Thrombocytopenia induced by the Friend leukemia virus.
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Animals↗
Biomedical subjects
I Brodsky
Publications and source records attributed to I Brodsky.
Effects of trimethoprim on folate metabolism in man.
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Bacteria↗
The effect of sublethal x-irradiation on erythropoiesis in the mouse.
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Animals↗
Heparin free hemodialysis does not cause fibrin consumptive coagulopathy and maintains alternate pathway complement activation.
Heparin-free hemodialysis allows demonstration of the intradialytic coagulation status not previously possible during standard heparin anticoagulant hemodialysis protocols in patients with end-stage renal disease. No evidence for consumptive coagulopathy was noted in the absence of heparin during hemodialysis with cuprophane hollow fiber dialyzers. Fibrinogen levels, euglobulin lysis time, and platelet counts remained stable throughout 3 hours of heparin-free hemodialysis. Serial thrombin times and platelet aggregation improved during heparin-free hemodialysis. Hemodialyzer volumes and the ultrafiltration coefficient decreased only minimally. The alternate pathway of complement activation associated with hemodialysis blood-membrane interaction is not prevented by heparin-free hemodialysis.
Adult↗
Heterogeneous nuclear RNA from hairy cell leukemia patients activates 2',5'-oligoadenylate synthetase.
Interferon treatment of cells induces double-stranded RNA (dsRNA)-dependent 2',5' oligoadenylate (2-5A) synthetase, an enzyme which has been implicated in the mechanism of growth arrest in tumour cells. Since interferon (IFN) can inhibit the growth of cells that are not infected with virus, natural non-viral dsRNAs should be present in these cells which can activate 2-5A synthetase. If such nuclear dsRNAs are associated with the mechanism of growth control, cells inherently sensitive to growth inhibition by IFN should contain significant levels of 2-5A synthetase-activating dsRNAs. We measured the ability of size fractionated nuclear dsRNAs isolated from patients with hairy cell leukemia (HCL) to activate purified 2-5A synthetase. Peripheral blood mononuclear cells from HCL patients were utilized because of the inherent sensitivity of these patients to IFN treatment. The heterogeneous nuclear RNA fraction from four out of five HCL patients showed high levels of 2-5A synthetase-activating dsRNAs. The 2-5A formed contained biologically active trimers, tetramers, pentamers and hexamers as demonstrated by HPLC analysis and their ability to activate RNase L. In contrast, the nuclear RNA fraction from three out of four healthy controls were unable to activate 2-5A synthetase. These results indicate that natural, nuclear dsRNAs inherently exist in IFN-sensitive cells and imply that these molecules may play a role in the inhibition of cellular growth.
2',5'-Oligoadenylate Synthetase↗
The differential diagnosis of the polycythemic states.
The clinical and laboratory characteristics that are essential for the differential diagnosis of the polycythemic states are reviewed. The various forms of polycythemia that present as increases in hemoglobin concentration or packed red cell volumes can often be distinguished on the basis of pathophysiology, predisposition to neoplasia, hematological and viral parameters, chromosomal patterns, and response to therapy. Polycythemia vera differs from secondary and relative polycythemic states in its basic pathophysiology and etiology. It appears to be a clonal disorder that is characterized by a generalized bone marrow panmyelosis. Although the primary event leading to this stem cell disorder is not known, recent studies suggest a possible etiology. Therapeutic regimens based on the parameters inherent in making a differential diagnosis of the polycythemic states are discussed. Prognosis for polycythemia vera also appears to be predicated by the choice of drugs used to treat the disease. The consequences of making the correct diagnosis and of choosing appropriate therapy in light of the differences in underlying pathophysiology and etiology of the polycythemic states are stressed.
Blood Platelets↗
Clinical studies with mismatched double-stranded RNA.
Mismatched inducer/activator therapy has demonstrated areas of definite clinical promise in its initial human trials. Indeed, the mismatched dsRNA may even prove more efficacious than conventional (exogenous) interferon therapy for several reasons including: (a) First, the potential for generating multiple species of interferons, thereby removing the possible necessity of targeting a specific type (or subtype) of interferon to a particular cell type, (b) Secondly, the known ability of the mismatched inducer to activate the intracellular mediators which are synthesized after cellular exposure to the various types of interferon, (c) Lastly, the recently demonstrated ability of the inducer/activator in combination with interferon to override acquired cellular resistance to interferon alone (13).
Adult↗
RNase L and increased endoribonuclease activities in the mononuclear cells of patients with chronic myelogenous leukemia.
During investigations of the interferon-induced 2',5' oligoadenylate synthetase/RNase L system in malignancy, RNase L activity and an increased endoribonuclease activity were observed in peripheral blood mononuclear cell (PBMC) extracts from patients with chronic myelogenous leukemia. The cleavage of rRNA from intact ribosomes was used as the assay for both RNase L and the increased endoribonuclease activities. Novel rRNA cleavage products (NCP) were generated by extracts of Ficoll-purified mononuclear cells from chronic myelogenous leukemia (CML) patients and in the granulocytic fraction of both patients and healthy controls. Determination of the time course of rRNA degradation demonstrated that the novel cleavage products were rapidly derived from the further endoribonucleolytic degradation of the RNase L derived specific cleavage products. Prolonged incubation of mononuclear cell extracts from healthy controls also yielded the novel rRNA cleavage products. Comparisons of the kinetics of NCP production suggest that the novel endoribonuclease activity can be approximately 240-fold greater in PBMC extracts from CML patients than controls. Analysis of peripheral blood WBC count and differential indicated that the increased RNase activities were associated with the presence of immature granulocytic cells in the peripheral blood (p = 0.001, Fisher's exact test). However, these activities were also found in the mononuclear cells of a CML patient in lymphoid blast crisis. Since CML is a stem cell disease, the novel endoribonuclease activity may be indicative of active disease, rather than a marker for immature granulocytes. Thus, the RNase L and increased endoribonuclease activities may play a functional role in the biology of chronic myelogenous leukemia and may be important in the mechanism of action of interferon therapy in this disease.
Endoribonucleases↗
Chemotherapy for advanced germinal cell neoplasms: preliminary report of an Eastern Cooperative Oncology Group Study.
A series of 45 evaluable patients with stage III germ cell tumors have been treated between July 1977 and May 1978, with two cycles of an intensive five-drug regimen including cyclophosphamide, actinomycin D, vinblastine, bleomycin, and cis-dichlorodiammineplatinum(II) (cis-platinum). The patients were randomly assigned to receive the cis-platinum as a high dose 1-hour infusion with mannitol diuresis or as a low-dose 8-hour infusion without diuresis. The overall response rates were 36% complete response (CR) and 47% partial response (PR) after two cycles of induction therapy. Patients who achieved a CR or PR after two cycles were randomized to continue treatment with either a three-drug program of vinblastine, actinomycin D, and cis-platinum or a cyclic crossover regimen of three regimens (each containing three drugs) given in sequence at 3-week intervals with the entire sequence repeated at 9 weeks. During continuing treatment a minimum of five patients improved from PR to CR, so that the minimum CR rate will be 47%. A major determinant of response was extent of disease, with limited-disease patients having an 83% CR rate and advanced-disease patients having 22% CR rate. At present, there are no statistically significant differences between response rates for the two induction regimens. Patients have not been followed long enough on the continuing treatment arms to allow evaluation of improvement from PR to CR, duration of response, or duration of survival. Hematologic and renal toxiciity were not significantly different on the two induction treatment arms.
Antineoplastic Agents↗