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Biomedical subjects

E Isolauri

Publications and source records attributed to E Isolauri.

At least 109 records · Page 6Linked to original sources

Suppression of lymphocyte proliferation in vitro by bovine caseins hydrolyzed with Lactobacillus casei GG-derived enzymes.

BACKGROUND: Processing of proteins in the gut and activation of T-cell suppression leads to systemic hyporesponsiveness to ingested protein antigens. OBJECTIVE: The study was designed to determine whether lactobacilli, a major part of human intestinal microflora, can contribute to degradation of food antigens in the gut and modify their immunoactivities. METHODS: Lymphocyte transformation tests were carried out in healthy adults to determine the mitogen-induced lymphocyte proliferative responses to bovine caseins hydrolyzed with pepsin and trypsin and to bovine caseins additionally hydrolyzed with enzymes derived from Lactobacillus casei strain GG (ATCC 53103). RESULTS: In experiments done with caseins hydrolyzed with pepsin and trypsin, beta- and alpha(s1)-caseins significantly suppressed the proliferation of lymphocytes at 0.1 and 10 micrograms/ml, respectively, when compared with corresponding control cultures without these hydrolysates. In contrast, kappa-casein significantly stimulated the proliferation of lymphocytes at 10 micrograms/ml. In experiments done with caseins additionally hydrolyzed with L. casei GG-derived enzymes, there was one consistent effect on lymphocyte proliferation: suppression by alpha(sl)-, beta-, and kappa-caseins at 0.1, 10, and 1000 micrograms/ml, respectively. CONCLUSIONS: Hydrolysis of caseins with L. casei GG-derived enzymes generates molecules with suppressive effects on lymphocyte proliferation. In addition, intestinal bacteria can be beneficial in the downregulation of hypersensitivity reactions to ingested proteins in patients with food allergy.

Adult↗

Combined skin prick and patch testing enhances identification of food allergy in infants with atopic dermatitis.

BACKGROUND: Early recognition of dietary allergies in infants with atopic dermatitis is essential for avoidance of unnecessary elimination diets, amelioration of the skin disease, and secondary prevention of the development of multiple food allergies. Simple and accurate methods of identifying provocative foods are urgently needed. METHODS: The usefulness of skin prick and patch tests as indicators of cow milk allergy was evaluated in 183 patients ranging in age from 2 to 36 months with double-blind, placebo-controlled (n = 118) or open (n = 65) cow milk challenges. RESULTS: The oral cow milk challenges were interpreted as positive in 54% of both challenge types. Positive challenge rapidly elicited pruritus, urticaria, and/or exanthema in 49% of cases and delayed-onset eczematous lesions in 51%. The skin prick and patch tests gave markedly discrepant results; prick tests were positive in 67% of the cases with acute-onset reactions to milk challenge, whereas patch tests tended to be negative. Patch tests were positive in 89% of those with delayed-onset reactions, although prick tests were frequently negative. CONCLUSIONS: The observations indicate that IgE and T cell-mediated responses to cow milk can be distinguished in atopic dermatitis. Parallel skin testing with combined prick and patch tests can significantly enhance the accuracy in diagnosis of specific dietary allergies in patients with atopic dermatitis.

Animals↗

Evaluation of the gut mucosal barrier: evidence for increased antigen transfer in children with atopic eczema.

BACKGROUND: Intestinal antigen handling determines subsequent immune response to the antigen. Antigens are absorbed across epithelium along two functional pathways. The main pathway is degradative, which reduces the immunogenicity of the antigen. A minor pathway allows the transport of intact proteins, which is crucial for antigen-specific immune responses. The Ussing chamber method allows the quantitative measurement of protein transfer across the intestinal mucosa. OBJECTIVE: This study was designed to explore the theory that altered antigen transfer across the intestinal mucosa is a factor in the pathogenesis of atopic eczema, characterized by hyperactivity to environmental antigens. METHODS: The absorption and degradation of horseradish peroxidase (molecular weight, 40,000 d) were studied in vitro in Ussing chambers. Eighteen biopsy specimens of upper small intestinal mucosa from 14 patients (aged 0.5 to 8 years) with atopic eczema and 18 specimens from 15 age-matched control subjects were examined. RESULTS: The mean (95% confidence interval) absorption of intact horseradish peroxidase was significantly higher in children with atopic eczema than in control subjects: 242 (81-404) pmol . hr(-1) . cm(-2) versus 23 (12-33) pmol . hr(-1) . cm(-2); t = 2.86, p = 0.007. The absorption of degraded horseradish peroxidase was 972 (732-1213) pmol . hr(-1) . cm(-2) in patients with atopic eczema and 672 (532-811) pmol . hr(-1) . cm(-2) in control subjects; t = 2.29, p = 0.03. CONCLUSIONS: Our results may reflect a primarily altered antigen transfer in patients who have atopic eczema, which may initiate and perpetuate prompt immune responses to common environmental antigens, including foods.

Allergens↗

Down-regulation of anti-CD3 antibody-induced IL-4 production by bovine caseins hydrolysed with Lactobacillus GG-derived enzymes.

A prerequisite for systemic hyporesponsiveness to dietary antigens is their processing in the gut. This study investigated whether bovine caseins degraded by enzymes of an intestinal bacterial strain, Lactobacillus GG (ATCC 53103), could regulate the cytokine production by anti-CD3 antibody-induced peripheral blood mononuclear cells of 14 atopic patients, aged 5-29 (mean, 16) months. Purified casein up-regulated the interleukin-4 and interferon-gamma production, P = 0.008 and P = 0.008, respectively. Conversely, Lactobacillus GG-degraded casein down-regulated the interleukin-4 production, P = 0.003, with no effect on interferon-gamma. These results indicate that intestinal bacteria may modify immunomodulatory properties of native food proteins and introduce a promising tool to provide protection from potentially harmful dietary antigens at a young age.

Adolescent↗

Increased bacterial urease activity in faeces in juvenile chronic arthritis: evidence of altered intestinal microflora?

The intestinal microflora was indirectly evaluated in juvenile chronic arthritis (JCA) by analysing enzyme activities--urease, beta-glucosidase and beta-glucuronidase--in faeces. In 18 out of 26 JCA patients, the illness had been diagnosed during the past year. The control group was composed of eight age-matched control patients and 18 family members of JCA patients (3-36 yr). The mean [95% confidence interval (CI)] urease activity, but not the activities of beta-glucosidase and beta-glucuronidase, in faeces from the JCA group differed from that in the control group: 32.3 (26.6-38.1) nmol/min/mg protein vs 24.0 (16.8-31.6), P = 0.07. The difference was more marked in a comparison of JCA patients with family members (P = 0.03). In a subgroup of subjects, the effect of 10 days oral bacteriotherapy with Lactobacillus GG on faecal enzyme activities was then investigated (n = 8 JCA patients, n = 8 control patients). This short-term oral bacteriotherapy reduced the increased urease activity in faeces of JCA patients. Keeping in mind the small number of subjects, it may be inferred from the present results that the increased urease activity in JCA is specific for the disease, suggesting altered intestinal microflora in JCA.

Administration, Oral↗

Intestinal inflammation in children with atopic eczema: faecal eosinophil cationic protein and tumour necrosis factor-alpha as non-invasive indicators of food allergy.

BACKGROUND: Food allergy is contemplated in atopic eczema. Early recognition of food allergies is difficult and the diagnosis is often missed because of the non-specificity of symptoms. New non-invasive tests are clearly needed. OBJECTIVE AND METHODS: We measured the concentrations of tumour necrosis factor-alpha, eosinophil cationic protein and alpha-1 antitrypsin in faeces as indicators of intestinal inflammation induced by double-blind placebo-controlled oral cow's milk challenge in infants and young children with atopic eczema. RESULTS: An increased alpha-1 antitrypsin concentration (> 2 mg/g) after cow's milk challenge was detected in 43% of the infants positive as compared with 11% of the infants negative to challenge, P = 0.02. The concentration of eosinophil cationic protein in faeces increased after cow's milk challenge in patients positive to challenge (P = 0.02) but not in those negative to challenge (P = 0.79). The concentration of eosinophil cationic protein was enhanced particularly in patients manifesting immediate-type reactions to the cow's milk challenge. The concentration of tumour necrosis factor-alpha increased after cow's milk challenge in patients positive to challenge (P = 0.005) but not in those negative to challenge (P = 0.25). The concentration of tumour necrosis factor-alpha in faeces was enhanced particularly in patients manifesting delayed-type reactions to the cow's milk challenge. CONCLUSION: We conclude that in children with atopic eczema food allergy is associated with intestinal inflammation indicating that more general immunologic disturbances than previously thought take place in these patients. We further suggest that faecal eosinophil cationic protein, tumour necrosis factor-alpha and alpha-1 antitrypsin distinctly indicate various reaction types of food allergy. Parallel testing with eosinophil cationic protein and tumour necrosis factor-alpha may significantly enhance the accuracy in diagnosis of food allergy in patients with atopic eczema.

Biomarkers↗

Age-dependent variation in the serum concentration of mannan-binding protein.

Mannan-binding protein (MBP) is an acute phase reactant, and its deficiency is associated with the common opsonic defect and suspectibility to infections and atopic constitution. The aim of this study was to investigate the changes occurring in the serum level of MBP in infancy and during later childhood. We studied the serum concentration of MBP in 611 Finnish children of different ages and 110 adults by using an enzyme immunoassay. In an analysis of successive serum samples from infants at the day of birth and at the ages of 1 and 5 months, and at 1 and 2 years, the serum concentration of MBP increased significantly after birth, and was at its highest (the mean and median were 8.13 and 8.49 mgl-1, respectively) at the age of 1 month. After that, it declined to the initial level until the age of 5 months. The MBP concentration continued to decrease during childhood, and after the age of 12 years the MBP values reached the adult level. In Finnish adults the mean and median concentrations of MBP were 4.48 and 4.02 mgl-1, respectively, which seem to be higher than those reported previously in other populations. The high concentration of MBP in infants may best be explained by exposure to novel environmental antigens in early childhood, which suggests a protective role for MBP during the period of immaturity of the immunosystem. In older children the high level of MBP can probably be explained by childhood infections and the ensuing need of MBP.

Acute-Phase Proteins↗

Promotion of IgA immune response in patients with Crohn's disease by oral bacteriotherapy with Lactobacillus GG.

The effect of oral bacteriotherapy with human Lactobacillus casei strain GG (10(10) colony-forming units twice daily for 10 days) was investigated in Crohn's disease and in juvenile chronic arthritis which are chronic inflammatory diseases associated with impaired mucosal barrier function. During oral bacteriotherapy, the gut immune response was indirectly assessed by solid-phase enzyme-linked immunoassay in 14 children with Crohn's disease, in 9 with juvenile chronic arthritis, and in 7 controls. The immunostimulatory effect of Lactobacillus GG was specific for Crohn's disease, irrespective of its activity: the mean (95% confidence interval) number of specific antibody secreting cells in the IgA class to beta-lactoglobulin increased significantly from 0.2 (0.04-1.3) to 1.4 (0.3-6.0)/10(6) cells and to casein from 0.3 (0.1-1.4) to 1.0 (0.2-4.8)/10(6) cells. The results indicate that orally administered Lactobacillus GG has the potential to increase the gut IgA immune response and thereby to promote the gut immunological barrier. Consequently, Lactobacillus GG could provide an adjunct nutritional therapy for Crohn's disease.

Adolescent↗

Improved immunogenicity of oral D x RRV reassortant rotavirus vaccine by Lactobacillus casei GG.

In a search for new strategies to improve oral vaccination, the effect of orally administered Lactobacillus casei strain GG (LGG) in conjunction with D x RRV rhesus-human reassortant live oral rotavirus vaccine was tested in 2-5-month-old infants. Infants who received LGG showed an increased response with regard to rotavirus-specific IgM secreting cells, measured using an ELISPOT technique, on day 8 after vaccination. In infants receiving LGG or placebo, respectively, a rotavirus IgM seroconversion was detected in 26/27 (96%), versus 23/27 (85%) cases (p = 0.15) and rotavirus IgA seroconversion was detected in 26/28 (93%) versus 20/27 (74%) cases (p = 0.05). These findings suggest that LGG has an immunostimulating effect on oral rotavirus vaccination. The clinical significance of LGG-enhanced immune responses to oral vaccines should be further evaluated.

Administration, Oral↗

Efficacy and safety of hydrolyzed cow milk and amino acid-derived formulas in infants with cow milk allergy.

OBJECTIVE: To determine the antigenicity, nutritional adequacy, and growth-promoting efficacy of protein hydrolysate or amino acid-derived formulas in infants with cow milk allergy. STUDY DESIGN: Several protein hydrolysate or amino acid-derived formulas were graded for beta-lactoglobulin content and skin reactivity in 74 atopic children with cow milk allergy proved by a double-blind, placebo-controlled challenge. A randomized, prospective follow-up study of 9 months included 22 infants with a mean age of 6 months (95% confidence interval, 4 to 7), who were fed an extensively hydrolyzed whey formula (group We), and 23 infants with a mean age of 17 (95% confidence interval, 4 to 7) months, who were given an amino acid-derived formula (group AA). RESULTS: Both formulas were clinically and biochemically tolerated. The mean concentration of essential amino acids in plasma was lower in group We but higher in group AA compared with values for breast-fed control infants (p = 0.001). There was a different trend between the groups in weight (p = 0.09) and length (p = 0.006). Growth was promoted in group AA during the follow-up; it was constant during the first months, followed by a gradual decline in rate in group We. In both groups, atopic eczema improved significantly and progressively, and a downward trend was found in serum total and milk-specific IgE concentrations, proving the efficacy of both formulas. CONCLUSIONS: Extensively hydrolyzed formulas are safe and effective for most infants; an amino acid-derived formula may be preferable for infants with multiple food allergies, especially for the maintenance of normal growth.

Amino Acids↗

Lactic acid bacteria in the treatment of acute rotavirus gastroenteritis.

We compared different lactic acid bacteria for their effect on the immune response to rotavirus in children with acute rotavirus gastroenteritis. After initial oral rehydration, 49 children aged 6 to 35 months with rotavirus gastroenteritis randomly received either Lactobacillus casei subsp. casei strain GG (LGG), L. casei subsp. rhamnosus (Lactophilus), or a combination of Streptococcus thermophilus and L. delbrückii subsp. bulgaricus (Yalacta) twice daily for 5 days. Serum antibodies to rotavirus, total number of immunoglobulin-secreting cells (ISC), and specific antibody-secreting cells (sASC) to rotavirus were measured at the acute stage and at convalescence. The mean (SD) duration of diarrhea was 1.8 (0.8) days in children who received LGG, 2.8 (1.2) days in those receiving Lactophilus, and 2.6 (1.4) days in those receiving Yalacta (F = 3.3, p = 0.04). The ISC response was comparable in the three study groups, but the rotavirus-specific immune responses were different. LGG therapy was associated with an enhancement of IgA sASC to rotavirus and serum IgA antibody level at convalescent stage. We conclude that certain strains of lactic acid bacteria, particularly LGG, promote serum and intestinal immune responses to rotavirus, and thus may be important in establishing immunity against rotavirus reinfections.

Acute Disease↗

Viable versus inactivated lactobacillus strain GG in acute rotavirus diarrhoea.

The effect of viable or heat inactivated human Lactobacillus casei strain GG on rotavirus immune responses in patients with rotavirus diarrhoea was assessed. Rotavirus serum IgA enzyme immunoassay antibody responses were higher in infants treated with viable L casei strain GG than in those treated with inactivated L casei strain GG. There was a significant difference at convalescence with rotavirus specific IgA secreting cells found in 10/12 infants receiving viable but only 2/13 infants receiving inactivated L casei strain GG. The results indicate that viable L casei strain GG stimulate rotavirus specific IgA antibody responses, theoretically significant in the prevention of reinfections.

Acute Disease↗

Gut flora in normal and disordered states.

Infections of the gastrointestinal tract are a major health problem for both adults and children worldwide. Changes in the normal human gut microflora result in the development of intestinal disorders. Pathogenic bacteria alter the intestinal microecology and intestinal colonization resistance. A healthy gastrointestinal microflora forms a barrier against invading organisms. Normal intestinal microbes and some probiotic bacteria can enhance the host's defence mechanisms against pathogens. They can also improve intestinal immunity by adhering to intestinal mucosa and stimulating local immune responses. Thus the maintenance of a balanced intestinal microecology improves the ability to preserve intestinal integrity.

Antibiosis↗

The treatment of cow's milk allergy.

Current approach to the treatment of food allergy is directed towards elimination diets. The treatment of choice of cow's milk allergy is complete avoidance of cow's milk antigens. In infants it is necessary to use substitute formulas. The completeness of the elimination diet is questionable since immunoreactive components of cow's milk protein can be detected in substitute formulas and even breast milk. In most cases, extensively hydrolyzed cow's milk-derived formulas can be safely introduced, and these are efficient and clinically and metabolically well tolerated. The approach to control allergic inflammation by antigen elimination, however, is not satisfactory, particularly in patients with multiple food allergies. New approaches are urgently needed for teh treatment of cow's milk allergy. These may include antigen elimination supplemented with synthetic amino acid-derived formulas, immunotherapy to counteract the immunologic dysfunction and stabilization of the gut mucosal barrier to strengthen endogenous defence mechanisms.

Humans↗

Oral bacteriotherapy for viral gastroenteritis.

The effect of orally administered lactobacilli on acute rotavirus diarrhea was tested in 42 well-nourished children ages 5-28 months. After oral rehydration, the patients were randomized to a study group, receiving human Lactobacillus casei strain GG 10(10) colony-forming units twice daily for five days, or a control group not given lactobacilli. Lactobacillus GG was found in the feces in 83% of the study group. The diarrheal phase was shortened in that group. Dietary supplementation with lactobacilli significantly influenced the bacterial enzyme profile: urease activity during diarrhea transiently increased in the control group but not in the study group; F = 8.6, P = 0.01. No intergroup differences were found in beta-glucuronidase, beta-glucosidase, and glycocholic acid hydrolase levels. We suggest that rotavirus infection gives rise to biphasic diarrhea, the first phase being an osmotic diarrhea and the second associated with overgrowth of specifically urease-producing bacteria. Oral bacteriotherapy appears a promising means to counteract the disturbed microbial balance.

Administration, Oral↗

Lymphocyte response to cow's milk proteins in patients with cow's milk allergy: relationship to antigen exposure.

The cellular immune response to cow's milk was measured in patients with challenge-proven cow's milk allergy (CMA), manifested with either gastrointestinal or skin symptoms. After 2-4 weeks on milk elimination, 44 children, mean (SD) age 15.7 (9.4) months, were challenged, and cow's milk-induced lymphocyte transformation was measured before the clinical challenge (Day 1) and/or one week later (Day 8). During the clinical challenge period, 17 (39%) patients showed gastrointestinal reactions, 9 (20%) had urticarial or eczematous skin eruptions, and 18 (41%) were negative to challenge. On Day 1, the mean [95% confidence interval] stimulation index for lymphocytes in patients manifesting CMA with gastrointestinal symptoms, 2.60 [1.60, 4.10], was significantly higher than that in patients with skin symptoms, 1.15 [0.60, 2.30], or patients with negative clinical challenge, 0.83 [0.64, 1.08], F = 9.0, p = 0.001. After the clinical challenge (Day 8), this cow's milk-induced lymphocyte proliferation response was abrogated. At the same time, CMA patients evidenced a significantly higher spontaneous lymphocyte proliferation response in RPMI medium-containing control cultures than those with negative clinical challenge. We conclude that in patients with CMA, the number of circulating cow's milk-sensitized lymphocytes is depleted or their function is impaired after clinical exposure to cow's milk antigens.

Administration, Oral↗