PubMed Health⌕ Search

Biomedical subjects

T T MacDonald

Publications and source records attributed to T T MacDonald.

At least 19 recordsLinked to original sources
PubMed1995

Serum interleukin-2 receptor in infants and young children.

Soluble interleukin-2 receptor (IL-2R) concentrations were measured in 110 serum samples from 102 children undergoing routine small bowel biopsy for a wide range of gastrointestinal symptoms. Young children in the control group who had no gastrointestinal disease and a normal intestinal mucosa were found to have high concentrations of IL-2R. There was a significant inverse relationship between IL-2R concentration and age in the control group. Children with a gastrointestinal diagnosis appeared to have increased IL-2R concentrations, although some of the diagnostic groups were too small in size for statistical analysis. Children with cow's milk sensitive enteropathy had IL-2R concentrations equivalent to those of age-matched controls. High concentrations of IL-2R in young healthy children implies that serum IL-2R is of no clinical use as an index of inflammation in this age group.

Adolescent↗
PubMed1995

Interferon gamma and interleukin 4 secreting cells in the gastric antrum in Helicobacter pylori positive and negative gastritis.

Little is known of the function of the T cells in the inflammatory infiltrate in Helicobacter pylori associated gastritis. This study thus measured T cell in vivo activation by enumerating the frequency of interferon gamma (IFN gamma) and interleukin 4 (IL 4) secreting cells isolated from the gastric antral mucosa in patients with or without gastritis and in H pylori positive and negative gastritis. Fifty four samples were examined for cytokine secretion. Four antral biopsy specimens from each patient (n = 51) were taken during diagnostic endoscopy. One was used to estimate histological gastritis and the presence of H pylori, and three of the samples were used to isolate T cells by enzymatic digestion. IFN gamma and IL 4 secreting cells were enumerated by ELISPOT. Thirty four samples had gastritis and 79% of those were H pylori positive. None of the samples from non-inflamed mucosa had H pylori. The numbers of IFN gamma secreting cells per 10(5) T cells were higher in gastritis than in normal mucosa (145 v 20 IFN gamma spots, p < 0.01), and higher in H pylori negative than H pylori positive gastritis (371 v 110 IFN gamma spots, p < 0.05). The frequencies of IL 4 secreting cells did not differ between gastritis and non-inflamed mucosa. In conclusion, there is an increase in IFN gamma secreting cells but not in IL 4 secreting cells in H pylori positive and negative gastritis. It is not known if this TH1 type reaction has a pathogenetic or protective role.

Adult↗
PubMed1995

Regional variation in the proliferative rate and lifespan of alpha beta TCR+ and gamma delta TCR+ intraepithelial lymphocytes in the murine small intestine.

Using double staining for T-cell receptor (TCR) and 5-bromo-2'-deoxyuridine (BRdU) we have examined the proliferation rates and lifespan of murine intraepithelial lymphocytes (IEL's) in vivo. After a 24-hr pulse of BRdU the number of labelled alpha beta TCR+ IEL was significantly higher in the ileum than the duodenum. In contrast, incorporation of BRdU into gamma delta TCR+ IEL was significantly higher in the duodenum than the ileum. This regional variation was also seen after a 4-hr pulse of BRdU indicating that the differences probably reflect local rates of proliferation in the epithelium. Over a 6-day labelling period, the accumulation of labelled alpha beta TCR+ and gamma delta TCR+ IEL was linear, which allowed IEL lifespan to be calculated. There was considerable variation between groups of mice but the 50% population renewal time for alpha beta TCR+ IEL was 12-36 days in the duodenum and 9-11 days in the ileum, and for gamma delta TCR+ IEL was 12-21 days in the duodenum and 26-100 days in the ileum. The incorporation of BRdU into V beta 8+ IEL showed the same regional variation as alpha beta TCR+ IEL and the V delta 4 population behaved like the total gamma delta TCR+ IEL population. In contrast V beta 11+, potentially self-reactive IEL, showed a regional pattern of labelling like gamma delta TCR+ IEL. Incorporation of BRdU into both alpha beta TCR+ and gamma delta TCR+ IEL in germ-free mice was very low and did not show marked regional variation. alpha beta TCR+ and gamma delta TCR+ IEL from both proximal and distal bowel were cytotoxic. Therefore alpha beta TCR+ and gamma delta TCR+ IEL show different rates of division in different sections of the gut, perhaps reflecting responses to different antigens. Both alpha beta TCR+ and gamma delta TCR+ IEL reside in the epithelium for weeks during which time the gut epithelial population will have been renewed many times.

Animals↗
PubMed1994

High frequency of CD8 alpha alpha homodimer-bearing T cells in human fetal intestine.

Immunohistochemistry on frozen sections was used to identify CD8 alpha alpha cells and CD8 alpha beta cells in human intestine. As observed previously, CD8 alpha beta cells predominate (> 95%) in tonsil and post-natal intestine. However in human fetal intestine (16-24 weeks gestation), almost half the CD8+ cells in the lamina propria are CD8 alpha alpha, and many CD8 alpha alpha cells can be identified in the epithelium. In contrast, in the T cell zones of the Peyer's patches, CD8 alpha beta cells are dominant. The CD8 alpha alpha cells are virtually all alpha beta T cell receptor positive. By analogy with the murine system, these CD8 alpha alpha cells in the fetal gut may be directly derived from the marrow, undergoing thymus-independent differentiation in the gut mucosa.

CD3 Complex↗
PubMed1994

Tumor necrosis factor alpha-producing cells in the intestinal mucosa of children with inflammatory bowel disease.

BACKGROUND/AIMS: Cytokines are thought to be important in mediating tissue damage in inflammatory bowel disease (IBD). Many of the in vivo activities of tumor necrosis factor alpha (TNF-alpha) match the changes found in IBD, but its importance is controversial. METHODS: A sensitive, reverse hemolytic plaque assay was used to determine the frequency of TNF-alpha secreting cells isolated from mucosal biopsy specimens of children with Crohn's disease or ulcerative colitis (UC) and non-IBD controls before and after medical treatment. RESULTS: Frequency of TNF-alpha secreting cells was significantly increased in biopsy specimens from children with mild, nonspecific inflammation compared with those with histologically normal intestine. Frequency did not increase in UC compared with children with nonspecific inflammation but was significantly greater in Crohn's disease than in UC. After treatment, the frequency of TNF-alpha secreting cells was reduced in patients receiving cyclosporin A, not reduced in patients with steroids or enteral nutrition, and not changed with treatment in UC. CONCLUSIONS: TNF-alpha secreting cells are increased in the mucosa of inflamed intestine, regardless of pathogenesis. In patients with IBD, higher levels are seen in Crohn's disease than in UC, probably reflecting the extensive T-cell activation in Crohn's disease. No relation existed between histological healing and the frequency of TNF-alpha-secreting cells.

Adolescent↗
PubMed1994

Aetiology and pathogenesis of chronic inflammatory bowel disease.

While Crohn's disease and ulcerative colitis are both conditions characterized by intestinal inflammation, with some overlap in their clinical and histological features, they are essentially different in pathogenesis. Crohn's disease appears to be primarily a condition of chronic T-lymphocyte activation, with tissue damage induced by secondary macrophage activation. What activates the T-cells is unknown. In this chapter we look at the evidence for and against cell-wall deficient mycobacteria species, viral infection of vascular endothelium and luminal contents as potential mechanisms of chronic activation. In ulcerative colitis, by contrast, there is no strong evidence for T-cell activation, and humoral mechanisms predominate. While the finding of atypical anti-neutrophil cytoplasmic antibodies (P-ANCAs) may be useful in screening, the only novel pathogenetic discovery is the co-localization of a 40 kD colonic autoantibody with immunoglobulins and complement on the apical enterocyte surface. Despite the fundamental differences in initiating mechanisms, the two conditions have many 'downstream' inflammatory processes in common. We discuss the evidence for local production of cytokines, arachidonic acid metabolites and reactive oxygen and nitrogen radicals, highlighting the potential adverse consequences for intestinal vascular integrity.

Colitis, Ulcerative↗
PubMed1994

Inflammatory bowel disease in children.

Inflammatory bowel disease in children and adults remains the most challenging problem in gastroenterology. There is an increasing body of immunologic and genetic evidence to suggest that Crohn's disease and ulcerative colitis are different diseases, but that once inflammation begins, many common secondary pathways of inflammation are initiated. The major recent conceptual advance is the observation that mice in whom different immunoregulatory pathways are disrupted develop an inflammatory bowel disease. In the case of interleukin-2 knockout mice, the lesion restricted to the colon, is virtually identical to ulcerative colitis in humans, and is initiated by the normal bacterial flora. Yet these mice possess anticolon antibodies, long-considered to be of pathologic significance in ulcerative colitis. These animal models will allow detailed longitudinal studies to be done, and less reliance will need to be placed on cross-sectional studies of chronically inflamed gut from patients.

Age Factors↗
PubMed1994

Polymeric nutrition as the primary therapy in children with small bowel Crohn's disease.

BACKGROUND: Recent studies in adults have shown that polymeric (whole protein) diets are as effective as semi-elemental and elemental formulae for the induction of remission in small bowel Crohn's disease. Whole protein diets are more palatable and cheaper. There have been no studies confirming efficacy in children. PATIENTS AND METHODS: We report our experience with seven children with active small bowel Crohn's disease given a casein-based, polymeric feed rich in TGF-beta 2 (Specific Polymeric Diet; Nestle-Clintec; Vevey, Switzerland) as complete nutrition for 8 weeks. RESULTS: Initial and follow-up assessments were performed. All children showed a significant improvement in disease activity, with C-reactive protein returning to normal, an increase in serum albumin and a good weight gain. Initial and follow-up ileal biopsies were assessed and showed reduced mucosal inflammation in six of seven children, with complete healing in two. CONCLUSION: In an uncontrolled descriptive study we have shown that a polymeric (whole protein) diet is a therapeutic option for small bowel Crohn's disease in children. By comprehensive follow-up we have demonstrated clinical and biochemical remission, with an improved endoscopic appearance and a reduction of mucosal inflammation in the terminal ileum.

Adolescent↗
PubMed1994

Development of mucosal immune function in man: potential for GI disease states.

The human mucosal immune system is structurally mature and has all the necessary cellular components to generate an immune response at birth. However, in the absence of dietary antigens and bacterial flora, there are no secondary follicles in the Peyer's patches and virtually no immunoglobulin A plasma cells in the lamina propria. Reactive follicle centers develop after birth but it takes 2 years for mucosal IgA plasma cell density to reach adult levels. T cells are present in the epithelium and lamina propria at birth, albeit at a lower frequency than later in life and there are major differences in phenotype between T cells in fetal intestine and postnatal intestine. There is no information on the impact of the massive antigenic challenge at birth on the mucosal immune system. Well-documented deficiencies in the ability of the blood T cells of the neonate to produce interleukin-4 and interferon-gamma may also occur in the intestine. It is still an open question whether it is better to try to prevent immunological sensitization of the newborn by avoiding potential allergens (i.e. cow's milk), or whether early exposure (as happens when premature infants are given formula feeds) might tolerize the infant. Hydrolysed cow's milk formulae are probably less antigenic than whole cow's milk and have been widely used in the treatment of cow's milk allergy. Some thought is now being given as to whether the prophylactic use of hydrolysates can reduce cow's milk allergy in 'at-risk' infants.

Gastric Mucosa↗