Biomedical subjects

J T Labrooy

Publications and source records attributed to J T Labrooy.

8 recordsLinked to original sources

PubMed1995

Antigen-specific B cells in tissues after oral typhoid vaccination.

Six human subjects who were to receive elective bowel surgery for a variety of diseases were vaccinated with the oral typhoid vaccine, Ty21a. Intestinal tissue (ileum in two, large intestine in four) removed 7-26 days after the first dose of vaccine was examined for the presence and distribution of antigen-specific B cells. This was compared with intestinal tissue derived from two unvaccinated controls. A number of B cell differentiation antigens were also assessed on these cells by immunofluorescence using dual-labelling. Antigen-specific cells were found randomly distributed in the lamina propria of all the vaccinated subjects in low frequency (6 +/- 0.5 to 37 +/- 31 [mean +/- s.e.m.] antigen specific cells/10 mm2 of tissue). The lymphocyte differentiation antigens CD45RA, CD45RO, L-selectin, CD-11a CD-38, CD-44 and VLA-4 were all found on antigen-specific cells, but no particular pattern was recognizable in this small series of six subjects with different disease processes affecting the intestine.

Administration, Oral↗

PubMed1990

Antibody response reveal differences in oral tolerance to wheat and maize grain protein fractions.

The influence of diet on humoral immune responses to gluten- and maize-derived proteins was examined using ELISA and protein blotting techniques. Mice raised on the maize-based (gluten-free) diet responded well to parenteral immunization with each of six gluten-derived protein preparations (whole gliadin, two omega-gliadin fractions, wheat salt-soluble proteins, a peptic-tryptic digest and a subtilisin digest of gluten), as serum antibody levels increased at least 300-fold in each case. In contrast, mice raised on the wheat-based diet responded poorly to immunization with either whole gliadin or omega-gliadin and were virtually non-responsive to enzymic digest of gluten. Diet had little effect on the magnitude of the antibody response to wheat salt-soluble proteins, with both groups showing a 300-fold increase in titre. Similarly, tolerance to alpha-zeins, the alcohol-soluble proteins of maize, did not occur on either diet. However, some oral tolerance was observed to maize glutelin. The specificity of the various antibody responses was then analysed by immunoblotting. Following immunization with gluten proteins or digests, antibodies from the maize-fed mice bound more or less equally to each of the main gliadin bands and to the glutenins while the mice on the wheat-based diet had antibody specific for omega-gliadin proteins. Serum antibodies from the maize-fed mice, immunized with either alpha-zein or maize glutelin, showed even labelling of the major maize endosperm proteins while antibodies from mice on the wheat diet showed strong labelling of the Mr 27,000 and 58,000 bands. These results show that diet influenced the specificity, as well as the magnitude of serum antibody responses to cereal proteins. In addition, oral tolerance appeared to affect the humoral response to some cereal proteins more than others. Both of these findings have important implications for our understanding of coeliac disease.

Animals↗

PubMed1990

The serum polymeric IgA antibody response to typhoid vaccination; its relationship to the intestinal IgA response.

The relationship between the IgA antibody response in serum (total and polymeric IgA) and intestinal secretions was examined in volunteers subjected to oral and parenteral typhoid vaccination. After oral vaccination (three doses of 10(11) live Ty21a vaccine given at 48-hr intervals), serum pIgA antibody to typhoid lipopolysaccharide (LPS) was detected in seven of the 14 subjects (46.4 +/- 59 U/100 microliters, mean +/- SD). However, all 14 showed a significant intestinal IgA response (993 +/- 2516 and 9349 +/- 6754 U/mg pre- and post-vaccine; t = 5.25, P = 0.0002). The level of pIgA antibody declined rapidly, whereas intestinal IgA antibody levels remained elevated. Serum pIgA antibody was also found after parenteral immunization (two doses of 5 X 10(8) heat-killed bacteria given 14 days apart to six subjects), but an intestinal IgA antibody response was detected in these individuals only after a subsequent course of the oral vaccine given 1 month after initial parenteral immunization. Changes in serum pIgA antibody followed those of total serum IgA antibody rather than those of intestinal antibody. The results indicate that a serum pIgA response can be induced by an antigenic stimulus delivered either orally or parenterally, whereas an intestinal IgA response is induced only by a local antigen stimulus. The regulation of serum pIgA and intestinal IgA appear to be independent.

Adult↗

PubMed1989

The effect of cyclosporin A in delaying maturation of the small intestine during weaning in the rat.

As maturation of the small intestine has similar features to an immunologically mediated reaction, we studied the effect of the immunosuppressive agent, cyclosporin A (CyA), on the development of the small intestine during weaning in the DA x PVG rat. Intestinal development was measured by villus area, crypt length, crypt cell production rate (CCPR), and disaccharidase activity. Rat pups received either cyclosporin A (7.5 mg/kg daily subcutaneously) or polyethoxylated castor oil (Cremophor, drug vehicle) subcutaneously from 12 days of age. Cremophor- and CyA-treated litters were killed at 18, 20, 22, 24, and 26 days of age. CyA-treated animals had retarded weight gain, lower mesenteric lymph node and spleen weights, fewer intraepithelial lymphocytes, and reduced systemic secretion of rat mucosal mast cell protease II. CyA treatment retarded any increase in villus area, crypt length and CCPR until day 26 of age. Lactase activity was retained longer, and sucrase and maltase induction was delayed. We conclude that CyA retarded normal development of the small intestine, but some maturation still occurred at the end of weaning.

Animals↗

PubMed1986

Intestinal and serum antibody in coeliac disease: a comparison using ELISA.

Intestinal and serum antibody to antigens derived from gluten and other food proteins in 16 children with coeliac disease and 15 control subjects was measured using an enzyme-linked immunosorbent assay (ELISA). High concentrations of antibody to gluten antigens were found in children with coeliac disease who were on a diet which contained gluten. This antibody was predominantly in the IgA and IgM classes in intestinal fluid, and in the IgG and IgA classes in serum. When coeliac children transferred to a gluten-free diet for 6 months or more, anti-gluten antibody fell much more rapidly in serum than in intestinal fluid. Although no single measure of antibody, in any immunoglobulin class, to a gluten-derived antigen proved sufficiently discriminating to be suggested as a diagnostic test for coeliac disease, serum antibody, particularly in the IgA class, may be of value in following the progress of patients and in assessing their adherence to a gluten-free diet.

Adolescent↗

PubMed1985

Gastric xanthomas.

Gastric xanthomas (GX) are uncommon intramucosal lesions which can be misinterpreted as early or signet ring adenocarcinoma. The histological features of eight gastric xanthomas are described. Mucin and Masson trichrome strains were valuable in distinguishing GX from adenocarcinoma.

Aged↗

PubMedDate not supplied

Polymeric IgA antibody to gliadin in the serum of patients with coeliac disease.

Secretory component (SC) binding assays which detect polymeric IgA (pIgA) in serum were used to measure serum antigliadin pIgA and total pIgA in patients with coeliac disease. Total IgA antigliadin antibody in serum and intestinal fluid was measured by enzyme linked immunosorbent assay (ELISA). The relationship of pIgA antibody to dietary gluten and the antigliadin IgA antibody in intestinal fluid was examined. Twenty-nine serum samples were assayed, twelve from patients ingesting gluten and seventeen from patients who had excluded gluten from their diet for 6 months. Eight of these were paired samples from 4 adults on and off gluten. In addition, paired samples of both intestinal fluid and serum were obtained from 7 children on and off gluten. Polymeric IgA antibody to gliadin was detected in 11 of 12 subjects on gluten but in only 3 of 17 who had excluded gluten. Three of the four adults from whom paired serum samples were obtained had pIgA antigliadin, but only while on gluten. Three of the seven children in whom intestinal and serum antibody were assayed had pIgA to gliadin, which could not be detected after exclusion of gluten, although their intestinal antibody level remained elevated. There was no change in total pIgA levels with diet although the levels were higher than those seen in normal subjects. We conclude that pIgA antibody to gliadin is frequently found in the serum of coeliac patients ingesting gluten. It disappears with gluten elimination at a time when the IgA antigliadin antibody in intestinal fluid has not altered.

Celiac Disease↗

PubMedDate not supplied

Recovery of the small intestine in coeliac disease on a gluten-free diet: changes in intestinal permeability, small bowel morphology and T-cell activity.

Intestinal permeability was assessed before and 1, 2, 4, 8 and 12 weeks after commencing a gluten-free diet (GFD) in eight coeliac subjects. Intestinal morphology was quantified in six coeliac subjects on a normal diet, six coeliac subjects on a GFD, and 21 normal subjects. T-cell activity was measured in the eight coeliac subjects by soluble interleukin-2 receptor (sIL-2R) concentration (normal less than 477 U/mL). Intestinal permeability was increased 10-fold with a geometric mean value of 0.72 on a normal diet, and decreased to 0.17 at 4 weeks (P = 0.04), to 0.07 at 8 weeks (P = 0.010), and to 0.20 at 12 weeks (P = 0.015) of a GFD. Two of the eight subjects showed a poor response to gluten withdrawal. Quantitative intestinal morphology showed no significant improvement after 3 to 6 months of a GFD. Mean +/- s.d. sIL-2R concentrations in the eight subjects were increased 5-fold higher than control values at 1400 +/- 530 U/mL on a normal diet and decreased to 750 +/- 200 U/mL after 12 weeks of a GFD (P = 0.004). We conclude that intestinal permeability improves rapidly in the majority of coeliac subjects after commencing a GFD, although some abnormal permeability and increased T-cell activity persists. This may be due to varying degrees of gluten ingestion resulting in continued immune activation.

Adult↗