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Biomedical subjects

D B McClelland

Publications and source records attributed to D B McClelland.

At least 19 recordsLinked to original sources

Rectal biopsy in patients presenting to an infectious disease unit with diarrhoeal disease.

The role of sigmoidoscopy and rectal biopsy was investigated in patients referred to an infectious diseases unit with diarrhoea. Seventy-four patients were studied. Nine patients (12%) had inflammatory bowel disease, either ulcerative colitis or Crohn's disease. Thirty-six patients (48%) had infective diarrhoea. A wide variety of conditions accounted for the diarrhoea in the remaining patients. Sigmoidoscopy was abnormal in 25 patients and rectal biopsy in 56. The abnormalities in rectal mucosal histology were classified into six grades. Some patients with infective diarrhoea showed rather characteristic histological changes which may be of diagnostic value. Eight showed features which suggested a diagnosis of inflammatory bowel disease. However, repeat rectal biopsy in the convalescent period showed a striking improvement in the patients with infective diarrhoea. In contrast, the histological changes persisted in the patients with inflammatory bowel disease. Repeat rectal biopsy may be essential before making a firm diagnosis of inflammatory bowel disease in some patients who present with diarrhoea and apparently typical histological changes.

Adult

Secretory IgA does not enhance the bacteriostatic effects of iron-binding or vitamin B12-binding proteins in human colostrum.

Human milk contains an unsaturated iron-binding protein (lactoferrin) and an unsaturated vitamin B12-binding protein. Lactoferrin has bacteriostatic properties, and a bacteriostatic role for the B12-binding protein has been postulated. In this study the bacteriostatic effect of lactoferrin was confirmed for strains of Escherichia coli, Pseudomonas and Proteus. Growth inhibition attributable to the unsaturated B12-binding protein could be demonstrated only with a known vitamin B12-dependent E. coli. It has previously been shown that the bacteriostatic effect of lactoferrin is potentiated by horse IgG antibody, and a similar potentiating effect of secretory IgA antibody in colostrum and milk would have obvious importance. An attempt was therefore made to demonstrate potentiation of bacteriostatic effects by naturally occurring secretory IgA antibody to E. coli. The results obtained indicate that secretory IgA antibody does not enhance the growth-inhibiting effects of either lactoferrin or the vitamin B12-binding protein.

Carrier Proteins

Preparation of lymphoid cells from small specimens of human gastrointestinal mucosa.

Several methods for the preparation of cell suspensions from human gastrointestinal mucosa were investigated. Satisfactory suspensions were obtained by incubating tissue fragments in a solution of collagenase and hyaluronidase overnight at 4 degrees C followed by 30 minutes at 37 degrees C. The resulting suspension contained large numbers of intact lymphoid cells; in addition, variable amounts of epithelial cells and cell debris were present. A high proportion of the lymphoid cells were shown by immunofluorescence to contain immunoglobulin (mainly IgA). Viability of these cells was demonstrated by dye exclusion, their ability to survive in short-term culture, and their ability to incorporate radio-labelled amino acid into immunoglobulin in vitro.

Cell Separation

Heating human milk.

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Bacterial Infections

Antimicrobial proteins in sterilised human milk.

Human milk contains factors such as IgA and lactoferrin that increase the newborn infant's resistance to infection. Preterm infants are fed pooled milk, which is normally sterilised by heating. After standard heat sterilisation IgA and lactoferrin were undetectable in milk samples. Pasteurisation also sterilised milk samples even after heavy artificial contamination and did not damage the proteins. Gamma-irradiation sterilised equally effectively but caused some denaturation of IgA and lactoferrin. Since most of the milk samples were sterile or had only light contamination with skin bacteria, there seems to be no need for routine sterilisation. If sterilisation is necessary, the method used should be chosen to minimise damage to milk proteins.

Immunoglobulin A

IGE in human urine and milk.

IgE was found in urine from healthy adult volunteers at very low levels (approximately 0.003-0.010 IU/ml), corresponding to a 24-h excrection rate of 3-16 IU. IgE was not detected in 36 out of 47 samples of milk and colostrum. In samples from six women the protein was present at low concentration 1-2 days postpartum but was not detected in later samples (usually day 5 or 6). Mammary secretions from four allergic donors were studied, and IgE was detected at low concentrations in samples from the two most severely affected individuals. The levels of IgE observed in both urine and milk suggest that there is no significant synthesis of the protein in either the urinary tract or in mammary tissue.

Adult

Clinical immunology.

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Allergy and Immunology

Immunoglobulin synthesis in the "resting" breast.

Nulliparous women have a greater risk of developing breast cancer than women who have borne children, but so far no functional differences in breast tissue have been reported between parous women and nulliparae. Macroscopically and histologically normal breast tissue was obtained from 74 women of reproductive age during biopsy of benign breast lesions and was examined for the presence of plasma cells by immunfluorescence. Immunoglobulin synthesis was detected by an in-vitro culture technique. Synthesis of IgA was detected in 81% of specimans of IgG in 45%, and of IgM in 3%. IgA synthesis much more intense than IgG or IgM synthesis. Plasma cells containing IgA were seen in 71% of the specimens examined, and 88% of specimens had deposits of IgA in the ductules. The findings were not significantly incluenced by the nature of the condition necessitating biopsy or by oral contraception. Nulliparous women showed no cyclical changes, but among parous women IgA synthesis was more intense during luteal phase of the menstrual cycle. This suggests that after the first pregnancy the breast is more sensitive to progesterone.

Adolescent

Clinical response of dermatitis herpetiformis skin lesions to a gluten-free diet.

Patients with dermatitis herpetiformis have been studied prospectively for 2 years to assess the effect of a gluten-free diet (GFD) on control of the skin lesions. Daily requirements for oral medication with sulphapyridine or dapsone were reduced by GFD treatment and if complete clinical remission of the skin disease occurred, it was maintained while the diet was strictly observed. However, complete remission did not occur significantly more often in GFD-treated patients than in patients taking a normal diet. Many of the latter group exhibited variation in their drug dose requirements during the period of study. GFD treatment seems desirable for the majority of patients with dermatitis herpetiformis, not only to correct the intestinal abnormality but also to minimize the dose of drugs necessary to control the skin lesions.

Adolescent

Peyer's-patch-associated synthesis of immunoglobulin in germ-free, specific-pathogen-free, and conventional mice.

The synthesis of immunoglobulins G, A, and M has been studied in Peyer's patches together with closely associated intestinal mucosa and in small intestine distant from Peyer's patches in specific-pathogen-free (SPF) Swiss mice and conventional and germ-free C3H mice. Thissue fragments were cultured in vitro in medium containing 14C-labelled amino acids, and newly synthesized proteins were detected by radioimmunoelectrophoresis. Small intestine from SPF and conventional animals synthesized almost exclusively IgA. No immunoglobulin synthesis was detectable in germ-free intestine. In contrast, the Peyer's patches and associated mucosa of all the groups of mice synthesized IgG, IgA, and IgM. This observation is discussed in relation to the possible role of the Peyer's patches as a source of precursors for immunoglobulin-producing cells in the intestine.

Animals

In vitro synthesis of immunoglobulins, secretory component, complement and lysozyme by human gastrointestinal tissues. II. Pathological tissues.

An in vitro culture technique has been used to study synthesis of proteins by biopsies of human gastrointestinal mucosa which were obtained at endoscopy or surgery from patients with biliary gastritis, atrophic gastritis, peptic ulcer, gastric cancer, coeliac disease, Crohn's disease and ulcerative colitis. As in normal mucosa, immunoglobulin synthesis was found in all sites, but marked increases, especially in IgG, were seen in biliary gastritis and ulcerative colitis. In untreated coeliac disease, synthesis of IgG and IgM was increased. Synthesis of complement components did not differ from that found in normal mucosa. Increased lysozyme synthesis was seen in Crohn's disease. This study shows that useful information may be acquired from short-term culture studies of the small biopsies obtained with fibre optic endoscopes.

Complement C3

In vitro synthesis of immunoglobulins, secretory component, complement and lysozyme by human gastrointestinal tissues. I. Normal tissues.

An in vitro culture technique has been used to demonstrate synthesis of proteins by human gastrointestinal tissues cultured in vitro. Histologically normal tissues were obtained endoscopically and surgically. IgA and secretory component (SC) were produced in all sites, but the relative intensity of IgA synthesis and SC synthesis varied. In stomach and small intestine the intensity of IgA synthesis was greater than that of SC, but in large bowel mucosa, there appeared to be an excess of SC synthesis. Synthesis of IgG and IgM was also found in all sites. Complement proteins were produced by some of the intestinal biopsies, and by parotid gland. Lysozyme was synthesized by parotid gland and by gastric mucosa, and to a lesser extent in small intestine, and rarely in large intestine. The results suggest that in addition to the local mucosal IgA system the local production of other immunoglobulins, as well as non-immunoglobulin humoral defence factors, may be important host defences of the normal gastrointestinal tract.

Complement C3