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Journal of Nuclear Medicine : Official... Jan 2005Radiolabeled cyclic peptides containing the amino acid sequence arginine-glycine-aspartate (RGD peptides) have successfully been used to image the expression of the... (Comparative Study)
Comparative Study
UNLABELLED
Radiolabeled cyclic peptides containing the amino acid sequence arginine-glycine-aspartate (RGD peptides) have successfully been used to image the expression of the alpha(v)beta(3) integrin in malignant tumors. However, the alpha(v)beta(3) integrin also plays an important role in angiogenesis induced by chronic inflammatory processes. Therefore, the aim of this study was to evaluate whether radiolabeled RGD peptides may also be used to assess alpha(v)beta(3) expression in inflammatory diseases. We studied a hapten-induced delayed-type hypersensitivity reaction (DTHR) as a model for inflammatory processes, since DTHRs are involved in many human autoimmune disorders.
METHODS
The abdominal skin of mice was sensitized by application of 2,4,6-trinitrochlorobenzene (TNCB). One week later, a DTHR was elicited by challenging the right ear with TNCB. Application of TNCB was then repeated every 48 h to induce chronic skin inflammation. Small-animal PET and autoradiography with the alpha(v)beta(3) ligands (18)F-galacto-RGD and (125)I-gluco-RGD were performed at various times after TNCB application. The time course of tracer uptake by the treated ears was compared with histologic skin changes.
RESULTS
The first challenge with TNCB caused, within 12 h, an acute inflammatory response with dense dermal infiltrates of polymorphonuclear leukocytes and lymphocytes. However, autoradiography revealed no significant increase in (125)I-gluco-RGD uptake at that time (mean uptake ratio for treated ear to untreated ear, 1.02 +/- 0.1 [SD]). Further challenges with TNCB resulted in chronic skin inflammation with markedly increased small-vessel density in the ear tissue. This was paralleled by a continuous increase in uptake of (125)I-gluco-RGD. After 13 challenges, the uptake ratio had increased to 2.30 +/- 0.27 (P < 0.005 compared with baseline). Enhanced uptake of radiolabeled RGD peptides in chronic inflammation was also demonstrated noninvasively by PET with (18)F-galacto-RGD. Pretreatment of the mice with nonradiolabeled cyclic peptide c(RGDfV) almost completely blocked uptake of (18)F-galacto-RGD by the challenged ear, thus confirming the specificity of tracer uptake.
CONCLUSION
Radiolabeled RGD peptides allow a noninvasive assessment of alpha(v)beta(3) expression in inflammatory processes. PET with (18)F-galacto-RGD might become a powerful tool to distinguish between the acute and chronic phases of T cell-mediated immune responses and may represent a new biomarker for disease activity in autoimmune disorders.
Topics: Animals; Autoradiography; Dermatitis, Contact; Galactose; Glucosides; Hypersensitivity, Delayed; Metabolic Clearance Rate; Mice; Mice, Inbred C57BL; Oligopeptides; Peptides, Cyclic; Picryl Chloride; Positron-Emission Tomography; Radiopharmaceuticals
PubMed: 15632051
DOI: No ID Found -
The Journal of Clinical Investigation Feb 1969Studies have been made of movement of various macromolecules into and out of the pleural space of guinea pigs during the course of a delayed hypersensitivity reaction to...
Studies have been made of movement of various macromolecules into and out of the pleural space of guinea pigs during the course of a delayed hypersensitivity reaction to purified protein derivative (PPD), and a passively transferred immediate hypersensitivity reaction to ovalbumin. While the immediate hypersensitivity reaction transiently alters vascular permeability as shown by increased movement of macromolecules into the chest, the delayed hypersensitivity reaction is marked by a decreased capacity to resorb macromolecules from the pleural space. The data suggest that the two hypersensitivity reactions may be distinguished by these physiologic differences. Additional data from studies of a chemically induced pleural effusion in these animals suggest that some type of outflow obstruction is necessary for the development of effusion, but that the outflow defect caused by the irritating chemical is based on a different mechanism than that seen during the delayed hypersensitivity reaction.
Topics: Animals; Biological Products; Guinea Pigs; Hypersensitivity, Delayed; Hypersensitivity, Immediate; Immune Sera; Iodine Isotopes; Ovalbumin; Pleural Effusion; Pleurisy; Turpentine; gamma-Globulins
PubMed: 4179171
DOI: 10.1172/JCI105981 -
British Medical Journal Nov 1980
Topics: Humans; Hypersensitivity, Delayed; Metals; Prostheses and Implants
PubMed: 7437772
DOI: No ID Found -
BMC Medicine Feb 2012A decade ago celiac disease was considered extremely rare outside Europe and, therefore, was almost completely ignored by health care professionals. In only 10 years,... (Review)
Review
A decade ago celiac disease was considered extremely rare outside Europe and, therefore, was almost completely ignored by health care professionals. In only 10 years, key milestones have moved celiac disease from obscurity into the popular spotlight worldwide. Now we are observing another interesting phenomenon that is generating great confusion among health care professionals. The number of individuals embracing a gluten-free diet (GFD) appears much higher than the projected number of celiac disease patients, fueling a global market of gluten-free products approaching $2.5 billion (US) in global sales in 2010. This trend is supported by the notion that, along with celiac disease, other conditions related to the ingestion of gluten have emerged as health care concerns. This review will summarize our current knowledge about the three main forms of gluten reactions: allergic (wheat allergy), autoimmune (celiac disease, dermatitis herpetiformis and gluten ataxia) and possibly immune-mediated (gluten sensitivity), and also outline pathogenic, clinical and epidemiological differences and propose new nomenclature and classifications.
Topics: Amino Acid Sequence; Autoimmune Diseases; Celiac Disease; Diet, Gluten-Free; Glutens; Humans; Hypersensitivity, Delayed; Intestinal Diseases; Molecular Sequence Data; Prevalence; Wheat Hypersensitivity
PubMed: 22313950
DOI: 10.1186/1741-7015-10-13 -
The Journal of Investigative Dermatology Feb 2013Immunity to sand fly saliva in rodents induces a T(H)1 delayed-type hypersensitivity (DTH) response conferring protection against leishmaniasis. The relevance of DTH to...
Immunity to sand fly saliva in rodents induces a T(H)1 delayed-type hypersensitivity (DTH) response conferring protection against leishmaniasis. The relevance of DTH to sand fly bites in humans living in a leishmaniasis-endemic area remains unknown. Here, we describe the duration and nature of DTH to sand fly saliva in humans from an endemic area of Mali. DTH was assessed at 24, 48, 72, and 96 hours post bite in volunteers exposed to colony-bred sand flies. Dermal biopsies were obtained 48 hours post bite; cytokines were quantified from peripheral blood mononuclear cells (PBMCs) stimulated with sand fly saliva in vitro. A DTH response to bites was observed in 75% of individuals aged 1-15 years, decreasing gradually to 48% by age 45, and dropping to 21% thereafter. Dermal biopsies were dominated by T lymphocytes and macrophages. Abundant expression of IFN-γ and absence of T(H)2 cytokines establishes the T(H)1 nature of this DTH response. PBMCs from 98% of individuals responded to sand fly saliva. Of these, 23% were polarized to a T(H)1 and 25% to a T(H)2 response. We demonstrate the durability and T(H)1 nature of DTH to sand fly bites in humans living in a cutaneous leishmaniasis-endemic area. A systemic T(H)2 response may explain why some individuals remain susceptible to disease.
Topics: Adolescent; Adult; Aged; Animals; Antigens, Protozoan; Bites and Stings; Child; Disease Susceptibility; Endemic Diseases; Female; Humans; Hypersensitivity, Delayed; Leishmania major; Leishmaniasis; Male; Mali; Middle Aged; Psychodidae; Rodentia; Saliva; Young Adult
PubMed: 22992802
DOI: 10.1038/jid.2012.315 -
Annals of the Academy of Medicine,... May 2010Food allergy is defined as reaction to a food which has an immunologic mechanism. Its prevalence is increasing in children globally and is therefore of increasing... (Review)
Review
Food allergy is defined as reaction to a food which has an immunologic mechanism. Its prevalence is increasing in children globally and is therefore of increasing clinical importance. A useful clinical approach is to distinguish food allergic reactions by the timing of clinical reaction in relation to food exposure and classified as immediate (generally IgE-mediated) and delayed (generally non-IgE-mediated), with the exception of eczema and eosinophilic gastrointestinal disease, which, when associated with food allergy may be associated with either mechanism. This review is aimed at providing the clinician with a Singaporean perspective on the clinical approach and management of these disorders.
Topics: Breast Feeding; Child; Child, Preschool; Eczema; Food Hypersensitivity; Humans; Hypersensitivity, Delayed; Immunoglobulin E; Infant; Infant, Newborn; Skin Test End-Point Titration
PubMed: 20535433
DOI: No ID Found -
Allergology International : Official... Jun 2012Atopic dermatitis (AD) is a common, chronic or chronically relapsing, multifactorial skin disease that mainly occurs in children but affects also adults. AD usually... (Review)
Review
Atopic dermatitis (AD) is a common, chronic or chronically relapsing, multifactorial skin disease that mainly occurs in children but affects also adults. AD usually begins early in life and often concerns people with a personal or family history of asthma and allergic rhinitis. AD is characterized by eczematous changes in the epidermis and originates from a late, T-cell mediated reaction associated to the formation and production of memory T-cell of TH2 type, occurrence of homing receptor at skin level and cutaneous lymphocyte-associated (CLA) antigens. Extrinsic or allergic AD, but not intrinsic AD, shows high total serum IgE levels and the presence of specific IgE for environmental and food allergens. A pivotal role in the pathogenesis of AD is played by filaggrin, a protein contained in the granular layer of the epidermis regulating the aggregation of keratin filaments. Mutation in the filaggrin gene causes decreased barrier function of the corny layers of the epidermis. This favours the enter through the skin of environmental allergens, especially the house dust mite, that further facilitates such entering by the proteolytic activity of its major allergen Der p 1. In fact, recent advances suggest that the dust mite, more than foods, is the major cause of allergic AD. As far as the causal diagnosis of AD is concerned, there is notable evidence supporting the capacity of the atopy patch test (APT) to reproduce the pathophysiologic events of AD. This makes APT a valuable diagnostic tool for AD.
Topics: Animals; Antigens, Dermatophagoides; Arthropod Proteins; Child; Cysteine Endopeptidases; Dermatitis, Atopic; Filaggrin Proteins; Gene-Environment Interaction; Humans; Hypersensitivity, Delayed; Immunologic Memory; Intermediate Filament Proteins; Mutation; Patch Tests; Pyroglyphidae; Skin; Th2 Cells
PubMed: 22361514
DOI: 10.2332/allergolint.11-RA-0371 -
Journal of Biomedicine & Biotechnology 2012Human oral mucosa is subjected to many noxious stimuli. One of these substances, in those who have restorations, is dental amalgam which contains mercury. This paper... (Review)
Review
Human oral mucosa is subjected to many noxious stimuli. One of these substances, in those who have restorations, is dental amalgam which contains mercury. This paper focuses on the local toxic effects of amalgam and mercury from dental restorations. Components of amalgam may, in rare instances, cause local side effects or allergic reactions referred to as oral lichenoid lesions (OLLs). OLLs to amalgams are recognised as hypersensitivity reactions to low-level mercury exposure. The use of patch testing to identify those susceptible from OLL is explored, and recommendations for removing amalgam fillings, when indicated are outlined. We conclude that evidence does not show that exposure to mercury from amalgam restorations poses a serious health risk in humans, except for an exceedingly small number of hypersensitivity reactions that are discussed.
Topics: Dental Amalgam; Humans; Hypersensitivity, Delayed; Lichen Planus, Oral; Mercury; Mouth Mucosa; Patch Tests
PubMed: 22888200
DOI: 10.1155/2012/589569 -
Immunology Jan 1959The capacity of denatured proteins to provoke anaphylactic sensitivity and delayed sensitivity in guinea pigs has been investigated. It has been found that...
The capacity of denatured proteins to provoke anaphylactic sensitivity and delayed sensitivity in guinea pigs has been investigated. It has been found that heat-denatured proteins are as effective as native proteins in provoking delayed hypersensitivity to either material, in spite of the fact that such denaturation greatly modifies their antigenicity from the point of view of antibody production. Pure delayed hypersensitivity, moreover, occurs regularly in response to extremely minute amounts of a good antigen, whether native or denatured. It is further shown that immunological cross-reactivity can be demonstrated regularly by means of the delayed hypersensitivity reaction in guinea pigs, at a time when no cross-reacting antibodies of conventional type can be found. The significance of these observations in regard to the relationship between delayed hypersensitivity and antibody production is discussed.
Topics: Animals; Guinea Pigs; Hypersensitivity; Hypersensitivity, Delayed; Immune System Diseases
PubMed: 13640681
DOI: No ID Found -
Immunology Jul 1978The induction and specificity of delayed hypersensitivity (DH) to Staphylococcus aureus in mice was evaluated in vivo by the footpad (FP) assay and in vitro by spleen...
The induction and specificity of delayed hypersensitivity (DH) to Staphylococcus aureus in mice was evaluated in vivo by the footpad (FP) assay and in vitro by spleen cell stimulation. Repeated infections result in a biphasic DH response. The first DH response, observed following three subcutaneous injections, was route and antigen specific, required viable organisms, and could not be enhanced by the incorporation of bacteria in adjuvants. Footpad reactivity was transferred to non-injected recipients by spleen cells but not serum and was inhibited by anti-thymocyte serum but not by cyclophosphamide. Spleen cell stimulation was maximal with homologous antigen, but, some cross reactivity was observed when cells were stimulated with hererologous gram-positive antigens. No cross reactivity was observed when antigens from gram-negative bacteria were used to stimulate spleen cells. The FP reactivity to homologous antigen following 7 injections, the second DH response, is of longer duration than that following 3 injections. Mice given seven injections exhibit a greater degree of cross reactivity to heterologous gram-positive but not gram-negative bacterial antigens. Similar results were observed when spleen cells from mice receiving 7 injections were simulated with gram-positive antigens. Furthermore, the degree of spleen cell stimulation following three of seven injections could be increased by elicitation prior to the vitro experiments.
Topics: Adjuvants, Immunologic; Animals; Antigens, Bacterial; Cross Reactions; Dose-Response Relationship, Immunologic; Epitopes; Female; Hypersensitivity, Delayed; Male; Mice; Spleen; Staphylococcus aureus
PubMed: 79546
DOI: No ID Found