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Biomedical subjects

A Ferguson

Publications and source records attributed to A Ferguson.

At least 199 records · Page 11Linked to original sources
PubMed1987

Roles of mucosal mast cells in intestinal cell-mediated immunity.

Mucosal mast cells in rats with GvHR have been studied by cell counts, tissue levels of the specific protease RMCPII, and, as an index of MMC activation, serum RMCPII. In semi-allogeneic GvHR without host irradiation, GvHR produced modest increases in these three indices. In contrast, irradiation profoundly depleted MMC even though enteropathy was more severe than in non-irradiated hosts. We suggest that enteropathy is not dependent on the presence of MMC. In rats given cyclosporin A, lesions of GvHR were mild and numbers of MMC were low.

Animals↗
PubMed1987

Oral tolerance in protein-deprived mice. I. Profound antibody tolerance but impaired DTH tolerance after antigen feeding.

We have examined the effects of protein deprivation on the induction of oral tolerance for systemic antibody and DTH responses to the protein antigen ovalbumin (OVA). Mice were fed 4% or 24% protein diets from weaning and given a single feed of OVA 2 weeks later (short-term deprivation) or after 10 weeks (long-term deprivation). Tolerance for serum antibody responses was more profound in protein-deprived animals than in 24% protein-fed control groups. Conversely, tolerance for DTH responses was impaired in protein-deprived mice. This was demonstrated both for short-term deprivation, where nutritional rehabilitation after OVA feeding was necessary to demonstrate this effect on DTH, and for long-term deprivation. Furthermore, the effect of short-term deprivation on tolerance for DTH responses was similar to that observed after cyclophosphamide pretreatment of OVA-fed mice. Protein deprivation has disparate effects on the humoral and cell-mediated limbs of oral tolerance, and our results support the hypothesis that this regime selectively depletes a population of suppressor T cells responsible for the fine control of DTH tolerance.

Administration, Oral↗
PubMed1987

Persistence of oral tolerance in mice fed ovalbumin is different for humoral and cell-mediated immune responses.

The duration of oral tolerance after a single feed of OVA at the age of 6 weeks was studied in BDF1 mice. Significant suppression of systemic antibody responses was present 3 months later, but not at 6.5 months; in contrast, at all times studied from 2 weeks to 17 months after an OVA feed there was suppression of systemic CMI to OVA as measured by an in vivo skin test. This indicates that the two limbs of the immune response differ in the factors responsible for the maintenance of oral tolerance.

Administration, Oral↗
PubMed1986

Prevalence and "incidence" of celiac disease in Edinburgh and the Lothian region of Scotland.

After review of hospital records and jejunal biopsy sections, 703 cases of celiac disease, including 74 cases with dermatitis herpetiformis, were identified in Edinburgh and the Lothian region up to December 31, 1979. Of these, 469 were resident in Lothian, resulting in an overall prevalence of 50/100,000 in men and 74/100,000 in women. The prevalence in men showed no significant variation with age, whereas in women age-specific prevalence varied markedly, with a peak of 126/100,000 at ages 35-44 yr and a low of 28/100,000 at ages 45-54 yr. This variation could not readily be explained, although reduced case ascertainment among women born between 1925 and 1934 could be the basis of a modest cohort effect. There was no evidence that migration or increased mortality at particular ages might be alternative explanations. In children the incidence of celiac disease, as measured by cumulative prevalence with age, increased more than twofold between 1960 and 1975, but since 1976 it has fallen sharply. The fall in incidence in children and the unexplained variations in prevalence in women provide epidemiologic evidence for the role of environmental factors other than gluten ingestion in the etiology of celiac disease.

Adolescent↗
PubMed1986

Women's health in a marginal area of Kenya.

As eco-demographic pressure on the cultivable areas of tropical Africa increases, women, the main food producers in such areas, are experiencing serious threats to their physical health. Eco-demographic pressure may be defined as the effect of a rapidly-growing population, dependent largely on subsistence production, on the human carrying capacity of an ecological region. Continued subdivision of plots from father to sons, over grazing, and soil erosion lower agricultural productivity and create periodic food shortages, the main burdens falling most heavily upon the poorest people. Migration to cities in search of wage employment, or to lower-potential areas in search of land are common responses. Eco-demographic pressure in the high potential areas of Kenya has been responsible over many years for the migration of agriculturalists into marginal lands. The partial break-up of traditional modes of production and the difficulties of cultivating in a semi-arid environment greatly increase the demands on available labour, whilst levels of health are poor and health care delivery inadequate. It is suggested that women, in particular, are subject to a high degree of stress and evidence of such stress and accompanying ill-health is presented using data from a survey conducted in Kibwezi Division of Machakos District, Kenya. Higher-than-average economic dependence on women is shown in the demographic structure. Water collection patterns show that 70% of all trips are made by women over 15 years over a median distance of 3.5 km and that 87% of women collecting water carry loads without any mechanical assistance compared with 42% of men. Fertility levels remain high and anthropometry revealed that women in the survey were thinner and shorter than a comparable group from a more fertile part of the district. Using functional criteria, the data suggest a higher prevalence of chronic disablement amongst women, compared with men, and the disabilities mentioned tend to reflect the hard lifestyle and high fertility levels of women in Kibwezi.

Adolescent↗
PubMed1986

Kinetic studies on the lactate dehydrogenase isozymes of the brown trout, Salmo trutta L.

Informative crosses have verified the genetic basis of a polymorphism at the Ldh-1 locus in brown trout and enzyme activity measurements indicate that the previously described polymorphism at this locus is best explained by a null allele. The LDH-1, LDH-2, LDH-3 and LDH-4 homotetrameric isozymes were purified and subjected to enzyme kinetic analysis. While LDH-1 and LDH-2 displayed catalytic equivalence, important kinetic differences were found between the LDH-3 and LDH-4 isozymes.

Animals↗
PubMed1986

Selective effects of graft-versus-host reaction on disaccharidase expression by mouse jejunal enterocytes.

Graft-versus-host reaction (GvHR) was induced in neonatal mice to produce crypt hyperplasia with and without stunted villi. Lactase activity was measured along individual villi of control and GvHR mice using quantitative cytochemistry. Lactase activity increased in control mice as enterocytes migrated over the lower part of the villus. This increase was followed by a period when lactase activity remained approximately constant. Effects produced by GvHR on this normal profile of development included an extension of the distance on the villus over which enterocytes could continue to increase lactase activity, a reduction in the time needed for an enterocyte to express lactase activity at maximal rate, and an overall decrease in the maximal lactase activity expressed by mature enterocytes. These effects have been quantified by fitting logistic curves to the experimental data. Parallel biochemical analyses of intestinal homogenates showed sucrase, isomaltase, trehalase and maltase activities to increase markedly 7-8 days after the injection of parental spleen cells. Attention is drawn to similarities between these results and steroid induced precocious development of intestinal function in neonatal mice.

Animals↗
PubMed1986

Food antibodies, intestinal permeability and HLA status in IgA deficient blood donors identified by a new rapid screening test.

Circulating food antibodies, intestinal permeability and HLA status were studied in twelve blood donors previously identified as being selectively IgA deficient from screening 10,000 donations by means of a latex agglutination inhibition test, and confirmed by laser nephelometry. Assessment of intestinal function also included clinical history and standard laboratory tests. The donors proved to be healthy with no evidence of autoimmune disease or allergy. Nine donors (75%) had precipitins to food antigens. None had increased intestinal permeability as measured by the cellobiose/mannitol absorption test. HLA-A, B and DR antigen distribution was normal. IgG sub-class distribution was normal with the exception of an IgG2 level slightly below normal in one donor (0.9 g/l). An unexpected finding was a return of IgA levels to normal in four donors (33%) within 6 months.

ABO Blood-Group System↗
PubMed1986

Intraepithelial lymphocyte mitosis in a jejunal biopsy correlates with intraepithelial lymphocyte count, irrespective of diagnosis.

When there is villus atrophy in a jejunal biopsy, intraepithelial lymphocyte (IEL) mitosis correlates with a diagnosis of coeliac disease. We have examined the significance of IEL mitosis in jejunal biopsies with normal villi. Counts of IEL per 100 villus enterocytes, and IEL mitosis per 1000 IEL, were carried out in 81 jejunal biopsies. Thirty one were from patients with coeliac disease or dermatitis herpetiformis, and many of these, from treated patients, were histologically normal; 40 were from patients with other diagnoses, selected to include biopsies with a high IEL count (greater than 40 IEL per 100 enterocytes) but normal villi. Three coeliacs and 10 dermatitis herpetiformis patients had an IEL count of less than 40, and no IEL mitoses were found in these biopsies. Two dermatitis herpetiformis patients had IEL counts of 43.7% and 43.9%, with no IEL mitoses, but in all other coeliac and dermatitis herpetiformis biopsies high IEL counts were associated with IEL mitotic indices between 0.05% and 1.77%. In the non-coeliac, non-dermatitis herpetiformis group, no IEL mitoses were found in the 22 biopsies with IEL count less than 43%. In the others, IEL counts ranged from 44.8% to 127.0%, and IEL mitoses were present, with mitotic indices ranging from 0.06% to 0.49%. This work shows that IEL mitosis in a jejunal biopsy is not specific for coeliac disease, but occurs whenever there is an increased density of IEL within the villus epithelium.

Biopsy↗
PubMed1986

Modulation of intestinal and systemic immune responses to a fed protein antigen, in mice.

Feeding of a protein antigen to normal adult mice results in systemic immunologic hyporesponsiveness (oral tolerance). Local mucosal cell mediated immunity is not usually elicited. The objectives of these experiments were to abrogate the induction of oral tolerance and concomitantly to induce a local mucosal cell mediated immune response in mice; and thereby to establish which facets of intestinal physiology or immunology are relevant to the induction of normal, mainly suppressor immune responses to a fed antigen. Protein antigen (ovalbumin) was fed to animals in whom immune status had been modulated by intraperitoneal injection of N-acetyl-muramyl dipeptide (MDP), by induction of a graft versus host reaction, or naturally, by virtue of immaturity. The induction of oral tolerance was prevented in all treatment groups. In a second series of experiments mice were orally immunised as before, rested for four weeks, and then challenged with ovalbumin in their drinking water for 10 days. Jejunal architecture was not altered by the antigen challenge, but MDP treated and immature animals which had been sensitised to ovalbumin and later re-exposed to the same antigen had significantly higher intraepithelial lymphocyte counts than appropriate controls. Factors which may lead to abrogation of oral tolerance and induction of intestinal hypersensitivity are discussed in relation to food allergic diseases in man.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1986

Oral tolerance to ovalbumin in mice: studies of chemically modified and 'biologically filtered' antigen.

Suppression of systemic immunity after the feeding of antigen was investigated in mice by means of serum transfer experiments. Serum collected from mice 1 hr after a single intragastric dose of 25 mg OVA induced suppression of systemic DTH when injected intraperitoneally into recipient mice. This suppression was found to be restricted to the cell-mediated limb of immunity and was antigen-specific. A postulated function of the intestine, conversion of antigen into tolerogenic form by means of intestinal antigen processing, was studied by attempting to mimic intestinal alteration of OVA by chemical modification of the antigen. Parenteral injection of mice with either deaggregated or denatured OVA did not produce the typical pattern of unresponsiveness seen in animals given intestinally processed OVA. Intestinal processing was also shown to be distinct from systemic antigen processing. Mice injected with serum containing systemically 'filtered' OVA did not become tolerant to OVA in the manner of recipients of serum from OVA-fed mice.

Administration, Oral↗
PubMed1986

Small bowel permeability in patients with nasal polyposis.

Small bowel absorption defects have been noted in a proportion of patients with atopic eczema. Eighteen patients with recurrent nasal polyps had the cellobiose/mannitol ratio test performed in order to assess their small bowel function. Evidence for atopy was found in 11 of 18 patients. Histologically the polyps were described as allergic but the cellobiose/mannitol ratio was normal in all cases. No evidence for a small bowel absorption defect was obtained.

Adult↗
PubMed1986

IgE antibodies to foods are not a feature of cystic fibrosis.

It has been suggested that patients with cystic fibrosis have abnormal immune responses to foods. We have measured IgE antibodies to inhalants and foods (by RAST) in 105 patients with cystic fibrosis aged between 8 months and 28 years. Serum IgE was elevated (greater than 180 kU/l) in 21 patients. In 43, IgE antibodies were detected in serum. The majority of positive results were with house-dust mite, grass pollen or Aspergillus. Only four of the patients had a positive RAST to a food--one to milk, one to wheat and two to egg. On the basis of high serum IgE or positive RAST results, 44.8 per cent of the patients were atopic and the frequency of atopy was age-related, being higher in patients aged 4 years or more. However, the presence of food antibodies was unrelated to age. This study confirms the high prevalence of atopy in patients with cystic fibrosis but unequivocally demonstrates that the presence of IgE antibodies to foods in their serum is rare.

Adolescent↗
PubMed1986

The influence of intestinal processing on the immunogenicity and molecular size of absorbed, circulating ovalbumin in mice.

The presence of a tolerogen in mouse serum within 1 hr of antigen feeding prompted further study. Therefore, serum from mice fed with ovalbumin (OVA) was subjected to various immunochemical and biological tests. The appearance of tolerogen in serum was concomitant with the presence of OVA detected by a specific ELISA. Absorption of tolerogenic serum with anti-OVA antibody coupled to Sepharose beads effectively removed the tolerogenic moiety from the serum and confirmed that not only was tolerogenicity associated with the presence of antigen, but that binding sites for antibody were intact on this tolerogenic form of OVA. Finally, serum fractions from antigen-fed mice were assayed for total protein content, ELISA-detectable OVA and in vivo effect on systemic immunity. The only serum fraction in which immunoreactive OVA was detected contained proteins close to the molecular weight of native OVA and induced significant immune suppression in recipients. Serum fractions lacking immunoreactive OVA were not significantly tolerogenic in vivo. These experiments confirm that when OVA is absorbed across the gut mucosa it is subtly altered into a tolerogenic form. The recognition of gut-processed OVA by T-suppressor cells is discussed.

Animals↗
PubMed1985

Lactate dehydrogenase isozymes and allozymes of the nine-spined stickleback Pungitius pungitius (L.) (Osteichthyes: Gasterosteidae).

Zymograms indicate the existence of three loci coding for lactate dehydrogenase in the nine-spined stickleback Pungitius pungitius. The skeletal muscle locus is polymorphic for two codominant alleles: Ldh-A(100). and Ldh-A(140). Differences in allele frequencies among nine samples, obtained from eight geographically isolated populations, proved not significant in 28/36 pairwise comparisons. The frequency of Ldh-A(100) varied from 0.426 to 0.715. Significant differences in apparent Km (pyruvate) values were found among the LDH-A allozymes suggesting a functional basis for the selective maintenance of this polymorphism.

Alleles↗
PubMed1985

Expression of MHC products and leucocyte differentiation antigens in gynaecological neoplasms: an immunohistological analysis of the tumour cells and infiltrating leucocytes.

Monoclonal antibodies directed against monomorphic determinants of Class I and Class II products of the major histocompatibility complex (MHC) and against leucocyte differentiation antigens were used in an indirect immunoperoxidase technique to compare their expression in normal and malignant disease of the ovary, cervix and endometrium. MHC Class I products, strongly expressed on normal ovarian epithelium, were uniformly absent from 7/8 ovarian carcinomas of varying histology. Lack of Class I expression was also a feature of 6/10 cervical carcinomas and of 4/8 endometrial carcinomas, in comparison with their respective normal tissues. Relative to normal tissue epithelium MHC Class II products, could be either lost or gained, the pattern of expression being either uniform or heterogeneous. Leucocytes were sparse in normal ovary but more numerous in cervix and endometrium. In tumours, with few exceptions, they were abundant, though usually confined to the stroma. T cells, largely of cytotoxic/suppressor (OKT8) phenotype, tended to predominate though in some tumours, particularly cervical carcinoma, large numbers of macrophages and to a lesser extent, B cells were sometimes detected. By contrast, leucocytes of natural killer (NK) phenotype were virtually non-existent in any tumour or normal tissue. The ingress of leucocytes into gynaecological neoplasms does not appear to be a random event and may be evoked by an immune response against tumour-associated antigens. However, the relationship between in situ mononuclear cell infiltration and MHC expression on epithelial tumour cells is complex and remains to be elucidated.

Adenocarcinoma↗