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Biomedical subjects

A Ferguson

Publications and source records attributed to A Ferguson.

At least 163 records · Page 9Linked to original sources
PubMed1990

Mucosal immunodeficiency in smokers, and in patients with epithelial head and neck tumours.

Cigarette smoking influences the risk of orogastrointestinal disease in both protective (ulcerative colitis), and inductive (squamous tumours of the head, neck and oesophagus) roles. In order to study the effects of smoking on mucosal immunity, salivary immunoglobulins were measured in pure parotid saliva from groups of healthy non-smokers, smokers, and exsmokers and from patients with epithelial head and neck tumours, both untreated and after radiotherapy. Of the healthy individuals, smokers had significantly lower salivary IgA and higher IgM concentrations than did non-smokers. The effect on IgA was dose related, and reversible after cessation of smoking. Likewise, in patients with head and neck tumours (the majority being smokers), salivary IgA concentration was reduced and IgM increased when compared with non-smoking controls. Results were similar before and after radiotherapy. This study provides evidence of the effects of smoking on mucosal immunity as evaluated by parotid salivary immunoglobulins. Further studies of the influence of smoking on secretory immunity are indicated.

Adult↗
PubMed1990

Coeliac disease and collagenous colitis.

We describe a case of collagenous colitis in a young man with coeliac disease who had responded clinically and histologically to a gluten-free diet three years previously. The collagenous colitis responded initially to oral corticosteroid therapy and he is now asymptomatic (and with normal rectal mucosa) on oral mesalazine. Collagenous colitis should be considered in the coeliac patient with diarrhoea despite adherence to a gluten-free diet.

Adult↗
PubMed1990

The immune system and mucosal transformation--historical perspective.

An intimate association between columnar epithelial cells and lymphocytes within the epithelial layer of the gut and other organs has been recognised for more than a century. Various roles have been postulated for intraepithelial lymphocytes (IEL), nutritive as well as immunopathological. Recently, the relevance of activation of mucosal lymphocytes to some of the development changes in the gut at weaning have been hypothesised, and the relevance of the IEL to the induction of specialised epithelium overlying Peyer's patches remains to be established. Interactions between lymphocytes and the structure of the gut mucosa can readily be studied by using defined animal models in which the state of development of the gut, luminal antigens and bulking agents, host factors such as nutritional status can be defined, and against such background various forms of immune-mediated intestinal injury can be created. The earliest work along these lines was purely descriptive, particularly of the weaning changes, and also concerned the lymphocyte mediated gut damage of allograft rejection and later other models of T cell injury. These experiments clearly showed stimulation of crypt mitosis in immune mediated enteropathy, with crypt hyperplasia, which could not be explained by a feedback stimulation from damaged villi or villus enterocytes. Further work is now showing that mediators released by lamina propria activated T cells influence mitotic activity and differentiation of crypt enterocytes, as well as modifying the rate and patterns of expression of brush border enzymes and expression of cell surface class II HLA antigens.(ABSTRACT TRUNCATED AT 250 WORDS)

Allergy and Immunology↗
PubMed1990

Clinical features, morbidity and mortality of Scottish children with inflammatory bowel disease.

From the Scottish Hospitals in-patients statistics for the years 1968-1983 all children and teenagers (a total of 1257) admitted to a National Health Service hospital with Crohn's disease or ulcerative colitis were identified. Case records of samples of patients with onset of symptoms at or before age 16 years were examined to establish the features, morbidity and mortality of unselected cohorts of young patients with inflammatory bowel disease. Median delay in diagnosis was less than six months. Anatomical distribution for Crohn's disease was similar to that in adults (small bowel 30 per cent; large bowel 28 per cent; small and large bowel 38 per cent) and almost half the patients with ulcerative colitis had extensive colitis. The morbidity was substantial in both. In-patient days for Crohn's disease ranged from seven to 322, median 64 days and for ulcerative colitis one to 275, median 30 days. At diagnosis, 11 of 40 young children with Crohn's disease but none of 14 with ulcerative colitis, were below the third centile for height. Despite treatment with corticosteroids 72 per cent of patients with Crohn's disease and 30 per cent of patients with ulcerative colitis required surgical treatment. Seventeen per cent have a permanent stoma. There were only six deaths, all before 1978.

Adolescent↗
PubMed1989

Mortality in celiac disease.

The mortality experienced by a cohort of 653 patients with celiac disease in Edinburgh and the Lothian region has been analyzed. Mortality overall was 1.9-fold (95% confidence limits, 1.5-2.2) that of the general population (115 deaths observed, 61.8 expected; p less than 0.0001). The increased mortality was greatest within 1 yr of diagnosis of celiac disease and steadily declined over time with the excess mortality being concentrated at ages 45-54 yr in men and 55-64 yr in women. Celiac disease was mentioned on the death certificate in 33 cases but in only 10 was it given as the underlying cause of death. Of 17 deaths from lymphoproliferative diseases (0.55 expected, p less than 0.001), 8 occurred within 2 yr of diagnosis of celiac disease compared with 8 (0.37 expected, p less than 0.001) occurring greater than 5 yr after diagnosis. Esophageal cancer was certified as the cause of four deaths (0.47 expected, p less than 0.01). In men mortality from all other malignant disease was also increased (15 deaths observed; 6.4 expected, p less than 0.01), but most of these deaths occurred within 5 yr of the diagnosis of celiac disease. In contrast, there was no deficit in deaths from ischemic heart disease or stroke and the mortality rate in those diagnosed in childhood as having celiac disease was similar to the general population.

Age Factors↗
PubMed1989

Inflammatory bowel disease and male infertility: effects of sulfasalazine and 5-aminosalicylic acid on sperm-fertilizing capacity and reactive oxygen species generation.

To investigate the mechanism of the antifertility action of sulfasalazine, we prospectively measured sperm density, motility, hamster oocyte penetration capacity, and reactive oxygen species production in six men with inflammatory bowel disease being treated with sulfasalazine and 8 and 16 weeks after changing to 5-aminosalicylic acid (5-ASA). An improvement was observed after changing to 5-ASA in those with poor (n = 3), but not in those with normal (n = 3), sperm function on sulfasalazine. There was no correlation between reactive oxygen species production or acetylator phenotype with egg penetration capacity, sperm motility, or sperm density. We conclude that the mechanism of impairment and recovery of sperm function on and off sulfasalazine treatment is not related to an excess in reactive oxygen species.

Adult↗
PubMed1989

Effect of cyclosporin A treatment on the enteropathy of graft-versus-host reaction in the rat: a quantitative study of intestinal morphology, epithelial cell kinetics and mucosal immune activity.

Mucosal graft-versus-host reaction (GvHR) of the small intestine exemplifies an immunologically mediated enteropathy that is associated with expansion of mucosal mast cells (MMC). Quantitative measures of intestinal morphology, epithelial cell kinetics and mucosal immune activity were used to assess the effect of the immunosuppressive agent, cyclosporin A (CyA), in ameliorating this enteropathy and on increased activity of MMC in the jejunum. GvHR was induced in two groups of PVGU x PVGC rats by irradiation (4.50 Gy) and intravenous injection of PVGC spleen cells (150 x 10(6)). One group remained untreated, while a second group of eight rats was treated with a 50 mg/kg dose of CyA subcutaneously given daily for the first 3 days and then every second day, and which had commenced the day before induction of GvHR. On day 14, all animals were killed. Treatment with CyA prevented intestinal crypt hyperplasia but did not affect villus length, and normalized the crypt cell production rate (CCPR) from 38 to 15 cells/crypt/h (P less than 0.0001). CyA reduced the number of MMC and jejunal content of the MMC associated protease, rat mucosal mast cell protease II (RMCPII). Mean serum RMCPII concentration was reduced from 302 (s.d. = 112) in GvHR animals to 10 (s.d. = 6) ng/mL in GvHR/CyA-treated rats (P less than 0.0001). We conclude that CyA ameliorates the enteropathy of GvHR and depresses the activation of MMC, as evident by the strongly depressed serum RMCPII concentration.

Animals↗
PubMed1989

Separate effects of irradiation and of graft-versus-host reaction on rat mucosal mast cells.

T cell mediated immune responses in the gut can produce enteropathy and malabsorption. We have investigated the relevance of mucosal mast cells (MMC) to the mechanisms of this enteropathy by using graft-versus-host reaction (GvHR) in the rat as a model of mucosal delayed type hypersensitivity. Measurements of mucosal architecture, intraepithelial lymphocytes (IEL) and MMC counts were performed in control and experimental rats, and release of rat mast cell protease II (RMCPII) into the bloodstream was used as an index of MMC activation. In unirradiated rats, jejunal MMC count was increased on day 14 of the GvHR (mean 272/mm2 v 182 in controls, p less than 0.01), as was serum RMCPII (p less than 0.01). Irradiated rats (4.5 Gy, reconstituted with isogeneic spleen cells) had low counts of IEL and crypt hyperplasia seven to 14 days after irradiation. Irradiated rats with GvHR (induced by ip injection of parental strain spleen cells) and studied on days 7, 10 and 14, had significant enteropathy with longer crypts and higher CCPR than matched irradiated animals (p less than 0.05 on day 14 when compared with irradiation alone). Intraepithelial lymphocytes counts, however, reflected only the effect of radiation. Irradiation, with or without GvHR, led to the virtual disappearance of jejunal MMC, undetectable jejunal RMCPII and very low levels of RMCPII in serum (all p less than 0.01 when compared with unirradiated controls). These experiments show that there is a modest expansion in jejunal MMC in unirradiated rats with semiallogeneic GvHR, whereas irradiation, alone or associated with GvHR, profoundly depletes MMC for at least two weeks. The enteropathy of GvHR can evolve in the virtual absence of MMC.

Animals↗
PubMed1989

Incidence of inflammatory bowel disease in Scottish children between 1968 and 1983; marginal fall in ulcerative colitis, three-fold rise in Crohn's disease.

Linked hospital admission data for 1968-1983 were used to identify 723 children aged 16 years or less at the time of first admission to any Scottish hospital with an ICD coded diagnosis of Crohn's disease (282) or ulcerative colitis (441). The accuracy of the coded diagnoses was checked by examination of the hospital notes of 144 patients. The coded diagnosis was incorrect in 11/83 coded as Crohn's disease and 13/61 as ulcerative colitis; frequency of incorrect coding did not change significantly with time. Despite an 18% fall in the population aged less than or equal to 16 during this time, the number of new cases of Crohn's disease rose from 10 in 1968 to 28 in 1983. Thus the recorded incidence of Crohn's disease in Scottish children has risen more than three-fold in 16 years, from 6.6 to 22.9 per million (p less than 0.0001), with no difference between the sexes. Parallel data for ulcerative colitis were rendered inaccurate by miscoding of infective gastroenteritis as colitis. In an attempt to reduce this source of error cases aged five years and under were excluded from analysis, resulting in an incidence of 19.1 cases per million aged six to 16 in 1968 and 15.6 in 1983, not a significant change (r = 0.42, p = 0.052). When males and females were analysed separately, however, there was a significant decrease in the incidence of UC in male children (r = -0.4, p = 0.028), with no change for female children (r = 0.1, p = 0.595).

Adolescent↗
PubMed1989

The immunological consequences of feeding cholera toxin. II. Mechanisms responsible for the induction of oral tolerance for DTH.

The mechanisms behind the induction of oral tolerance after feeding cholera toxin (CT) were examined using cell and serum transfer protocols. The feeding of CT or cholera toxoid (TD) induced a splenic cell capable of inhibiting the induction of systemic delayed-type hypersensitivity (DTH) but not humoral immunity. Depletion studies showed that this cell was Thy-1.2 positive. Transfer experiments suggested that suppressor cell activity was present in the mesenteric lymph nodes (MLN) and spleens of donor mice 1 week but not 3 days after feeding CT. When spleen cells were transferred to syngeneic recipients at various times after immunization, they were more effective at inhibiting systemic DTH when transferred within a short time of immunization. If the cells were transferred 6 days after immunization they no longer suppressed the development of DTH, which suggested that they inhibit the afferent limb of this immune response. This has been confirmed by the failure of a tolerogenic dose of CT, administered by gavage, to suppress the activity of mature effector TDTH cells. Serum collected 1 hr after feeding CT also suppressed the induction of systemic DTH. However, the tolerogenic activity of CT-fed serum was abrogated by the pretreatment of recipients with cyclophosphamide (Cy) (100 mg/kg), suggesting that this activity is mediated through the induction of suppressor cells. Transfer of fed serum, however, did not induce the splenic suppressor cell described above and we would suggest that several mechanisms may operate in the mucosal regulation of systemic DTH.

Administration, Oral↗
PubMed1989

The immunological consequences of feeding cholera toxin. I. Feeding cholera toxin suppresses the induction of systemic delayed-type hypersensitivity but not humoral immunity.

Immunization of adult BALB/c mice with 1 microgram cholera toxin (CT) in complete Freund's adjuvant (CFA) induced both humoral (IgG and IgA) and cell-mediated (DTH) immunity. Although an immunopurified, formalinized, cholera toxoid (TD) in CFA was inferior to the native holotoxin at inducing antitoxin antibodies, both cholera-derived antigens were equally immunogenic for specific DTH. When mice were fed either 1 microgram CT or 5 microgram TD 1 week before immunization, the induction of DTH was inhibited but the development of specific antibody was the same as in sham-fed controls. A feed of 10 micrograms CT not only suppressed the induction of DTH but also enhanced the IgG antitoxin responses measured 1 week after immunization. A dose of TD (50 micrograms), with a similar cholera toxin B subunit content, also induced oral tolerance for DTH but had no effect on the subsequent development of humoral immunity. The smallest doses of CT or TD fed (0.1 microgram and 0.5 microgram, respectively) failed to affect the development of either limb of the systemic immune response. These results suggest that oral tolerance for DTH is not consequent upon the metabolic actions of CT but that stimulation of systemic antibodies after enteric administration may be. Pretreating mice with cyclophosphamide (Cy) (100 mg/kg) before feeding CT abrogated the induction of oral tolerance for DTH but had no effect on humoral immunity, suggesting that suppressor T cells may be responsible for the induction of oral tolerance in these animals.

Administration, Oral↗
PubMed1989

Systemic delayed-type hypersensitivity to cholera toxin and a detoxified derivative.

The delayed-type hypersensitivity (DTH) response to cholera toxin (CT) and an immunopurified formalinized toxoid (TD) was studied in adult BALB/c mice. Intradermal injection of CT in non-immune animals produced substantial footpad oedema which interfered with the measurement of specific DTH but TD proved satisfactory as a challenge antigen. DTH to CT was induced by doses ranging from 0.1 to 10 micrograms, in complete Freund's adjuvant (CFA). The optimal reaction was primed for by 1 microgram CT. Doses of TD with an equivalent B subunit content were equally capable of inducing DTH as the holotoxin. The time-course of the footpad swelling revealed that the DTH response was biphasic. Histological examination showed that the initial swelling was due to tissue oedema and the subsequent increase in footpad thickness was associated with a mononuclear cell infiltrate at the site of antigen challenge. Adoptive transfer experiments were used to demonstrate that the DTH was antigen-specific and could be passively transferred by immune effector T cells. This is the first study to demonstrate an effector T cell response to CT. A role for T cell reactions in the intestinal mucosa must now be examined as a potential contributory mechanism in the prevention of choleraic diarrhoea.

Animals↗
PubMed1988

Nutritional status in patients with dermatitis herpetiformis.

Nutritional status of 86 patients with dermatitis herpetiformis (DH) was defined by anthropometric measurements and hematological and biochemical laboratory tests to establish prevalence of malabsorption and malnutrition. Anthropometric measurements in DH patients were comparable to normal control patients. Four individuals were of short stature; two had had diarrhea and failed to thrive in childhood. Abnormalities attributable to nutritional deficiency were detected in only 6 of the 86, whereas drug-associated hematological or biochemical changes were present in 36 of 55 subjects treated with dapsone or sulfapyridine. Twenty patients had hemolytic anemia or macrocytosis related to drug therapy. Only two had anemias attributable to malabsorption; one was iron deficient, the other folate deficient. Two other patients were mildly Fe deficient and two had slight folate deficiency; they lacked other stigmata of malabsorption. Drug-induced hematological and biochemical abnormalities were more common than changes that suggest nutritional disease, even though most DH patients had an enteropathy at presentation.

Adolescent↗
PubMed1988

Prevalence of atopy is unrelated to presence of inflammatory bowel disease.

The prevalence of atopy (assessed by prick testing and serum IgE measurement), and of symptoms associated with atopy, has been defined in 122 patients with inflammatory bowel disease (IBD) and 103 age-matched controls. History analysis for atopic symptoms, and serum IgE levels, showed no differences between controls and IBD patients, or IBD subgroups (Crohn's disease, ulcerative colitis, ulcerative proctitis). Both in controls and in IBD patients, the prevalence of positive skin tests was higher in young people (aged less than 30) than in others; taking account of age distribution within the groups, there were no differences between controls and IBD patients, or subgroups, in the prevalence of positive skin tests. Our finding do not support the hypothesis that reaginic hypersensitivity plays a significant role in the pathogenesis of IBD.

Adolescent↗
PubMed1988

Giardia muris infection in mice with concurrent graft-versus-host reaction.

The effects of concurrent graft-versus-host reaction (GvHR) on the course of Giardia infection in CBA x BALB/c F1 mice have been examined, to test the hypothesis that T-cell-mediated immunity, in the form of a local DTH reaction, alters the host-parasite relationship in favour of the host by changing the physical environment of the parasite. GvHR did not enhance immunity, indeed mice infected with Giardia at a late stage of GvHR had significantly higher faecal cyst excretion and prolongation of the plateau phase of infection, indicating a degree of immunodeficiency.

Animals↗