pyrophosphate and Lymphoma

The necropsy findings of a large cell lymphoma involving only the pericardium and myocardium in a 62-year-old woman are reported. The initial presenting symptoms were heart failure followed by rapidly progressive heart block. The diagnosis of cardiac lymphoma was suggested by gallium and blood pool isotope studies, and was subsequently confirmed by operative myocardial biopsy. The clinical course was abrupt, and the patient died before therapy was instituted. While primary cardiac lymphoma is an extremely rare condition, experience in this case suggests that noninvasive isotope studies, particularly gallium and blood pool, are helpful in the diagnosis of atypical cardiomyopathy.

Topics: Diphosphates; Female; Gallium Radioisotopes; Heart Neoplasms; Humans; Lymphoma; Middle Aged; Myocardium; Necrosis; Radionuclide Imaging; Technetium; Technetium Tc 99m Pyrophosphate

Human γδ T cells are innate-like T cells which are able to kill a broad range of tumour cells and thus may have potential for cancer immunotherapy. The activating receptor natural killer group 2 member D (NKG2D) plays a key role in regulating immune responses driven by γδ T cells. Here, we explored whether recombinant immunoligands consisting of a CD20 single-chain fragment variable (scFv) linked to a NKG2D ligand, either MHC class I chain-related protein A (MICA) or UL16 binding protein 2 (ULBP2), could be employed to engage γδ T cells for tumour cell killing. The two immunoligands, designated MICA:7D8 and ULBP2:7D8, respectively, enhanced cytotoxicity of ex vivo-expanded γδ T cells against CD20-positive lymphoma cells. Both Vδ1 and Vδ2 γδ T cells were triggered by MICA:7D8 or ULBP2:7D8. Killing of CD20-negative tumour cells was not induced by the immunoligands, indicating their antigen specificity. MICA:7D8 and ULBP2:7D8 acted in a dose-dependent manner and induced cytotoxicity at nanomolar concentrations. Importantly, chronic lymphocytic leukaemia (CLL) cells isolated from patients were sensitized by the two immunoligands for γδ T cell cytotoxicity. In a combination approach, the immunoligands were combined with bromohydrin pyrophosphate (BrHPP), an agonist for Vδ2 γδ T cells, which further enhanced the efficacy in target cell killing. Thus, employing tumour-directed recombinant immunoligands which engage NKG2D may represent an attractive strategy to enhance antitumour cytotoxicity of γδ T cells.

Topics: Antigens, CD20; Cytotoxicity, Immunologic; Diphosphates; Drug Therapy, Combination; GPI-Linked Proteins; Histocompatibility Antigens Class I; Humans; Immunization; Immunotherapy; Intercellular Signaling Peptides and Proteins; Lymphoma; NK Cell Lectin-Like Receptor Subfamily K; Receptors, Antigen, T-Cell, gamma-delta; Single-Chain Antibodies; T-Lymphocytes; Tumor Cells, Cultured

Topics: Animals; Diphosphates; Iron-Dextran Complex; Lymphoma; Mice; Radionuclide Imaging; T-Lymphocytes; Technetium; Technetium Tc 99m Pyrophosphate; Tissue Distribution

To determine the scintigraphic findings in children with distal femoral defects (or subperiosteal desmoids) the authors retrospectively examined 94 sets of radiographs and technetium-99m pyrophosphate bone scans of 54 children. Twenty-four examples of distal femoral defects were identified in 19 children. Only two children demonstrate focally increased uptake of radionuclide in the distal femur. The positive bone scan was caused by osteomyelitis in one of these patients and by metastatic lymphoma in the other. None of the 17 other children with distal femoral defects on radiography had a corresponding focal increase in uptake of radionuclide. The bone scan appears to be a useful method for confirming that a distal femoral defect is benign and, when positive, indicates the presence of other disease.

Topics: Adolescent; Child; Child, Preschool; Diphosphates; Female; Femoral Neoplasms; Femur; Fibroma; Humans; Knee; Lymphoma; Osteomyelitis; Radiography; Radionuclide Imaging; Retrospective Studies; Technetium; Technetium Tc 99m Pyrophosphate

Topics: Child, Preschool; Diphosphates; Female; Humans; Jaw Neoplasms; Lymphoma; Male; Maxillary Neoplasms; Radionuclide Imaging; Technetium; Technetium Tc 99m Pyrophosphate

The isolation and characterization of a mutant murine T-cell lymphoma (S49) with altered purine metabolism is described. This mutant, AU-100, was isolated from a mutagenized population of S49 cells by virtue of its resistance to 0.1 mM 6-azauridine in semisolid agarose. The AU-100 cells are resistant to adenosine mediated cytotoxicity but are extraordinarily sensitive to killing by guanosine. High performance liquid chromatography of AU-100 cell extracts has demonstrated that intracellular levels of GTP, IMP, and GMP are all elevated about 3-fold over those levels found in wild type cells. The AU-100 cells also contain an elevated intracellular level of pyrophosphoribosylphosphate (PPriboseP), which as in wild type cells is diminished by incubation of AU-100 cells with adenosine. However AU-100 cells synthesize purines de novo at a rate less than 35% of that found in wild type cells. In other growth rate experiments, the AU-100 cell line was shown to be resistant to 6-thioguanine and 6-mercaptopurine. Levels of hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) measured in AU-100 cell extracts, however, are 50-66% greater than those levels of HGPRTase found in wild type cell extracts. Nevertheless this mutant S49 cell line cannot efficiently incorporate labeled hypoxanthine into nucleotides since the salvage enzyme HGPRTase is inhibited in vivo. The AU-100 cell line was found to be 80% deficient in adenylosuccinate synthetase, but these cells are not auxotrophic for adenosine or other purines. The significant alterations in the control of purine de novo and salvage metabolism caused by the defect in adenylosuccinate synthetase are mediated by the resulting increased levels of guanosine nucleotides.

Topics: Adenylosuccinate Synthase; Animals; Clone Cells; Diphosphates; Leukemia, Experimental; Ligases; Lymphoma; Mice; Mutation; Purines; T-Lymphocytes

Topics: Animals; Antimetabolites; Carbon Isotopes; Carcinoma, Ehrlich Tumor; Chromatography; Diphosphates; Drug Synergism; Lymphoma; Male; Mercaptopurine; Mice; Neoplasms, Experimental; Nucleosides; Nucleotides; Pentosephosphates; Ribose

Topics: Adenine; Animals; Carbon Isotopes; Carcinoma, Ehrlich Tumor; Diphosphates; Glucose; Glucosyltransferases; In Vitro Techniques; Lymphoma; Male; Mice; Neoplasms, Experimental; Nucleosides; Nucleotides