Biomedical subjects
Publications and source records attributed to G A Turner.
The ability of collagenase to disaggregate a solid metastasizing lymphosarcoma has been shown to considerably increase with reducing environmental pH. It is suggested that this effect may be operating in vivo to release cells from a primary tumour.
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Methods have been developed which isolate single viable cells from the primary growths of two tumour systems (a lymphosarcoma and a carcinoma) and their secondary deposits. Subsequent comparisons of the surface-membrane structure of pairs of these primary and secondary cells, using lactoperoxidase-catalysed radioiodination coupled with polyacrylamide-gel electrophoresis, suggest that their overall structures are qualitatively very similar. This latter picture is still maintained when the isolated cells are treated with trypsin or incubated in complete medium before radioiodination. Analysis of the incorporated label into defined sections of the electrophoretic patterns revealed small quantitative differences between primary and secondary cells. In particular, slightly reduced incorporation into certain surface components of secondary cell preparations was seen. However, these did not occur for all the animals investigated, and also they did not consistently occur if the isolated cells were incubated in complete medium. The most similar overall change observed for the two tumour systems was a slight reduction in the secondary cells of a 20K mol. wt surface component.
The effect of treatment with either whole calf thymus histones, or individually isolated histones, or polyarginine, or polylysine, on the nuclear size of BHK21 cells has been investigated. Incubation of the cells with mixed histones (12.5--44 microgram/ml) for 1 h considerably increased nuclear size. Increasing the histone concentration and/or the incubation time resulted in a decrease in the effect and could result in no change in nuclear size. Treatment of the cells with polyarginine or polylysine did not affect nuclear size. Experiments with individually isolated histones showed that the nuclear size effect was almost exclusively due to the histone H4. It is argued that the changes observed most likely resulted from interaction of H4 with the nucleus, and could reflect the properties of this particular histone molecule.
A very simple, rapid and reproducible method has been developed for studying the interaction of lectins with the cell surface. This involves determining the number of adherent cells after shaking cell suspensions in Petri dishes which have had a lectin coupled to their surface using 1-cyclohexyl-3-(2-morpholinoethyl) carbodiimide metho-p-toluene sulfonate. Using concanavalin A coupled to 60 mm diameter dishes and between 1.5 and 2 x 10(6) tumour cells, this adhesion reached a maximum after 10 min shaking. Maximum cell adhesion also varied according to the particular lectin used. Adhesion was absent or was very low if cells were shaken in untreated dishes, or in dishes coupled to bovine serum albumin, or in the presence of the lectin-specific sugar-competitor. Under conditions of maximum cell adhesion, the binding of two different lymphosarcoma lines to four different lectins was very similar, whereas the binding of a carcinoma line to these lectins was completely different from that observed for the lymphosarcomas.
Lysozyme was measured using the synthetic substrate 3',4-dinitrophenyl tetra-N-acetyl-beta-chitotetraoside and the LKB Reaction Rate Analyser. This method has been evaluated by comparing levels obtained with serum samples from healthy individuals and patients with either cancer or inflammatory bowel disease with those obtained from the same specimens using a turbidimetric method. In terms of standard egg-white lysozyme, the colorimetric method gave much higher levels for all samples than the turbidimetric method; however, similar group differences were maintained. For individual serum specimens significant correlation between the two methods was found to occur only in the healthy group. Assay precision for the two methods was similar but the turbidimetric method could detect levels of lysozyme activity which were 10 times lower than those detected by the colorimetric method.
Cyclic adenosine 3', 5' monophosphate (cyclic-AMP) has been estimated in mucosal biopsy samples removed from the descending colon and rectum at endoscopy to investigate the possibility of using this substance for monitoring pre-malignant changes in the large bowel. Four groups of patients have been studied: those with normal large bowel and rectal mucosa; those with non-malignant inflammatory bowel disease; those with an adenomatous polyp in the descending colon or sigmoid colon; and those with a rectal adenocarcinoma. No difference was found in the cyclic-AMP content of 'normal' rectal mucosa, 'normal' colonic mucosa, 'diseased' colonic mucosa, carcinomas, and uninvolved mucosa adjacent to the polyps. Less cyclic-AMP was found in the polyps than in adjacent uninvolved mucosa. Conversely, more cyclic-AMP was found in the carcinomas than in adjacent uninvolved mucosa. It is concluded that although cyclic-AMP may be a very useful parameter for delineating the extent of the disease in individual patients, it is not a suitable biochemical marker for the screening of neoplastic changes in the large bowel in the population as a whole.
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1. The effects of phenol and phenyl glucuronide on the responses of normal rat brain adenyl cyclase to noradrenaline and dopamine have been investigated. Neurotransmitter responses have also been examined in brains from uraemic and normal rats. 2. A depressive effect of phenol on the adenosine 3' :5' -cyclic monophosphate response of the neostriatum to dopamine was shown to be completely abolished if the toxin was present in the conjugated form; the response of the cortex to noradrenaline was stimulated by the presence of phenyl glucuronide, even though the unconjugated form had no effect. 3. The uraemic state in the rat also resulted in a depression of the neostriatum response to dopamine, yet an enhancement of the cortical response to noradrenaline. 4. The action of phenols of the brain is relevant to hepatic and uraemic coma.
The effect of treatment with 0.04% (w/v) trypsin (EC 3.4.4.4) for 3 h on the electrophoretic mobility (EPM) of polyoma-virus malignantly transformed BHK21 cells (Py6) and their normal counterparts has been investigated. These particular conditions were chosen because an earlier study had shown that such treatment released material from the Py6 cells which was not obtained from the BHK21 cells. The negative EPM of the Py6 cells at pH 7.5 was greatly increased by this treatment; whereas the EPM of the BHK21 cells remained unchanged. Active enzyme was required to produce the change. No evidence was obtained for cytolysis, cytotoxicity or uptake of the enzyme by the treated Py6 cells. Measurement of the EPM of the Py6 cells at different pH levels before and after trypsin treatment suggested that the enzyme was removing cationic groupings from the cell surface.
A very sensitive method is described for the assay of guanosine 3',5'-cyclic monophosphate (cGMP) based on a competitive protein-binding technique. The procedure is simple to carry out, and does not require the purchase of expensive reagents. The binding-protein used is extracted from rat lungs and the bound and unbound cGMP are separated by ammonium sulphate precipitation. Although prior extraction of the cGMP is required, the time for this extra step is easily compensated for by the shortness of the assay time. The mean cGMP found in the blood plasma of normal young males and females is 9.9 +/- 2.4 (S.D.) nmol/l (range 5.9--14.3 nmol/l) and 9.5 +/- 2.1 (S.D.) nmol/l (range 6.9--12.7 nmol/l), respectively.
The surface of single cells isolated from solid tumours by either a mechanical or an enzymatic method have been compared, using lactoperoxidase-catalyzed radioiodination of the tyrosine-containing proteins. Qualitatively, the patterns of surface labelling were similar, and duplicate experiments indicated that each method of isolation gave reproducible results. Analysis of incorporated label into 4 defined sections of the electrophoretic pattern illustrated quantitative differences. When the cells were isolated mechanically, the incorporation into low-mol.- wt. components was considerably reduced, whereas that into the high-mol.-wt. components was unaffected. Treatment of enzymatically isolated cells with trypsin also reduced incorporation into low-mol.-wt components.
Previous studies suggested that aprotinin might enhance the host's immunological resistance to tumours. This possibility has now been further investigated by studying the behaviour of tumours in both hamsters and mice. A second tumour graft in tumour-bearing hamsters appeared more rapidly than the first. Prior administration of aprotinin abolished this effect. Pretreatment of non-cancerous mice with cortisone nullified the effectiveness of aprotinin in inhibiting the growth of a subsequent tumour graft. These results are interpreted as additional evidence that aprotinin enhances the immunological system against tumour cells.
Previous studies have demonstrated a rise in serum alpha-1-antitrypsin at advanced stages of malignancy. These, together with results of animal experiments with another anti-proteinase, aprotinin, have prompted studies of the plasma alpha-1-antitrypsin in the early stages of malignancy, using cervical carcinoma as a model. Measurements were made in three groups of individuals; negative cervical-smear women volunteers; hospitalised women with a positive result from the cervical-smear test; hospitalised women with a clinical cervical carcinoma. Elevated plasma alpha-1-antitrypsin levels were found in the "smear-positive" and "cancer" groups. Possible explanations for this increase are discussed and it is concluded that it occurs in direct response to the early stages of development of the tumor. Once a frank carcinoma has developed, maximal response has been attained, regardless of the degree of invasion or metastasis.