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Biomedical subjects

H D Preisler

Publications and source records attributed to H D Preisler.

At least 235 records · Page 13Linked to original sources

Sensitization in vitro to murine myeloblastic leukemia cells by xenogeneic immune RNA.

Normal murine spleen cells were sensitized to syngeneic myeloid leukemia cells by RNA extracted from the lymph nodes and spleens of Hartley guinea pigs immunized with the murine leukemia cells. Sensitization mediated by RNA was an active process that required physiologic temperature and at least a 10-minute incubation. RNA extracted from unimmunized guinea pigs of guinea pigs immunized with normal spleen cells failed to sensitize the mouse spleen cells. Sensitization was specifically directed toward leukemia cells, whereas the spleen cells remained unreactive toward normal spleen or bone marrow cells. The sensitizing moiety was RNA itself inasmuch as it was inactivated by RNase and not by DNase or pronase. Preparations whose RNA patterns on sucrose density centrifugation gave evidence of degradation of the RNA did not sensitize normal spleen cells. These studies demonstrate that xenogeneic immune RNA can specifically sensitize normal spleen cells to syngeneic myeloid leukemia cells.

Animals↗

Effects of partially thiolated polycytidylic acid on the clonogenicity of murine leukemic stem cells.

The effect of partially thiolated polycytidylic acid (MPC) on the colony-forming ability of the progenitor cells (CFUC) of RF/Un leukemic mice was investigated using the plasma clot method in order to study the mode of action of the modified polynucleotide. The results showed that MPC inhibited the CFUC in a dose-dependent and time-dependent manner. Once a maximum level of inhibition of CFUC (approximately 40%) was observed, no further inhibition occurred whether the concentration of MPC was increased or whether the duration of incubation was lengthened. High-specific-activity [3H]thymidine, an S-phase-specific agent, showed a similar inhibition profile on the CFUC as did MPC. When MPC and high-specific-activity [3H]thymidine were incubated together with the bone marrow cells, there was no additive or synergistic inhibitory effect on the CFUC. Thus, it appears that MPC is an S-phase-specific agent. When injected i.v. into the mice, MPC decreased the number of CFUC of both the bone marrow and the spleen significantly.

Animals↗

A method for obtaining human bone marrow specimens enriched for myeloblasts and promyelocytes.

A simple method has been developed for obtaining specimens of human marrow which are enriched for myeloblasts and promyelocytes. The erythrocytes are lysed, the marrow is incubated with iron particles, and the cells that phagocytize the iron are removed with a powerful magnet. The marrow is then subjected to a density-cut centrifugation using Ficol-Hypaque with a density of 1.084 gm/mm3. The cells that do not enter the Ficol-Hypaque are removed from the surface and studied. The proportion of myeloblasts and promyelocytes in this subpopulation of cells exceeds 50%. Total recovery of these immature myeloid progenitor cells is 50% of that in the original marrow specimen. This method has been used for cell suspensions containing as many as 10(9) cells. Cells prepared using this method incorporate 3H-TdR, 3H-UR, and 3H-Leu at a higher rate than the unseparated specimens and have a cloning efficiency of 2.0% to 19.4% compared with 0.1% to 2.17% for the unseparated marrows.

Cell Separation↗

Treatment of acute nonlymphocytic leukemia: use of anthracycline-cytosine arabinoside induction therapy and comparison of two maintenance regimens.

Patients with acute nonlymphocytic leukemia were given remission induction therapy consisting of cytosine arabinoside and an anthracycline. Those patients who experienced complete remission received two courses of consolidation therapy and were randomized to receive maintenance therapy consisting of either daily chemotherapy with reinforcements every 3 mo or reinforcement therapy only every 6 wk. The overall complete remission rate was 66%, with 80% complete remission for previously untreated patients less than 60 yr of age who did not have a prior history of malignancy. Remission durations were the same for patients treated with both maintenance regimens. The major determinant for successful remission induction therapy was patient age, with older patients frequently succumbing to intercurrent infection. Documented leukemic cell resistance to the therapy employed was only rarely encountered. Once remission was achieved, age was no longer a determinant of patient survival, since duration of remission was independent of age. Remission durations were directly related to leukemic cell retention of cytosine arabinoside triphosphate. Hence therapy for acute nonlymphocytic leukemia can be divided into two separate areas: remission induction and remission maintenance.

Adolescent↗

Friend leukemia cells: relationship between differentiation, clonogenicity and malignancy.

Friend leukemia cells were cultured in vitro in the presence or absence of agents which induce erythroid differentiation. The cultures were harvested and the degree of differentiation determined. Clonogenicity of the cells in vitro and malignancy in vivo were determined as well. There was an inverse exponential relationship between the degree of differentiation and the clonogenicity of the culture. Differentiation was also associated with a modest decline in malignancy. Of interest was the observation that bromodeoxyuridine inhibited the biochemical manifestations of erythroid differentiation, but did not prevent the decline in clonogenicity which accompanied differentiation.

Animals↗

Growth of human marrow in plasma clot diffusion chambers.

Unseparated as well as nonadherent human bone marrow cells produced colonies while suspended within plasma clots contained within diffusion chambers implanted into irradiated mice. The majority of colonies consisted of granulocytes or macrophages. Colony size was significantly increased by the administration of endotoxin prior to implantation of the chambers.

Acute Disease↗

Carcinoma of unknown primary: natural history and response to therapy.

Twenty-three consecutive patients with metastatic carcinoma of unknown primary referred to a medical oncology service over the past two years were studied. In the majority of patients, death occurred within one year of diagnosis and a priamry site of disease was identified at postmortem examination. Of patients who had a primary site identified, findings suggestive of involvement of that site were present during the course of their illness. Survival was greatest in patients with adenocarcinoma histology, with lymph node site of presentation and in those treated with both radiation therapy and chemotherapy, although these differences were not statistically significant. Despite the prolonged survival of a few patients, it is clear that failure to extensively evaluate subtle clinical findings and the lack of efficacious therapy for the malignancies commonly encountered seriously limit the survival of the vast majority of these patients. The identification of new tumor markers and the use of adjunctive chemo-immunotherapy to excisional surgery may ultimately improve to outlook for these patients.

Adenocarcinoma↗

Migration inhibition of sensitized mouse spleen cells by cell-associated transplantation antigens: effect of method of antigen presentation.

The migration of specifically sensitized mouse spleen cells following exposure to allogeneic cells (antigen) in vitro was studied. The migration inhibition recorded when sensitized cells were admixed with allogeneic cells in capillary tubes (mix method) was compared to the inhibition observed when allogeneic cells were suspended in the culture chamber media (non-mix method). Specificity as well as a higher degree of migration inhibition were obtained using the mix method, suggesting that this method is superior to the nom-mix method.

Animals↗

Blindness in a patient with malignant histiocytosis.

Malignant histiocytosis (MH) is a rapidly fatal systemic disease for which there is no adequate therapy. A case of MH with involvement of both eyes resulting in bilateral blindness is presented. Infiltration with malignant cells was seen in the ciliary bodies at autopsy. Attempts at treatment for this complication are discussed.

Adult↗

Acute myelogenous leukemia subsequent to therapy for a different neoplasm: clinical features and response to therapy.

The clinical characteristics of 10 patients with acute myelogenous leukemia (AML) which developed subsequently to treatment for another neoplasm are described. This disease appears to differ from "spontaneous" AML in being associated with lesser degrees of leukemic infiltration of the marrow and more frequent chromosomal aberrations. Only one of the nine patients who received chemotherapy attained remission status, and the mean and median survivals from the initiation of chemotherapy were 2.7 months and one month respectively. Nine of the 10 patients died as a result of infection. The refractoriness of this form of AML to chemotherapy was borne out by a review of the literature, which revealed only two remissions in 32 treated patients. The implications for the management of this disease are discussed.

Bone Marrow↗

Drug uptake and ribonucleotide profiles of blast-enriched and blast-depleted human bone marrow cell populations.

A density cut method was used to prepare two subpopulations of bone marrow cells which were enriched (BE) and depleted (BD) respectively of blast cells. Marrow aspirates were obtained from 32 patients, 26 of whom had acute leukaemia. The uptake of a variety of chemotherapeutic agents by these two subpopulations and the acid-soluble ribonucleotide profiles of the populations were compared and significant differences were found in drug uptake by BE and BD subpopulations. For some drugs such as cytosine arabinoside, uptake was greatest by the BE cells, while for 5-azacytidine the BD subpopulation took up the greatest amount of the drug. The preparation of the BE subpopulation also permitted the recognition of several patients with acute leukaemia whose blast cells possess nondetectable levels of ATP, UTP, and GTP components in their acid-soluble fractions. The studies presented demonstrate the necessity of using purified cell populations when characterizing the drug uptake patterns and the soluble ribonucleotide profiles of the leukaemic cells. A simple method for enriching bone marrow aspirates for leukaemic cells is also presented.

Antimetabolites↗

Murine myeloid leukemia: I. Pathophysiology and drug sensitivity.

The pathophysiology of serially passaged myeloid leukemia of the RFM mouse was studied. The disease was characterized by progressive splenomegaly and infiltration of both marrow and spleen by myeloblasts. The animals became anemic and there was an associated erythroid hyperplasia in the spleen. Leukemic spleen cells obtained from animals early in the course of the leukemia were less malignant than those obtained from preterminal mice. The leukemia is most sensitive to alkylating agents but is also responsive to antimetabolites.

Alkylating Agents↗