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J Manaster

Publications and source records attributed to J Manaster.

30 records · Page 2Linked to original sources

Viral-related information in oncornavirus-lik particles isolated from cultures of marrow cells from leukemic patients in relapse and remission.

Characterization of ribonucleic acid content of particles released from cultures of marrow cells of leukemic patients indicates the presence of RNA molecules of size and base sequence characteristic of oncornarviruses. Seventeen marrow samples obtained from leukemic patients in relapse or in a chronic phase of the disease yielded particles containing high-molecular-weight RNA with a sedimentation velocity (about 70 S) similar to that obtained for murine oncornavirus RNA. Eight of nine marrow samples from non-leukemic patients did not yield detectable high-molecular weight RNA. Among patients in firm hematological remission, three of three samples from patients with acute lymphoblastic leukemia and three of nine samples from patients with acute myeloblastic leukemia were positive for high-molecular-weight RNA. The base sequence of the RNA in particles was characterized by synthesizing complementary (3-H)DNA in an endogenous reaction and hybridizing to excess RNA from known oncornaviruses. Hybridization of 40-60% of input complementary DNA to simian sarcoma virus RNA was detected. No monology was detected with an avian oncornavirus (Rous sarcoma virus) while an intermediate level of homology (10-30%) was detected in hybridization to murine sarcoma virus (Kirsten) and murine leukemia viruses (Rauscher, Moloney, and Gross).

Avian Sarcoma Viruses↗

Particles with characteristics of leukoviruses in cultures of marrow cells from leukemic patients in remission and relapse.

An enzyme activity with the characteristics of RNA-directed DNA polymerase (reverse transcriptase) was detected in marrow from patients with leukemia in relapse and in firm hematological remission. Material having the enzyme activity, when analyzed in sucrose gradients, appeared as two distinct homogeneous bands of particles with densities of about 1.17 and 1.23 g/ml. The enzyme activity was stimulated by exogenous template poly(rC).(dG)(12-18) but not by (dT)(12-18). The enzyme activities in these bands also increased (1.7- to 24-fold) after culture, and both bands with enzyme activity were obtained from the cultured cells and from the supernatant medium. Electron microscopic studies showed that the two bands contained particles resembling leukoviruses or their cores.

Bone Marrow↗

Mode of action of chemotherapy in vivo on human acute leukemia. I. Daunomycin.

The leukocytes of 16 adult patients with acute myeloblastic leukemia were studied by autoradiographic methods to elucidate the mode of action of daunomycin. It was shown that daunomycin, at clinically useful doses, exhibits a cytolytic effect on all leukemic blasts whatever their cell-cycle phase. This cytolytic action affects, however, preferentially S-phase cells. It was shown also that blasts of patients less sensitive to daunomycin or receiving a lesser dose of the drug are temporarily blocked in G(2) phase (delayed mitosis) or in G(2) phase (prolonged generation time). Finally daunomycin appeared to hamper the passage of G(2)-blocked blasts from the bone marrow to the blood, while G(2)-phase cells crossed freely.

Autoradiography↗

Remission maintenance of acute nonlymphoblastic leukemia with BCNU (NSC-409962) and cyclophosphamide (NSC-26271).

Thirteen of 29 patients with acute nonlymphoblastic leukemia achieved complete remission with cyclophosphamide, cytosine arabinoside, and vincristine, and remissions were maintained with a combination of BCNU and cyclophosphamide. The maintenance drugs (200 and 1000 mg/m respectively) were given at 8-week intervals intravenously. Only six of the 13 patients achieving a complete remission have relapsed. The projected median duration of complete remission is 65 weeks and of survival from diagnosis is 144 weeks. These remission and survival durations compare favorably with the results achieved using other forms of remission-maintenance therapy. The advantage of our form of maintenance therapy is that only overnight hospitalization is required at 8-week intervals.

Adolescent↗