Cow's milk proteins and insulin-dependent diabetes mellitus. Something to worry about?
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Amino Acid Sequence↗
Biomedical subjects
R J Meijer
Publications and source records attributed to R J Meijer.
Effects of inhaled fluticasone and oral prednisolone on clinical and inflammatory parameters in patients with asthma.
BACKGROUND: Guidelines state that oral and inhaled corticosteroids are the cornerstone of asthma treatment. The effect of both types of treatment can be assessed by measuring lung and systemic parameters. Treatment for two weeks with either oral prednisolone (30 mg/day), high dose fluticasone propionate (2000 microg/day, FP2000), or lower dose FP (500 microg/day, FP500), both given by a dry powder inhaler, were compared. METHODS: One hundred and twenty patients with asthma were treated for two weeks in a double blind parallel group design. Lung function, asthma symptoms, airway hyperresponsiveness (PC(20) methacholine and adenosine-5'-monophosphate), sputum eosinophil and eosinophilic cationic protein (ECP) levels were measured as lung parameters. In addition, morning serum blood cortisol, blood eosinophil, and serum ECP levels were measured as systemic parameters. RESULTS: PC(20) methacholine and adenosine-5'-monophosphate showed significantly greater improvement with FP2000 (1.99 and 4.04 doubling concentrations (DC), respectively) than prednisolone (0.90 DC, p = 0.02; 2.15 DC, p = 0. 05) and marginally more than with FP500 (1.69 and 3.54 DC). Changes in sputum eosinophil and ECP concentrations showed similar trends; the decrease in ECP was significantly greater with FP2000 than with FP500. In contrast, the systemic parameters of steroid activity (cortisol, peripheral blood eosinophils, and serum ECP) decreased to a similar extent with FP2000 and prednisolone but significantly less with FP500. CONCLUSIONS: Oral prednisolone (30 mg/day) was inferior to FP2000 in improving airway hyperresponsiveness to both methacholine and AMP, with similar trends in forced expiratory volume in one second (FEV(1)), sputum eosinophil and ECP concentrations. Systemic effects were similar with prednisolone and FP2000 and less with FP500.
Administration, Inhalation↗
Nitric oxide measured with single-breath and tidal-breathing methods in asthma and COPD.
Nitric oxide (NO) can be measured in exhaled air with the single-breath (SB) and tidal-breathing (TB) methods. To allow comparison between different laboratories, a European Respiratory Society task force recently reported guidelines for standardization of both methods. To facilitate comparison between laboratories further, this study investigated whether there is a difference between NO values measured with SB and TB methods in subjects with asthma or chronic obstructive pulmonary disease (COPD), and in healthy subjects. Moreover, the differences between groups were studied and the influence of smoking in asthma was assessed. Sixteen atopic nonsmoking asthmatics, 16 atopic currently smoking asthmatics, 16 nonatopic nonsmoking healthy controls, 16 nonatopic exsmokers with COPD and 16 nonatopic exsmoking healthy controls were studied. NO concentrations differed substantially between both methods. Mean NO concentrations were higher with the SB than with the TB method in nonsmoking and in smoking asthmatics and especially so with the higher NO values. Furthermore, NO values with both methods were higher in nonsmoking asthmatics than in nonsmoking healthy subjects. NO was not significantly different between exsmokers with COPD and healthy exsmokers. In conclusion nitric oxide values of the single-breath and tidal-breathing methods are not interchangeable. Both methods can be used to measure differences between groups.
Adolescent↗
Selective hydrolysis of milk proteins to facilitate the elimination of the ABBOS epitope of bovine serum albumin and other immunoreactive epitopes.
Milk proteins are hydrolyzed to prevent immunological reactions, but immunoreactive epitopes, including the ABBOS epitope of bovine serum albumin (BSA), can still be detected in commercially available milk protein hydrolysates. We used lactococcal cell-envelope proteinase (CEP) for the hydrolysis of the individual milk proteins and of mixtures thereof, or for the hydrolysis of sodium caseinate (contaminated with whey proteins). CEP exclusively degraded casein, leaving the four major whey proteins intact. This property facilitated the removal of the intact whey proteins from the casein fragments by ultrafiltration. Depending on the molecular mass of the whey protein to be removed, membranes with cutoff values between 3 and 30 kDa were used, resulting in casein hydrolysates free of protein fragments with cross-reactive whey-protein-specific IgE (immunoglobulin E) or ABBOS antibody-binding sites. Even the casein itself was degraded in such a way by CEP that cross-reactive casein-specific IgE antibody-binding sites could be eliminated. The product could find application in infant formulas for therapeutic and preventive treatment of children with cow's milk allergy; in addition, the preventive use of such formulas in children genetically susceptible to the development of insulin-dependent diabetes mellitus (IDDM) should be considered if a relationship between the consumption of BSA and IDDM were to become more apparent. The method is also applicable for preparing casein-free whey protein preparations.
Animals↗
Collateral projections from the rat hippocampal formation to the lateral and medial prefrontal cortex.
Projections from the hippocampal formation to the medial prefrontal cortex are well known. In this report we used two retrogradely transported tracers to show that a small but significant subpopulation of pyramidal neurons in area CA1 and subiculum of the hippocampal formation projects to the lateral prefrontal cortex. About half of these neurons also possess collateral projections to the medial prefrontal cortex. The neurons projecting only to the lateral PFC are found in the intermediate hippocampal formation and in the most ventral part of the temporal subdivision. On the other hand, most of the neurons projecting to the medial prefrontal cortex only are present in the temporal and ventral intermediate hippocampal formation, and their number decreases in the dorsal intermediate subdivision. The distribution of neurons having collateral projections is comparable to that of neurons projecting to the medial prefrontal cortex only. In view of proposed functional differences between the septal one-third and the temporal two-third of the hippocampal formation, it is of interest that the neurons projecting to the prefrontal cortex are only present in the temporal two-thirds.
Amidines↗
Comparison of guidelines and self-management plans in asthma.
Since the rise in asthma mortality and morbidity, many guidelines and self-management plans have been published. Many of these guidelines and self-management plans are not, however, based on results of previous studies but on the opinion of experts. We compared the five most frequently cited asthma guidelines concerning treatment steps and self-management plans with special regard to peak expiratory flow (PEF)-guided plans in asthma. We also compared results of published studies with asthma-management in the context of the guidelines. Classification of asthma severity differed considerably between the guidelines. This was also true for PEF-guided patient self-management plans. Although there was agreement on the type of drug to be used, guidelines varied with respect to when to use the drug, the "best" strategy to increase the dose, and the maximum dose. The studies available on self-management do not make it possible to determine which part of the programme is most important or cost-effective. The latter is an important issue.
Asthma↗
Water vapour and carbon dioxide decrease nitric oxide readings.
Measurement of nitric oxide levels in exhaled air is commonly performed using a chemiluminescence detector. However, water vapour and carbon dioxide affect the chemiluminescence process. The influence of these gases at the concentrations present in exhaled air, has not yet been studied. For this in vitro study, mixtures of 50, 100 and 200 parts per billion (ppb) NO in air were prepared and fed into the NO analyser either directly or bubbled through water. Mixtures with CO2 were prepared by adding 0-10% CO2 to the diluent air. We found a significant decrease in NO readings in the water-saturated samples compared to the dry gas (p < 0.001), strongly dependent on the partial pressure of water. NO levels in exhaled air (mean 10 +/- 2 ppb) showed a decrease of 17 +/- 3% when water vapour was not absorbed. From the experiments with CO2 we found a decrease in NO reading of 1.04 +/- 0.07% per volume CO2 (%). Presence of water vapour, thus, leads to a systematic underestimation of NO levels. Insertion of a water absorber might, therefore, be advantageous. The influence of CO2 concentrations in the normal respiratory range is negligible. With high expiratory CO2 levels as applied in permissive hypercapnia, the effects may be substantial.
Carbon Dioxide↗
Incomplete elimination of the ABBOS epitope of bovine serum albumin under simulated gastrointestinal conditions of infants.
OBJECTIVE: Because the bovine serum albumin residues 126-144 (ABBOS) have been reported to be responsible for the autoimmune reaction directed against pancreatic islet cells, it was our aim to study the potential survival of the ABBOS epitope during digestion in the gastrointestinal tract. RESEARCH DESIGN AND METHODS: Either nontreated (commercially available) or heat-treated bovine serum albumin (BSA) was hydrolyzed in vitro with pepsin at a pH of 2.0, 3.0, and 4.0 and subsequently with pancreatic enzymes at a pH of 7.5. Cross-reactivity between the ABBOS peptide and the BSA hydrolysates was determined by competitive enzyme-linked immunosorbent assay (ELISA) using a rabbit polyclonal antibody raised against the ABBOS peptide in BSA. RESULTS: Biochemical findings clearly showed that the degradation of BSA during simulated physiological digestion depended on its conformation and on the pH of its pepsin-catalyzed hydrolysis. Raising the pH of the pepsin-catalyzed hydrolysis from 2.0 to 4.0 decreased the efficiency of the process, especially when BSA had first been denatured by heat treatment. As a consequence, a large proportion of the cross-reactive anti-ABBOS antibody-binding sites was still intact in the final hydrolysates. CONCLUSIONS: The present results suggest that the ABBOS epitope of BSA will not be completely eliminated during digestion under conditions that prevail in the stomach of infants (pH 3-4).
Amino Acid Sequence↗
Home assessment of peak inspiratory flow through the Turbohaler in asthmatic patients.
BACKGROUND: The efficacy of dry powder inhalers depends on the patient's inspiratory flow. Drug delivery from the Turbohaler (Turbuhaler in some countries), a multidose powder inhaler, is optimal at flows of > 40 l/min. The aim of this study was to investigate the peak inspiratory flow that can be generated by asthmatic patients through the budesonide Turbohaler (PIFTBH) during maintenance treatment at home. METHODS: Thirty asthmatic patients, consecutively recruited from the outpatient clinic, inhaled their maintenance dose of 800 (n = 16) or 1600 micrograms/day (n = 14) for two months or one month, respectively. The Turbohaler was connected to a modified Vitalograph Compact installed at home to obtain printed PIFTBH values for all inhalations. Peak expiratory flow (PEF) was measured twice daily. RESULTS: Flows were remarkably constant with individual mean PIFTBH values ranging from 55 l/min to 95 l/min. Only 13 of the 5248 PIFTBH recordings taken at home (three patients) were < 40 l/min and all were > 30 l/min. Weekly mean morning PEF values ranged from 114 l/min to 733 l/min. PIFTBH values could not be accurately predicted from lung function parameters in individual patients. CONCLUSIONS: In a group of stable asthmatic patients inspiratory flow rates rarely fell below the 40 l/min needed to operate a Turbohaler.
Adolescent↗
Exhaled nitric oxide concentration is influenced by alcohol containing disinfectants.
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Asthma↗
Detection by competitive enzyme-linked immunosorbent assay of a bovine serum albumin peptide (ABBOS) in infant formulas based on hydrolyzed cow's milk protein.
OBJECTIVE: Our aim was to determine whether currently available products based on hydrolyzed milk protein and a small peptide (ABBOS) in bovine serum albumin (BSA) (positions 126-144) share common antigenic sites. The commercial products are primarily developed to reduce cow's milk protein-associated allergenicity, but whether they also could be used in intervention trials to elucidate the role of BSA in the etiology of IDDM is not known. RESEARCH DESIGN AND METHODS: A sensitive competitive enzyme-linked immunosorbent assay (ELISA) using a rabbit polyclonal antibody raised against the ABBOS peptide in BSA was developed. With this method, we determined cross-reactivity between the ABBOS peptide and commercially available products: four milk protein hydrolysates and eight infant formulas based on hydrolyzed milk protein. The products were further characterized by physicochemical techniques. RESULTS: Hydrolyzed milk protein products are found to inhibit competitively the binding of ABBOS peptide to antibody. The number of residual reactive sites varied considerably among products and was not strongly related to the degree of hydrolysis (DH) or the molecular mass distribution of the hydrolysates. CONCLUSIONS: The presence of possible immunoreactive peptides in infant formulas based on hydrolyzed cow's milk protein cannot be adequately predicted by the DH or molecular mass distribution of the hydrolysates. Its specific determination is needed to ensure infant formulas free of cross-reactive ABBOS antibody binding sites for use in ongoing and forthcoming intervention trials to elucidate the role of BSA as a possible environmental triggering agent of IDDM.
Amino Acid Sequence↗
Residual antigenicity of hypoallergenic infant formulas and the occurrence of milk-specific IgE antibodies in patients with clinical allergy.
BACKGROUND: Milk protein hydrolysates are frequently used in milk substitutes for children with cow's milk allergy. However, cases of hypersensitivity to commercially available hypoallergenic infant formulas based on milk protein hydrolysates have been reported. OBJECTIVE: Our purpose was to determine the immunologic response of milk protein-specific IgE and IgG in the serum of patients allergic to cow's milk against four commercially available hypoallergenic milk protein hydrolysates and eight infant formulas. METHODS: Antibody levels in patients' serum and milk protein-specific residual antigenicity of the hypoallergenic products were determined by indirect and competitive ELISA. RESULTS: Patients allergic to cow's milk had IgE and IgG antibodies to several protein fractions of cow's milk; intraindividual and interindividual variation in the concentrations of these antibodies was considerable. In general, IgE and IgG residual antigenicity of individual milk proteins in the hypoallergenic products was lower compared with that of the intact milk protein, but immunoreactive epitopes could still be detected in all products. Their number varied considerably among the individual milk proteins and also differed among products. CONCLUSIONS: The individual sensitization pattern of the patient allergic to cow's milk and the milk protein-specific residual antigenicity might be considered as possible laboratory predictors of adverse reactions to hypoallergenic products. Their determination could be a useful preclinical screening test for pediatricians to select a formula adapted to the individual patient.
Animals↗
Raising the pH of the pepsin-catalysed hydrolysis of bovine whey proteins increases the antigenicity of the hydrolysates.
BACKGROUND: Hypersensitivity to cow milk protein is frequently observed in infancy. Since the pH in the infant's stomach is relatively high (pH 3-4) compared with adults (pH 2), an incomplete digestion of the milk proteins is expected to occur. OBJECTIVE: The determination of the degree of hydrolysis by pepsin of the four main proteins of bovine whey, i.e. alpha-lactalbumin (alpha La), beta-lactoglobulin (beta Lg), bovine serum albumin (BSA) and bovine immunoglobulin G (B-IgG), in the pH range 2.0-4.0 and of the antigenic properties of the resulting hydrolysates. METHODS: Whey proteins were successively hydrolysed with pepsin at pH values ranging from 2.0 to 4.0 and with pancreatic enzymes at pH 7.5 using a pH-stat. The resulting hydrolysates were characterized by their degree of hydrolysis, and analysed by sodium dodecyl sulfate polyacrylamide gel electrophoresis, gel permeation chromatography and immunologically by competitive enzyme-linked immunosorbent assay. RESULTS: In general, the degree of hydrolysis, the gel electrophoretic patterns, the contents of peptides of molecular mass > 5 kDa and the residual human-immunoglobulin E and G antigenicities of the hydrolysates did not differ much whether the pepsin incubation was done at pH 2.0 or 3.0. Pepsin incubation at pH 4.0, however, resulted in a decreased hydrolysis and enhanced residual antigenicity of alpha La, BSA and B-IgG, but not of beta Lg. CONCLUSION: The poor and slow degradation of the antigenic epitopes of whey proteins when pepsin digestion occurs under conditions that prevail in the stomach of infants could be of much importance for the development of cow milk hypersensitivity. The immature gastrointestinal mucosal barrier of infants allows large antigenic fragments of these proteins to pass into the systemic circulation.
Adult↗
Cultured skin fibroblasts: useful for diagnosis of Wilson's disease?
The copper content of and radiocopper uptake in fibroblast cultures were studied to evaluate their usefulness for the diagnosis of Wilson's disease. We used methods closely related to those described in the literature, and applied these to cell lines of six patients with Wilson's disease and 12 controls. The results were: (1) The copper content of the cytosol of skin fibroblasts derived from patients with Wilson's disease was lower than that of controls when the cells were grown in a medium with a low copper concentration (0.7 mumolL-1); increased copper concentration (157 mumol L-1 in the medium failed to demonstrate any difference between normal fibroblasts and those derived from patients with Wilson's disease. (2) Radiocopper uptake studies did not differentiate between normal fibroblasts and fibroblasts from patients with Wilson's disease. We conclude that the cytosolic copper content of fibroblasts grown in a low copper medium is a potential diagnostic tool in Wilson's disease. At present not all controls can be distinguished from the Wilson cells; ways must be sought, therefore, of improving the technique.
Adult↗