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Biomedical subjects

D B McClelland

Publications and source records attributed to D B McClelland.

At least 91 records · Page 5Linked to original sources

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↗

Synthesis of immunoglobulin and secretory component by gastrointestinal mucosa in patients with hypogammaglobulinaemia or IgA deficiency.

Biopsies of intestinal mucosa from patients with adult hypogammaglobulinaemia or selective IgA deficiency have been studied for the ability to synthesize immunoglobulins and secretory component. Tissue fragments were cultured in vitro in medium containing 14C-labelled amino acids and newly snythesized proteins were detected by radioimmunoelectrophoresis. Synthesis of IgA, and in some cases IgG and IgM, was found in intestinal mucosal biopsies from hypogammaglobulinaemics and IgA-deficient subjects. Biopsies from all the patients also synthesized secretory component, but evidence was obtained which indicated that secretory component does not combine normally with IgA. Tissue sections of these biopsies have also been studied by immunofluorescence and immunoglobulin bearing cells have been demonstrated. The present findings demonstrate that immunoglobulin synthesizing cells are present in the intestinal mucosa of immunoglobulin-deficient individuals. Local immunoglobulin synthesis may partially explain why these patients do not often have major problems with intestinal infections.

Adolescent↗

Antimicrobial factors in the exudates of skin windows in human subjects.

The "skin window" technique in which the horny layer of the skin is abraded with a high speed grinder has been used to study the appearance of proteins with antimicrobial activity in the fluid accumulating in damaged human skin. The fluid was absorbed into paper discs and protein levels measured by radial diffusion. The skin exudates contained about 45% as much IgG and IgM as the subjects' serum, but the amount of IgA (68% of the serum level) in the exudate was significantly greater, suggesting selective transport into the lesion. The fluid also contains complement proteins, lysozyme and lactoferrin. The methods used in this study may provide useful information about clinical situations in which susceptibility to cutaneous infection is increased.

Complement System Proteins↗

In vitro synthesis of beta1C/beta1A globulin (the C3 component of complement) by tissues and leucocytes of mice.

The synthesis of beta1C/beta1A globulin (the C3 component of complement) was studied in in vitro cultures of mouse tissues and leucocytes. Often culture in medium containing 14C-labelled amino acids, the newly synthesized radioactively-labelled protein was identified by radioimmunoelectrophoresis. Synthesis was found in spleen, liver, trachea, lung and Peyer's patch tissue, but was only occasionally detectable in cultures of intestine. Cultures of the glass-adherent cells from bone marrow, blood, lung washings and subcutaneous tissue all showed strong synthesis, indicating that the ability to synthesize beta1C/beta1A is a property shared by mononuclear phagocytes from many sites. In contrast, the nonglass adherent cells showed no synthesis of beta1C/beta1A, although these cells were shown to be viable by their ability to synthesize immunoglobulins.

Amino Acids↗

In vitro synthesis of lysozyme by human and mouse tissues and leucocytes.

Previous studies have shown that lysozyme can be detected in many body fluids, in extracts of tissues, and also in granulocytes, monocytes and macrophages. However, the sites of synthesis of lysozyme have not been defined. In the present report, the synthesis of lysozyme by tissues, and by defined cell populations cultured in vitro has been studied by detecting the incorporation of 14-C-labelled amino acids into lysozyme. This method detects only lysozyme newly synthesized during the incubation of the specimen and therefore shows unequivocally which tissues and cell types are capable of lysozyme synthesis. The validity of the method has been shown by parallel studies using an independent method to detect lysozyme production in vitro. In studies in humans and mice, lysozyme synthesis has been demonstrated in the mucosa of the respiratory and gastrointestinal tracts, and in lymphoid organs. In studies of defined cell populations, monocytes and macrophages (mononuclear phagocytes) have been shown to synthesize lysozyme. Granulocytes from peripheral blood contain lysozyme but do not synthesize it, and lymphocytes neither contain nor synthesize lysozyme. The present findings provide further evidence that lysozyme has an important role in the defence of the host against micro-organisms, and the findings suggest that lysozyme may reach its target by several routes. At an intracellular level it is delivered from lysosomes into the phagocytic granules of granulocytes and macrophages. Local synthesis of the mucous membranes contributes lysozyme to secretions. Synthesis and secretion by mononuclear phagocytes which reach a tissue in response to an inflammatory stimulus contribute lysozyme to the exudate, and the release of lysozyme from breakdown of granulocytes has the same effect.

Animals↗

Appearance of specific colostrum antibodies after clinical infection with Salmonella typhimurium.

Colostrum and serum antibodies to Salmonella typhimurium have been found in three patients after clinical gastrointestinal infection during pregnancy. High levels of colostrum IgA agglutinins were directed specifically against both the flagellar and somatic antigens of the infective organism. The levels of colostrum agglutinating activity exceeded those found in the patients sera, while control colostrum gave negative results.

Agglutination Tests↗