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Biomedical subjects

A Ferguson

Publications and source records attributed to A Ferguson.

At least 253 records · Page 14Linked to original sources

Immunological responses to fed protein antigens in mice. I. Reversal of oral tolerance to ovalbumin by cyclophosphamide.

Feeding ovalbumin over a wide range of doses is known to reduce subsequent systemic immune responses to parenteral immunization. In the present study, we have fed mice 2 mg and 25 mg ovalbumin (OVA) 2 weeks before systemic immunization and followed the resulting humoral antibody and cell-mediated immune (CMI) responses. The results indicate that while 25 mg OVA will reduce subsequent IgM, IgG and CMI responses to OVA, feeding 2 mg OVA will only suppress CMI responses and to a lesser extent the IgM response. Furthermore, the tolerant state induced by feeding 25 mg OVA was only partially prevented by 100 mg/kg cyclophosphamide (CY) while the suppressed CMI after feeding 2 mg OVA was completely blocked by CY pretreatment. These findings suggest that the humoral and cell-mediated limbs of the immune response may be controlled by different regulatory systems after feeding antigen, and that activation of these systems is dependent on the dose of oral antigen use. In addition, the results are in agreement with our previous finding that CY pretreatment will allow the development of CMI in the gut and gut-associated lymphoid tissue (GALT) after oral OVA and suggest that this phenomenon is related to breakdown of oral tolerance induction.

Administration, Oral↗

Migration inhibition of lymph node lymphocytes as an in vitro assay for cell-mediated immunity in the draining lymph nodes of parenterally immunized mice.

This paper describes a method for in vitro measurement of specific cell-mediated immunity in the mouse. Animals were immunized parenterally with ovalbumin in Freund's incomplete or complete adjuvant, and a direct migration inhibition assay was performed, using lymphoid cells from the draining lymph nodes. Migration inhibition was found to be antigen specific, correlated with systemic delayed-type hypersensitivity measured in vivo by skin testing, and had a high degree of sensitivity for ovalbumin. The migrating cells were identified as lymphocytes. Lymph node lymphocyte migration inhibition provides a reliable in vitro assay for regional CMI in the mouse.

Animals↗

Intraepithelial lymphocyte count and crypt hyperplasia measure the mucosal component of the graft-versus-host reaction in mouse small intestine.

We have used measurements of intestinal epithelial cell kinetics and counts of intraepithelial lymphocytes and mucosal mast cells to measure small intestinal mucosal changes during the proliferative and recovery phases of graft-vs.-host reaction in neonatal mice. Unirradiated (CBA x BALB/c)F1 mice were injected with parental spleen cells or with culture medium at 6-8 days of age, and followed up for 9 wk thereafter. The spleen index was used as a measure of the graft-vs.-host reaction, a stathmokinetic technique with microdissection was used to measure villus and crypt lengths and crypt cell production rate, and intraepithelial lymphocytes and mucosal mast cells were counted in histologic sections. Intraepithelial lymphocyte count rose within 24 h of induction of the graft-vs.-host reaction and increases in crypt length and in crypt cell production rate occurred within 3 days. These indices exactly parallel the spleen index during the proliferative phase of the graft-vs.-host reaction and the changes occurred in the absence of any villus damage. Mucosal mast cell numbers also increased, but the rise was delayed and sustained when compared with other mucosal changes. These results show that measurements of mucosal architecture and intraepithelial lymphocyte counts can be used to quantify mucosal cell-mediated immune reactions. In addition, this study provides further evidence to support our hypothesis that the mechanism of these changes is due to a delayed-type hypersensitivity reaction in the intestinal mucosa rather than to the action of cytotoxic T lymphocytes.

Animals↗

Migration inhibition of lymph node lymphocytes as an assay for regional cell-mediated immunity in the intestinal lymphoid tissues of mice immunized orally with ovalbumin.

A migration inhibition assay, using lymph node lymphocytes, has been used as an in vitro assay for cell-mediated immunity (CMI) to ovalbumin in the mesenteric lymph nodes of mice fed ovalbumin. Migration inhibition developed only if an ovalbumin feed was preceded by cyclophosphamide administration; sensitization developed within 24 hr of a single ovalbumin feed, persisted for 14 days and could be recalled on secondary oral challenge with ovalbumin. The intestinal CMI occurred in the absence of detectable systemic immunity and was found only in mice given cyclophosphamide before oral immunization. These results confirm earlier reports on induction of CMI to ovalbumin in the intestinal mucosa, and support the hypothesis that abrogation of a gut-associated suppressor system is necessary to allow induction of intestinal CMI to a dietary protein.

Administration, Oral↗

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Colonic Diseases, Functional↗

Hypersensitivity reactions in the small intestine. 6. Pathogenesis of the graft-versus-host reaction in the small intestinal mucosa of the mouse.

The intestinal phase of the graft-versus-host reaction (GVHR) has been investigated in adult F1 mice bearing grafts of fetal gut using an H-2-incompatible and an H-2-compatible, Mls-incompatible combination. The results indicate that the mitotic activity of the intestinal crypts and the number of intraepithelial lymphocytes are sensitive parameters of the mucosal cell-mediated immune response in the GVHR. Using these indices, indirect evidence has been obtained that soluble factors may be responsible for the damage to the intestine in the GVHR. Possible pathways of lymphocyte activation and migration to the gut are proposed to explain the role of gut-associated T cells in the production of these mediators.

Animals↗

Mixed neuromuscular block: the effect of precurarization.

The effects of precurarisation, with small doses of pancuronium, curare or gallamine, on the neuromuscular blockade following suxamethonium, 1 mg/kg, were studied using train-of-four stimulation. The duration of the block was reduced by pretreatment with d-tubocurarine and gallamine but increased with pancuronium. The degree of competitive neuromuscular blockade, both after administration of the precurarising dose and at full recovery from suxamethonium was mild and was insufficient to be a cause of postoperative muscle weakness.

Adolescent↗

Lactose tolerance in lambs with rotavirus diarrhoea.

It has been suggested that lactose malabsorption is an important factor in producing the diarrhoea of acute rotavirus infection. Accordingly, the lactose tolerance of gnotobiotic newborn lambs, infected with lamb rotavirus, has been investigated by clinical studies and tissue enzyme assays. Although lactase activity is low in affected areas of the small intestine, rotavirus infected lambs are not lactose intolerant as assessed by the measurement of reducing substances in the faeces, or by the clinical effects and blood glucose levels after a 5.8 mmol (2 g)/kg lactose load on the second day post-infection. Lactose intolerance could be demonstrated by using extremely high (29.2 mmol (10 g)/kg) doses of lactose, three or four times the normal dietary lactose intake. These experiments suggest that lactose-containing feeds (such as maternal milk) are not necessarily contraindicated in patients or animals with rotavirus diarrhoea.

Animals↗

Reduction of gastrointestinal protein loss by elemental diet in Crohn's disease of the small bowel.

Seven patients with hypoalbuminaemia and extensive jejunoileal Crohn's disease were treated with an elemental diet for 28 to 56 days. Over this time there was an increase in total plasma proteins from mean of 49.1 to 59.0 g/l and a mean rise in serum albumin from 20.7 to 30.0 g/l (P less than 0.05). In addition, there was a 47% mean reduction in plasma protein loss into the gastrointestinal tract and a rise in blood lymphocyte count in all patients (P less than 0.05). These results suggests that, as well as providing nutritional support, elemental diets reduce protein and lymphocyte loss from the diseased intestine.

Adult↗

Corticosteroid treatment increases parasite numbers in murine giardiasis.

Corticosteroid therapy is known to be hazardous in patients with occult infection but the mechanism by which the host parasite relationship is altered by steroids is not known. We have used an intestinal protozoal parasite, Giardia muris, to examine the effects of corticosteroids on the number of parasites in the intestine in the course of a primary infection. A single injection of cortisone acetate, subcutaneously, one day before oral inoculation of CBA mice with 1000 cysts of Giardia muris, resulted in significantly higher trophozoite counts in animals studied at one, two, three, four, and eight weeks post-infection, when they were compared with saline injected controls. Recrudescence of occult infection was also achieved by cortisone acetate treatment of mice which had been infected with Giardia muris eight months previously. Clinical studies are required to establish if recrudescence of occult protozoal infection is an important cause of morbidity when immunosuppressive therapy is given to patients in areas where giardiasis is endemic.

Animals↗

Duodenal mucosal architecture in non-specific and ulcer-associated duodenitis.

This study was done to determine the severity and extent of abnormalities of duodenal mucosal architecture in non-specific (non-ulcerative) and ulcer-associated duodenitis. The effect of successful treatment with cimetidine on these changes has also been assessed. A method of microdissection and measurement of villus height, crypt depth, and mitotic figure count per crypt was applied to endoscopic biopsies from the duodenum. Five groups of patients were studied: untreated ulcer-associated duodenitis, untreated non-specific duodenitis, healed ulcer-associated and non-specific duodenitis after cimetidine treatment, and controls. Significant reduction in villus height, increase in crypt length, and increase in mitotic figure count per crypt were all found in both ulcer-associated and severe non-specific duodenitis as compared with controls. These changes were localised to visually inflamed areas and regressed after healing of these lesions with cimetidine. This is the first quantitative comparison of the architectural features between diseased states in the duodenum and control in the same study. Identical morphological changes in the form of crypt hyperplasia and villus atrophy were demonstrated in areas of non-specific and ulcer-associated duodenitis. No evidence could be found from this study that non-specific duodenitis constitutes a different disease from ulcer-associated duodenitis.

Cimetidine↗

Measurements of intestinal villi non-specific and ulcer-associated duodenitis-correlation between area of microdissected villus and villus epithelial cell count.

Measurements of villus height, villus area, together with counts of epithelial cells in individual villi, were performed on endoscopic duodenal biopsies from five groups of patients: controls, ulcer-associated duodenitis, mild and severe non-specific (non-ulcerative) duodenitis, cimetidine healed ulcer-associated duodenitis and cimetidine healed non-specific duodenitis. The objectives of the study were two-fold: to establish if epithelial cell count correlated with simpler measurements of villus height or area; and to compare the findings in ulcer-associated and in non-specific duodenitis. Villus area correlated well with epithelial cell count per villus (r = 0.96); villus height correlated less well (r = 0.66). When compared with controls, there was a significant decrease in the epithelial cell count per villus in ulcer-associated and severe non-specific duodenitis, but this was confined to the visually inflamed area of the duodenal bulb. After healing of inflammation with cimetidine villus height, area, and epithelial cell count returned to values similar to those in controls. This study confirms that the effects of ulcer-associated and severe non-specific duodenitis on duodenal villi are identical.

Cell Count↗