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Proteomic Profile Differences in Immune-Related Diseases in Pediatric Patients Under Five Years Old: Asthma and IgE-Dependent Allergies-A Pilot Study.

Asthma is a heterogeneous disease that often begins in childhood and frequently occurs alongside allergic conditions. In asthma research, it is important to focus on proteins that are the primary regulators of cellular physiology. The differences in the proteome between children with asthma and those with an atopic background remain poorly understood. The present study included 130 serum samples from four groups of pediatric patients under the age of five: (1) with asthma and IgE-dependent allergies; (2) with non-atopic asthma; (3) non-asthmatics with IgE-dependent allergy; and (4) a control group without asthma and IgE-dependent allergies. The serum samples were used for protein-peptide profiling and proteomic identification using nanoLC-MALDI-TOF/TOF MS/MS. The obtained data were analyzed using univariate statistics and the STRING tool v12.0 to identify protein-protein potential interactions. A total of seven proteins were identified as discriminative between the study groups: A2M, AACT, IgG3, C3, ITIH2, IgG3 and IGK. All of them were upregulated in patients with IgE-dependent allergy compared to other study groups. STRING analysis identified functional associations among four proteins (AACT, A2M, C3, and ITIH2) with discriminatory potential for distinguishing between non-atopic asthma and non-asthmatic patients with IgE-dependent allergy. The results suggest that the identified putative protein markers overlap in cellular pathways, including those associated with the pathophysiology of asthma and allergic disorders. These findings provide further insight into the overall proteomic profile of pediatric patients with asthma and IgE-dependent allergy, highlighting its heterogeneity across the analyzed groups.

Humans

"Insulin" allergy due to zinc.

An investigation of two unrelated patients who had local cutaneous hypersensitivity reactions after injection of any commercially available insulin preparation has shown that the cause of the allergy was zinc. Zinc-insulin and zinc sulphate induced transformation and proliferation of peripheral-blood lymphocytes from these patients; they also induced the production of a specific leucocyte inhibitory factor. Intradermal skin-tests for zinc were positive in both patients. Similar studies carried out in a patient whose cutaneous allergy to insulin was corrected by changing from mixed beef-pork to pure pork insulin were negative. Zinc-free insulin did not produce any allergy in the first patients. The number of patients in whom zinc (which is present in all commercially available insulin preparations) is a cause of "insulin" allergy is unknown. These patients may by identified by intradermal skin-tests. This previously unrecognised allergy should be considered in all patients whose insulin allergy does not respond to conventional therapy.

Cell Migration Inhibition

Food allergy in children with hyperactivity, learning disabilities and/or minimal brain dysfunction.

Ninety hyperactive children, 22 children with learning disability and eight emotional-inattentive children were tested for allergy to 43 food extracts using the in vitro radioallergosorbent test (RAST). Fifty-two percent of all children exhibited allergy to one or more of the foods tested. Within the hyperactive group a statistically significant association was found between the number of allergies and teachers' (Conners) scores of hyperactivity. This association was statistically significant only in those hyperactive children who also had learning disability and minimal brain dysfunction. A statistically weak association was also found between a small number of children clinically diagnosable as hyperactive and the number of allergies or total allergy scores. A causal relationship between food allergy and a small subgroup of children with a primary diagnosis of hyperactivity is suspected.

Attention Deficit Disorder with Hyperactivity

Parasites and allergies: a complex bidirectional relationship from evolutionary origins to modern therapeutics.

Parasites and allergic diseases are linked by a complex, bidirectional relationship shaped by long-term host-parasite coevolution. This review discusses how different parasites may either promote or attenuate allergic responses through immunological, epithelial, and microbiome-mediated mechanisms. IgE-mediated immunity, mast cell activation, eosinophilia, and pruritus may have evolved as protective responses against helminths and blood-feeding ectoparasites. In contrast, modern allergies may partly reflect misdirected responses to harmless environmental antigens. The effects of parasites on allergy are not uniform and depend on parasite type, infection site, exposure intensity and chronicity, host immune status, and the degree of host-parasite adaptation. Protozoa such as Giardia intestinalis may contribute to food allergy-related manifestations by disrupting the intestinal barrier, altering gut microbiota composition, and modifying mucosal immune responses, particularly in atopic individuals. In contrast, selected helminths may attenuate allergic inflammation by inducing regulatory T and B cells, anti-inflammatory cytokines, antigen-presenting cell modulation, and IgG4-associated mechanisms that can limit IgE-mediated effector responses. Molecular similarities between parasite-derived antigens and environmental allergens, including conserved protein families and carbohydrate epitopes, may contribute to cross-reactive IgE responses and complicate allergy diagnostics. Therefore, current research is shifting from live helminth therapy toward defined parasite-derived molecules and immunomodulatory pathways that may inspire safer and more controlled therapeutic strategies. A clearer understanding of parasite-allergy interactions may improve diagnostic interpretation and support the development of new approaches to the management of allergic disease.

Humans

Allergy to rubber condom urinals and medical adhesives in male spinal injury patients.

In the National Spinal Injuries Unit at Stoke Mandeville Hospital, rubber condom urinals, kept on the penis with a medical adhesive, are used for incontinent male patients where possible. However, contact allergy to rubber condoms and/or the adhesives is a common problem and can cause considerable morbidity in paralysed patients. This paper investigates the rubber chemicals and adhesives most commonly implicated in causing contact allergy. The survey was divided into two parts: 1. Patch testing symptomatic inpatients 2. A questionnaire sent to new patients from January 1974 to ascertain the overall incidence of contact allergy. It was found that allergy to mercaptobenzthiazole (MBT)- and thiuram-containing condoms was relatively common and that latex/petroleum tube medical adhesives most commonly caused adhesive allergy. It is suggested that a condom made of the least allergenic rubber and an adhesive causing the least number of allergic reactions should be used from the outset for paralysed patients requiring a condom urinal.

Adhesives

[The value of the thrombocytopenia test in the specific diagnosis of drug allergy, especially drug-exanthema].

125 thrombocytopenia tests (so-called thrombocytopenic index) from 94 patients with suspected drug allergies and negative skin tests were critically examined to determine the value of this in vivo method in the clarification of drug allergy. A consistent decrease of 20% or more in thrombocytes was rated as significant and therefore indicative of drug sensitization. 78.4% of the tests were in agreement with the expected result. Clinically relevant drug sensitivity was apparent in 30.4% of the tests, while the possibility of allergy could be eliminated in 48%. 16.8% of the results were inconclusive and 4.8% were false negatives. A flare-up occurred after 5.6% of the tests. A leukocyte count was considered unnecessary since it proved to be unrelated to a drop in thrombocytes and the existence of drug allergy. The thrombocyte test is a practical and valuable method for investigation of drug allergies, especially as the available in vitro tests are too complex to be used routinely in a diagnostic test program. However, the results must be considered critically in conjunction with an accurate case history, the clinical symptoms and the course of the disease. In the case of blisters and erythema exsudativum multiforme-like drug exanthema, renewed exposure to the suspected drug must be avoided due to the possible danger of a drug reaction. The latest research results have helped to clarify the underlying mechanism of the thrombocyte decrease.

Aspirin

Nasal smear as a screening test for immediate-type nasal allergy.

From a previous sample of 634 students and school children, 115 subjects were selected for a thorough rhinological examination and allergy work-up in order to assess the value of nasal secretion eosinophilia in screening for immediate-type nasal allergy. Part of the subjects had, in the previous study, been found to have secretion eosinophilia and a history of chronic/allergic rhinitis, part of the subjects had either a secretion eosinophilia or a rhinitis history, and part of them had neither a secretion eosinophilia nor a rhinitis history. A significant correlation was obtained between secretion eosinophilia and allergy. Nasal provocation tests correlated with skin tests in 87%, whereas the correlation between nasal provocation tests and Ige determinations in the serum was poorer. Thickening of the maxillary sinus was, when present, usually attributable to infection and not to allergy. Reasons for "false positive or false negative" smears for eosinophils are discussed.

Adult

Respiratory allergy in the dog: induction by the respiratory route and the effect of passive antibody.

A technique for inducing hypersensitivity to prairie sage pollen (Artemisia gnopheles) in the dog was developed. The allergen induced skin reactivity in most dogs and respiratory hypersensitivity in 7 of the 17 animals tested. The respiratory hypersensitivity resembled naturally occurring respiratory allergies in both man and dog. The route of allergy induction resembles the natural route and it is felt that this system provides a useful model system for the study of respiratory allergies. Animals in which hypersensitivity was induced were used to investigate the role of passive 'blocking' antibody in respiratory allergy. It was observed that passive antibody will greatly inhibit the respiratory response to inspired allergen while completely inhibiting the cutaneous response. The results of these studies are discussed in relation to other studies.

Administration, Intranasal

[Effects and mechanisms of Jiawei Yigong San on the Th17/Treg balance in food allergy].

Objective To explore the effects and mechanisms of Jiawei Yigong San (JWYGS) on the T helper type 17 (Th17)/regulatory T (Treg) cell balance in food allergy (FA). Methods Active components, action targets of JWYGS, and FA-related targets, were screened via network pharmacology. Overlapping targets between JWYGS and FA were used to construct a protein-protein interaction (PPI) network. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses were performed to predict key signaling pathways. Molecular docking was conducted to validate the binding affinity between the main active components and the predicted targets. Mice were randomly divided into control group, model group, JWYGS low-dose, medium-dose, and high-dose groups, and dexamethasone (DXM) group. An ovalbumin (OVA)-induced FA model was established. During the OVA challenge period, mice received daily intragastric administration, after which allergy and diarrhea scores were assessed. Small intestinal pathology was evaluated by HE staining. Serum ovalbumin-specific immunoglobulin E (OVA-sIgE), interleukin 6 (IL-6), IL-17, IL-2, and IL-10 were measured by ELISA. Small intestinal IL-6, IL-17, and IL-10 protein expression was detected by immunohistochemistry. Splenic Th17 and Treg cells were quantified by flow cytometry, and the Th17/Treg ratio was calculated. The mRNA expression of IL-6, retinoic acid receptor-related orphan receptor γt (RORγt), and forkhead box protein P3 (FOXP3) in the small intestine was detected by qPCR. Results Network pharmacology identified 235 active components of JWYGS and 136 common targets. GO and KEGG enrichment analyses highlighted cytokine response and Th17 differentiation. Molecular docking confirmed stable binding between core components and targets. Compared with the control group, the model group exhibited aggravated allergy and diarrhea scores, marked small intestinal inflammation and mucosal damage, elevated serum levels of OVA-sIgE, IL-6, IL-17 and IL-2, along with increased splenic Th17 cell frequency and Th17/Treg ratio. Intestinal IL-6 and IL-17 protein levels as well as IL-6 and RORγt mRNA expression were upregulated, whereas serum IL-10 levels were decreased, and intestinal expression of IL-10 protein and FOXP3 mRNA was downregulated. After JWYGS treatment, allergy and diarrhea scores were significantly reduced. Small intestinal inflammation and mucosal damage were alleviated. Serum levels of OVA-sIgE, IL-17, IL-6 and IL-2, Th17 cell frequency and the Th17/Treg ratio, intestinal IL-6 and IL-17 protein levels were decreased. IL-6 and RORγt mRNA expression was downregulated. Serum IL-10 levels were increased and intestinal expression of IL-10 protein and FOXP3 mRNA was upregulated. Moreover, the JWYGS high-dose group demonstrated comparable efficacy to the DXM group. Conclusion JWYGS can ameliorate symptoms and reverse the Th17/Treg imbalance in FA mice, potentially by inhibiting IL-6 transcription and regulating RORγt/FOXP3 expression.

Animals

[The allergic focal reaction phenomenon. Significance for the testing, therapy and theory of clinical allergy. Study in bronchial asthma and other allergic diseases].

On the basis of examinations of 654 cases of clinical allergy (487 cases of bronchial asthma) a new allergenic phenomenon is described: "The allergic focal reaction phenomenon". It is associated with the demonstration of a regularly reproducible, clinical, allergic initiating effect of very small doses of specific antigen only on the allergically diseased tissue (focus). The findings made it possible to elaborate a new method for allergy testing and therapy without any danger, and offers quite new ideas for the interpretation of allergic mechanisms. The authors tried to integrate this phenomenon into the picture of clinical allergy, and some so far unclear problems of allergy may, on this basis, have found a probable solution."

Adolescent

The Role of In Vivo, In Vitro and Pharmacogenomic Diagnostic Approaches to Sulfonamide Allergy.

Sulfonamide antibiotics are commonly reported as a medication allergy, presenting as both immediate IgE-mediated reactions and delayed hypersensitivity reactions ranging from benign cutaneous eruptions to severe cutaneous adverse reactions. Sulfonamide antibiotics have retained importance as treatment for multiple indications and are especially relevant in immunocompromised patients wherein use is indicated for prevention of opportunistic infections. Sulfonamide antibiotic allergy labels may lead to inappropriate avoidance of other "sulfur"-containing medications, because cross-reactivity is unlikely between antibiotic and nonantimicrobial sulfonamides. In this review, we discuss the typical presentation of sulfonamide antibiotic hypersensitivity reactions. We also review risk stratification tools and current in vivo procedures and experimental in vitro evaluation methods. Lastly, we will provide an update on emerging pharmacogenomics data associated with sulfonamide medication adverse reactions.

Humans

Insulin antibodies in the pathogenesis of insulin allergy and resistance.

Insulin allergy developed in a patient treated with beef/pork insulin. Desensitization therapy led to cessation of the allergy, but it was associated with the development of diabetic ketoacidosis with apparent insulin resistance which was successfully treated with fish insulin. The patient's initial serum contained a high titer of anti-insulin immunoglobulin E (IgE) antibody directed primarily against beef insulin. Desensitization therapy with pork insulin was associated with the production of anti-insulin immunoglobulin G (IgG) antibody with highest immunologic reactivity to pork insulin. This IgG antibody may have blocked the interaction of insulin with tissue-fixed IgE antibody but, in addition, led to significant increases in total serum insulin-binding capacity and transient insulin resistance. The favorable clinical response to fish insulin was likely due to the negligible immunologic reactivity of this patient's anti-insulin antibodies with fish insulin. This report suggests that desensitization therapy for insulin allergy can lead to insulin resistance of the immune type.

Animals

Allergies of the dental pulp.

A review of publications relating to the allergies of the dental pulp is presented. The pulp--especially when inflamed--contains antigens, lymphocytes, plasmocytes, IgG, IgM, IgA, and IgE antibodies, mast cells, histamine, and possibly C3. However, no antibody-mediated allergy (hypersensitivity) of the pulp has yet been demonstrated. On the other hand, two types of cell-mediated allergy--the graft-rejection reaction and contact hypersensitivity--have been reported, as well as autoimmunity.

Animals

Lactiplantibacillus plantarum SLpl116 attenuates OVA-induced food allergy with ecological restoration of the gut microbiota and immune rebalancing.

Gut dysbiosis is increasingly recognized as a key contributor to food allergy, yet probiotic strains capable of restoring allergic microbiota and rebalancing host immunity remain limited. Here, we identified Lactiplantibacillus plantarum SLpl116 through a multi-criteria screening pipeline integrating anti-allergic activity, safety, and processing stability, and evaluated its efficacy in a prophylactic ovalbumin (OVA)-induced murine food allergy model. SLpl116 significantly attenuated allergic symptoms, including diarrhea and hypothermia, and suppressed serum IgE, IgG1, OVA-specific immunoglobulins, and mucosal mast cell protease-1. It was also associated with suppression of Th2-related responses and enhancement of systemic Th1-associated signaling, indicating restoration of Th1/Th2 immune balance. Microbiome analysis showed that SLpl116 was associated with ecological restoration of the dysbiotic gut community, including suppression of allergy-associated taxa such as Alistipes finegoldii and Bacteroides and enrichment of beneficial commensals, particularly Lachnospiraceae. Correlation analysis supported an association between microbial reconfiguration and immune rebalancing, while PICRUSt2-based functional prediction suggested enriched butyrate-associated metabolic potential in the effective strain groups. Comparative genome-informed analysis further indicated that SLpl116 possessed distinctive phenotype-linked features, providing a plausible molecular rationale for its favorable phenotype. Together, these findings identify SLpl116 as a promising strain-level probiotic candidate associated with direct immune rebalancing and microbiome-associated ecological restoration.

Journal Article

[Cross allergy between sulphonamide diuretics, probenecid, sulphamethoxazole and sulphonyl-urea compounds (author's transl)].

Typical signs and symptoms of type III allergy occurred in a 55-year-old diabetic during diabetes and diuretic treatment with glisoxepid, glibenclamide, furosemide and probenecid. Symptoms of this type of allergy unintentionally recurred with every subsequent therapeutic administration of each one of these drugs. The possibility of a cross allergy between sulphonamide diuretics, chemotherapeutic sulphonamides and sulphonyl-urea compounds has only rarely been described.

Cross Reactions

Frequency of atopy and allergy in an anaesthetic patient population.

Ten thousand patients presenting for anaesthesia in the British Isles were questioned about a possible history of atopic or allergic disorders. The overall percentage frequency of atopy was 8.5, comprising eczema 2.4, hay fever 3.8 and asthma 3.5. The frequency of allergies was 13.5, of which penicillin was the most common (6.2). Females had a significantly greater frequency of atopy or allergy than males. Patients with a history of atopic disorders had a higher frequency of allergies than the non-atopic group (36.2% compared with 11.4%) and vice versa.

Adolescent

In vitro histamine release from leukocytes in penicillin allergies.

The definite diagnosis of Type I allergy against penicillin is very important. The in vivo tests used for this purpose may have some disadvantages for the patient. Among the in vitro tests used for the evidence and differential diagnosis of Type I allergy against penicillin, the determination of histamine release from leukocytes and the detection of IgE by the RAST test are the most promising. We have used the test of histamine release from leukocyte in this study of 18 cases, nine of whom had Type I hypersensitivity reactions to penicillin and comprised the study group, the rest were control cases. The per cent of histamine release in the control group was "zero" while in the study group it ranged from 3.9 to 51.7 per cent. The results indicate that the method used in this study is a sensitive and reliable method for the diagnosis of Type I penicillin allergies.

Adolescent

Food sensitivity reported by patients with asthma and hay fever. A relationship between food sensitivity and birch pollen-allergy and between food sensitivity and acetylsalicylic acid intolerance.

Among adult patients with bronchial asthma and/or allergic rhinitis undergoing allergological investigation with skin test, nasal provocation test and RAST, 1129 answered a questionaire regarding food sensitivity (FS). 276 (24%) of the patients reported some kind of allergic symptoms on eating or handling various foods, of which hazel nut, apple and shell fish were the most often named. Females reported FS more often than males. A correlation was found between birch pollen allergy and FS with nuts, apple, peach, cherry, pear, plum, carrot and new potato. The higher the degree of birch pollen allergy, according to skin test, RAST or provocation test, the higher the frequency of FS. A correlation was found too between acetylsalicylic acid intolerance and FS with some foods, e.g. nuts, strawberry, almond, green pepper, hip, chocolate, egg, cabbage, milk and wine. The connection between birch pollen allergy and FS is probably explained by the structural relationship between birch pollen allergen and some allergens of the foodstuffs, whereas the high incidence of FS in acetylsalicylic acid-intolerant patients is probably explained by additives in foods as well as salicylates or benzoates naturally occurring in some food.

Adolescent