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1.
The healthy young infant is immunologically adapted to receiving vast amounts of antigens in diet. At the age of 6 months, nine infants were put on a CM elimination diet for 3 weeks and then challenged with CM. Gut immune response was evaluated indirectly with ELISPOT assay at 6 months, after CM elimination (Day 1) and challenge (Day 8), and at 11 months. CM elimination decreased the numbers of immunoglobulin secreting cells (ISC): in the IgM class from mean [95% CI] 4969 [2555, 9653] at 6 months to 1716 [1024, 2873]/106 cells on Day 1 (t = 3. 14. p = 0.01); and in the IgG class from 5547 [3562, 8630] to 2684 [1383, 5208)/106 cells (t = 3. 29, p = 0.01). CM challenge further reduced interindividual variation, and at 11 months the scatter of ISC was comparable to that at 6 months. Specific antibody-secreting cells of the IgA and IgG class were seen at 6 months and again at 11 months, while specific IgM-secreting cells persisted throughout the dietary manipulation. The results indicate that diet profoundly affects the immune defense system, and further suggest that a focused immune response is vital in acquisition of tolerance to dietary antigens.  相似文献   

2.
The amounts of lactoferrin, lysozyme, total IgA, secretory IgA (SIgA), and specific SIgA antibodies to a pool of Escherichia coli O antigens were measured in 96-h collections of feces obtained from 28 very low birth weight infants, 28-30 wk of gestation, studied at 2.5 and 6 wk of age. Eighteen of these infants were fed their mothers' milk fortified with fractions of skim and cream derived from pasteurized, lyophilized, mature human milk (FM) and 10 infants were fed commercial cow's milk-based formula. The concentrations of these selected immune factors in the FM and formula also were measured. Specific SIgA antibodies to E. coli O antigens were detected in the feces of 90% of the FM-fed infants, but in none of the feces of the formula-fed infants. The feces obtained from FM-fed infants had markedly greater quantities of lactoferrin (p less than 0.001), lysozyme (p = 0.006), and IgA (p less than 0.001) than those of cow's milk formula-fed infants. The concentrations of total and secretory IgA were correlated significantly (r = 0.88, p less than 0.001) and 95% of total IgA was SIgA. The fecal concentration of specific SIgA antibodies to E. coli O antigens in FM-fed infants correlated with the concentration of these antibodies in their milk (p less than 0.001). However, there were no direct relationships between the milk concentrations or the infant's intakes of the other selected immune factors and the excretion of these factors in the feces.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

3.
To assist in identifying factors that determine the clinical outcome of cow milk allergy, we subjected to rechallenge 37 patients with a history of cow milk allergy, mean (+/- SD) age 27.6 +/- 7.1 months, after a follow-up of 13.5 +/- 5.1 months with a milk-free diet. A solid-phase enzyme-linked immunoassay was used to assess the total number of immunoglobulin-secreting and specific antibody-secreting cells among peripheral blood lymphocytes primed during provocation by milk antigens, giving indirect evidence of local immune response in the gut. Patients with persistent cow milk allergy (n = 13) had milder reactions at rechallenge than they had shown at the time of diagnosis. Numbers of immunoglobulin-secreting cells in these patients increased significantly from a geometric mean (95% confidence interval) in the IgA class of 1570 (1009, 2445) to 2984 (1941, 4583) IgA-secreting cells/10(6) cells, in the IgG class of 1445 (1067, 1959) to 2740 (1698, 4425) IgG-secreting cells/10(6) cells, and in the IgM class of 842 (534, 1325) to 2235 (1429, 3495) IgM-secreting cells/10(6) cells. By contrast, in patients (n = 24) who had acquired cow milk tolerance, the number of immunoglobulin-secreting cells did not increase during provocation. The total number of IgA-secreting cells before rechallenge was significantly higher than it had been before the initial challenge. The patients who acquired cow milk tolerance also had specific antibody-secreting cells of IgA isotype before the second challenge. These results indicate that in cow milk allergy the ability to mount a local immune response against cow milk antigens, particularly in the IgA class, is related to the suppression of clinical sensitivity.  相似文献   

4.
The first months of life represent a critical period for the maturation of the infant's immune system and, thus, a window of opportunity for measures to reduce the risk of disease. We hypothesized that specific probiotics might promote mucosal immunologic maturation in formula-fed infants. The numbers of cow's milk-specific and total IgA-secreting cells were measured at 3, 7, and 12 mo of age in a double-blind placebo-controlled study of 72 infants with early artificial feeding. The infants consumed infant formula supplemented with specific probiotics (Lactobacillus GG and Bifidobacterium lactis Bb-12) or placebo during the first year of life. Further analyses of the serum concentrations of the IgA-inducing cytokine TGF-beta2 and the soluble innate microbial receptor sCD14 were conducted. The numbers of cow's milk-specific IgA secreting cells were significantly higher in infants receiving probiotics compared with those receiving placebo (p = 0.045, ANOVA for repeated measures). At 12 mo of age, the serum concentrations of sCD14 were 1479 pg/mL [95% confidence interval (CI) 1373-1592] in infants receiving probiotics and 1291 pg/mL (95% CI 1152-1445) in infants receiving placebo (p = 0.046). Administration of the probiotics Lactobacillus GG and Bifidobacterium lactis Bb-12 at the time of introduction of cow's milk in the infant's diet results in cow's milk-specific IgA antibody responsiveness that may be the result of increased production of sCD14.  相似文献   

5.
Breastfeeding may increase the rate of mucosal maturation and IgA production. We sought to determine the effect of breastfeeding vs. formula-feeding on the maturation of oral mucosa by measuring the salivary total antibodies and cow's milk protein-specific IgA. Fifty-eight saliva samples were collected from 39 healthy, full term infants. At the age of 3 months (n = 25) eight infants received only breast milk and seventeen formula (cow's milk based n = 10, hydrolysed n = 7) and breast milk; and at the age of 6 months (n = 33) eleven received breast milk, seventeen formula and breast milk and five were not breastfed any more (cow's milk based n = 14, hydrolysed n = 8). Total IgA, IgG, IgM and protein, and β-lactoglobulin specific IgA were measured from saliva with enzyme-linked immunoassay (ELISA). The antibody results were proportioned to total protein. No differences in antibody levels between the feeding groups were found at 3 months of age. At 6 months, total IgA, total IgM and β-lactoglobulin-specific IgA were higher among the breastfed infants compared to those receiving formula as supplement to breast milk or not breastfed any more (breast milk vs. any formula p = 0.029, p = 0.015, p = 0.058; breast milk vs. cow's milk formula p = 0.025, p = 0.044, p = 0.038). To conclude, breastfeeding stimulated the mucosal immune system to produce IgA to saliva, which is a marker for immunological maturation and likely provides protection against environmental antigens.  相似文献   

6.
Between April 1984 and August 1984, a national survey, the Ross Laboratories Infant Nutrition Survey, was undertaken to assess patterns of food consumption of American infants ranging in age from 6.5 months to 13.4 months. Nutrient intakes of 865 infants were evaluated according to different foods (milk and milk products, non-iron-fortified formula, iron-fortified formula, infant cereal, commercial baby foods, and home-prepared table foods). Results indicated that most American infants consumed nutrients in appropriate amounts. However, a large proportion of infants who were fed a diet that included cow's milk received amounts of sodium, potassium, and chloride that exceeded the recommended safe and adequate ranges. The median intake of iron of infants fed either cow's milk or a non-iron-fortified formula was below the recommended dietary allowance; a low percentage of these infants received medicinal iron supplementation. The results also indicated that the median estimated renal solute load of the diet of infants fed cow's milk was approximately twice the amount of that of infants fed formula. These data may be useful in the development of nutritional programs for older infants.  相似文献   

7.
OBJECTIVE--To study the hypothesis that ingestion of a modified soy-based formula with an improved mineral suspension system may result in bone mineral content similar to that observed in infants fed human milk or cow milk-based formulas. DESIGN--Prospective, self-selected group of infants fed human milk randomized between the two formula-fed groups. SETTING--University-based hospital nursery and follow-up. PARTICIPANTS--Fifty-six normal, healthy, full-term infants, free of major malformations or disorders, including 17 infants fed human milk, 19 infants fed a cow milk-based formula, and 20 infants fed a soy protein formula were followed up to 6 months' postnatal age. The soy-based formula studied was modified to improve the suspendability of the minerals. INTERVENTIONS--Infants were fed human milk or the study formula for the first 4 months, at which time beikost was permitted. Infants fed human milk received vitamin supplementation to provide 400 IU of vitamin D per day. MEASUREMENTS--Anthropometric variables, serum calcium, magnesium, phosphorus, alkaline phosphatase, and parathyroid hormone levels were measured at enrollment, and at 8, 16, and 24 to 26 weeks' postnatal age. Bone mineral content at the distal third radius site was measured with single photon absorptiometry at these times. Growth in the infants did not differ significantly among the groups. There was no significant difference in serum calcium, magnesium, alkaline phosphatase, or parathyroid hormone concentrations among the infants during the study. Serum phosphorus was significantly lower at 8 weeks in the group fed human milk than in that fed the cow milk-based formula. Bone mineral content at 16 and 24 to 26 weeks was higher in the group fed the soy-based formula than in that fed human milk, and bone width was also higher at 16 weeks in the infants fed the soy-based formula. CONCLUSIONS--Improving the suspendability of the mineral system in the soy formula results in bone mineralization in infants fed the soy-based formula similar to that measured in infants fed human milk and cow milk-based formula. We suggest that the suspendability of the minerals used is an important variable in the interpretation of the effect of feedings on the bone mineral status of infants.  相似文献   

8.
OBJECTIVES: In order to measure the immune response evoked in breast-fed infants with cow's milk allergy (CMA) by cow's milk challenge through human milk, mothers were given increasing doses of cow's milk after they had been on a cow's milk elimination diet. Another objective was to study the secretion of beta-lactoglobulin (BLG) into human milk before and during milk challenge in relation to the appearance of symptoms in infants. STUDY DESIGN: Seventeen asymptomatic mothers who had infants with challenge-proven CMA and 10 asymptomatic mothers who had healthy infants were recruited. Infants ranged in age from 1.8 to 9.4 months. A solid-phase enzyme-linked immunoassay (ELISPOT) was used to assess the total number of immunoglobulin-secreting and specific antibody-secreting cells. Flow cytometry was used to enumerate different lymphocyte subpopulations among peripheral blood lymphocytes primed during provocation by cow's milk antigens. BLG levels were assessed in human milk before the challenge and 1, 2, 3, and 4 hours after the commencement of the challenge. RESULTS: All but one of the infants with CMA showed symptoms of CMA during cow's milk challenge through human milk. There was a significant rise in the total number of immunoglobulin-secreting cells in the IgA and IgG classes associated with a positive cow's milk challenge response, but the proportions of peripheral blood B cells bearing CD19, CD23, CD19 and 23, CD5, or CD19 and CD5 were comparable. BLG levels were comparable in both study groups. CONCLUSIONS: Most of the infants with CMA reacted to cow's milk challenge through human milk. Hypersensitivity reactions to food antigens through human milk may be more common than previously thought.  相似文献   

9.
The objective of this study was to evaluate the benefit of screening for anemia in infants in relation to their previous diet. The iron status of 854 nine-month-old infants on three different feeding regimens and on a regimen including iron dextran injection was determined by analysis of hemoglobin, serum ferritin, and erythrocyte protoporphyrin levels and of serum transferrin saturation. Infants were categorized as having iron deficiency if two or three of the three biochemical test results were abnormal and as having iron deficiency anemia if, in addition, the hemoglobin level was less than 110 gm/L. The prevalence of iron deficiency was highest in infants fed cow milk formula without added iron (37.5%), intermediate in the group fed human milk (26.5%), much lower in those fed cow milk formula with added iron (8.0%), and virtually absent in those injected with iron dextran (1.3%). The corresponding values for iron deficiency anemia were 20.2%, 14.7%, 0.6%, and 0%, respectively. The use of iron supplements is therefore justified in infants fed cow milk formula without added iron, even when there is no biochemical evidence of iron deficiency. The low prevalence of iron deficiency in the group fed iron-fortified formula appears to make it unnecessary to screen routinely for anemia in such infants. These results also support the recommendation that infants who are exclusively fed human milk for 9 months need an additional source of iron after about 6 months of age.  相似文献   

10.
The effects of fortified human milk feedings on the urinary excretion of lactoferrin, lysozyme, secretory component, IgA, and secretory IgA antibodies to Escherichia coli O antigens were investigated in very low birth wt infants. Infants were maintained on either a human milk or a cow's milk preparation. The amounts of each immune factor that were ingested and excreted were quantified during balance studies conducted at 2.5 and 5 wk of age. Serum levels of these immune factors were similar in both feeding groups. The urinary excretion of all factors except lysozyme was 7- to 150-fold greater in infants fed human milk than in those fed cow's milk formula. IgA was the only factor for which the amount of the factor excreted correlated with the amount ingested. Fragments as well as whole molecules of lactoferrin were found in the urine of the infants fed human milk, but the molecular sizes of the excreted proteins exceeded those normally filtered by the kidneys. Therefore, the genesis of the enhanced levels of host defense factors in the urine of infants fed human milk is not clear. Gastrointestinal absorption and subsequent renal excretion as well as enhanced production of immune factors in the infant's urinary tract are possible explanations.  相似文献   

11.
Background: Early exposure to cow’s milk (CM) proteins have been implicated in the pathogenesis of type 1 diabetes (T1D). Objective: We analyzed the development of the humoral immune response to dietary CM proteins in early childhood and its relation to later T1D. Subjects and methods: We studied a subgroup of 94 children randomized to be weaned to a CM‐based infant formula in the trial to reduce insulin‐dependent diabetes mellitus in the genetically at risk (TRIGR) pilot study. All subjects carried human leukocyte antigen‐conferred T1D susceptibility and had an affected first‐degree relative. After 7 years of follow‐up, 8 subjects had progressed to T1D, 15 had at least one disease‐associated autoantibody, and 71 remained autoantibody negative (controls). Immunoglobulin (Ig) G and IgA class antibodies to whole CM formula, beta‐lactoglobulin (BLG), bovine serum albumin, and alpha‐casein and IgG antibodies to bovine insulin (BI) were measured with enzyme‐linked immunosorbent assays from sequential samples. Results: The children with later T1D showed increased IgG levels to BLG from 3 to 18 months of age (p = 0.028) and enhanced IgA levels to CM formula at the age of 9 months (p = 0.022) compared with controls. In the children with an affected father or sibling, IgG antibodies to BI were higher in autoantibody‐positive subjects than in autoantibody‐negative subjects at 18 months of age (p = 0.022). Conclusion: An enhanced humoral immune response to various CM proteins in infancy is seen in a subgroup of those children who later progress to T1D. Accordingly, a dysregulated immune response to oral antigens is an early event in the pathogenesis of T1D.  相似文献   

12.
Immunologic consequences of feeding infants with cow milk and soy products   总被引:1,自引:0,他引:1  
Various products and regimens proposed for feeding infants when the mother's milk is not available have been evaluated intensively for capacity to achieve optimal nutrition. The immunologic consequences of feeding the foreign proteins contained in the various products have received much less attention and no systematic investigations have been done for comparable immunologic evaluation. Sera obtained at intervals from normal infants fed cow milk and soybean products from birth in different regimens were analyzed for antibodies to five major milk proteins and a soy protein isolate. Antibody levels increased slowly during the first 4 months, reaching a peak about 6 months of age. In infants fed cow milk products or a soy product from birth to 112 days of age and then given various cow milk products the following antibody responses were observed: The level of serum antibodies attained was highest with pasteurized cow milk and lower with heat-treated cow milk or a milk base formula of lower protein content. Feeding a soy product from birth for 112 days did not prevent a brisk antibody response to cow milk introduced subsequently, comparable to or greater than the antibody response seen when cow milk products were fed from birth. Clinically no immunologic disorders were detected in association with antibody responses to the various products and regimens. The implications of the findings for infant feeding and immunologic disorders are discussed.  相似文献   

13.
IMMUNOLOGIC CONSEQUENCES OF FEEDING INFANTS WITH COW MILK AND SOY PRODUCTS   总被引:1,自引:0,他引:1  
ABSTRACT. Various products and regimens proposed for feeding infants when the mother's milk is not available have been evaluated intensively for capacity to achieve optimal nutrition. The immunologic consequences of feeding the foreign proteins contained in the various products have received much less attention and no systematic investigations have been done for comparable immunologic evaluation. Sera obtained at intervals from normal infants fed cow milk and soybean products from birth in different regimens were analyzed for antibodies to five major milk proteins and a soy protein isolate. Antibody levels increased slowly during the first 4 months, reaching a peak about 6 months of age. In infants fed cow milk products or a soy product from birth to 112 days of age and then given various cow milk products the following antibody responses were observed: The level of serum antibodies attained was highest with pasteurized cow milk and lower with heat-treated cow milk or a milk base formula of lower protein content. Feeding a soy product from birth for 112 days did not prevent a brisk antibody response to cow milk introduced subsequently, comparable to or greater than the antibody response seen when cow milk products were fed from birth. Clinically no immunologic disorders were detected in association with antibody responses to the various products and regimens. The implications of the findings for infant feeding and immunologic disorders are discussed.  相似文献   

14.
BACKGROUND: Hypoallergenic infant formulas (HAF) were developed for atopy prevention in infants with high risk of atopy if these cannot be breastfed. HAF mount an antigen-specific immune response in infants. The aim of the study was to analyse the immune response in infants fed with a new infant formula based on a whey hydrolysate (HAF) and to compare it with that of exclusively breastfed controls. PATIENTS AND METHODS: Plasma concentrations of cow milk-specific IgE were analysed in 94 infants with high risk of atopy, 44 were exclusively breastfed, 50 were fed with HAF. In addition, cow milk-specific IgG antibodies (26 breastfed, 30 fed with HAF) as well as proliferation of periph-eral blood mononuclear cells to bovine beta-lactoglobulin (BLG) (41 breastfed, 47 fed with HAF) were tested. Specific IgE and IgG antibodies were determined using enzymoimmunometric assay (Alastat). Cellular proliferation was measured using tritiated thymidine incorporation assay after 6 day stimulation with BLG. RESULTS: Elevated IgE to cow milk antibodies (> 0.35 kU/L) were detected in two infants from the breastfed group and in one from the HAF-fed group. The plasma concentrations of milk specific IgG antibodies in HAF-fed infants were insignificantly higher than those in breastfed ones. No significant difference was found in bovine BLG-specific cell proliferation between both groups. CONCLUSION: Concerning the properties investigated like antigenicity, allergenicity and immunogenicity, the extensively hydrolysed whey based hypoallergenic formula does not significantly differ from mother milk in 6 month-old infants with an increased atopy risk.  相似文献   

15.
Because feeding of cow milk causes normal infants to lose increased amounts of occult blood from the gastrointestinal tract, we conducted a prospective trial to measure intestinal blood loss quantitatively and to monitor iron nutritional status. Fifty-two infants entered the trial at 168 days of age and were assigned at random to receive either cow milk or a milk-based formula. Initially, 31 infants had been breast-fed and 21 had been fed formulas. With the feeding of cow milk, the proportion of guaiac-positive stools increased from 3.0% at baseline to 30.3% during the first 28 days of the trial (p less than 0.01), whereas the proportion of positive stools remained low (5.0%) with the feeding of formula. The proportion of guaiac-positive stools among cow milk-fed infants declined later, but for the entire trial it remained significantly (p less than 0.01) elevated. Stool hemoglobin concentration increased markedly with the introduction of cow milk, rising from a mean (+/- SD) of 622 +/- 527 micrograms/gm dry stool at baseline to 3598 +/- 10,479 micrograms/gm dry stool during the first 28 days of ingestion of cow milk. Among infants fed formula, stool hemoglobin did not increase and was significantly (p less than 0.01) less than in the cow milk group. Among infants fed cow milk, the increase in hemoglobin concentration tended to be greater for those who had initially been fed human milk than for those who had initially been fed formulas. Iron nutritional status was not significantly different between the two feeding groups. However, one infant became iron deficient after 4 weeks of ingesting cow milk. We conclude that cow milk feeding leads to increased intestinal tract blood loss in a large proportion of normal infants and that the amount of iron lost is nutritionally important.  相似文献   

16.
The incidence of necrotizing enterocolitis in the newborn infant has increased within the same time period that increasing emphasis has been placed on oral alimentation of very small infants. A prospective investigation was conducted to determine the nutritional efficacy as well as the incidence of necrotizing enterocolitis of a standard cow milk formula compared with an elemental formula. Sixteen infants who weighed less than 1,200 gm were randomized and fed one of the two formulas. The clinical status of the two groups was similar. Seven of eight (87.5%) infants fed the elemental formula and two of eitht (25%) fed the standard cow milk formula developed necrotizing enterocolitis (p less than 0.02). The hypertonicity of the elemental diet may have contributed to the increased incidence of necrotizing enterocolitis in infants fed this formula.  相似文献   

17.
This study investigated the effect of changing the formulas of colicky infants and addressed the methodologic flaws of earlier studies. Attention was paid to issues of designing a blind study, providing a washout period, and measuring and reproducing the effect. In this randomized, double-blind trial, three changes of formula were made: for each of four 4-day periods, colicky infants alternately received a casein hydrolysate formula (Nutramigen) and a formula containing cow milk. Mothers recorded crying in diaries and indicated which crying episodes they considered to have been caused by colic. Nine infants were started on Nutramigen and eight on the cow milk formula. With the first formula change there was significantly less crying and colic in infants when they were fed Nutramigen than when they were fed cow milk (p less than 0.01); with the second change there was less colic when infants were fed Nutramigen (p less than 0.05) but not significantly less crying. By the third change there were no significant differences between formulas. Further analyses demonstrated that there were more clinically meaningful positive responses (a change in crying by at least one third) to Nutramigen than to cow milk (p less than 0.05). However, only one subject had a clinically meaningful response in colic to all three formula changes. These results demonstrate that in some instances, colic improves with elimination of cow milk formula. However, the effect diminishes with time, and only infrequently is the effect reproducible.  相似文献   

18.
Breast feeding is thought to result in a lower incidence of iron deficiency than does the use of unfortified cow milk forumalas, but there is scant documentation for this belief. The relationship of breast and cow milk feeding to absorption of iron and to iron status was investigated in a total of 45 term infants at about six months of age. Iron absorption was measured by total body counting. Laboratory assessment of iron status was based on the serum ferritin, hemoglobin, mean corpuscular volume, and transferrin saturation. The results indicated that infants fed breast milk during the entire first six to seven months of life attained greater iron stores than did those fed a cow milk formula. Breast-fed infants absorbed an average of 49% of a trace dose of extrinsic iron administered during a breast feeding in contrast to about 10% reported to be absorbed from cow milk under similar conditions. The data indicate that term infants who are breast fed may not require routine administration of supplemental iron.  相似文献   

19.
The fatty acid profile of red blood cell phospholipids and the total phospholipid and cholesterol contents of erythrocyte membrane in preterm infants in the first month of life were studied. Influences of human milk and adapted formula and dietary nucleotides supplementation at a level similar to that found in human milk were evaluated. Nineteen preterm newborn infants with adequate weight for gestational age were fed their own mother's preterm human milk, 18 with a standard milk formula and 18 with the same formula supplemented with nucleotides. Blood samples were obtained at birth from cord blood, and at 30 days of age. At 1 month of life, linoleic acid rose in formula fed infants compared to those fed human milk (p less than 0.05) and relative amounts of 20:3w6, 20:4w6, 22:4w6, 22:5w6, and total polyunsaturates of the w6 series greater than 18 carbon atoms were significantly decreased in standard milk formula fed infants (p less than 0.05-0.01). No significant differences for these fatty acids were found between human milk and nucleotide milk formula infants. Docosahexaenoic acid (22:6w3) decreased from birth to 1 month of age in formula fed infants (p less than 0.01) but not in human milk fed infants. Infants fed nucleotide milk formula showed intermediate values for 20:3w6 and 20:4w6 (p less than 0.1) between infants fed human milk and those fed standard milk formula.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

20.
Small intestinal mucosa from 129 necropsies and 15 surgical specimens from infants aged from birth to 21 months was examined for the presence of cells containing IgA, IgM, and IgG using the PAP immunoperoxidase technique. Immunoglobulin containing cells were nearly always absent in infants under 1 week of age but occurred in the second week of life in infants who had had milk feeds. At this time, IgM containing cells were predominant, but IgA containing cells were more numerous by the sixth week. IgG containing cells were generally sparse. Parenterally fed infants who had received little or no intestinal milk showed significantly fewer immunoglobulin containing cells than those who had been fed normally, irrespective of gestation. Lack of stimulation by food and bacterial antigens may contribute to immunoglobulin containing cells failing to occur in these parenterally fed neonates.  相似文献   

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