ABSTRACT
We report a case of small bowel obstruction secondary to coin ingestion. A 22-year-old woman presented to the Emergency Department (ED) with a 3-week history of abdominal pain. Upon initial history the patient denied any foreign body ingestion. Only after computed tomography (CT) scanning of the abdomen and pelvis did the patient admit to deliberate ingestion of a single United States penny coin. During surgical evaluation it was found that the coin had lodged near the ileocecal valve and an inflammatory mass had formed around the intraluminal coin, causing a 10 x 7 cm fibrous tumor to completely obstruct the small bowel. It is thought that oxidation of the coin, with subsequent exposure of its high zinc content, instigated the inflammatory cascade.
Subject(s)
Foreign Bodies/complications , Intestinal Obstruction/etiology , Numismatics , Abdomen, Acute/diagnostic imaging , Abdomen, Acute/surgery , Abdominal Pain/etiology , Abdominal Pain/surgery , Adult , Emergency Medical Services , Female , Foreign-Body Reaction/etiology , Humans , Intestinal Obstruction/diagnosis , RadiographyABSTRACT
To study the induction of anti-"self" CD8+ T-cell reactivity against the tumor antigen gp100, we used a mouse transgenic for a chimeric HLA-A*0201/H-2 Kb molecule (A2/Kb). We immunized the mice with a recombinant vaccinia virus encoding a form of gp100 that had been modified at position 210 (from a threonine to a methionine) to increase epitope binding to the restricting class I molecule. Immunogens containing the "anchor-fixed" modification elicited anti-self CD8+ T cells specific for the wild-type gp100(209-217) peptide pulsed onto target cells. More important, these cells specifically recognized the naturally presented epitope on the surface of an A2/Kb-expressing murine melanoma, B16. These data indicate that anchor-fixing epitopes could enhance the function of recombinant virus-based immunogens.
Subject(s)
Autoimmunity/immunology , CD8-Positive T-Lymphocytes/immunology , Cancer Vaccines/immunology , HLA-A Antigens/immunology , Melanoma, Experimental/immunology , Membrane Glycoproteins/immunology , Neoplasm Proteins/immunology , Peptide Fragments/immunology , Transfection , Animals , Antigen Presentation/genetics , Antigen Presentation/immunology , Autoimmunity/genetics , Cancer Vaccines/genetics , Epitopes/immunology , HLA-A Antigens/genetics , Immunity, Cellular , Membrane Glycoproteins/genetics , Mice , Mice, Transgenic , Neoplasm Proteins/genetics , Peptide Fragments/genetics , Vaccinia virus/genetics , Vaccinia virus/immunology , gp100 Melanoma AntigenABSTRACT
To isolate melanoma Ags recognized by T cells, cDNA libraries made from melanoma cell lines were screened with four CTLs derived from tumor infiltrating lymphocytes (TIL) that were able to recognize melanoma cells in a HLA-A1, -A2, or -A3 restricted manner. Although cDNAs encoding the previously identified melanoma Ags, tyrosinase and gp100, were isolated, these TIL were found to recognize previously unidentified peptides. An HLA-A1-restricted CTL, TIL1388, was found to recognize a tyrosinase peptide (SSDYVIPIGTY), and an HLA-A3-restricted CTL, TIL1351, recognized a gp100 peptide (LIYRRRLMK). CTL clones isolated from the HLA-A2-restricted TIL1383 recognized a gp100 peptide (RLMKQDFSV). HLA-A2-restricted CTL, TIL1200, recognized a gp100 peptide (RLPRIFCSC). Replacement of either cysteine residue with alpha-amino butyric acid in the gp100 peptide, RLPRIFCSC, enhanced CTL recognition, suggesting that the peptide epitope naturally presented on the tumor cell surface may contain reduced cysteine residues. Oxidation of these cysteines might have occurred during the course of the synthesis or pulsing of the peptide in culture. These modifications may have important implications for the development of efficient peptide-based vaccines. These newly identified peptide epitopes can extend the ability to perform immunotherapy using synthetic peptides to a broader population of patients, especially those expressing HLA-A1 or HLA-A3 for whom only a few melanoma epitopes have previously been identified.
Subject(s)
Antigens, Neoplasm/immunology , Epitopes/immunology , HLA-A1 Antigen/immunology , HLA-A2 Antigen/immunology , HLA-A3 Antigen/immunology , Lymphocytes, Tumor-Infiltrating/immunology , Melanoma/immunology , Membrane Glycoproteins/immunology , Monophenol Monooxygenase/immunology , Neoplasm Proteins/immunology , Peptide Fragments/immunology , T-Lymphocytes, Cytotoxic/immunology , Adult , Alleles , Amino Acid Sequence , Amino Acid Substitution , Antigens, Neoplasm/chemistry , Cysteine/chemistry , DNA, Complementary/genetics , DNA, Neoplasm/genetics , Epitopes/chemistry , Female , HLA-A1 Antigen/genetics , HLA-A2 Antigen/genetics , HLA-A3 Antigen/genetics , Humans , Male , Melanoma/secondary , Membrane Glycoproteins/chemistry , Molecular Sequence Data , Monophenol Monooxygenase/chemistry , Neoplasm Proteins/chemistry , Oxidation-Reduction , Peptide Fragments/chemistry , Sequence Alignment , Sequence Homology, Amino Acid , Tumor Cells, Cultured , gp100 Melanoma AntigenABSTRACT
Recombinant human MART-1 protein was produced by bacterial and baculoviral-insect cell expression systems. By immunization with bacterial MBP-MART-1 fusion protein or MBP cleaved MART-1 protein, a rabbit polyclonal and two murine monoclonal antibodies specific for MART-1 were produced. These antibodies specifically detected MART-1 in immuno-precipitation, Western blotting, flow cytometric assays and in immunohistochemical analysis of tissue sections. They also stained cytoplasmic components in melanocytes and most melanoma cells in frozen or paraffin embedded tissue sections, indicating that these antibodies may be useful for the diagnosis of melanoma. One of the monoclonal antibodies M2-7 C10 recognized only human MART-1, but the other monoclonal antibody M2-9 E3 recognized both human and murine MART-1. The size of the human MART-1 molecule detected by SDS-PAGE with these antibodies was approximately 18 kDa, suggesting possible posttranslational modifications in the MART-1 protein. Subcellular fractionation studies suggested that MART-1 was present in melanosomes and endoplasmic reticulum, although known melanogenic enzymatic activities were not detected in the MART-1 protein. These reagents may be useful for biological studies on melanocytes and melanoma cells as well as for the development and monitoring of immunotherapy for patients with melanoma.
