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Biomedical subjects

B Lönnerdal

Publications and source records attributed to B Lönnerdal.

At least 19 recordsLinked to original sources
PubMed2005

Mammalian lactoferrin receptors: structure and function.

Mammalian lactoferrin (Lf) receptors are suggested to have pivotal roles for mediating multiple functions of Lf. In this review, we focus on current knowledge of the structure and function of mammalian Lf receptors, mainly the first cloned Lf receptor that has been shown to be expressed in the infant small intestine at high levels but also in virtually all other tissues. The small intestinal Lf receptor takes up iron from Lf into cells and presumably exerts other physiological functions. Other Lf receptors in various tissues have also been reported to mediate some functions of Lf, such as modulating immune function, inhibiting platelet aggregation and enhancing collagen gel contractile strength. The detailed mechanisms behind the receptor-Lf interactions still need to be elucidated.

Animals↗
PubMed2004

Effect of iron supplementation on cognition in Greek preschoolers.

OBJECTIVE: To examine effects of iron supplementation on vigilance, attention and conceptual learning in preschool children in Greece. DESIGN: Randomized Double-Blind Placebo Controlled trial of iron. Randomization stratified by iron status and day care center (DCC). SETTING: Nine public DCCs in Athens, Greece. SUBJECTS: In all, 49 3-4-y olds (21 anemic, 28 good iron status) with birth weight not less than 2500 g, currently healthy; benign past medical history, IQ > or =1 s.d. below the age-adjusted mean, serum Pb < or =200 ppb (none exceeded 50 ppb), and height, weight and head circumference for age > or =10th percentile. Anemia defined as: (1) pretreatment Hgb <112 g/l and TS <16% and ferritin <12 microg/L OR (2) Hgb rise of >10 g/l (T2-T0) with iron supplementation. Good iron status was defined as baseline levels of Hgb >120 g/l and either TS >20% or serum ferritin >12 microg/l. INTERVENTION: The intervention consisted of a 2-month supplementation of 15 mg iron (and MV) vs placebo (MV alone). RESULTS: After iron treatment, the anemic subjects made significantly fewer errors of commission (14% higher specificity, P<0.05), exhibited 8% higher accuracy (P<0.05) and were significantly more efficient (mean difference=1.09, P<0.05) than those given placebo. These effects of iron were not found among preschoolers with good iron status. No effects of iron treatment were found on the Oddity Learning task. CONCLUSIONS: This study demonstrated that iron supplementation of iron-deficient anemic preschoolers results in an improvement in discrimination, specifically selective attention.

Anemia, Iron-Deficiency↗
PubMed2004

Effects of weaning cereals with different phytate content on growth, development and morbidity: a randomized intervention trial in infants from 6 to 12 months of age.

BACKGROUND: Phytate decreases iron and zinc bioavailability and contributes to deficiencies of iron and zinc, potentially causing anaemia, poor psychomotor development, impaired growth and increased risk of diarrhoea and respiratory infections. AIM: To investigate whether a reduced dietary intake of phytate, either via extensively phytate-reduced infant cereals [milk cereal drinks (MCDs) and porridge] or a milk-based infant formula, would improve growth and development and reduce morbidity in infants. DESIGN: Infants (n = 300) were, in a double-blind design, randomized to three diet intervention groups from 6 to 12 mo of age-commercial MCD and porridge (CC group), phytate-reduced MCD and phytate-reduced porridge (PR group), or milkbased infant formula and porridge with regular phytate content (IF group)-then followed until 18 mo. Dietary intake, anthropometry, development (Bayley Scales of Infant Development) and episodes of infectious diseases were registered. RESULTS: There were no significant differences between study groups in growth, development or morbidity until 12 mo of age. The IF group had a 77% higher risk (95% CI: 1.05-2.97) of diarrhoea compared to the PR group during the 12-17-mo period. Infants with haemoglobin concentration (Hb) < 110 g/l at 12 mo had lower attained weight at 18 mo (11.14 kg vs 11.73 kg, p = 0.012). Infants with serum zinc (S-Zn) <10.7 pmol/l at 12 mo had higher risk of respiratory infections (RR = 1.74, 95% CI: 1.19-2.56) compared to controls. CONCLUSION: Phytate reduction had no effect on growth, development or incidence of diarrhoeal or respiratory infections. Infants with low Hb or low S-Zn may be at higher risk of poor growth and respiratory infections, even in this high-income population.

Anthropometry↗
PubMed2004

Is iron deficiency in infants and young children common in Scandinavia and is there a need for enforced primary prevention?

A significant problem in diagnosing infants and young children with iron deficiency (ID) and iron deficiency anemia (IDA) is that it is not clear how the biochemical markers used correspond to physiological outcomes such as growth, neurodevelopment and morbidity. Thus, the prevalence of iron deficiency and iron deficiency anemia in infants and young children is difficult to assess and therefore not really known. Recent studies have shown that iron metabolism is subjected to developmental changes during infancy, which affect indicators of iron status. Hence, better defined cut-off values for the indicators used are needed and, in particular, how they are correlated to functional outcomes.

Adolescent↗
PubMed2003

Serum ferritin and transferrin receptor concentrations during the transition from adolescence to adulthood in a healthy Swedish population.

AIM: As part of a longitudinal nutrition study of adolescents, changes in serum ferritin (s-Ft), serum transferrin receptors (s-TfR) and the TfR/Ft ratio from 15 to 21 y of age were studied in randomly selected Swedish adolescents. METHODS: Blood samples from 60 males and 66 females were drawn at 15, 17 and 21 y of age. RESULTS: In males, median s-Ft increased significantly from 33 microg l(-1) at 15 y to 96 microg l(-1) at 21 y, and in females, after a non-significant decrease at 17 y, from 27 at 15 y to 34 microg l(-1) at 21 y. Between 15 and 17 y, s-TfR increased significantly, in males from 5.9 to 7.7 microg l(-1), and in females from 5.2 to 7.6 microg l(-1), whereas s-TfR decreased significantly in both genders between 17 and 21 y. The log (TfR/Ft) ratio did not change in males between 15 and 17 y, but decreased significantly from 2.2 +/- 0.3 to 1.8 +/- 0.3 by the age of 21 y. In females, the TfR/Ft ratio increased significantly between 15 and 17 y, whereas a significant decrease was found by the age of 21 y. S-Ft <12 microg l(-1) at 15, 17 and 21 y was 3, 2 and 2% in males, and in females 18, 26 and 21%, respectively. CONCLUSION: This study shows an increase in s-Ft and a decline in s-TfR in males, indicating increased iron stores. In females, s-Ft did not increase significantly, whereas s-TfR and the TfR/Ft ratio decreased between 17 and 21 y, indicating that cellular iron needs were met.

Adolescent↗
PubMed2001

Molecular cloning and functional expression of a human intestinal lactoferrin receptor.

Lactoferrin (Lf), a major iron-binding protein in human milk, has been suggested to have multiple biological roles such as facilitating iron absorption, modulating the immune system, embryonic development, and cell proliferation. Our previous binding studies suggested the presence of a specific receptor for Lf (LfR) in the small intestine of newborn infants, which may facilitate iron absorption. We here report the cloning and the functional expression of the human intestinal LfR and the evidence of its involvement in iron metabolism. The entire coding region of the LfR cDNA was cloned by PCR based on amino acid sequences of the purified native LfR (nLfR). The recombinant LfR (rLfR) was then expressed in a baculovirus-insect cell system and purified by immobilized human Lf (hLf) affinity chromatography where binding of hLf to the rLfR was partially Ca(2+) dependent. The apparent molecular mass was 136 kDa under nonreducing conditions and 34 kDa under reducing conditions. 125I-hLf bound to the rLfR with an apparent K(d) of approximately 360 nM. These biochemical properties of the rLfR are similar to those of the nLfR. RT-PCR revealed that the gene was expressed at high levels in fetal small intestine and in adult heart and at lower levels in Caco-2 cells. PI-PLC treatment of Caco-2 cells indicated that the LfR is GPI anchored. In Caco-2 cells transfected with the LfR gene, 125I-hLf binding and 59Fe-hLf uptake were increased by 1.7 and 3.4 times, respectively, compared to those in mock-transfected cells. Our findings demonstrate the presence of a unique receptor-mediated mechanism for nutrient uptake by the newborn.

Adult↗
PubMed2001

High affinity binding of the transcobalamin II-cobalamin complex and mRNA expression of haptocorrin by human mammary epithelial cells.

Little is known about the acquisition of cobalamin by the mammary gland and its secretion into milk. Human milk and plasma contain at least two types of cobalamin binding proteins: transcobalamin II (TC) and haptocorrin (HC). In plasma, TC is responsible for the transport of cobalamin to tissues and cells; however, cobalamin in milk is present exclusively bound to HC. We show that human mammary epithelial cells (HMEC) exhibit high affinity for TC; Scatchard analysis revealed a single class of binding sites for the TC-[(57)Co]cyanocobalamin complex with a dissociation constant (K(d)) of 4.9 x 10(-11) M. Uptake of the TC-[(57)Co]cyanocobalamin complex at 37 degrees C was saturable by 24 h. Binding of free [(57)Co]cyanocobalamin to HMEC was not saturable and very limited binding of the HC-[(57)Co]cyanocobalamin complex was observed. Expression of the haptocorrin gene by HMEC was confirmed by Northern blot and PCR analysis. Thus, a specific cell surface receptor for the TC-cobalamin complex exists in the mammary gland and once cobalamin is internalized, it may be transferred to HC and subsequently secreted into milk as a HC-cobalamin complex.

Biological Transport↗
PubMed2001

DMT1 gene expression and cadmium absorption in human absorptive enterocytes.

Divalent metal transporter 1 (DMT1) is a transmembrane, proton-coupled metal ion transporter that is upregulated in the duodenum of iron-deficient rodents and in hereditary hemochromatosis patients, suggesting that it may constitute a key factor in the uptake of dietary iron. Functional expression studies in Xenopus oocytes have shown that DMT1 not only mediates transport of iron but also other divalent metal ions, including the toxic metal cadmium. In the present study, the correlation between the cadmium absorption process and gene expression of DMT1 was investigated in an experimental model of human absorptive enterocytes. Fully differentiated Caco-2 cells were grown in monolayers and treated with iron supplemented medium or control medium for 1, 3 or 7 days. At each time point, cadmium transport experiments across the Caco-2 cell monolayers were performed and gene expression of DMT1 measured. Iron treatment for 3 and 7 days resulted in a 50% reduction in the cadmium uptake and a 75% reduction in the transport of the metal across the basolateral membrane. No effects were observed at 24 h. Gene expression of DMT1 in the iron-treated Caco-2 cells was reduced by about 50% at 3 and 7 days and thus, correlated well with the uptake of cadmium. In summary, our results indicate that the uptake of cadmium into human absorptive enterocytes may be mediated by DMT1.

Animals↗
PubMed2001

Mutations affecting the calcium-binding site of myeloperoxidase and lactoperoxidase.

Both myeloperoxidase (MPO) and lactoperoxidase (LPO) contain high affinity bound calcium, which has been suggested to play a structural role. Asp-96 in MPO, a residue next to the histidine distal from the heme prosthetic group, has been assigned to the calcium-binding site of the enzyme by X-ray crystallography. Multiple sequence alignment of known animal peroxidases has revealed that the calcium-binding site is highly conserved. In this study, we replaced Asp-96 in MPO and the counterpart Asp-227 in LPO both with Ala by site-directed mutagenesis. The level of peroxidase activity in insect cells infected with recombinant baculoviruses and their culture supernatants was reduced to virtually zero as a result of these mutations. Immunoblotting revealed that these mutant peroxidases were expressed in the cells but not secreted as effectively as the wild-type enzymes. Our findings suggest that a functional calcium-binding site is essential for the biosynthesis of active animal peroxidases.

Amino Acid Sequence↗
PubMed2001

Immunological activities associated with milk.

Milk contains a multitude of components that can, or may, provide immune protection to the suckling offspring and that also may promote development of neonatal immune competence. In addition, these specialized factors are essential for the protection of the mammary gland, the offspring's food source, from pathogen colonization and lactation failure. Breast milk also facilitates the establishment of a gut flora that inhibits colonization by many pathogens and stimulates the growth of beneficial microorganisms. Maternal immunity can be transferred to the infant via antibodies, primarily of the sIgA type in humans, as well as by leukocytes including effector and memory T lymphocytes. In this way, protection is provided passively against the pathogens to which the mother has been exposed. Currently, there is much interest in determining the protective efficacy of oral supplementation with immunoglobulins from the milk of lactating animals hyperimmunized against specific pathogens. An array of immunostimulatory components in milk, notably cytokines, may be protected against intestinal proteolysis, thereby providing the offspring with a prepackaged immune response system. These components may help to boost the infant's immature immune system. At the same time, anti-inflammatory factors in breast milk help to modulate cytokine responses to infection, thereby facilitating defense while minimizing tissue damage such as that which occurs in infants with necrotizing enterocolitis. Undoubtedly, the many components constituting the repertoire of immune and immunomodulating agents in milk interact synergistically to protect both the mammary gland and the offspring from invading pathogenic microorganisms.

Animals↗
PubMed2001

Binding of transcobalamin II by human mammary epithelial cells.

The presence of nutrient binders in milk may have an important role during milk production and may influence the nutrient's bioavailability to the infant. Human milk and plasma contain at least two types of vitamin B12 binders: transcobalamin II (TCII) and haptocorrin (Hc). Vitamin B12 in milk is exclusively bound to Hc (Hc-B12). In plasma, the major vitamin B12 binding protein that is responsible for delivering absorbed vitamin B12 to most tissues and cells is TCII (TCII-B12). Currently, little is known about the route of secretion of vitamin B12 into human milk. It is possible that a receptor-mediated pathway is involved, since maternal vitamin B12 supplementation increases the amount of the vitamin secreted into human milk if the mother's vitamin B12 consumption is low, but remains unchanged if her intake is adequate. In this study, we investigated the process by which the mammary gland acquires vitamin B12 from maternal circulation, whether as a free vitamin or as a Hc-B12 or TCII-B12 complex. TCII was purified from plasma incubated with [57Co]vit B12 (B12*), while Hc was purified from whey incubated with B12*. Both proteins were separated by fast protein liquid chromatography using gel filtration and anion-exchange columns. Purity of the separated proteins was assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Binding studies were carried out on a monolayer of normal human mammary epithelial cells (HMEC) at 4 degrees C using free B12* and TCII-B12* and Hc-B12* complexes. Minimal binding of free B12* and Hc-B12* to HMEC was observed; however, HMEC exhibited a high affinity for the TCII-B12* complex. This study suggests that a specific cell surface receptor for the TCII-B12 complex exists in the mammary gland. It is possible that once vitamin B12 is in the mammary gland it is transferred to Hc (which may be synthesized by the mammary gland) and then secreted into milk as a Hc-B12 complex.

Breast↗
PubMed2001

Effects of type of fat in the diet on iron bioavailability assessed in suckling and weanling rats.

Differences in iron bioavailability from human milk and milk formulas may in part be due to differences in lipid composition. We investigated the short and long term effects of diets based on different fats [corn, coconut, olive, or soy oil, human milk fat (HMF) and a formula fat blend (FF)] on iron absorption in rats. Suckling rat pups dosed with 59Fe-labeled diets containing different fat sources were killed after 6 h, and blood and individual tissues were counted. Iron availability was estimated by % 59Fe in blood. Pups dosed with a more saturated fat (coconut oil) had a higher % 59Fe in blood than those fed other fat sources. Weanling rats were used to determine iron bioavailability from fat sources using both the hemoglobin repletion method and whole body counting. Hemoglobin regeneration was significantly higher for rats fed the HMF diet (8.4 +/- 0.5 g/dl) than from the FF diet (6.5+/-0.6 g/dl) or the corn oil diet (less saturated) (6.4 +/- 0.3 g/dl). Rats fed diets based on coconut oil (more saturated) had significantly higher % 59Fe retention (61.6 +/- 1.4) than rats fed diets based on FF (49.8 +/- 3.4). There was a significant positive association between oleic acid in the diet and oleic acid in the intestinal mucosa (r = 0.95, p < 0.05) and between linoleic acid in the diet and linoleic acid in the intestinal mucosa (r = 0.97, p < 0.05) suggesting that the dietary treatment altered the fatty acid composition of the brush border membrane. Our results suggest that saturated fats may increase iron absorption and that part of this may be achieved by changes in the fatty acid composition of the intestinal mucosa. Hemoglobin regeneration and % 59Fe retention data suggest that differences in iron absorption from infant diets may in part be due to differences in fat composition. Therefore, lipid composition of infant formulas should also be taken into consideration as a factor influencing iron bioavailability.

Animals↗
PubMed2001

Inhibition of Escherichia coli respiratory enzymes by the lactoperoxidase-hydrogen peroxide-thiocyanate antimicrobial system.

AIMS: The lactoperoxidase-hydrogen peroxide-thiocyanate antimicrobial system (LPAS) is known to inhibit bacterial respiration. In the present study, several respiratory enzymes of Escherichia coli were compared in terms of their susceptibility to the LPAS. METHODS AND RESULTS: Exposure of E. coli to the LPAS, upon which 99.6% of the bacteria were killed, resulted in the following percentage of inactivation of substrate-specific membrane oxidases: succinate (94.2%) > NADH (84.6%) > glycerol-3-phosphate (67.8%) > DL-lactate (64.1%). With the same treatment, substrate-specific membrane dehydrogenases were inactivated as follows: succinate (99.1%) > DL-lactate (53.8%) > glycerol-3-phosphate (45.0%) > NADH (36.8%). Terminal oxidase, however, measured using a ubiquinone analogue (2,3-dimethoxy-5-methyl-6-decyl-1,4-benzoquinone) after reduction, was only 21.4% inactivated by the LPAS. CONCLUSION: These data suggest that dehydrogenases are the primary targets of the LPAS in the respiratory chain of E. coli. SIGNIFICANCE AND IMPACT OF THE STUDY: This study has determined for the first time the primary targets of LPAS in the bacterial respiratory chain.

Anti-Bacterial Agents↗
PubMed2001

Iron supplementation of breast-fed Honduran and Swedish infants from 4 to 9 months of age.

OBJECTIVE: The objective was to study the effects of iron supplementation on hemoglobin and iron status in 2 different populations. STUDY DESIGN: In a randomized, placebo-controlled, masked clinical trial, we assigned term Swedish (n = 101) and Honduran (n = 131) infants to 3 groups at 4 months of age: (1) iron supplements, 1 mg/kg/d, from 4 to 9 months, (2) placebo, 4 to 6 months and iron, 6 to 9 months, and (3) placebo, 4 to 9 months. All infants were breast-fed exclusively to 6 months and partially to 9 months. RESULTS: From 4 to 6 months, the effect of iron (group 1 vs 2 + 3) was significant and similar in both populations for hemoglobin, ferritin, and zinc protoporphyrin. From 6 to 9 months, the effect (group 2 vs group 3) was significant and similar at both sites for all iron status variables except hemoglobin, for which there was a significant effect only in Honduras. In Honduras, the prevalence of iron deficiency anemia at 9 months was 29% in the placebo group and 9% in the supplemented groups. In Sweden, iron supplements caused no reduction in the already low prevalence of iron deficiency anemia at 9 months (<3%). CONCLUSION: Iron supplementation from 4 to 9 months or 6 to 9 months significantly reduced iron deficiency anemia in Honduran breast-fed infants. The unexpected hemoglobin response at 4 to 6 months in both populations suggests that regulation of hemoglobin synthesis is immature at this age.

Age Factors↗
PubMed2001

Absorption of iron from unmodified maize and genetically altered, low-phytate maize fortified with ferrous sulfate or sodium iron EDTA.

BACKGROUND: Reducing the phytate content in grains by genetic manipulation is a novel approach to increasing nonheme-iron absorption from mixed diets. Fractional iron absorption from a genetically modified strain of low-phytate maize (LPM) increased significantly, by 50%. OBJECTIVE: We assessed iron absorption from porridges prepared from the same LPM (lpa-1-1 mutant) and unmodified wild-type maize (WTM), both of which were fortified with either ferrous sulfate or sodium iron EDTA. DESIGN: Porridges providing 3.4 mg Fe were fortified with either ferrous sulfate or sodium iron EDTA to provide an additional 1 mg Fe/serving. In 14 nonanemic women, iron absorption was measured as the amount of radioiron incorporated into red blood cells (extrinsic tag method) 12 d after consumption of the study diets. RESULTS: No significant effect of phytate content on iron absorption was found when porridge was fortified with either sodium iron EDTA or ferrous sulfate. Fractional absorption of iron from WTM porridge fortified with sodium iron EDTA (5.73%) was 3.39 times greater than that from the same porridge fortified with ferrous sulfate (1.69%). Fractional absorption of iron from the sodium iron EDTA-fortified LPM porridge (5.40%) was 2.82 times greater than that from LPM porridge fortified with ferrous sulfate (1.91%) (P<0.0001 for both comparisons, repeated-measures analysis of variance). Thus, the previously identified benefit of LPM was no longer detectable when maize porridge was fortified with additional iron. CONCLUSION: Iron was absorbed more efficiently when the fortificant was sodium iron EDTA rather than ferrous sulfate, regardless of the type of maize.

Adult↗
PubMed2001

Extent of thermal processing of infant formula affects copper status in infant rhesus monkeys.

BACKGROUND: Infant rhesus monkeys are excellent models in which to study the effect of infant formulas on trace element absorption and status. Infants fed powdered formula from birth exhibit normal growth and have blood variables similar to those of breast-fed infants. OBJECTIVES: The objectives were to evaluate the effects of feeding ready-to-feed (RTF) formulas exposed to different heat treatments to infant monkeys, and, for one of these formulas, to compare the effect of fortification with 2 iron concentrations. DESIGN: From birth to age 5 mo, infant monkeys (n = 6/group) were fed one of the following formulas exclusively: 1) 12 mg Fe/L processed in cans (RTF-12), 2) formula in glass bottles with 12 mg Fe/L and manufactured by an ultrahigh-temperature (UHT) process (UHT-12), or 3) formula manufactured by a standard thermal process (STP), containing either 8 (STP-8) or 12 (STP-12) mg Fe/L. All formulas had similar copper concentrations (0.6 mg Cu/L). Anthropometric measures and venous blood samples were taken monthly. RESULTS: Weight and length gain did not differ among groups; however, the STP-12 group weighed less than the UHT-12 group at ages 2, 4, and 5 mo. Hemoglobin values were significantly lower in the RTF-12 group than in all other groups at ages 4 and 5 mo and serum ferritin was lower in the RTF-12 group than in the STP-12 group at age 5 mo. Copper status was lower in STP-12 infants than in STP-8 infants. There was a progressive and significant decline in plasma copper, ceruloplasmin, and Cu/Zn superoxide dismutase activity in infants fed canned formula (RTF-12). Furthermore, coat color changed from normal brown to silver. These outcomes suggest that the canned formula induced copper deficiency in infant monkeys. CONCLUSIONS: Excessive heat treatment of formula can have a pronounced negative effect on copper status. High iron concentrations did not improve iron status but may adversely affect copper status.

Animals↗
PubMed2001

Purification and quantification of lactoperoxidase in human milk with use of immunoadsorbents with antibodies against recombinant human lactoperoxidase.

BACKGROUND: Two heme-containing peroxidases, secretory lactoperoxidase and leukocyte-derived myeloperoxidase, which play host defense roles through antimicrobial activity, were previously identified in human colostrum. Within several days after the start of lactation, the relative contribution of myeloperoxidase to the peroxidase activity in milk was shown to decline as the number of milk leukocytes decreased. OBJECTIVE: Our knowledge of lactoperoxidase in human milk is still limited. The objective of this study was to use specific antibodies as a means of simplifying the purification and quantification of lactoperoxidase. DESIGN: Polyclonal antibodies were raised against recombinant human lactoperoxidase. Immunoglobulin G (IgG) was isolated by means of a protein A column and was characterized by immunoblotting. For the purification of lactoperoxidase from whey, a cation-exchange column and an immunoaffinity column with coupled IgG were used. The concentration of lactoperoxidase was determined by a sandwich enzyme-linked immunosorbent assay by using purified native lactoperoxidase as a standard. Native and biotinylated IgG were used as capture and detector antibodies, respectively. RESULTS: Two bands with molecular masses of approximately 80 and 100 kDa were detected in an immunoblot of human whey. Similar heterogeneity was observed in the sodium dodecyl sulfate-polyacrylamide gel electophoresis profile of purified lactoperoxidase. The mean (+/-SD) concentration of lactoperoxidase in 26 whey samples was estimated to be 0.77 +/- 0.38 mg/L. The concentrations were positively correlated with the peroxidase activity detected in these samples. CONCLUSION: Lactoperoxidase is commonly present in human milk throughout the lactation period and is likely to contribute to the protective effects of milk.

Antibodies↗