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Biomedical subjects

D C Candy

Publications and source records attributed to D C Candy.

At least 19 recordsLinked to original sources
PubMed1992

Serological diagnosis of infection by Shigella dysenteriae-1 in patients with bacillary dysentery.

A total of 192 samples of serum from 113 Sri Lankan patients with clinical dysentery was examined for antibodies of the IgM class to the lipopolysaccharides (LPSs) of Shigella dysenteriae-1 and Escherichia coli O157:H7. By means of ELISA and immunoblotting, 59 patients were found to have serum antibodies to the LPS of S. dysenteriae-1 only. Four samples from one patient were found to contain serum antibodies to the LPSs of both S. dysenteriae-1 and E. coli O157:H7. Antibodies to the LPS of S. dysenteriae-1 were also detected in 16 samples from 25 children, from Sri Lanka, with no previous history of dysentery; one of these children also had antibodies to the LPS of E. coli O157:H7. Analysis of 16 samples from apparently healthy children in the U.K. showed that only one serum contained antibodies to the LPS of S. dysenteriae-1. This patient had a history of recent travel to Pakistan. The isolation of S. dysenteriae-1 remains the preferred test for the diagnosis of bacillary dysentery. The use of serology as a means of providing evidence of infection with S. dysenteriae-1, however may prove to be a useful adjunct to cultural techniques but needs to be validated in an area where this organism is endemic.

Child, Preschool↗
PubMed1990

An in vitro model to study aspects of the pathophysiology of murine rotavirus-induced diarrhoea.

An in vitro system is described and validated for studying transport of solutes and water in both uninfected and rotavirus-infected neonatal mouse intestine. Control intestine exhibited stable water absorption for periods of up to 40 min. Water absorption was temperature-dependent. Na-dependent, and enhanced by glucose-containing perfusion solutions. Theophylline induced net secretion of water by control intestinal tissue. Water transport by rotavirus-infected lower small intestine was significantly depressed as compared to control levels, and rotavirus-infected middle small intestine exhibited net secretion of water. Upper small intestine and colon from infected animals did not differ significantly from control tissues in their ability to transport water. Water secretion by infected middle small intestine was reversed to absorption by glucose-containing solutions.

Animals↗
PubMed1990

X-ray microanalysis of rotavirus-infected mouse intestine: a new concept of diarrhoeal secretion.

Neonatal mice were infected at 7 days of age with rotavirus [epizootic diarrhea of infant mice (EDIM) virus] and killed at 24-h intervals postinfection (PI). Cytoplasmic concentrations of Na, Mg, P, S, Cl, K, and Ca intestinal epithelial cells from infected and age-matched control animals were measured by x-ray microanalysis. In villus tip cells, Ca concentration increased at 24-96 h PI; Na concentration increased at 24-72 h PI; Ca and Na concentrations were near normal by 168 h PI. K concentration decreased 24-72 h PI, and Cl concentration decreased 48-96 h PI. In crypt cells, changes were observed without a discernible pattern: at 96 h PI, Na, Mg, S, and Cl concentrations increased and K concentration decreased; at 120 h PI, the concentrations of all elements except Na and Ca increased. In villus base cells, the mean concentrations of all elements except Ca peaked at 48-72 h PI and at 120 h PI. Na and Cl concentrations increased dramatically in some cells from 48 h PI onward. All the above concentration values were obtained from freeze-dried specimens and expressed in millimoles per kilogram of dry weight. Conversion of a limited number of data, pertaining to villus base cells, from dry weight to wet weight was possible. This conversion revealed that villus base cells in infected animals were more hydrated than corresponding cells from control animals. Also, the Na and Cl concentrations in mmol/kg H2O were significantly higher in villus base cells from infected animals than in those from corresponding controls: 137 +/- 7 versus 38 +/- 4 (Na) and 121 +/- 5 versus 89 +/- 6 (Cl). Wet weight concentrations of other elements were either the same (Mg) or lower (P, S, and K) after infection with virus. From these studies, a new concept of the pathophysiology of rotavirus-induced diarrhoeal secretion is proposed: stimulation of villus base cells to rapid cell division is accompanied by transient accumulation of Na and Cl; excess NaCl is secreted into the lumen, which is the driving force for fluid loss.

Animals↗
PubMed1990

Transport of water and electrolytes by rotavirus-infected mouse intestine: a time course study.

The movement of water and transport of Na+ and Cl- by mid-small intestine (M-SI) of rotavirus-infected neonatal mice was investigated by an in vitro perfusion technique. The concentrations of Na+, K+, and Cl- in the luminal contents of upper, middle, and lower small intestine and colon of infected mice were determined by flame photometry (Na+, K+) and an ion selective microelectrode (Cl-). In M-SI, maximal disturbance of water transport occurred at 72 h postinfection (PI): Infected tissue exhibited net water secretion. Water transport was also impaired at 144 h PI. Net secretion of Cl- occurred at 72 h PI, with some evidence of a second phase of reduced magnitude at 120-144 h PI. The magnitude and statistical significance of changes in Na+ transport were both less than those for Cl-, but the pattern of change was similar to that for Cl-. Luminal concentrations of Na+ were elevated between 48 and 144 h PI in the small intestine; this was particularly so in distal regions. Luminal Cl- concentration was maximally elevated to a considerable degree at 72 h PI and remained high at 96 h PI throughout the small intestine; thereafter, Cl- concentration returned to near normal. K+ concentration was unchanged in the small intestinal lumen; in the colon, however, K+ concentrations were depressed 72-168 h PI. In the light of previous data from this laboratory, the present data are interpreted as evidence for a secretory component in rotavirus-induced diarrhea.

Animals↗
PubMed1990

Disaccharidase activities in small intestine of rotavirus-infected suckling mice: a histochemical study.

A histochemical study of the time course of the appearance and location of lactase and alpha-glucosidase (used to detect sucrase and maltase) activities was carried out on control and rotavirus-infected mice from 7 to 14 days old. The overall pattern of enzyme activity was in agreement with previous quantitative studies on the activities of these enzymes. No evidence was obtained to support the idea that lactase deficiency was the result of repopulation of villi (denuded of lactase-producing villus cells) with immature lactase-negative cells. Low lactase activity was more likely to reflect profound changes in metabolically crippled cells, and recovery of lactase activity with recovery of normal metabolic functions. The location of enzyme activity to brush border regions rather than the cytoplasm of villus enterocytes enhances the significance of previous quantitative studies on these enzymes. The timing and duration of diminished lactase activities were such that they were unlikely to cause the induction or perpetuation of diarrhea in murine rotavirus diarrhea. The appearance in infected animals of alpha-glucosidase 3 days earlier than normal indicates that, in addition to reversible changes seen with lactase, developmental changes were accelerated that affected both crypt and villus cells.

Animals↗
PubMed1990

The role of leucocytes in the induction of fluid secretion by Salmonella typhimurium.

Nitrogen mustard (N2M) treatment of rabbits induced neutropenia, and, in ligated ileal loops, it inhibited fluid secretion induced by salmonella or by cholera toxin (CT). Pretreatment of rabbits with indomethacin almost abolished salmonella-induced fluid secretion and significantly reduced that induced by CT. Similar effects of N2M and indomethacin on fluid secretion induced by salmonella, but not by CT, have been reported by other workers and used to implicate prostaglandins, from the salmonella-induced inflammation, as mediators of fluid secretion. In contrast, we show that N2M treatment, in addition to reducing CT-induced secretion, caused severe morphological alterations to ileal mucosa. Irradiation techniques were developed for inducing neutropenia, but they did not totally inhibit salmonella-induced leucocyte influx into ileal mucosa. We propose an alternative mechanism for the inhibitory effect of N2M on salmonella- and CT-induced secretion, based on the known anti-mitotic activity of N2M. Also, the anti-secretory effect of indomethacin cannot be attributed uniquely to its anti-inflammatory activity because it depressed CT-induced secretion as well as salmonella-induced secretion. These results support the concept of pathophysiological secretion in infectious diarrhoea, developed previously for rotavirus and extended to bacterial infections.

Animals↗
PubMed1989

Studies on early association of Salmonella typhimurium with intestinal mucosa in vivo and in vitro: relationship to virulence.

The abilities of six strains of Salmonella typhimurium to associate with rabbit ileal mucosa have been measured in vitro. Two were "virulent" strains (TML and W118 which are invasive and inducers of fluid secretion in rabbit ileal loops); four were "avirulent" (LT7, M206 and SL1027 which are invasive but induce negligible fluid secretion, and Thax-1 which is neither invasive nor an inducer of fluid secretion). A special organ-culture apparatus was designed to expose only the luminal surface of the mucosa to organisms. Viable counts of washed homogenised tissue taken 30 min after challenge showed that virulent strains TML and W118 and avirulent strains LT7 and M206 could not be distinguished from each other. Avirulent strain SL1027 associated less well than the other four strains, and Thax-1 associated less well than SL1027; both these strains were non-motile whereas the other four were motile. Thus, early association with gut mucosa did not discriminate all avirulent strains from the virulent strains. Qualitative examination of tissues by scanning electronmicroscopy did not detect strains LT7 and M206 on the mucosal surface whereas strains TML and W118 were readily seen, suggesting that the nature of association of virulent and avirulent strains was different. Qualitative examination by transmission electronmicroscopy of tissues challenged in vivo for 120 min showed virulent strains TML and W118 invading epithelial cells; similar events were reproduced after 120-min challenge in vitro. In contrast, invasion by avirulent strains was observed only very rarely.

Animals↗
PubMed1989

Quantification of the leucocyte influx into rabbit ileal loops induced by strains of Salmonella typhimurium of different virulence.

Leucocyte influx into rabbit ileal loops, induced by strains of Salmonella typhimurium of different virulence, was assessed with 111Indium-labelled leucocytes. Strains fell into two groups on the basis of their leucotactic potential: "virulent" strains (which induced fluid secretion) caused a dose-dependent leucocyte influx; strains which did not induce fluid secretion failed to induce a significant leucocyte influx. Fluid secretion was never observed in the absence of leucocyte influx, but leucocyte influx per se did not induce fluid secretion. The phenotype of the challenge inoculum influenced fluid secretion; young log-phase organisms induced fluid secretion with a higher frequency than overnight cultures. These findings support earlier evidence implicating leucocytes in an interactive but not exclusive role in the genesis of salmonella-induced fluid secretion. They suggest, though do not prove, that interaction of leucocytes with the appropriate phenotype of organisms results in the release of a host-derived or bacterial secretagogue, or both. The bacterial factor may or may not be the antigen related to cholera toxin, described previously.

Animals↗
PubMed1988

Expression of an antigen in strains of Salmonella typhimurium which reacts with antibodies to cholera toxin.

Six strains of Salmonella typhimurium (W118, TML, SL1027, LT7, M206 and Thax 1) of different virulence were examined for the presence of antigens which react with antibodies to cholera toxin (anti-CT). A fluorescent-antibody-labelling technique employing anti-CT was used to analyse antigen expression. A rapid increase in the proportion of cells producing a CT-related antigen was demonstrated in cells in early log phase (1-4 h growth) followed by a rapid decline during mid-late log phase in each of the six strains. The nature of the CT-related antigen was analysed by immunoblotting using anti-CT. An antigen of mol. wt equivalent to a high-mol. wt species of CT B subunit was detected in polymyxin-B extracts of all strains but greater amounts were observed in the strains that we consider avirulent. Nothing equivalent to a CT A-related subunit was observed in any of the strains. The relatedness of the salmonella antigen to CT was limited. The high-mol. wt antigen was not disrupted in the denaturing conditions of SDS-PAGE; nothing was detected by enzyme-linked immunosorbent assays with either ganglioside or anti-CT as anchor.

Antibodies, Bacterial↗
PubMed1987

The effects of Clostridium difficile crude toxins and purified toxin A on stripped rabbit ileal mucosa in Ussing chambers.

Clostridium difficile crude toxins and purified toxin A had similar effects on stripped rabbit ileal mucosa in Ussing chambers. Both toxin preparations caused secretion of sodium and chloride ions by increasing serosa to mucosa (s----m) fluxes. Transmural potential difference and resistance decreased after toxin treatment. Onset of changes in electrical measurements and ion fluxes coincided with onset of histological changes. The response to theophylline was greatly reduced in toxin-treated tissue compared with control tissue.

Animals↗
PubMed1987

Biological mode of action of Clostridium difficile toxin A: a novel enterotoxin.

Antibody neutralisation and toxin A elution experiments showed that toxin A uptake from rabbit intestinal lumen was a continuous process. The kinetics of the ileal and colonic responses were significantly different; a much longer incubation (4 h) with toxin was required for colon, compared with 45 min for the ileum, to induce fluid accumulation at 12 h. Fluid secretion was induced only when toxin had gained access to deeper tissues, probably achieved by several toxin uptake-tissue damage cycles. Toxin A induced haemorrhage in both ileal and colonic tissues. In ileum, the villus architecture was severely damaged and this gave rise to protein-rich bloody luminal fluid. In the colon, although colonocytes were removed, the basement membrane remained intact; this resulted in a tissue-localised haemorrhage and a protein-low watery ultrafiltered luminal fluid. Toxin A is thus a novel type of histotoxic enterotoxin.

Animals↗
PubMed1987

The effects of Clostridium difficile crude toxins and toxin A on ileal and colonic loops in immune and non-immune rabbits.

Rabbits were solidly immunised by parenteral injection of purified Clostridium difficile toxin A such that they resisted an intravenous challenge with a normally lethal dose of toxin A. Ileal and colonic loops constructed in non-immune and immune animals received challenge injections of crude culture filtrate or purified toxin A of C. difficile. Protection of ileum was manifest after sufficient initial mucosal damage resulted in release of high levels of antitoxin A into the loop lumen of immune animals. There was less fluid accumulation in ligated ileal loops of immune than of non-immune rabbits. Less protection was observed when loops were challenged with crude culture filtrate containing toxins A and B than when challenged with purified toxin A. In-vitro studies with Ussing chambers yielded no evidence for tissue-localised immunity as judged by electrical responses and histology of toxin-treated tissue from non-immune and immune animals. No differences were found in the degree of epithelial damage, or volume or composition of fluid accumulating in colonic loops of non-immune and immune rabbits challenged with toxin A or crude culture filtrate. However, in colonic loops of immune rabbits there was no overt tissue-localised haemorrhage, whereas in those of non-immune rabbits tissue-localised haemorrhage was marked. In contrast to our findings with ileal loops, fluid accumulating in colonic loops was watery and contained substantially less total protein and (in immune animals) antitoxin A.

Animals↗
PubMed1986

Kinetics, tissue specificity and pathological changes in murine rotavirus infection of mice.

Mice that did not contain antibodies to rotavirus were orally infected with murine rotavirus (EDIM strain) and observed over 7 days. As judged by ELISA, only the small intestine was infected, not the colon. The infection was biphasic, viral antigen peaks being observed at 48 h and approximately 120 h post-infection. Clinically evident diarrhoea was maximal at 72 h. Virus in the upper, middle and lower regions of the small intestine was mainly tissue-associated; most virus was found in the middle small intestine. Two peaks (48 h and 120 h post-infection) of virus antigen were observed in the colon, but these corresponded to luminal, not tissue-associated viral antigen. Only enterocytes in the upper two-thirds of villus epithelia were infected as judged by fluorescent-antibody analysis and transmission electron microscopy. Scanning electron microscopy revealed morphological appearances not hitherto correlated with the progress of the infection: villus tips were convoluted, corresponding to the shedding of virus-infected cells but the lower regions of infected villi were shrunken and considerably narrowed compared to tips.

Animals↗