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Biomedical subjects

A Ferguson

Publications and source records attributed to A Ferguson.

At least 181 records · Page 10Linked to original sources
PubMed1988

Effect of cyclosporin A on rat mucosal mast cells and the associated protease RMCPII.

The effects of Cyclosporin A (CyA) on rat mucosal mast cells (MMC) have been investigated by cell counts in the jejunal mucosa and assays of the MMC-specific granule protease RMCPII in tissues and serum. CyA was administered by subcutaneous injection; for the majority of experiments the rats received 50 mg/kg daily for 3 days as a loading dose, then 50 mg/kg on alternate days. Treatment with this drug has two actions on MMC, a gradual reduction in the number of MMC and in the tissue content of RMCPII in the jejunum; and a rapid fall in the serum concentration of RMCPII, detectable 3 h after i.v. administration of CyA, 50 mg/kg. These phenomena were demonstrated in normal rats and in animals with an expanded jejunal MMC population due to graft vs host reaction or recent helminth infection. The functional relevance of the MMC depletion was demonstrated in immune rats given CyA for 3 days prior to induction of systemic anaphylaxis; intestinal permeability to i.v. Evan's blue was significantly reduced by CyA treatment. We suggest that CyA depletes intestinal MMC by suppression of T-cell-mediated regulatory stimuli to proliferation of mast cell precursors and/or their migration. The effects of the drug on serum RMCPII, evident before there were changes in the number of intestinal MMC, indicate that it also suppresses the secretion of granule mediators by MMC, probably indirectly via effects on mucosal T cells.

Anaphylaxis↗
PubMed1988

T lymphocyte function in protein deprived mice.

The thymus-dependent (T-dependent) limb of the immune response in protein malnourished mice was examined by using several tests of T cell function, both in vivo within the intact animal, and after removal of lymphocytes from the protein deprived host. The capacity to provide help for IgG antibody responses and the DTH response to antigen were diminished after short-term (3 weeks) deprivation. However, both these responses were normal in mice maintained on a protein deficient diet for 11 weeks. The depressed DTH responses of protein deprived mice were due, at least in part, to a failure to mount the inflammatory phase of the response. Finally, using a graft-versus-host reaction (GvHR) as an index of T lymphocyte function, we found that spleen cells from malnourished donors were fully capable of inducing the splenic and intestinal changes associated with a GvHR in unirradiated F1 animals. Overall, these results suggest that T cell function is not irreversibly damaged by protein deprivation. However we propose that cell-mediated immune responses are influenced indirectly by the restrictive environment which interferes with cell migration, and by the impaired capacity of protein-deprived animals to mount a non-specific inflammatory reaction.

Animals↗
PubMed1988

Suppression of an established DTH response to ovalbumin in mice by feeding antigen after immunization.

Experiments were designed to examine whether systemic delayed-type hypersensitivity responses (DTH) to ovalbumin (OVA) can be suppressed when antigen is fed after immunization, and to investigate the immunological mechanisms involved. A single 25 mg feed of OVA given 7 or 14 days after immunization with OVA in complete Freund's adjuvant (CFA) suppressed the DTH response of BDF1 mice, but had no significant effect on the serum IgG antibody response. DTH suppression was greatest when antigen was fed soon after immunization, and became less pronounced as the time interval between feeding and immunization increased. The phenomenon was also demonstrated in mice of the BALB/c strain. Cell transfer experiments suggested that the post-immunization suppression was not due to a population of suppressor cells that have been described previously in association with classical oral tolerance for DTH. We conclude that there are separate and distinct mechanisms for the prevention of induction of DTH by antigen feeding in naive mice and the suppression of expression of DTH in sensitized animals.

Administration, Oral↗
PubMed1988

Gliadin presented via the gut induces oral tolerance in mice.

When an antigen is first presented via the gut, either priming or suppression of the systemic immune response may result. Many factors influence the outcome, including physico-chemical properties of the antigen. The aim of this study is to establish if wheat gliadin behaves as an oral immunogen or tolerogen. Mice reared on a gluten-free diet were fed gliadin, either as wheat flour in a standard rodent diet or as the purified molecule. Immune status (tolerant or sensitized) was then defined by measuring specific systemic immune responses after parenteral immunization of gliadin-fed and control mice. A single feed of 25 or 125 mg of purified gliadin resulted in a dose-dependent suppression of both cell-mediated and humoral immune responses. Similar oral tolerance was achieved by feeding mice with a gluten-containing diet for a week. Finally, mice reared on a normal, gluten-containing diet showed evidence of established oral tolerance, with significantly lower systemic immune response to gliadin than mice reared on gluten-free diet. These results indicate that gliadin is an effective oral tolerogen. In vivo studies on the immunogenicity of gliadins should be conducted in animals from gluten-free colonies.

Administration, Oral↗
PubMed1988

In mice, gluten in maternal diet primes systemic immune responses to gliadin in offspring.

We have demonstrated recently immunological tolerance to gliadin in mice maintained on a diet that contains gluten. The aim of this study was to investigate whether oral tolerance is recreated in each generation by the ingestion of dietary gluten at weaning, or whether it is transferred from mother to young (as immune status or via passage of antigen) before birth or during lactation. Surprisingly, instead of transfer of tolerance we found priming of the immune response to gliadin in young mice. Mice born to mothers from normal, gluten-containing diet colonies had significantly greater systemic immune responses to gliadin after parenteral immunization than mice born to mothers from a gluten-free diet colony. Furthermore, feeding mothers gluten-containing diet for defined periods before and during pregnancy and during lactation also resulted in priming of the specific systemic immune responses of the offspring. These findings indicate that, in mice, sensitization to maternal dietary antigens readily occurs in utero or shortly after birth. This animal model should allow investigation of the immunological mechanisms concerned.

Animals↗
PubMed1987

Phosphoglucose isomerase isozymes and allozymes of the brown trout, Salmo trutta L.

1. In brown trout the Pgi-1 and Pgi-2 loci are predominantly expressed in white skeletal muscle; Pgi-3 being mainly expressed in most other tissues. 2. Total PGI activity determinations revealed that the allele formerly designated Pgi-2(65) is a null allele, Pgi-2(n). 3. Enzyme kinetic studies on the partially purified PGI homodimeric isozymes revealed that from 5 to 25 degrees C both PGI-1 and PGI-2 had significantly higher mean Km(F6P) values compared to PGI-3. 4. Distinct metabolic roles for the "muscle" (PGI-1, PGI-2) and "liver" (PGI-3) isozymes are proposed. 5. Significant Km (F6P) differences were found among the PGI-2 allozymes and among the PGI-3 allozymes.

Animals↗
PubMed1987

A comparison of two incubation temperatures for the isolation of gram-negative contaminants from raw materials and non-sterile pharmaceuticals.

Selective and non-selective broth enrichment techniques may be used in the isolation of microbial contaminants from pharmaceutical products. A non-selective method may give better recovery rates for damaged organisms. A trial was carried out to determine whether the recovery of Gram-negative contaminants could be improved by using an incubation temperature of 30 degrees C for 48 h, rather than the more widely used 37 degrees C for 24 h. Contaminants were isolated from 3.2% of samples incubated at the lower temperature compared with 0.8% at the higher temperature. The recovery rate from raw materials improved noticeably (9.0% compared with 0.9%).

Alcaligenes↗
PubMed1987

Effects of additional dietary gluten on the small-intestinal mucosa of volunteers and of patients with dermatitis herpetiformis.

In an attempt to confirm the existence of latent coeliac disease--dose-related gluten-sensitive enteropathy--we have increased dietary gluten by 20 g daily for 2 weeks, in 6 healthy adults and 11 patients with dermatitis herpetiformis (DH). Six of the DH patients had entirely normal jejunal morphology on a normal diet. Jejunal biopsy specimens were taken before and at the end of the study. Measurements of crypts, villi, and crypt mitoses were made on microdissected specimens; disaccharidases were assayed, and intraepithelial lymphocyte counts performed. In one of the six adult volunteers, gluten loading produced diarrhoea and jejunal biopsy abnormalities. Five DH patients on a gluten-free diet had deterioration of biopsy pathology after the gluten challenge. Features suggestive of a latent gluten-sensitive enteropathy were found in one of the other six DH patients; he developed disaccharidase deficiencies and villus atrophy when 20 g gluten was added to his usual gluten-containing diet. This study supports previous suggestions that a gluten-sensitive enteropathy may be latent and dose-related.

Adult↗
PubMed1987

Are the focal microscopic jejunal lesions in Crohn's disease produced by a T-cell-mediated immune response?

In animal models of intestinal hypersensitivity, lymphocyte-mediated damage to the small-bowel mucosa produces a characteristic pattern of morphologic abnormalities. Similar findings in human jejunal biopsy specimens may also indicate that T cells are involved in a disease process. To test the hypothesis that there is a generalized activation of mucosal T cells throughout the small-intestinal mucosa in Crohn's disease, measurements of the lengths of crypts and villi and intraepithelial lymphocyte (IEL) counts were made on jejunal specimens from 33 patients with this condition, and the results compared with the established reference values and with results of specimen measurements in a group of normal subjects. Taken as a group, the specimens from Crohn's patients had abnormal villus length, crypt length, and IEL counts. Focal histologic abnormalities such as ulcers, fissures, or granulomas were present in 10 of the specimens. When specimens with and without a focal abnormality were compared, the former showed shorter villi (median, 249.6 versus 331 microns, p less than 0.01), longer crypts (median, 330.4 versus 108.2 microns, p less than 0.01) and higher IEL counts (60.5 versus 32 IEL/100 enterocytes, p less than 0.01). These findings suggest that there is a mucosal cell-mediated immune response in the jejunum in Crohn's disease and that this is pronounced in the vicinity of microscopic, focal lesions.

Crohn Disease↗
PubMed1987

Oral tolerance in protein-deprived mice. II. Evidence of normal 'gut processing' of ovalbumin, but suppressor cell deficiency, in deprived mice.

The induction of oral tolerance for DTH responses to ovalbumin is impaired in protein-deprived mice. This may be via the effects of protein malnutrition on short-lived Ts cells, but an alternative explanation is that the gut handling of antigen is abnormal. We have attempted to transfer tolerance from protein-deprived and control mice to naive recipients by using spleen cells, collected 7 days after an OVA feed at a time when Ts cells should be present, or by using serum, collected 1 hr after feeding, which should contain tolerogenic, 'gut-processed' antigen. Suppression of DTH was transferred with 7-day spleen cells and with 1-hr serum from normal, protein-sufficient mice. Mice that received spleen cells from protein-deprived donors were not tolerant, but suppression was readily transferred with serum from deprived mice, indicating that their capacity for intestinal antigen processing was normal. Furthermore, the quantity of absorbed antigen in the serum 1 hr after feeding was similar in both protein-deprived and normal groups. The results obtained are consistent with the hypothesis that short-term protein deprivation depletes a population of short-lived Ts cells which control DTH oral tolerance.

Administration, Oral↗
PubMed1987

Irradiated mice lose the capacity to 'process' fed antigen for systemic tolerance of delayed-type hypersensitivity.

'Intestinal antigen processing' is a function of the gastro-intestinal tract whereby shortly after an animal has been fed an immunogenic protein antigen, such as ovalbumin (OVA), a tolerogenic form of the protein is generated and can be detected in the circulation. The effect of damage to the intestinal epithelium on the processing of OVA has been examined in lethally irradiated mice. Irradiated animals were fed 25 mg OVA and their serum collected 1 h later. When this serum was transferred intraperitoneally into naive recipient mice, this did not induce the typical suppression of systemic delayed-type hypersensitivity. Results were similar when the serum donors were at 2 days after irradiation, with crypt hypoplasia, and at 5 days after irradiation when there was reactive crypt hyperplasia. However reconstitution of donors with normal spleen cells immediately after irradiation restored their capacity to generate a tolerogenic form of the antigen. Immunoreactive OVA was detected by ELISA in both tolerizing and non-tolerizing sera, and the immunological properties of these sera were not related to serum levels of OVA after feeding. Thus subtle immunochemical alterations in the nature of a protein antigen are likely to be more important than the quantity of absorbed antigen, in influencing systemic cell-mediated immune responses after feeding. The lack of generation of a tolerogenic form of the protein in irradiated mice, unrelated to the pattern of epithelial cell kinetics, and the restoration of this function by normal spleen cells, suggests that lymphoid cells may be involved in the phenomenon of antigen processing.

Animals↗