slightly with respect to the following properties: mol.wt., alpha1 macroglobulin 7.46 X 10(5), alpha2 macroglobulin 7.16 X 10(5); isoelectric focusing, alpha1, macroglobulin pI 4.4, alpha2 macroglobulin pI4.5. Amino acid analyses were identical, except with respect to tyrosine: alpha1 macroglobulin 3.96 +/- 0.24, alpha2 macroglobulin 3.16 +/- 0.32 mol/100 mol of total amino acids. When isolated from the serum of uninjured rats, alpha1 macroglobulin retained the capacity to bind 1.05 mol of trypsin/mol. However, if isolated from serum 2 days after injury only 0.78 mol of trypsin/mol of alpha1 macroglobulin was bound. alpha2 macroglobulin isolated from this latter serum bound on average 0.97 mol of trypsin/mol. When reduced with N-acetylcysteine, both molecules formed subunits of size corresponding to that expected for quarter molecules. When alpha2 macroglobulin was reduced with dithiothreitol, quarter molecules were again produced. alpha1 macroglobulin, however, when thus treated gave a more complex mixture, containing a component having a mol.wt. of less than 6 X 10(4). Antisera raised against the two proteins permitted estimation of the concentration of each protein in the plasmas or sera of normal and injured rats. Plasma from normal male rats contained 3.76 +/- 0.56 mg of alpha1 macroglobulin/ml (n = 33) and 0.016 +/- 0.001 mg of alpha2 macroglobulin/ml (n=33). After injury by injection of turpentine and cortisone, the concentrations in plasma were at 3 days 5.19 +/- 0.81 mg of alpha1 macroglobulin/ml (n = 12) and at 2 days 1.38 +/- 0.35 mg of alpha2 macroglobulin/ml (n = 12). Antisera to the two proteins did not cross-react with one another. The quarter molecules formed by reduction of both proteins showed increased antigenicity.

Amino Acids↗
PubMed1976

Effects of injury on the concentration of alpha1-macroglobulin and alpha2-macroglobulin in the plasmas of male and remale rats.

The effects of injury on the concentration of alpha1-macroglobulin and alpha2-macroglobulin in the plasmas of male and remale rats has been investigates. At 5 days after injury to the male rats the alpha1-macroglobulin concentration increased to 131% of its preinjury value. The alpha2-macroglobulin concentration increased more rapidly to a maximum of 86 times its initial value. In the female rats alpha2-macroglobulin increased only slightly and alpha1-macroglobulin not at all.

Animals↗
PubMed1976

The role of the acute phase reaction in inflammation.

Inflammation and injury to tissue results in a variety of local and systemic events, however although the local events of oedema formation and cellular infiltration have received considerably more attention the systemic response to inflammation is no less profound. The particular systemic event which forms the substance of this communication is the change in the circulating levels of plasma proteins which occurs after inflammatory injury, and the manner in which these changes in plasma concentration are controlled by changes in plasma concentration are controlled by changes in the rate of synthesis. A discussion of the role of the liver in controlling inflammatory events, in relation to the synthesis of an anti-inflammatory protein has been given; the present work is an extension of this and describes the changes in concentration and synthesis rate of albumin, fibrinogen and alpha1 acid glycoprotein during adjuvant arthritis in the rat. The changes which occur are regulated at the liver by alteration of the rate of synthesis of the individual protein. For example albumin at the height of adjuvant arthritis falls to a third of its normal plasma level whereas the level of alpha1 acid glycoprotein increases up to twenty-fold; these changes are reflected by similar changes in their synthesis rate by the liver. The effect of the fall in albumin concentration on the plasma binding of anti-inflammatory drugs (and their toxicity) in relation to these findings will be discussed along with the biological role of the acute phase plasma proteins and hence the influence of the liver in the response to injury.

Animals↗
PubMed1976

Kininogen and kininogenase synthesis by the liver of normal and injured rats.

Isolated livers from normal rats or from others at 2 days after subcutaneous injection of turpentine have been perfused with a simplified medium. Estimation of kininogen, kininogenase and 2 plasma proteins in the perfusates thus obtained indicate that both kininogen and kininogenase are synthesized in the liver. Furthermore, because twice as much kininogen and kininogenase was synthesized by the livers from the rats which had been injected with turpentine as by those from the normal rats, these two proteins must be considered to be members of the group of plasma proteins known as acute phase reactants.

Animals↗
PubMed1975

Acetyl groups in cell-wall preparations from higher plants.

O-Acetyl groups were detected by i.r. spectroscopy in cell-wall preparations from grasses and other higher plants and their presence was confirmed chemically. The amounts present are likely to influence both the physical state of the cell-wall polysaccharides and also their digestion by enzymes.

Acetates↗
PubMed1974

Co-operative action by endo- and exo-beta-(1 leads to 3)-glucanases from parasitic fungi in the degradation of cell-wall glucans of Sclerotinia sclerotiorum (Lib.) de Bary.

1. Two fungi, Coniothyrium minitans Campbell and Trichoderma viride Pers. ex Fr., were grown on autoclaved crushed sclerotia of the species Sclerotinia sclerotiorum, which they parasitize. 2. In vitro the crude culture filtrates would lyse walls isolated from hyphal cells or the inner pseudoparenchymatous cells of the sclerotia, in which a branched beta-(1-->3)-beta-(1-->6)-glucan, sclerotan, is a major constituent. 3. Chromatographic fractionation of the enzymes in each culture filtrate revealed the presence of several laminarinases, the most active being an exo-beta-(1-->3)-glucanase, known from previous studies to attack sclerotan. Acting alone this brought about a limited degradation of the glucan, but the addition of fractions containing an endo-beta-(1-->3)-glucanase led to almost complete breakdown. A similar synergism between the two enzymes was found in their lytic action on cell walls. 4. When acting alone the endo-beta-(1-->3)-glucanase had a restricted action, the products including a trisaccharide, tentatively identified as 6(2)-beta-glucosyl-laminaribiose. 5. These results are discussed in relation to the structure of the cell walls and of their glucan constituents.

Ascomycota↗
PubMed1972

1 -Acute-phase globulins of rats. Microheterogeneity after isoelectric focusing.

1. Improved resolution of mixtures of alpha(1)-globulins was obtained by the use of isoelectric focusing. 2. Because material recovered after isoelectric focusing in polyacrylamide gels behaved in a manner which suggested interaction with components derived from the gel, isoelectric focusing when used for preparative purposes was done in a matrix of Sephadex G-75. 3. By this means material from the individual bands formed by isoelectric focusing in 6m-urea could be isolated. The stability of these substances was examined by further isoelectric focusing. 4. Analysis of material that had been shown to be homogenous by isoelectric focusing in the absence of urea and of that from several individual bands derived from the same sample by isoelectric focusing in 6m-urea showed different proportions of sialic acid but no change in amino acid composition. 5. In the presence of 6m-urea the isoelectric points found were increased by 0.14-0.25 pH unit. After removal of most of the sialic acid with neuraminidase the increase was 0.36-0.72 pH unit. After treatment with 0.025m-H(2)SO(4) at 80 degrees C for 1h, which removed all the sialic acid, the increase was 0.40-0.87 pH unit. 6. Because removal of all the sialic acid did not decrease the number of bands formed by isoelectric focusing the observed heterogeneity could not be caused entirely by the presence of various proportions of sialic acid.

Alpha-Globulins↗