[Animal experiments. Scientists spread smoke screens to calm public opinion].
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Biomedical subjects
Publications and source records attributed to B Carlsson.
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It is still not known when the secretory IgA response, important for defence of the mucous membranes, becomes fully competent in the human infant. The infant is, however, provided with 0.25--0.5 g of secretory IgA/day via the maternal milk. The milk contains secretory IgA antibodies against a wide variety of antigens from microorganisms, including bacteria, viruses and parasites. Many of the antibodies are directed against important virulence factors such as bacterial pili, enterotoxins, capsular polysaccharides and endotoxic lipopolysaccharides. The passive transfer of antibodies through the milk may explain why breast-fed infants are resistant to enteric infections in particular. The antibodies in the milk are often directed against antigens in the mother's milieu and intestine. An entero-mammary gland link, possibly consisting of lymphoid cells homing from the Peyer's patches in the intestine to the mammary gland, has been suggested. A limited selective uptake of oligomeric IgA from serum in exocrine glands, including the mammary glands, has also been indicated. Whichever the mechanism, the antibodies transferred via breast milk are composed to meet the needs of the infant.
A cost benefit analysis of chemotherapy in unselected patients with advanced malignant disease originating in a defined population (250 000 inhabitants) demonstrated that the use of this therapy as the main treatment in hospitalised patients increased from a few per cent during 1973 to 60 per cent during 1977, corresponding to an increase in the cost of drugs from 10 000 to 200 000 dollars. At the same time the capacity for hospital care of patients with advanced malignancies increased from 317 to 488 patients without any enlargement of other resources. As more than 90 per cent of the medical budget consists of expenditures for salaries and localities, a cheaper medical care was obtained, but, above all, the survival rate and the quality of life for many patients was improved.
1) Milk and salivary s-IgA antibodies are via the homing of IgA producing cells from the Peyer's patches closely connected with antigenic stimuli in the intestine. This explains the presence in human milk of s-IgA antibodies against E. coli O and K antigens, V. cholerae and Shigella O antigens, E. coli and V. cholerae enterotoxins. These secretory antibodies can be induced by intestinal exposure and boosted by parenteral vaccination. 2) Preliminary data suggest that the IgA response in the urinary tract and possibly in the lung may be involved in the homing mechanism as well. 3) The protective role of the milk s-IgA antibodies to enterobacterial virulence antigens is strongly suggested, as is the protection mediated by urinary antibodies against urinary tract infections.
One of the anti-infection principles of maternal milk is the predominant milk immunoglobulin, secretory IgA. This immunoglobulin contains antibodies against many pathogens and potential pathogens, viruses as well as bacteria, including several members of Enterobacteriacae. The antigenic stimuli for these milk antibodies seem to take place in the Peyer's patches of the intestine. Lymphoid cells leaving the patches after antigenic exposure seem to home to the mammary glands via the lymph and blood circulation. As a result, the milk contains secretory IgA antibodies against, among other things, the intestinal bacteria of the mother. These milk antibodies might reflect the spectrum of bacteria and viruses in the community and may be important for the protection of the breast-fed baby. Via the same homing mechanism the maternal milk obtains antibodies against dietary antigens, including cow's milk proteins. Studies of infants on mixed feeding suggest that the secretory IgA antibodies against the bovine proteins diminish the antigenic exposure, indicating the possibility of an anti-allergic mechanism.
At a number of slaughters nephropathy and high ochratoxin A contents in kidneys have been observed in fattening pigs from two Swedish farms. In one herd the source of contamination was barley grown on the home farm and stored under such conditions that the growth of fungal species (Penicillium verrucosum var. verrucosum) producing ochratoxin A occurred, with the subsequent formation of the toxin. In this case high ochratoxin A levels in fattening pigs were found during a period of about 18 months. In the second herd, where compounded feed was used, it was impossible to locate the source of contamination. It was presumed that a consignment of feed was damaged by rain during storage at the farm. Ochratoxin A was found in fattening pigs from this herd for a period of about 2 months. Ochratoxin A appeared in the kidneys of all investigated pigs. In some animals the livers, whole blood, and plasma were analyzed, too. The livers contained somewhat lower amounts of ochratoxin A than the kidneys, whereas the content in whole blood and plasma, respectively, was 5 and 13 times greater. Kidneys spontaneously contaminated with ochratoxin A, when stored for 10 months at -70 degrees C, showed no systematic decrease in toxin content.
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A method to quantitate specifically secretory IgA (SIgA) has been developed using the enzyme-linked immunosorbent assay. The IgA in the test sample was adsorbed to anti-alpha antibodies attached to plastic tubes via a cost of IgA myeloma protein. The reacted SIgA was determined using anti-secretory component antiserum conjugated with alkaline phosphatase. The technique permitted quantitation of secretory IgA in biological fluids like milk, urine, and saliva with a reproducibility of +/-7%, down to 0.03 mg/l. In contrast to earlier techniques, the presence of up to 157% of serum IgA without secretory component (SC) and free SC did not disturb the measurements of SIgA. Furthermore, variations in pH and osmolarity, within biological ranges in secretions, did not influence the estimations.
Antibodies of the secretory IgA type against cow's milk proteins were consistently found in human milk. With the assumption that such antibodies can help to prevent or at least diminish the contact between native cow's milk proteins and the lymphoid system of babies on mixed feeding, the levels of antibodies of various immunoglobulin classes against bovine milk proteins were measured in different groups of babies. Those on artificial feeds who had been on mixed feeding of human milk and cow's milk for less than 1 week had significantly higher levels of IgG antibodies to cow's milk proteins than those who had been on mixed feeding for a period longer than 3 weeks.
A male infant with bilateral iris coloboma who had had repeated infections and malabsorption was studied. The levels of total lymphocytes and of T and B cells were normal or high, but IgA became undectable and IgG low, whereas IgM was normal. His lymphocytes did not respond to phytohemagglutinin (PHA), concanavalin A, pokeweed mitogen (PWM) or in mixed lymphocyte reactions (MLR), nor did they respond in vitro when thymosin was included in the test systems. He was skin-test-negative, even to dinitrochlorobenzene. His crudely isolated T lymphocytes and the supernatant of his PHA-stimulated lymphocytes inhibit the response of normal lymphocytes to PHA, PWM, and in MLR. During thymosin treatment skin test and lymphocyte reactivity to mitogen remained negative. He became faintly positive in MLR, and the suppressor activity in the supernatant of his PHA-stimulated lymphocytes no longer inhibited the response of normal lymphocytes to PHA, PWM, or in MLR. In parallel with thymosin treatment he showed quite marked clinical improvement.
The antibody content of milk from healthy Swedish mothers was compared with that of milk from mothers of a very low socio-economic group in a developing country. Antibodies of various immunoglobulin classes against E. coli O antigens were determined with the enzyme-linked immunosorbent assay (ELISA). The milk antibodies which mainly belonged to the secretory IgA class appeared in similar concentrations in milk from the two groups using E. coli antigens of Swedish as well as Pakistani origin. The secretory IgA antibodies could be demonstrated in the stool of the breast-fed infants of the undernourished mothers. Also the concentration of serum IgG and IgA antibodies to E. coli O antigens were similar in the Pakistani and Swedish mothers. The serum IgM antibody levels of the Pakistani mothers were higher, however, presumably due to a higher frequency of infections. It was noted that the milk production decreased considerably upon the hospitalization of the healthy and well-to-do Swedish mothers. The small milk volumes of the undernourished Pakistani mothers suggest that the lactation failure observed was mainly due to inadequate milk flow and not to decreased milk quality. The results indicate the necessity of studying the nutritional, psychological and social factors responsible for low milk yield and add yet another reason to stimulate prolonged breastfeeding.
Studies of Escherichia coli O antigen specific antibodies in human milk, maternal serum and cord blood. Acta Paediatr Scand, 65:216, 1976.--The quantity and class specificity of E. coli O antibodies in human milk, maternal serum and cord blood was determined by the enzyme-linked immunosorbent assay. The predominant Ig-class of these antibodies in milk was IgA. The initially high levels of antibodies decreased 10-fold during the first days, but there seemed to be a fairly constant daily production of IgA antibodies during the first two months of the nursing period. There was no obvious decline in antibody content from morning to night or during a meal. The ratio milk antibody/serum antibody was very high for IgA, suggesting a local production. The ratios for the IgG were all less than 1, suggesting a restricted transfer from the serum. Ratios around 1 for IgM did not exclude some local production. In umbilical cord serum the amount of IgG E. coli O antibodies was higher than that in maternal serum. Small amounts of IgM and IgA antibodies was also demonstrated in some cases. In milk as well as in serum there were antibodies against a wide variety of E. coli O groups, not only to the actual E. coli strain dominating the mother's gut flora.
From 29 healthy newborn infants and their mothers faecal, serum and milk specimens were obtained on several occasions from one to nine weeks after delivery. Predominant faecal E. coli were serotyped with regard to the O antigen and milk and serum were analysed for their content of E. coli O antibodies by the enzyme-linked immunosorbent assay. In five cases the babies acquired the same O serotype as was found in the stools of their mothers but in 12 out of 29 cases infant and mother never had any dominating faecal E. coli O type in common. There was no apparent correlation between the patterns of feeding and interchange of bacteria. Klebsiella/Enterobacter was the dominating facultative organism on at least one occasion in half the infants. The newborns received colostral IgA and transplacental circulating IgG antibodies against a great number of E. coli O serotypes. These antibodies did not prevent intestinal colonization, as judged from cultures of faeces.
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The production of antibody by human colostral cells was assayed by the hemolysis in-gel technique. When sheep erythrocytes coated with O antigens from frequently encountered Escherichia coli bacteria were used as detector cells and anti-IgA serum was added for development, numerous plaque-forming cells (PFC) were demonstrated in all samples tested. In contrast, plaques were rarely seen in the presence of anti-IgG developing serum. The direct (IgM) plaques occasionally noted with both antigen-coated and uncoated sheep erythrocytes were mainly due to the production of heterophil antibodies, since they were not formed when human erythrocytes were used as O-antigen carriers. A strikingly high number of the colostral lymphocytes formed antibodies to the E. coli antigens, up to 8%. This suggests that these cells represent a rather selective population--possibly cells from the gastrointestinal tract exposed to enteric bacteria. The large number of plaques observed, the predominance of the cells forming IgA antibodies, and the marked changes in PFC number in relationship to parturition pose a number of questions relevant to the antibody-producing colostrum cells and their relationship to the secretory immune system.
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