Characterization of adenosine cyclic 3':5'-monophosphate-binding proteins in human neuroblastoma.
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Animals↗
Biomedical subjects
A A Green
Publications and source records attributed to A A Green.
Tetany: a complication of cis-dichlorodiammineplatinum(II) therapy.
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Adolescent↗
Combination chemotherapy for osteosarcoma.
Because of the great risk for development of pulmonary metastases following amputation for osteosarcoma, 24 consecutive patients with "clinically localized" osteosarcoma of an extremity were given adjuvant combination chemotherapy with adriamycin-cyclophosphamide-high-dose methotrexate-citrovorum factor. Thirteen of these patients remain free of tumor from 11 to 48 months following amputation. The median disease-free survival is estimated to be 18 months and the median survival 27 months. No relapses have been observed in any patients surviving free of disease beyond 23 months. Combination chemotherapy was also given to 16 patients whose disease was not localized; eight with pulmonary metastases at or following diagnosis, one with nodal metastases at diagnosis, two with osteosarcoma following radiation therapy for other malignant tumors, three with osteosarcoma of flat bones, one with parosteal osteosarcoma, and one with multifocal osteosarcoma. Three of this latter group of patients are surviving free of tumor at 8, 17, and 19 months from diagnosis. Two young patients died from complications of methotrexate and adriamycin toxicity.
Adolescent↗
Correlation of cell kinetic and clinical response to chemotherapy in disseminated neuroblastoma.
Mitotic and labeling indices of bone marrow tumor cells were determined from patients with disseminated neuroblastoma. Although pretreatment values were variable, the median indices indicated that only a small proportion of tumor cells were proliferating. The pretreatment indices could not be correlated with presenting clinical features or with the response to chemotherapy. Studies were repeated after 7 daily doses of cyclophosphamide (150 mg/sq m) and serially after Adriamycin (35 mg/sq m) given on Day 8. Changes in the mitotic and labeling indices during the first course of therapy could be directly correlated with the clinical response as evaluated after 4 months of induction chemotherapy. In all patients who attained a complete or partial remission, an increase in these indices was observed after 7 days of cyclophosphamide. If this increase was associated with an observed kinetic effect of Adriamycin in the G1, S, and G2 phases of the cell cycle, a complete remission was attained. If, following Adriamycin, kinetic evidence of an effect was not present in all three phases of the cell cycle, only partial remission was attained. No clinical response to therapy was observed in those patients in whom the mitotic index and labeling index did not increase after 7 days of cyclophosphamide.
Bone Neoplasms↗
Total-body sequential segmental irradiation and combination chemotherapy for children with disseminated neuroblastoma.
Fourteen children with disseminated neuroblastoma were treated with segmental total-body irradiation and a combination of cyclophosphamide, vincristine and Adriamycin. Six others had localized tumors and were treated with either surgery alone or limited irradiation and chemotherapy. The main objective of the study was to find out if this aggressive therapy for disseminated neuroblastoma would be tolerated and would promote longer disease-free remissions and possibly, cures. Complete responses were obtained in all patients with localized tumors. Of the 14 patients with disseminated disease, three had complete responses, five had partial responses, two had objective responses, and four were classified as nonresponders. Survival rates for this group are poor. Only two patients are still alive, and the single patient who survives free of disease has had a complex clinical course that is only indirectly a result of treatment. The median survival for patients with disseminated tumor was 9 months, not appreciably different from earlier result. Although toxicity was clinically manageable, it interfered with the planned schedule of therapy. Continuous weight loss combined with severe bone marrow suppression due to irradiation prevented about 50% of the scheduled drug dose from being administered. This resulted in poor control of tumor outside of radiation ports and eventually led to progressive disease within previously irradiated sites. We conclude that irradiation used in this manner will not improve disease-free survival of children with disseminated neuroblastoma. It is essential that disseminated disease be controlled before extensive irradiation is attempted.
Antineoplastic Agents↗
Immunotherapy of osteosarcoma patients with virus-modified tumor cells.
Twelve patients 11-20 years of age with recurrent osteosarcoma were immunized with either autologous or allogeneic tumor cells infected with influenza virus, strain B/Michigan or A/Port Chalmers. Six patients received only the vaccine, and the remaining six patients continued to receive methotrexate chemotherapy. The main objectives of this study were to determine if immunizations were toxic, if antibodies developed to the influenza virus antigen component of the vaccine, if this vaccine increased tumor-specific cellular and humoral immunity, and if the increase in immune response could be correlated with clinical course and prognosis. In all 12 cases, toxicity was negligible, and immunizations boosted antibody titers to both tumor cell and influenza virus antigens. However, in four of the six patients with advanced disease who received immunotherapy only, the vaccine did not stimulate mixed lymphocytes nor did it increase cell-mediated immunity. By contrast, five of six patients with minimal disease who continued methotrexate therapy developed cellular and humoral immunity in response to both allogeneic and autologous tumor cells. Although no clear-cut relationship between responses to the tumor cell vaccine and clinical course and prognosis could be demonstrated, three of the six patients with minimal disease have survived for 7-8 months after the first vaccination, without progression of disease. This study demonstrates that plasma membrane preparations derived from different lines of virus-infected osteosarcoma tumor cells will elicit an antibody response in patients with drug-resistant progressive osteogenic sarcoma.
Adolescent↗
Evidence for the existence of two types of cAMP binding sites in aggregating cells of Dictyostelium discoideum.
Inhibition by dithiothreitol of the cell-bound phosphodiesterase has allowed the measurement of cAMP binding to aggregation-competent Dictyostelium discoidium amebae. Two classes of binding sites were demonstrated: Type 1, of low affinity (Kd approximately 160 nM) and high capacity (Ro approximately 1 X 10(5) sites per cell); and Type 2, of high affinity (Kd approximately 9 nM) but low capacity (Ro approximately 1.5 X 10(4) sites per cell). Both sites are developmentally regulated and are expressed during aggregation. The specificities of both sites are consistent with the specificity observed in vivo for the chemotactic response.
3',5'-Cyclic-AMP Phosphodiesterases↗
Myelofibrosis in children with chronic renal insufficiency.
During investigation of splenomegaly in a boy with chronic renal failure and osteodystrophy, bone marrow aspirates resulted in "dry taps," whereas biopsied material provided evidence that the marrow had been replaced by fibrous tissue. In a study of six other children with chronic renal failure, similar changes were observed. These findings suggest that the anemia of chronic renal failure may in part be a result of myelofibrosis, and the resulting reduction of functional bone marrow may limit the tolerance to immunosuppressive agents in patients who undergo renal transplantation.
Adolescent↗
Fatal "iron heart" in an adolescent: biochemical and ultrastructural aspects of the heart.
Histochemical and ultrastructural aspects of the heart were investigated in an adolescent with fatal congestive heart failure resulting from exogenous hemochromatosis. Extensive iron deposits were found in all four chambers, papillary muscles, and the conduction system. These deposits were most prominent over the outer third of the left ventricular myocardium, with no significant difference between deposits in the middle and inner thirds. Quantitative analysis of iron from different chambers and all zones of the left ventricular myocardium confirmed the aforementioned pattern of iron distribution. Iron deposits in sinoauricular and atrioventricular nodes were similar to those in the right atrial myocardium. Degenerative changes and fibrosis were minimal. Ultrastructural studies showed that intracytoplasmic iron deposition followed a perinuclear, paranuclear, or diffuse pattern. In addition, some iron was consistently present in the nucleus and mitochondria. It is postulated that the presence of iron in the mitochondria may adversely affect the cellular enzyme system; this could provide a biochemical basis for myocardial dysfunction in patients with acquired iron-storage disease.
Adolescent↗