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Biomedical subjects

D C Candy

Publications and source records attributed to D C Candy.

At least 55 records · Page 3Linked to original sources

The nature and role of mucosal damage in relation to Salmonella typhimurium-induced fluid secretion in the rabbit ileum.

The time course and nature of mucosal damage induced in rabbit ileal loops by two strains of Salmonella typhimurium (TML and W118) isolated from human infections was assessed by immunofluorescence microscopy and by scanning and transmission electronmicroscopy. Salmonella-induced fluid secretion occurred in the presence or absence of gross mucosal architectural damage. Neither strain caused mucosal ulceration. When damage did occur, the villi were shortened by loss of their tip regions with concomitant reforming of an intact mucosal surface. Immediately preceding the onset of fluid secretion, marked infiltration of the mucosa with polymorphonuclear leukocytes and occasional macrophages was seen. This revives an earlier suggestion that interaction between invading salmonellae and acute inflammatory cells may be an important factor in initiation of fluid secretion. Brush-border invasion by salmonellae cannot per se be the immediate cause of fluid secretion, because the latter occurred several hours after initial invasion.

Animals↗

Effect of toxin A and B of Clostridium difficile on rabbit ileum and colon.

The effect of purified toxin A and partially purified toxin B on rabbit ileum and colon was investigated. Toxin A caused tissue damage which was followed by permeability changes and fluid accumulation in both tissues. Toxin A did not increase the permeability of the colon to the extent observed for ileum; secreted fluid contained less protein of plasma origin. Toxin B had no effect on either tissue. Secretory and tissue damaging properties of crude C difficile toxins were found to be due to toxin A.

Animals↗

The microcomputer: an aid to paediatric parenteral nutrition.

Approximately 50% of the pharmacy man-hours committed to providing a parenteral nutrition service at the Children's Hospital, Birmingham were spent in calculations, form filling and record keeping. An increasing demand for the service, with no extra staff available, meant that the service had to be made more efficient. A 90% time saving was achieved by using a microcomputer to free the pharmacy staff from many of the laborious mathematical and clerical chores. The program was developed by a member of the nutritional care team; this meant that it was designed with the specific needs of the service in mind. In addition the detail and accuracy of patient data recording have been greatly improved.

Child↗

New enteric vaccines: application of new knowledge of receptors and recognition in enteric infections.

Advances in understanding of the "receptors and recognition" mechanisms of virulence factors of enteric pathogens have been important in the development of enteric vaccines. Sophisticated techniques of molecular biology have proved essential to this endeavour. This review summarizes progress in development of vaccines against disease due to Vibrio cholerae, Escherichia coli, Salmonella typhi, Shigella and rotavirus enteric infections. All of these vaccines are undergoing, or are about to undergo, field trials.

Animals↗

Widespread cutaneous Crohn's disease presenting in childhood.

Cutaneous lesions containing Crohn's granulomata are rare and tend to occur in submammary or abdominal wall skin folds when they are to be found (1). Crohn's disease of the skin in nonflexural locations has been reported (2,3) although not in children. We report a 5-year-old girl with extensive colonic Crohn's disease, who at presentation was noted to have a generalised erythematous papular rash which histologically showed typical noncaseating granulomata.

Cecum↗

Adhesion of enterotoxigenic Escherichia coli to human small intestinal enterocytes.

An improved enterocyte adhesion assay has been used to examine a collection of 44 strains of enterotoxigenic Escherichia coli (ETEC) for their ability to adhere to the brush border of isolated human duodenal enterocytes. Fourteen strains showed good adhesion; in each case the ability to adhere correlated with the production of colonization factor antigen I or II (CFA/I or CFA/II) fimbriae. CFA/II-positive producing coli surface antigens 1 and 3 (CS1 and CS3), coli surface antigens 2 and 3 (CS2 and CS3), and only coli surface antigen 3 (CS3) each showed good adhesion. CS3-mediated brush border attachment of CFA/II-positive ETEC was demonstrated by electron microscopy with monospecific antibody and an immunogold labeling technique. One CFA/I-positive ETEC strain was nonadherent in the assay, as were ETEC producing type 1 somatic fimbriae. Five animal ETEC strains producing K88, K99, F41, and 987P fimbriae were slightly more adhesive than control strains, but adhesion was significantly less than that of CFA-positive ETEC. Twenty five human ETEC strains that lacked CFA/I and CFA/II were nonadherent, suggesting either that the surface antigens responsible for adhesion to human intestinal mucosa in these strains were not being produced or that mucosal receptors for these strains are present in regions of the small intestine other than the duodenum.

Adhesiveness↗

Portable bedside microcomputer system for management of parenteral nutrition in all age groups.

A microcomputer program has been designed to provide comprehensive assistance to the clinician in prescribing parenteral nutrition in children of all ages. It is implemented on a fully portable, independent machine that can be taken to the bedside anywhere in the hospital. The user is guided through a standardised prescribing process based on a well tried protocol and taking into account the patient's age, clinical condition, concurrent parenteral infusions, laboratory findings, and enteral intake. A printout is produced for insertion into the patient's clinical record, giving all concerned in the care of the child a clear, legible record of when, how, and by whom the prescription was calculated. The user can review and amend the proposed prescription before printing, giving ultimate control to the prescriber, not the computer. The system saves time by performing accurately the necessary calculations, and provides financial savings by reducing wastage of parenteral nutrition during the re-introduction of enteral feeding.

Adolescent↗

Salmonellosis: in retrospect and prospect.

Despite years of study and the accumulation of much potentially relevant information, neither the microbial determinants nor the pathophysiological mechanisms of salmonella-induced enteritis are known with precision. Earlier work is reviewed on the experimental pathology of salmonellosis, the pathophysiology of the disease and the biotyping of salmonella strains in closed rabbit ileal loops. The same strains have been confirmed by us to be (i) invasive and diarrhoeagenic, (ii) invasive and non-diarrhoeagenic, and (iii) non-invasive and non-diarrhoeagenic. At least two mechanisms have been put forward to explain fluid exsorption. One implicates prostaglandins released from polymorphonuclear cells (PMNs) interacting with invading organisms, whereas the second involves salmonella enterotoxin(s). This subject is in a state of confusion and requires clarification. The toxin has been shown by some to bear partial likeness to either cholera toxin (although the evidence is in fact contradictory) or Shiga toxin. Since both 'cholera-like' and 'Shiga-like' toxins are produced by all three biotypes in vitro, production of toxin (of whatever class or subclass) cannot per se be the sole explanation for salmonella-induced fluid secretion. In our experiments the onset of fluid secretion in rabbit ileal loops was coincident with the appearance of large numbers of infiltrating PMNs. We have also shown that organisms from all three biotypes, grown for 6 h in iron-containing but not in iron-deficient media, yielded polymyxin B extracts which are enterotoxic in rabbit ileal loops; culture supernatants were negative. Structural damage occurred to villus tips but not crypts in infected loops, succeeded the onset of fluid secretion, and was not reproduced by polymyxin B enterotoxic extracts. Thus salmonella diarrhoea may be a complex phenomenon with multiple determinants which might include the release of endogenous secretagogues and bacterial enterotoxin(s), if such are shown to be synthesized and released in vivo at appropriate times and in appropriate sites. Structural damage to villus tips leading to shortened villi may also contribute to diarrhoea by altering absorption (tip function)/secretion (crypt function) ratios as well as to the expulsion of those organisms which have not migrated to deeper tissues.

Animals↗

Production and release of toxins A and B by Clostridium difficile.

The production and release of toxins A and B by Clostridium difficile during in-vitro culture was investigated. Cell-associated toxin A was detected by immunoelectrophoresis of bacterial extracts released by ultrasonication and by fluorescent antibody labelling of whole cells. Extracellular toxin A was detected by immunoelectrophoresis and by enzyme-linked immunosorbent assay; extracellular toxin B was detected by cytotoxin assay. Both toxins A and B were produced and released during the decline phase of the bacterial growth cycle. The possible significance of these results in relation to the pathogenesis of pseudomembranous colitis is discussed.

Bacterial Proteins↗

In vitro adhesion of enterotoxigenic Escherichia coli to human intestinal epithelial cells from mucosal biopsies.

An adhesion assay with isolated human enterocytes prepared from duodenal biopsies has been developed and tested by using human enterotoxigenic Escherichia coli expressing colonization factor antigens I and II (CFA/I and CFA/II) and type 1 fimbriae. Enterotoxigenic E. coli strains H10407 (CFA/I) and B2C (CFA/II) bound to duodenal enterocytes to a much greater extent (mean of 4.6 and 4.0 bacteria per brush border) than did strain H10407P, a CFA/I- mutant of H10407 (mean of 0.1 bacteria per brush border). Type 1 fimbriae also promoted adhesion of strain H10407P to duodenal enterocytes but attachment was to basolateral rather than brush border surfaces. CFA/I and CFA/II, on the other hand, promoted adhesion only to human enterocyte brush borders.

Adult↗

Ultrastructural study of adhesion of enterotoxigenic Escherichia coli to erythrocytes and human intestinal epithelial cells.

The adhesion to erythrocytes and human intestinal epithelial cells of enterotoxigenic Escherichia coli strains H10407, B2C, and H10407P, expressing colonization factor antigen I (CFA/I), CFA/II, and type 1 fimbriae, respectively, was examined by electron microscopy. CFA and type 1 fimbriae were visualized by negative staining in thin sections after en bloc staining with ruthenium red and by immune labeling with antisera raised against purified fimbriae. By negative and ruthenium red staining, CFA/I, CFA/II, and type 1 fimbriae were indistinguishable and appeared as approximately 7-nm-diameter hollow cylindrical structures up to 1.5 micron in length; strain B2C also produced 2- to 3-nm-diameter flexible fibrillar fimbriae. Bacteria producing CFA/I, CFA/II, and type 1 fimbriae adhered to and agglutinated human, bovine, and guinea pig erythrocytes, respectively; CFA/I and CFA/II also mediated attachment of bacteria to the brush border of isolated human duodenal enterocytes. Electron microscopy of agglutinated erythrocytes and enterocytes with adherent bacteria showed, in each case, that bacterial adhesion involved the formation of many interactions between the tips of fimbriae and receptors on the erythrocyte or enterocyte brush border membrane. Immune labeling allowed different fimbrial antigens mediating bacterial attachment to human enterocytes to be identified.

Animals↗

Characterization of nonfimbrial mannose-resistant protein hemagglutinins of two Escherichia coli strains isolated from infants with enteritis.

Escherichia coli strains 444-3 and 469-3, isolated from patients with severe infantile enteritis, are able to adhere to and penetrate human epithelial cells in culture. In addition to type 1 fimbriae and glycocalyces , both strains elaborate mannose-resistant nonfimbrial protein hemagglutinins specific for human erythrocytes. Purified agglutinins are aggregates (greater than 4 X 10(6) daltons) of a single protein subunit of apparent Mr 14,000 (469-3) to 14,500 (444-3). The optimal temperature for expression of the agglutinins is 37 degrees C. Bacteria grown at 22 degrees C, which show 1% or less of maximal activity, and mutants deficient in the ability to agglutinate human erythrocytes do not synthesize detectable levels of these surface proteins and, moreover, do not adhere to cultured epithelial cells. Coupled with the observation that purified agglutinins competitively inhibit bacterial adherence to cultured cells, these data indicate that the nonfimbrial surface proteins expressed by strains 444-3 and 469-3 are essential for adherence both to erythrocytes and to cultured epithelial cells.

Adhesiveness↗

Ultrastructural study of adherence to and penetration of cultured cells by two invasive Escherichia coli strains isolated from infants with enteritis.

The adherence of invasive Escherichia coli strains 444-3 and 469-3 to human erythrocytes and to cultured HeLa and HEp-2 cells has been examined by electron microscopy. Bacteria elaborating type 1 fimbriae, glycocalyces , and nonfimbrial mannose-resistant hemagglutinins specific for human erythrocytes were identified in cultures of both strains, and each of these different bacterial surface components appeared to be involved in attachment of 444-3 and 469-3 to cultured epithelial cells or human erythrocytes (or to both). Both strains, which were isolated from infants with dysentery-like illness, penetrated cultured epithelial cells and existed within membrane-bounded intracellular vesicles. Mutants of 444-3 and 469-3 selected for deficiency in mannose-resistant hemagglutination did not adhere to or penetrate cultured cells. These ultrastructural studies demonstrate the complexity of the bacterial surface and show that E. coli strains 444-3 and 469-3 can elaborate several different adhesions , each of which could function to promote attachment to host intestinal epithelial cells. Mucosal invasion may also be an important virulence property of these strains.

Adhesiveness↗