Search PubMed⌕ Search

Biomedical subjects

C F Culling

Publications and source records attributed to C F Culling.

At least 19 recordsLinked to original sources
PubMed1984

Chemical and histochemical studies of normal and diseased human gastrointestinal tract. I. A comparison between histologically normal colon, colonic tumours, ulcerative colitis and diverticular disease of the colon.

Chemical and histochemical methods were used to compare the epithelial glycoproteins from formalin-fixed surgical specimens of normal human large intestine, colonic tumours, ulcerative colitis and diverticular disease. All the epithelial glycoproteins contained fucose, galactose, glucosamine, galactosamine and, in addition, sialic acids both with and without O-acyl substituents in the side chain and/or at position C4. The glycoproteins of the normal ascending and descending colons differed significantly with respect to the percentage of the sialic acids released following digestion of the de-O-acylated glycoprotein with Vibrio cholera neuraminidase and to the molar fucose-sialic acid ratio. Statistical analysis of the chemical data showed that (a) compared to normal, the sialic acids of the tumour and ulcerative colitis glycoproteins from the descending colon were significantly less substituted in the side chain and at position C4; (b) the O-acetyl substitution pattern of the sialic acids of the ulcerative colitis glycoproteins from the ascending colon and the quantitative composition of the carbohydrate prosthetic groups of the ulcerative colitis glycoproteins from both ascending and descending colons differed from normal; (c) it was not always possible to distinguish between the ulcerative colitis and tumour glycoproteins on the basis of the O-acetyl substitution pattern of their sialic acids; and (d), there were minor differences between normal glycoproteins and those from cases of diverticular disease.

Colitis, Ulcerative↗
PubMed1984

Chemical and histochemical studies of normal and diseased human gastrointestinal tract. II. A comparison between histologically normal small intestine and Crohn's disease of the small intestine.

Comparative chemical and histochemical studies were performed on formalin-fixed, surgical specimens of human small intestine from cases of Crohn's disease and normal controls. The sialic acids of the crude glycoproteins isolated from normal ileum were significantly less neuraminidase-susceptible and more C4 substituted (P less than 0.01) than those of the glycoproteins isolated either from normal upper small intestine (duodenum and jejunum) or from cases of Crohn's disease of the ileum. Fractionation yielded two major sialic acid-containing fractions, eluting from DEAE-cellulose with 0.2 M or 0.3 M sodium chloride. Both fractions contained fucose, galactose, glucosamine and galactosamine in addition to sialic acids both with and without O-acyl substituents at position C4 and/or in the side-chain (side-chain O-acylated sialic acids were also detected by histochemical procedures). The fractions differed significantly from one another with respect to the neuraminidase susceptibility of their sialic acids (P less than 0.01), the percentage of C4 (P less than 0.01) and side-chain substituted sialic acids (P less than 0.05), and the molar fucose-sialic acid ratio (P less than 0.05). The O-acyl substitution patterns of the sialic acids of both the 0.2 M and 0.3 M fractions of the upper small intestine glycoproteins differed significantly from those of the corresponding fractions from normal ileum, while the sialic acids of the 0.2 M fractions from Crohn's disease of the ileum differed significantly from normal with respect to neuraminidase susceptibility (P less than 0.01) and percentage C4 substitution (P less than 0.01); the 0.3 M fractions differed only in the percentage of sialic acids substituted at C4. The differences between the sialic acids from the normal and Crohn's disease specimens were shown to be independent of either the anatomical origin of the specimen or the histopathological sub-group of the Crohn's disease specimens; no significant differences were noted between the sub-groups but all the sub-groups differed from normal.

Crohn Disease↗
PubMed1984

Studies of the degraded carrageenan-induced colitis of rabbits. I. Changes in the epithelial glycoprotein O-acylated sialic acids associated with ulceration.

Ulceration of the large intestine, induced in New Zealand white rabbits by the administration of 1% w/v degraded carrageenan for periods of up to nine weeks, was studied by a combination of histochemical and chemical procedures for the identification of O-acylated sialic acid. The onset of the disease was rapid, visible faecal blood being observed within five days. Caecal ulceration was diffuse throughout the mucosa being more prominent and frequent on the transverse folds. In some cases large, discrete ulcers were observed in the rectal portion of the lower colon, while in a small number of cases there were ulcers at the caecal end of the upper colon. The ulceration was characterized by oedema, congestion, haemorrhage, inflammation and mucosal ulceration. The inflammatory exudate consisted of macrophages, lymphocytes, a few plasma cells and, in animals treated for a long period, aggregates of eosinophils. The ulceration was associated with a marked reduction in the proportion of the caecal epithelial glycoprotein sialic acids which were neuraminidase-resistant and/or substituted in the side chain. Histochemical studies indicated that changes in side chain substitution were more marked at the margins of the ulcers and could be observed in sections of colon that showed no evidence of ulceration.

Animals↗
PubMed1984

Studies of the degraded carrageenan-induced colitis of rabbits. II. Changes in the epithelial glycoprotein O-acylated sialic acids associated with the induction and healing phases.

Rabbits fed freely with a 1% aqueous solution of degraded carrageenan developed a progressive colitis characterized after five days by severe inflammation and mucosal ulceration of the caecum. Histochemical and chemical studies indicated that there was a marked reduction in intracellular mucin and in the proportion of the epithelial glycoprotein sialic acids with substituents in the side chain and at position C4. Changes in the O-acylated sialic acids occurred rapidly and, apparently, prior to either mucosal ulceration or a significant inflammatory response. Following the removal of carrageenan from the diet, there was evidence of progressive healing characterized by re- epitheliazation and a reduction in the inflammatory response until, at 12 days, the mucosa was comparatively normal. Healing was accompanied by an apparent increase in intracellular mucin and in the proportion of the epithelial glycoprotein sialic acids with substituents in the side chain and at position C4. Animals sacrificed 20 days after withdrawal of the carrageenan showed a renewal of ulceration characterized by an active inflammatory process, congestion, haemorrhage, and an inflammatory exudate consisting of a massive aggregation of eosinophils together with lymphocytes and plasma cells. This was accompanied by a reduction in the proportion of side chain and C4 substituted sialic acids.

Animals↗
PubMed1983

Apparent failure of 2-hydroxy-3-naphthoic acid hydrazide to block the periodic acid-Schiff reactivity of sialic acids. Implications for the PANFOPAS method.

Histochemical studies of the mechanism of staining of the periodic acid/2,-hydroxy-3-naphthoic acid hydrazide/Fast Black B/saponification/periodic acid-Schiff (PANFOPAS) method indicate that while 2-hydroxy-3-naphthoic acid hydrazide blocks the periodate engendered Schiff reactivity of vicinal diols unassociated with anionic groups, it fails to block such reactivity in sialic acid residues. It is suggested, therefore, that the positive Schiff staining observed following application of the PANFOPAS method to colonic epithelial mucins may be due to sialic acids without side chain substituents (or which are substituted at C7 or C9) in addition to sialic acids substituted at C8 (or which are di- or trisubstituted). Consequently the PANFOPAS method cannot be used to study the side chain substitution pattern of the sialic acids of epithelial mucins.

Animals↗
PubMed1980

Specific techniques for the identification of O-acylated sialic acids in colonic mucins.

The development of methodology for the histochemistry of mucins based upon their PAS reactivity is discussed in terms of mechanism, specificity and application. Two new histochemical methods (PB/KOH/PAS and PAT/KOH/PAS), supplemented by a variety of new and standard histochemical techniques, and correlated by parallel chemical studies, were used to demonstrate and identify C4 and side chain O-acylated sialic acids in colonic epithelial mucins. The application of these methods in the field of histopathology is discussed.

Animals↗
PubMed1980

Differences between the O-acetylated sialic acids of the epithelial mucins of human colonic tumors and normal controls: a correlative chemical and histochemical study.

Chemical analyses, together with histochemical assessments, were carried out on specimens of adenocarcinoma of the colon and histologically normal colonic epithelium (from resection margins from cases of carcinoma of the colon). In the epithelial glycoproteins of the normal tissue, both chemical and histochemical investigations indicated that the great majority of the sialic acids contained a side-chain O-acyl substituent located at position C8, whereas the side-chain substitution of the sialic acids of tumor glycoproteins was markedly reduced. Chemical analysis of the normal glycoproteins indicated that the great majority of the sialic acids were resistant to digestion with Vibrio cholerae neuraminidase, presumably due to an ester substituent at C4. The sialic acids of the tumor glycoproteins were significantly different from normal, in that they were less resistant to digestion with neuraminidase (p greater than 0.01), and therefore had a lower percentage of substitution at C4 (p greater than 0.01).

Adenocarcinoma↗
PubMed1979

Spin-labelling of sialic acid in soluble and cell-surface glycoproteins.

A new, mild method is described for spin-labelling sialic acid residues in situ. The procedure involves the formation of C-1 sialamides and has been applied to a serum glycoprotein, a mucin, tissue sections from human colon, and erythrocyte membrane components. The selectivity of the method and its possible applicability to other types of labelling are discussed.

Colon↗
PubMed1979

A histochemical comparison of the O-acylated sialic acids of the epithelial mucins in ulcerative colitis, Crohn's disease, and normal controls.

Two histochemical techniques, the PAT/KOH/PAS and the PBT/KOH/PAS, were used to investigate the side chain O-acyl substitution patterns of the sialic acids of the colonic epithelial mucins in cases of ulcerative colitis and Crohn's disease. In both diseases there was, as compared to normal, a reduction in the proportion of sialic acids O-acylated at C7C8, the reduction being greater in ulcerative colitis. Further, there appeared to be an association between the severity of the disease and the reduction in the staining of O-acylated sialic acids. This relationship was more marked in ulcerative colitis. In some cases of both diseases there was evidence for epithelial mucins containing predominantly C7-substituted sialic acids. This study has confirmed our previous conclusion that, in Crohn's disease of the terminal ileum, the disease is associated with an increase in the proportion of sialic acids bearing side chain substituents.

Colitis, Ulcerative↗
PubMed1979

The histochemistry of colonic mucins.

This presentation could perhaps better be titled the histochemistry of colonic mucins, as based upon PAS reactivity, since it mainly concerns development of methods for the identification of the various patterns of o-acylation of sialic acid as measured by alteration in PAS staining.

Animals↗
PubMed1978

A correlative chemical and histochemical study of the O-acetylated sialic acids of human colonic epithelial glycoproteins in formalin fixed paraffin embedded tissues.

Procedures are described for the isolation and identification of epithelial glycoproteins from formalin fixed, paraffin embedded specimens of human large intestine. The side chain O-acetylation patterns of the sialic acids of these glycoproteins were surprisingly similar to those of purified glycoproteins prepared from epithelial cells obtained from the same tissue before fixation. These results were consistent with those obtained by histochemical procedures performed on representative sections taken from the same tissue blocks. The methodology described permits a direct correlation of chemical and histochemical results obtained from the study of colonic epithelial glycoproteins of both normal and diseased tissues. It eliminates some of the difficulties associated with interpretation of the results by either discipline and may provide new information which would be unavailable by either chemistry or histochemistry alone.

Acetylation↗
PubMed1978

A histochemical method for the identification of 9-O-acyl sialic acid. An investigation of bovine submaxillary gland and intestinal mucins.

Prolongation of the initial periodate oxidation step of the periodate-borohydride technique/potassium hydroxide/periodic acid-Schiff and periodic acid-Thionin Schiff/potassium hydroxide/periodic acid-Schiff sequences produced little or no change in the diagnostic staining for the potassium hydroxide/periodic acid-Schiff effect, exhibited by the colonic epithelial mucins of man and rat and the Brunner's gland mucin of rabbits. In contrast, there was a gradual, but clear decrease in the intensity of such staining of bovine submaxillary gland mucins. It was concluded that, in the intestinal mucins studied the potassium hydroxide/periodic acid-Schiff effect was due to sialic acids bearing O-acyl substitutents at positions C7 and/or C8 whereas in bovine submaxillary gland mucin the potassium hydroxide/periodic acid-Schiff effect is probably due, at least in part, to the presence of 9-O-acyl sialic acids. This investigation has led to the development of a technique which can be used to identify 9-O-acyl sialic acids.

Animals↗
PubMed1977

The apparent failure of sodium borohydride reduction to block further PAS reactivity in rat epithelial mucins.

Sections of rat small intestine were oxidized with 1% periodic acid for periods of 1, 2, 5, 10 and 30 min and were subsequently either (a) stained with Schiff reagent, or (b) reduced with sodium borohydride and then treated with either Schiff reagent alone or by the standard PAS procedure. It was found that whereas sodium borohydride reduction abolished all Schiff staining, initial periods of oxidation in excess of 10 min were necessary to abolish any subsequent PAS reactivity. The theoretical and practical significance of these data is discussed in relation to the recent publication of Bayliss & Adams (1976).

Animals↗
PubMed1977

A new histochemical technique of use in the interpretation and diagnosis of adenocarcinoma and villous lesions in the large intestine.

The periodic acid-thionin Schiff/potassium hydroxide/periodic acid-Schiff (PAT/KOH/PAS) procedure has been used to investigate the histochemical staining characteristics of the mucins found in adenocarcinoma and villous lesions of the large intestine. The 46 blocks examined represented 58 lesions from 37 patients, all of whom had had resections for carcinoma of the colon. tin sharp contrast to normal colon, none of the adenocarcinomas stained red with the PAT/KOH/PAS. With two exceptions the poorly and moderately differentiated adenocarcinomas stained blue, whereas of the well differentiated lesions half were blue and half purple. The malignant villous lesions demonstrated the same trends, although a larger percentage were purple. None of the benign lesions stained blue. It is suggested that malignancy in the colon is accompanied by an increase in blue staining in the PAT/KOH/PAS technique and that such staining may be of value in the interpretation of highly atypical adenoma where it might identify the onset of malignancy. This change in staining indicates a distinct alteration in the chemistry of the mucins which we interpret as a reduction in the degree of side chain O-acylation of their constituent sialic acids.

Adenocarcinoma↗
PubMed1977

Histochemical comparison of the epithelial mucins in the ileum in Crohn's disease and in normal controls.

A comparison of routine and special histochemical methods that were applied to the epithelial mucins of small intestine from patients with Crohn's disease and from normal controls showed that the normal small intestine (ileum) goblet cells secrete a predominantly non-sulphated sialomucin and that, in contradistinction to the colon, the neuraminidase insensitivity of the sialic acids of the small intestine was not due to either O-acylation at C4 or an ester substituent at C1. Presumably this implies that the protection against enzyme attack afforded to the mucosa by the mucin coat in the small intestine utilises a different mechanism from that in the colon and that, although in many respects the small intestinal mucins in Crohn's disease, and in normal controls are similar, there is an increase in side-chain O-acylated sialic acids in such mucins in Crohn's disease. This difference has not been described before, probably because it can be seen only after staining such sections by the PAT/KOH/PAS and the PBT/KOH/PAS techniques.

Crohn Disease↗