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 28,634 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Specific allergy vaccination is an efficient treatment for allergic disease; however, the development of safer vaccines would enable a more general use of the treatment. Determination of molecular structures of allergens and allergen-Ab complexes facilitates epitope mapping and enables a rational approach to the engineering of allergen molecules with reduced IgE binding. In this study, we describe the identification and modification of a human IgE-binding epitope based on the crystal structure of Bet v 1 in complex with the BV16 Fab' fragment. The epitope occupies approximately 10% of the molecular surface area of Bet v 1 and is clearly conformational. A synthetic peptide representing a sequential motif in the epitope (11 of 16 residues) did not inhibit the binding of mAb BV16 to Bet v 1, illustrating limitations in the use of peptides for B cell epitope characterization. The single amino acid substitution, Glu(45)-Ser, was introduced in the epitope and completely abolished the binding of mAb BV16 to the Bet v 1 mutant within a concentration range 1000-fold higher than wild type. The mutant also showed up to 50% reduction in the binding of human polyclonal IgE, demonstrating that glutamic acid 45 is a critical amino acid also in a major human IgE-binding epitope. By solving the three-dimensional crystal structure of the Bet v 1 Glu(45)-Ser mutant, it was shown that the change in immunochemical activity is directly related to the Glu(45)-Ser substitution and not to long-range structural alterations or collapse of the Bet v 1 mutant tertiary structure.
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PMID:Dominating IgE-binding epitope of Bet v 1, the major allergen of birch pollen, characterized by X-ray crystallography and site-directed mutagenesis. 1296 Mar 34

Idiopathic anaphylaxis (IA) has been described as a clinical entity by North America authors. The symptoms are brisk and relapsing episodes of angioedema, urticaria, bronchospasm, digestive symptoms, cardio-vascular collapse. Adults, females more than males, are mainly concerned. The seriousness is linked to laryngeal angioedema or to hypotension. Nevertheless lethality is rare. The first step of the procedure is aimed at the detection of several rare pathologies mimicking IA: the paroxystic capillary leak syndrome induced by a monoclonal gammapathy or by a release of cytokines, a carcinoid syndrome, cutaneous or visceral mastocytosis, hereditary or acquired deficiency of C1 esterase inhibitor, relapsing benign flushes and factitious anaphylaxis. These diseases being excluded, the diagnosis of anaphylaxis is established, and the diagnostic process searches for exceptional causes: food allergy elicited by unusual trophallergens, exercise-induced anaphylaxis, allergy to parasitic antigens, to inhalants, or hormonal allergy. The negativity of thorough investigations establishes the plausibility of IA. Several unconfirmed pathogenic hypotheses have been put forward: abnormal easiness to non specific release of mediators from mast cells and/or basophils, anti-IgE antibodies as a specific kind of auto-immunity, angiotensin II deficiency. Treatment of emergency relies on self-administration of epinephrine. A daily therapeutic regimen using corticosteroids and anti-H1 drugs is currently prescribed and can be efficient, but no randomized studies have asserted the validity of this management. The lack of immunological studies, contrasting with numerous clinical reports, questions whether IA is really an entity or solely anaphylaxis in search of unknown eliciting allergenic agents.
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PMID:[Idiopathic anaphylaxis]. 1501 47

Anaphylaxis is a rarely anticipated, potentially life-threatening systemic allergic reaction with symptoms ranging from mild flushing to upper respiratory obstruction with or without vascular collapse. Early recognition of symptoms with prompt institution of therapy is central to a successful outcome. Anaphylaxis is IgE mediated, whereas non-IgE mediated anaphylatic reactions are termed anaphylactoid. Food-induced anaphylactic reactions, particularly peanut, are being recognized with increasing frequency. Central to appropriate therapy of the acute reaction is adminstration of intramuscular adrenalin. However, with the advent of humanized anti-IgE monoclonal antibody, such reactions may be reduced in frequency and severity.
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PMID:Anaphylaxis: clinical aspects. 1505 59

Anaphylactic and anaphylactoid reactions during anaesthesia are rare, but potentially life-threatening allergic events. The worst manifestations are cardiovascular collapse, bronchospasm and laryngeal oedema. Anaphylactic and anaphylactoid reactions are clinically indistinguishable. The most incriminated agents are neuromuscular blocking drugs and latex. Treatment consists of instant interruption of contact with possible antigens, 100% oxygen, intubation, adrenaline and volume expansion. The incidence of cross-reactivity between neuromuscular blocking drugs is high. Further investigation of a suspected anaphylactic reaction is mandatory to find the responsible drug and to make future anaesthesia safe. Diagnosis is made with intraoperative tests (serum histamine and mast cell tryptase) and postoperative tests (skin tests and RASTs for specific IgE antibodies).
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PMID:Anaphylaxis during anaesthesia: diagnosis and treatment. 1551

Allergic reactions after vaccination are considered as an important practical problem in dogs; however, their immunological mechanism has not been well understood. The present study was designed to investigate the relationship between IgE reactivity to the vaccines and immediate-type allergic reactions after vaccination in dogs. Sera from 10 dogs that developed immediate-type allergic reactions such as circulatory collapse, cyanosis, dyspnea, facial edema, and vomiting within 1h after vaccination with non-rabies monovalent or combined vaccines and sera from 50 dogs that did not develop allergic reactions after vaccination were collected. Serum IgE reactivity to the injected vaccines was measured by fluorometric ELISA using a mouse monoclonal anti-dog IgE antibody. Then, IgE reactivity to fetal calf serum (FCS) and stabilizer proteins (gelatin, casein, and peptone) included in the vaccines was measured in sera that had high levels of IgE to the vaccines. Levels of serum specific IgE to the vaccines in dogs with immediate-type allergic reactions (59-4173 fluorescence units [FU], mean +/- S.D.: 992.5 +/- 1181.9 FU) were significantly higher than those in control dogs (38-192 FU, 92.4 +/- 43.3 FU) (P < 0.001). Of the eight dogs that developed immediate-type allergic reactions and had high levels of serum specific IgE to the vaccines, seven had specific IgE directed to FCS. The IgE reactivity to the vaccines in sera from these dogs was almost completely inhibited by FCS. The other one dog had serum IgE directed to gelatin and casein included in the vaccine as stabilizers. The results obtained in this study suggest that immediate-type allergic reactions after vaccination in dogs were induced by type I hypersensitivity mediated by IgE directed to vaccine components. In addition, FCS, gelatin, and casein included in vaccines could be the causative allergens that induced immediate-type allergic reactions after vaccination in dogs.
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PMID:IgE reactivity to vaccine components in dogs that developed immediate-type allergic reactions after vaccination. 1573 45

A 42-year-old woman with hysteromyoma underwent total abdominal hysterectomy under general and epidural anesthesia. Three years before, she had undergone resection of lipoma on her left shoulder under local anesthesia uneventfully. She had no previous history of hypersensitivity. General anesthesia was induced by intravenous injection of fentanyl, propofol, and vecuronium followed by inhalation of nitrous oxide, oxygen, and sevoflurane. Lidocaine and fentanyl were injected through a lumbar epidural catheter. After the start of open laparotomy, there was a sudden onset of hypotension. Administrations of ephedrine and phenylephrine, and volume loading were ineffective. Moreover, she showed profound hypotension, tachycardia, oxygen desaturation, decreased endtidal carbon dioxide and increased airway pressure. She broke out in a sweat with flushing on her chest and upper extremities. Therefore, we interrupted the surgery, checked her arterial blood gas analysis, performed echocardiography, and inserted a pulmonary artery catheter. We made a diagnosis of anaphylactic shock and administered methylprednisolone, albumin, epinephrine, norepinephrine, and dopamine to treat the circulatory collapse. The gynecologists changed their surgical gloves from a powdered-latex type to a powder-free latex type, and the surgery was resumed. She responded well to appropriate emergent therapy and all vasopressor drugs were gradually decreased and eventually stopped. After the end of the surgery, she recovered completely from the signs and symptoms of shock. Later, we found a high level of plasma latex protein-specific IgE antibody and confirmed the events as anaphylactic shock due to latex. We assumed that the anaphylactic shock was powder-induced latex allergy following use of powdered latex gloves in this case. Latex allergy should be suspected if an anaphylactic reaction or shock accompanied by circulatory collapse, respiratory failure, and skin symptoms of unknown origin occurs during surgery. As women more often come into contact with household articles containing latex, we suspect that women are prone to developing sensitivity towards latex. We recommend that powder-free or latex-free surgical gloves should be available not only for patients with a high risk of developing latex allergy, but also for patients indicated for gynecological open laparotomy.
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PMID:[Powder-induced anaphylactic shock following use of powdered latex gloves during gynecological open laparotomy]. 1678 84

Angioedema can be a symptom of anaphylaxis; it may be more hazardous that the circulatory collapse in otherwise healthy patients. Angioedema can be part of IgE- and histamine-mediated allergic reactions or part of NSAID-induced hypersensitivity with disturbances in arachidonic acid metabolism. If angioedema occurs without urticaria or other symptoms of anaphylaxis, it is usually mediated by increased bradykinin synthesis (HANE, EANE) or reduced metabolism (ACE inhibitors). These observations have led to new therapeutic approaches in HANE. Icatibant is a bradykinin-receptor-2 antagonist and blocks bradykinin-induced angioedema in HANE. How applicable this will be to ACE-inhibitor angioedema remains to be seen.
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PMID:[Angioedema]. 1800 29

NO is known to suppress mast cell activation, but the role of NO in mast cell survival is unclear. Ligation of the high-affinity receptor for IgE (FcepsilonRI) resulted in NO production in mast cells within minutes. This NO production was largely dependent on NO synthase (NOS) activity and extracellular Ca(2+). The NO production required an aggregation of FcepsilonRI and was accompanied by increased phosphorylation of endothelial NOS (eNOS) at Ser1177 and Akt at Ser473. The phosphorylation of eNOS and Akt and the production of NO were abolished by the PI-3K inhibitor wortmannin. Although thapsigargin (TG) induced NO production as well, this response occurred with a considerable lag time (>10 min) and was independent of FcepsilonRI aggregation and PI-3K and NOS activity. Mast cells underwent apoptosis in response to TG but not upon FcepsilonRI ligation. However, when the NOS-dependent NO production was blocked, FcepsilonRI ligation caused sizable apoptosis, substantial mitochondrial cytochrome c release, caspase-3/7 activation, and collapse of the mitochondrial membrane potential, all of which were inhibited by the caspase-3 inhibitor z-Asp-Glu-Val-Asp-fluoromethylketone. The data suggest that the NO produced by the PI-3K-Akt-eNOS pathway is involved in protecting mast cells from cell death.
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PMID:Nitric oxide protects mast cells from activation-induced cell death: the role of the phosphatidylinositol-3 kinase-Akt-endothelial nitric oxide synthase pathway. 1828 1

The true incidence of anaphylactic latex reactions and their associated morbidity and mortality remain poorly defined. It is noteworthy that a number of groups of individuals are at risk for anaphylactic reactions to latex during surgical and medical procedures; one of these groups is represented by the obstetric and gynaecologic population. A case of unrecognized first anaphylactic reaction to latex in a pregnant woman patient who underwent a caesarean section is presented. The diagnosis of latex allergy was missed and the following day the woman underwent a surgical re-exploration complicated by fatal cardiovascular arrest. At post-mortem examination, pulmonary mast cells in the bronchial walls and capillary septa were identified and a great number of degranulating mast cells with tryptase-positive material outside the cells was documented. A post-mortem latex-specific IgE test showed a high titre (14.00 U/I). Latex-induced fatal anaphylactic shock was recorded as the cause of death. This case highlights some of the practical difficulties in the initial diagnosis and subsequent investigation of fatal anaphylactic reaction during anaesthesia. Anaphylaxis is often misdiagnosed because many other pathologic conditions may present identical clinical manifestations, so anaphylactic shock must be differentiated from other causes of circulatory collapse. Although latex allergy usually has a delayed onset after the start of the surgery and most often a slow onset too, it should be always suspected if circulatory collapse and respiratory failure occur during surgery, even if the patient does not belong to a risk group; in the presence of identified risk factors for latex allergy a well-founded suspicion must be stronger, leading to an immediate discontinuation of the potential trigger.
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PMID:Anaphylactic latex reaction during anaesthesia: the silent culprit in a fatal case. 1846 22

Advanced glycation end products (AGEs) accumulate during aging and to higher extents under pathological conditions such as diabetes. Since we previously showed that mast cells expressed the AGE-binding protein, receptor for AGEs (RAGE) on their cell surface, we examined whether AGE affected mast cell survival. Herein, we demonstrate that mast cells undergo apoptosis in response to AGE. Glycated albumin (GA), an AGE, but not stimulation with the high-affinity IgE receptor (FcepsilonRI), can induce mast cell death, as measured by annexin V/propidium iodide double-staining. GA (> or =0.1 mg/ml) exhibited this pro-apoptotic activity in a concentration-dependent manner. GA and FcepsilonRI stimulation increased the cytosolic Ca(2+) levels to a similar extent, whereas GA, but not FcepsilonRI stimulation, caused mitochondrial Ca(2+) overload and membrane potential collapse, resulting in mitochondrial integrity disruption, cytochrome c release and caspase-3/7 activation. In addition, GA, but not FcepsilonRI stimulation, induced extracellular release of superoxide from mitochondria, and this release played a key role in the disruption of Ca(2+) homeostasis. Knockdown of RAGE expression using small interfering RNA abolished GA-induced apoptosis, mitochondrial Ca(2+) overload, and superoxide release, demonstrating that RAGE mediates the GA-induced mitochondrial death pathway. AGE-induced mast cell apoptosis may contribute to the immunocompromised and inflammatory conditions.
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PMID:Extracellular superoxide released from mitochondria mediates mast cell death by advanced glycation end products. 1882 20


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