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Biomedical subjects

B Lönnerdal

Publications and source records attributed to B Lönnerdal.

At least 19 recordsLinked to original sources

Recombinant human milk proteins - an opportunity and a challenge.

Several human milk proteins have physiologic functions in infants. These proteins are involved in defense against infectious agents and in the optimization of nutrient uptake from milk. Therefore, interest in producing recombinant human milk proteins to use in infant formula has been growing. Microorganisms and transgenic animals can now be used for the production of bioactive proteins. However, the benefits of each protein must be evaluated in cells, animal models, and infants before claims can be made that adding them to formula improves the health or nutrition of infants. Once benefits are shown, proper manufacturing conditions must be developed for introducing the protein or proteins into formula. Processing conditions must be evaluated to ensure that biologic activity is maintained. Dry blending, aseptic processing, sterile filtration, and other techniques will likely be necessary for introducing proteins that require specific tertiary structure for activity. The importance of posttranslational modifications must also be considered: some proteins may require proper glycosylation or phosphorylation for physiologic activity.

Animals

Bioavailability of copper.

Copper intakes of infants and adults are often much lower than current recommendations. Copper status, however, appears adequate in most populations. This suggests that copper requirements may be lower than believed earlier, except those for premature infants, who have high requirements as a result of low prenatal stores. Infants, in general, constitute a risk group because milk is low in copper. Bioavailability of copper from human milk is high, whereas it is lower from cow milk and infant formula. Protein source, amino acids, carbohydrates, and ascorbic acid can affect copper availability, whereas phytate, zinc, and iron appear to have little influence on copper absorption, at least physiologic intakes.

Adult

Effect of infant formula zinc and iron level on zinc absorption, zinc status, and immune function in infant rhesus monkeys.

To evaluate the effects of marginal zinc (Zn) deficiency on Zn absorption and metabolism, three groups of infant rhesus monkeys (n = 4/group) were fed from birth to 5 months of age either a regular infant formula (5 mg Zn/L) or a low-Zn formula (1 mg Zn/L). Since iron (Fe) intake may affect Zn absorption, the low-Zn formula was given without (1 mg Fe/L) or with Fe fortification (12 mg/L). At monthly intervals, Zn absorption and retention were assessed by gavage feeding with 65Zn and whole-body counting immediately after and on days 4, 7, and 11 after intubation. Blood samples were drawn before dosing for analyses of various potential markers of Zn status. Infants fed low-Zn formula had lower weight gain than controls; however, length growth was similar in all groups. 65Zn retention was considerably higher in both groups fed low-Zn formula (40%) than in the control group (20%), whereas plasma Zn levels were normal in all infants. Plasma metallothionein levels were generally very low and detectable in only 5 samples of 48; however, 4 of these were found in control infants. Neutrophil chemotaxis assessed at the end of the study was impaired in low-Zn infants compared to controls. In addition, low-Zn infants had increased levels of interleukin-2 at the end of the study. No differences were seen between the groups in hemoglobin levels, total white blood cells/absolute neutrophil counts, or plasma activities of 5'-nucleotidase or angiotensin converting enzyme. In conclusion, marginal Zn intake in infant rhesus monkeys resulted in increased Zn retention, which was not enough to completely compensate for the lower Zn intake. The higher level of iron fortification studied did not affect Zn retention significantly.

5'-Nucleotidase

Effect of acute maternal infection on quantity and composition of breast milk.

To investigate the potential effects of maternal infection during lactation on breast-milk quantity and composition, we examined low-income Peruvian women who had an acute febrile infection and were exclusively breast-feeding a child from 1 to 6 mo of age (n = 36). Women who were not ill (n = 38) served as controls; all women had body mass indexes (in kg/m2) > 19.5. Blood and milk samples were collected on days 1, 7, and 14 after identification of the episode of illness. C-reactive protein in maternal serum was significantly elevated by infection, whereas two other acute-phase reactants, ceruloplasmin and alpha 2-macroglobulin, showed no change. Serum zinc concentrations were significantly lower in ill women than in women who were not ill, whereas serum copper concentrations were elevated initially in ill women. Serum iron concentrations increased significantly with time, but there was no significant difference between groups. Milk intake, as assessed by 12-h test-weighing, was not affected by the infection. Concentrations of milk total protein, casein, and whey proteins were similar in the two groups and there was no significant effect of illness on milk trace element concentrations. Thus, acute maternal infections during established lactation did not affect milk volume, milk protein, or trace element concentrations, despite expected changes in serum protein and trace element concentrations.

Acute Disease

Sex differences in iron stores of adolescents: what is normal?

We evaluated iron status and its determinants in healthy adolescents. Fasting morning blood samples from a school-based cross-sectional study were analyzed for serum ferritin (SF), serum iron, total iron-binding capacity, and circulating transferrin receptors. Physical development, chronic disease, medication, dietary intake, and physical activity were assessed using clinical examination, questionnaires, and 7-day records. The risk of having low serum ferritin values was estimated using bivariate and multivariate regression. Subjects were 867 healthy Swedish adolescents, 14- and 17-year-olds (472 boys and 395 girls). SF values increased with pubertal stage in boys but not in girls. Five percent of the boys and 15% of the girls had SF values < 12 micrograms/L. Of the 17-year-old boys, 7% compared to 1% of the 17-year-old girls had SF values > 100 micrograms/L. Forty-one percent of cases with SF values > 12 micrograms/L had serum iron values < 15 microM, and 22% had transferrin saturation values < 16%. Mean total iron intakes of the boys were high [1.6 times recommended daily allowance (RDA)] and mean intakes of the girls were adequate (0.9 times RDA). Low heme iron intakes increased the risk of low iron stores (< 12 micrograms/L) in girls but not in boys. Total iron intake or other dietary factors, physical development, or level of physical activity did not influence the risk of low SF. The findings of this study suggest that the differences in iron status between boys and girls in adolescence results primarily from biological differences other than menstrual bleeding or insufficient iron intake. Furthermore, the results question the role of SF as an indicator of iron deficiency in adolescence, in particular if age and sex are not taken into consideration. We suggest that different reference values for SF, including the cut-off limit for low SF, adjusted for age and sex, should be considered. The high iron intakes and corresponding high SF values found in the older boys are noticeable in light of the possible negative health consequences of iron overload.

Adolescent

Receptor-mediated binding of milk lactoferrin to nursing piglet enterocytes: a model for studies on absorption of lactoferrin-bound iron.

Lactoferrin, an iron-binding glycoprotein that is abundant in milk of some species, has been suggested to play a key role in the absorption of iron in human infants. This hypothesis is based on the dominant role of lactoferrin as an iron-binding component in human milk and on the occurrence of lactoferrin receptors in brush-border membranes in infants' intestines. The piglet may be a useful model to evaluate the biological activity of lactoferrin because we have previously found the presence of a lactoferrin receptor in brush-border membranes from suckling piglets. In this study, viable enterocytes were isolated from 6- to 20-day-old suckling piglets. Binding studies were performed at 4 degrees C using 125I-labeled porcine lactoferrin. Scatchard analysis of equilibrium binding data showed an apparent binding constant (Kd) of 2 x 10(-6) M (SD = 0.6 x 10(-6)). This affinity is in close agreement with previous results obtained using isolated brush-border membrane vesicles. Bovine lactoferrin inhibited the binding of porcine lactoferrin. Porcine transferrin, however, did not affect porcine lactoferrin binding significantly. Thus, lactoferrin binding is highly specific. When enterocytes were incubated with 125I-labeled lactoferrin at 37 degrees C, the amount of cell-associated radioactivity exceeded the surface binding capacity of the cells by almost fivefold. This finding agrees with the continuous binding and subsequent internalization of 125I-labeled lactoferrin. The isolated piglet enterocyte seems to provide a useful model for further studies of the mechanism of receptor-mediated absorption of lactoferrin.

Animals

Human milk kappa-casein and inhibition of Helicobacter pylori adhesion to human gastric mucosa.

Readily digested caseins, which account for almost half of the protein content in human milk, are important as nutritional protein for breast-fed infants. It has also been advocated that part of the antimicrobial activity of human milk resides in the caseins, most likely the glycosyated K-casein. Top explore this possibility, we purified K-casein from human milk to homogeneity by a two-step size-exclusion chromatography procedure. Purified human K-casein, in contrast to K-casein purified from bovine milk, effectively inhibited the cell lineage-specific adhesion of fluoroisothiocyanate-labeled Helicobacter pylori to human gastric surface mucous cells. The inhibitory activity was abolished by metaperiodate oxidation and considerably reduced by preincubation with alpha-L-fucosidase but not with alpha-N-acetylneuraminidase or endo-beta-galactosidase. These results strongly support the view that fucose containing carbohydrate moieties of human K-casein are important for inhibition of H. pylori adhesion and, thus, infection. They also suggest that breastfeeding may protect from infection by H. pylori during early life and that species-specific glycosylation patterns, as illustrated by human bovine K-casein, partly determine both the narrow host spectrum of this human gastric pathogen and the capacity to resist infection.

Animals

Lactoferrin: molecular structure and biological function.

Lactoferrin is an 80-kDa, iron-binding glycoprotein present in milk and, to a lesser extent, in exocrine fluids such as bile and tears. It consists of a single-chain polypeptide with two gobular lobes and is relatively resistant to proteolysis. The complete cDNAs for lactoferrin from human milk, neutrophils, and bovine milk have been reported, and recombinant proteins have been produced. Owing to its iron-binding properties, lactoferrin has been proposed to play a role in iron uptake by the intestinal mucosa and to act as a bacteriostatic agent by withholding iron from iron-requiring bacteria. Its presence in neutrophils and its release during inflammation suggest that lactoferrin is also involved in phagocytic killing and immune responses. Additionally, lactoferrin may function in ways not related to iron-binding, e.g. as a growth factor and as a bactericidal agent. This review attempts to evaluate these proposed functions and their biological significance in more detail.

DNA

Magnesium nutrition of infants.

Our knowledge of magnesium absorption in infants and dietary factors affecting magnesium bioavailability from infant diets is limited. The magnesium concentration of human milk is about 30 mg/litre, while infant formulas provide about 40-80 mg/litre and cows milk approximately 130 mg/litre. Most of the magnesium in these diets is present in soluble form and in vitro digestibility studies show the remainder to be easily solubilized. The soluble magnesium in infant diets is largely in a low molecular weight form, most likely explaining the high bioavailability of magnesium from infant diets in experimental animals (50-90 per cent). Limited studies in preterm and term infants also indicate a high level of magnesium absorption (55-75 per cent) from human milk and milk-based formulas. Thus, infant diets are likely to supply adequate amounts of magnesium for the growing infant. Magnesium deficiency and toxicity are therefore rare in term infants and usually a consequence of hormonal abnormalities and maternal use of pharmacological doses of magnesium. Low birth weight infants may exhibit hypomagnesaemia and benefit from magnesium supplementation.

Biological Availability

Structure of the human beta-casein encoding gene.

The entire human beta-casein-encoding gene, Bca, was cloned and sequenced. The gene consists of eight exons ranging from 21 to 531 nucleotides (nt) in length and extending over 10,466 nt. Exon-2 contains the translational start, the entire signal sequence and the codons for the two first amino acids of the mature protein. This corresponds to the organization found in other species. The translational stop is localized to exon-7. Exon/intron boundaries are in accordance with the AG/GT rule and conform to suggested consensus sequences. Splice junctions are located between coding triplets. In all other species analyzed, Bca has been found to consist of nine exons; however, within intron-2 of the human gene, a sequence omitted from human mRNA, but corresponding to exon-3 of other known Bca genes, was revealed.

Amino Acid Sequence

A randomized study of the effects of aerobic exercise by lactating women on breast-milk volume and composition.

BACKGROUND: The potential risks and benefits of regular exercise during lactation have not been adequately evaluated. We investigated whether regular aerobic exercise had any effects on the volume or composition of breast milk. METHODS: Six to eight weeks post partum, 33 sedentary women whose infants were being exclusively breast-fed were randomly assigned to an exercise group (18 women) or a control group (15 women). The exercise program consisted of supervised aerobic exercise (at a level of 60 to 70 percent of the heart-rate reserve) for 45 minutes per day, 5 days per week, for 12 weeks. Energy expenditure, dietary intake, body composition, and the volume and composition of breast milk were assessed at 6 to 8, 12 to 14, and 18 to 20 weeks post partum. Maximal oxygen uptake and the plasma prolactin response to nursing were assessed at 6 to 8 and 18 to 20 weeks. RESULTS: The women in the exercise group expended about 400 kcal per day during the exercise sessions but compensated for this energy expenditure with a higher energy intake than that recorded by the control women (mean [+/- SD], intake, 2497 +/- 436 vs. 2168 +/- 328 kcal per day at 18 to 20 weeks; P < 0.05). Maximal oxygen uptake increased by 25 percent in the exercising women but by only 5 percent in the control women (P < 0.001). There were no significant differences between the two groups in maternal body weight or fat loss, the volume or composition of the breast milk, the infant weight gain, or maternal prolactin levels during the 12-week study. CONCLUSIONS: In this study, aerobic exercise performed four or five times per week beginning six to eight weeks post partum had no adverse effect on lactation and significantly improved the cardiovascular fitness of the mothers.

Adult

Acrodermatitis enteropathica, zinc metabolism, copper status, and immune function.

OBJECTIVE: To study zinc metabolism, copper status, and immune function in a patient with acrodermatitis enteropathica. RESEARCH DESIGN: Case report. PATIENT: A 16-year-old boy with acrodermatitis enteropathica. INTERVENTION: Change of zinc supplementation dosage from 1000 to 525 mumol/d. MEASUREMENTS AND RESULTS: Zinc metabolism was studied with an oral dose of zinc chloride Zn 65 and whole-body counting at both zinc dosages. Zinc, copper status, and immune indexes were also measured at both dosages. The higher dosage of zinc supplementation was found to induce a state of low copper status and immune dysfunction. Lowering the dosage normalized these indexes. Zinc absorption in this patient was found to be within the reference range for healthy subjects. At the lower dosage, zinc retention and the rate of whole-body turnover also normalized. These results suggest that the primary lesion in acrodermatitis enteropathica is a cellular defect in zinc metabolism rather than an impairment of zinc absorption. CONCLUSION: Zinc and copper status and immune function should be monitored regularly in patients with acrodermatitis enteropathica to provide a proper dosage of zinc during different physiologic stages.

Acrodermatitis

Lactoferrin receptors in intestinal brush border membranes.

Lactoferrin from milk may have a physiological effect on the neonate by stimulating iron acquisition and/or mucosal growth. We have hypothesized that in order to achieve such an effect(s), lactoferrin will bind to a specific receptor located on the mucosal surface of the enterocyte. We have studied the presence of lactoferrin receptors in the brush border membrane from infant rhesus monkey intestine and from fetal and infant human intestine. The receptor exhibits saturation kinetics and the binding is specific for human and monkey lactoferrin--bovine lactoferrin or human transferrin do not bind to the receptor or compete with the binding of the primate lactoferrins. Enzymatic deglycosylation does not affect the binding of human lactoferrin to its receptor, suggesting that the glycan(s) is not needed for receptor recognition. Competitive binding experiments showed that holo-lactoferrin was more effective than less Fe-saturated forms of lactoferrin with regard to receptor binding. Mn-lactoferrin bound to the receptor, while we were unable to prepare Zn-lactoferrin in any physiological buffer. The human lactoferrin receptor was isolated and found to have a MW of approximately 110 kDa. This receptor has now been cloned and is being sequenced.

Animals

Isolation and characterization of a 21 kDa whey protein in rhesus monkey (Macaca mulatta) milk.

A soluble protein in Rhesus monkey milk was isolated to apparent homogeneity by FPLC gel filtration, anion-exchange and reverse-phase chromatography. It is a major milk protein and is present at 2.5-3.0 mg/ml milk throughout lactation. It is only found in the whey fraction of milk; acid precipitation of casein does not result in any significant change in its concentration. A molecular weight (MW) of about 21.6 kDa was estimated from gel filtration and SDS gel electrophoresis and also calculated from its amino acid composition. The amino acid composition of this protein is similar to that of bovine beta-lactoglobulin (beta-Lg), but it is larger in size, possibly representing a family of primate beta-Lgs.

Amino Acids

Nutritional aspects of soy formula.

Soy formula is a commonly used alternative to cows' milk formula. While its primary use has been for infants with milk protein allergy and lactose intolerance, soy formula is used increasingly for infants with gastrointestinal discomfort. The nutritional composition of soy formula has been designed to cover the nutrient needs of the newborn infant; however, some aspects of its composition need further consideration. The protein level of soy formula is usually higher than that of milk-based formulae, partially because of differences in protein digestibility and partly because of differences in amino acid composition. The presence of phytic acid in soy formula presents a problem with regard to mineral and trace element bioavailability. Several steps can be taken to minimize this problem, either by reducing the phytate content of soy protein isolate or by changing levels of minerals/trace elements in the formula. Finally, the high levels of manganese in soy formula present a potential problem in that manganese absorption and retention are high during infancy.

Amino Acids

Iron, zinc, copper and selenium status of breast-fed infants and infants fed trace element fortified milk-based infant formula.

Infants were fed cow's milk-based formulas containing 4 mg of iron/l from 1.5 to 6 months of age and their hematological status was compared to infants receiving the same formula but with 7 mg of iron/l and with breast-fed infants. One formula with 4 mg of iron/l contained iron as ferrous sulfate, in another, part of the iron was provided as bovine lactoferrin. We also studied the effect of selenium (10 micrograms/l) and copper (0.4 mg/l) supplementation on selenium and copper status. There were no significant differences in hematological indices among the groups at 6 months of age; all infants had satisfactory iron status. Serum transferrin receptor levels, a potential novel indicator of iron status, were highest in breast-fed infants, suggesting a cellular need for iron, and lowest in infants receiving formula with 7 mg of iron/l. Selenium status, as assessed by serum glutathione peroxidase activity, was similar at 6 months of age in breast-fed infants and infants fed formula fortified with selenium but lower in infants fed unfortified formula. The lowest levels of glutathione peroxidase activity were found in infants fed the highest concentration of iron (7 mg/l). Serum copper concentrations were similar in all groups, but the lowest levels were found in infants fed the highest concentration of iron. These results suggest that 4 mg of iron/l is adequate for infants up to 6 months of age and that higher levels may have some negative effects.

Blood Urea Nitrogen