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Biomedical subjects

D B McClelland

Publications and source records attributed to D B McClelland.

At least 73 records · Page 4Linked to original sources

Antibodies in milk.

The lactating human breast is a large scale producer of a form of antibody which is particularly adapted to protecting mucosal surfaces. The breast is part of a generalized mucosal-associated lymphoid system which permits immunization of the breast against organisms experienced by the mother as a result of colonization of the intestine and other sites. This secretory antibody-producing system in the breast is conserved throughout a very wide range of species and therefore appears to be of evolutionary importance. The possibility now exists for manipulating the production of antibodies in breast milk by immunization. Many other constituents of milk are also important in protecting the neonate against infection. These factors, like antibodies, may be damaged by processing milk: if milk must be fed to infants by an indirect route, it should be treated in ways which preserve these fragile but important components (Björksten et al., 1980).

Animals↗

Milk protein concentrations in the mammary secretions of non-lactating women.

Milk protein concentrations were determined either by double antibody radioimmunoassay (IgA and IgG) or single radial immunodiffusion (lactoferrin) in the mammary secretions of seven healthy non-lactating subjects and eight patients with breast disease. IgA and IgG were detected in all samples of breast secretion (whether from normal or diseased breasts) and the concentrations observed were very similar to those in post-partum colostrum and milk. However, because the volume of secretion obtained was very small compared with colostrum and milk, total IgA synthesis by the non-lactating breast is very much less than in the lactating breast. The IgA detected in the mammary secretions was demonstrated to be secretory IgA by gel filtration and it is therefore suggested that the secretory immune system is functional in the non-lactating breast.

Adult↗

Selection of plasma for hepatitis B immune globulin using a low cost radioimmunoassay.

Polystyrene beads coated with pasteurised polyethylene glycol-precipitated HBsAg were used to detect anti-HBs by a solid phase inhibition assay employing unreacted 125I-anti-HBs which had previously been "processed" by polyethylene glycol precipitation and used to test for the HBsAg. A weak anti-HBs (approximately 0.1 IU/ml) positive control was used to establish a target level of reactivity. 16,035 freshly donated units of blood, a 90-sample coded anti-HBs panel and a selection of hyperimmune globulins were investigated. All positive results were confirmed by a standard commercial assay. Antibody content of selected samples was quantitated in international units. A target level of anti-HBs activity is suggested for donor plasma to be fractionated for the production of hepatitis B immune globulin.

Adsorption↗

The development of mammary secretory immunity in the human newborn.

Milk protein concentrations were determined either by radioimmunoassay (IgA and IgG) or single radial immunodiffusion (IgM, lactoferrin, albumin and lysozyme) in single or serial samples of neonatal milk (witch's milk) obtained from 33 healthy newborns (seven of whom were light for dates), four ill newborns following major surgery and four newborns suffering from one of a variety of infections. In addition, paired neonatal milk and heel prick blood samples were collected from seven newborns, and paired neonatal milk and maternal milk samples were collected from a further seven neonates and their respective mothers. The concentrations of secretory IgA (11S IgA) in neonatal milk, although 300-fold lower than the corresponding IgA concentrations in maternal milk, when compared with neonatal serum IgA concentrations, were consistent with local synthesis of IgA occurring in the neonatal mammary gland. Among the milk protein studies, on 11S IgA concentrations increased significantly after birth in neonatal milk, the rise being unrelated to the gestational age of the newborn. As an entero-mammary circulation of IgA precursor lymphocytes exists in adults, it is suggested that the entry of foreign antigens into the neonatal gut after birth may be an important factor influencing the development of neonatal secretory immunity.

Breast Feeding↗

Milk protein concentrations in galactorrhoeic mammary secretions.

Milk protein concentrations were determined either by double antibody radioimmunoassay (IgA) or single radial immunodiffusion (IgG, lactoferrin, lysozyme and albumin) in the mammayr secretions of one nulliparous and three parous female patients with galactorrhoea due to hyperprolactinaemia. Concentrations of all the proteins studied were found to be similar to the concentrations observed in post-partum colostrum. In particular, secretory IgA was the only form of IgA detected in galactorrhoeic secretions. It is suggested that hyperprolactinaemia alone can result in increased mammary synthesis of the milk proteins since the steroid changes associated with a full-term pregnancy and delivery of the placenta did not immediately precede the galactorrhoea in three of the four patients studied.

Adult↗

Vitamin B12 in human colostrum and milk. Quantitation of the vitamin and its binder and the uptake of bound vitamin B12 by intestinal bacteria.

The concentration of vitamin B12 was measured by microbiological assay in 229 samples of normal human colostrum and milk taken at various stages of lactation. Colostrum obtained within 48 hours of delivery contains high concentrations of vitamin B12 (mean 2 431 pg/ml), but within a few days the levels fall to a range similar to the levels in normal serum. The vitamin B12 binding capacity of 111 samples of colostrum and milk was estimated by gel filtration or charcoal binding. Colostrum samples have a mean binding capacity of 72 ng/ml, while the binding capacity in milk is only one third of this value. The ability of a range of intestinal bacteria to take up colostrum-bound vitamin B12, was assessed. All the organisms took up free vitamin B12, but when the vitamin was bound in colostrum, there was little or no uptake even after 24 hours incubation.

Bacteria↗

The effect of digestive enzymes on the binding and bacteriostatic properties of lactoferrin and vitamin B12 binder in human milk.

Human milk contains unsaturated lactoferrin and vitamin B12 binding protein. It has been suggested that these proteins may exert antibacterial effects in the intestine of the breast fed infant, but the effect of the intestinal environment on the antibacterial effect of these proteins has not been described. In this study human milk was treated with pepsin and trypsin and the influence of digestion on iron and vitamin B12 binding capacity, bacterial uptake of iron and vitamin B12 from milk and bacteriostatic effect was studied. Pepsin digestion had no effect on vitamin B12 binding capacity, or the ability of bacteria to take up vitamin B12, or the growth inhibitory effect on a vitamin B12 dependent strain. In contrast, trypsin digestion did not affect iron binding or bacteriostatic effects attributable to lactoferrin. The. findings support an in vivo bacteriostatic role for lactoferrin in the breast fed neonate's intestine but do not support a similar role for the vitamin B12 binding protein.

Bacterial Proteins↗

Milk protein concentrations in neonatal milk (witch's milk).

Milk protein concentrations were determined in five samples of neonatal milk (witch's milk) by either double antibody radioimmunoassay (IgA) or by single radial immunodiffusion (IgG, lactoferrin, lysozyme and albumin). Neonatal milk IgA concentrations ranged from 0.43 to 118.2 mg/l; the corresponding mean neonatal serum IgA concentration was 2.6 +/- s.e. 1.45 mg/l (n = 48). Sucrose density gradient ultracentrifugation indicated that the IgA detected was of the 11S type. IgG, lactoferrin, lysozyme and albumin were detected in neonatal milk in similar concentrations to those found in maternal milk.

Albumins↗

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↗