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Biomedical subjects

G Spitzer

Publications and source records attributed to G Spitzer.

At least 163 records · Page 9Linked to original sources
PubMed1981

Human myeloid leukaemic cell interactions in vitro with normal myeloid colonies.

To determine whether myeloid leukaemic cells could inhibit normal myeloid colony formation, leukaemic cells at concentrations ranging from 0.5 to 8 X 10(6)/ml were co-cultured in agar but separated by a 1 ml underlayer from 10(5) low-density (less than 1.077 g/ml) nonadherent normal marrow cells. Inhibition of normal-marrow myeloid colony formation occurred regularly at high cell concentrations (8 X 10(6)) at a leukaemic:normal cell ratio of 80:1. This suppression persisted with addition of indomethacin (10(-6)M). On the other hand, both low leukaemic cell numbers and irradiated leukaemic cells frequently stimulated normal colony growth. No inhibitor of colony growth could be detected in leukaemic-conditioned media, and absorption of colony-stimulating activity (CSA) with leukaemic cells improved CSA activity. These experiments point to the difficulty in unravelling the effect of leukaemic cells on normal haemopoiesis (both inhibitory and stimulatory) by in vitro agar culture.

Cell Count↗
PubMed1981

Human leukocyte interferon preparation-mediated block of granulopoietic differentiation in vitro.

We have recently reported that human leukocyte-interferon preparation (HLIF) blocks granulopoietic differentiation. In the current study, using suspension cultures, we further demonstrate that HLIF can effectively block granulopoietic differentiation, resulting in an accumulation of granulocyte-macrophage progenitor cells (GM-CFC), cluster-forming cells and the morphologically identifiable myeloid precursors. Using semisolid agar cultures, we have also demonstrated that the effect of HLIF on GM-CFC and cluster-forming cells is reversible and that human placental conditioned medium (HPCM), used as a source of colony-stimulating factor (CSF), can effectively counteract the effect of HLIF action on the granulopoietic precursors. The interferon preparation derived from human fibroblasts, on the other hand, was found to be less effective in blocking granulopoietic differentiation compared to HLIF; indicating a tissue-specificity of interferon action. These data suggest that HLIF may have a regulatory role in the control of granulopoietic proliferation and differentiation.

Bone Marrow Cells↗
PubMed1981

Adherent cell inhibition of human leukemic in vitro agar clonal growth by short-term cell-to-cell contact.

The effects of peripheral blood adherent cells from normal donors on human myeloid leukemic cluster growth in agar were studied. A prior co-incubation of nonadherent leukemic cells with adherent cell monolayers from 9 out of 10 donors in liquid cultures over a 4-hr period was sufficient to reduce subsequent leukemic growth in semisolid agar cultures. Inhibition was seen with adherent to leukemic cell ratios of as low as 0.5:1. Conversely, identical numbers of adherent cells in agar cultures but separated from the leukemic cells enhanced growth more than the cultures containing human placental conditioned media alone. Because leukemic cell exposure to adherent cells was brief, a cytotoxic mechanism appeared likely; however, this could not be detected by 51Cr release. Human peripheral blood adherent cells not activated by any in vitro mechanism suppress clonal growth of human myeloid leukemic cells by a mechanism requiring cell to cell contact. Examination of the inhibition of clonal growth appears to be more sensitive than 51Cr release as an indicator of adherent cell effects on myeloid leukemia.

Agar↗
PubMed1981

Piperazinedione (NSC 135758) and total body irradiation as an ablative bone marrow transplantation regimen in mice.

Piperazinedione, an antitumor antibiotic with activity against leukemia, has been incorporated into a regimen for clinical bone marrow transplantations. Studies were conducted to evaluate the effect of piperazinedione on hemopoietic stem cells and the recovery of hemopoiesis after syngeneic transplantation. The effect of piperazinedione on hemopoietic stem cells is short in duration (nadir day 1). Myelosuppression does not appear to be its limiting toxicity, since mice could not be rescued by syngeneic bone marrow at increased doses of piperazinedione. Piperazinedione given prior to total body irradiation has an enhancing effect on colony-forming unit culture (CFUC) and colony-forming unit spleen (CFUS) recovery from day 7 to day 90 post transplantation when compared with total body irradiation alone.

Animals↗
PubMed1980

High-dose combination chemotherapy with autologous bone marrow transplantation in adult solid tumors.

In order to determine whether high-dose combination chemotherapy was active in chemotherapy resistant patients, 19 patients, (9 with small cell bronchogenic carcinoma, 6 with embryonal cell carcinoma, 2 with diffuse histiocytic lymphoma, 1 with Hodgkin's disease and 1 with chondrosarcoma), 18 of whom had had extensive prior chemotherapy and failed, received 23 courses of high-dose chemotherapy with autologous bone marrow infusion (ABMT). Three patients received four courses of cytoxan (2-6 g/m2) and VP-16 (500-600 mg/m2) and 16 patients received 19 courses of cytoxan and VP-16 in these doses plus BCNU (300 mg/m2). Activity was observed in 6 of 8 evaluable small cell bronchogenic carcinoma patients (1 complete response (CR), 4 partial responses (PR), 1 less than PR), in 6 embryonal cell carcinoma patients (3 CR, 2 PR, 1 less than PR), in both patients with diffuse histiocytic lymphoma (1 CR, 1 less than PR), in the patient with Hodgkin's disease (1 PR); and in the patient with chondrosarcoma (stable). Only 2 patients who had received prior cytoxan and VP-16 extensively showed resistance to these programs. The median response duration was 11 weeks (range = 4-55 + weeks). Major toxicity consisted of bacterial infections. Two patients died from treatment related causes. Neutrophils recovered to levels of greater than or equal to 1.5 x 10(9)/liter by days 20-42 (median, day 27) and platelets to levels of greater than 100 x 10(9)/liter by days 21-56 (median, day 32) without any delayed BCNU toxicity. High-dose combination chemotherapy with ABMT causes acceptable toxicity and high response rates of relatively short duration in tumors refractory to conventional chemotherapy.

Adult↗
PubMed1980

Factors related to length of complete remission in adult acute leukemia.

Two hundred and two adult patients with acute leukemia were analyzed to determine pretreatment and treatment factors that could predict for duration of bone marrow remission. Several factors had a significant effect on remission duration, including morphologic diagnosis (AML greater than ALL greater than AUL), initial blast cell count, age, serum LDH, fibrinogen level, labeling index, and in vitro agar colony growth. Patients who attained a remission quickly or in whom leukemic cells in blood and bone marrow were rapidly cleared had long remissions. After applying regression model fitting methods, the six major factors, in order of significance, were the initial serum LDH level, pretreatment fibrinogen level, the number of courses of treatment to obtain a remission, morphologic diagnosis, the halving rate of leukemic cells in the blood, and the age of the patient. The model derived from this study was applied to the 202 patients and suggested that patients likely to have short or long bone marrow remission can be identified.

Adolescent↗
PubMed1980

Diurnal changes in circulating myeloid progenitor cells in man.

To examine the diurnal changes in circulating myeloid progenitor cells (CFU-Cs), 15 normal human volunteers were studied. Total and differential peripheral blood leukocyte counts and CFU-C levels, using the in vitro agar culture method, were obtained at 8 AM, 11 AM, 3 PM, and 8 AM the following morning (in nine subjects) or only at 8 AM and 3 PM (in six subjects). On the average, an approximate twofold rise in circulating CFU C levels (per ml of blood) was found at 3 PM as compared to the 8 AM levels (P 0.002), and a smaller rise at 11 AM was found than at 8 AM levels (P 0.03). The ratios of CFU-C per ml of blood to mononuclear cells per ml of blood and neutrophils per ml of blood, respectively, were significantly higher at 3 PM than at 8 AM (p 0.002 and 0.004, respectively). The rise in CFU-C levels is usually significantly higher when compared to that in peripheral leukocyte counts.

Adult↗
PubMed1980

Autologous bone marrow transplantation in relapsed adult acute leukemia.

From March, 1976 to February, 1979, 28 cases of adult acute leukemia of which 24 were evaluable were treated in irreversible relapse with high dose chemotherapy (piperazinedione) and supra-lethal total body irradiation (TBI) in conjunction with autologous bone marrow transplantation (ABMT). The marrow cells grafted were collected and stored in liquid nitrogen at the time of remission. In 12 patients the marrow cells were fractionated using discontinuous albumin gradients in an attempt to separate normal cells from residual leukemic cells. Twelve patients achieved complete remission (CR); in 9 additional patients signs of engraftment were evident but death occurred before achievement of CR. Seven of 12 AML patients, which were treated with bone marrow transplantation as first treatment of their relapse, achieved CR. Four of 5 patients with ALL, whose bone marrows were collected during first remission, reached CR. The median CR duration was 4+ months and the median survival of the patients reaching CR was 6+ months. Autologous bone marrow transplantation offers a good chance of CR (66%) when marrow is collected during first remission and used as first treatment for AML in third relapse and ALL in second relapse.

Acute Disease↗
PubMed1980

Colony stimulating factor augmentation in human placental conditioned medium.

Because of the variability of different placentas to condition culture medium for colony-stimulating factor (CSF), we have attempted to augment CSF elaboration using endotoxin and bacillus Calmette Guerin (BCG) during the incubation period. Of 14 batches of human placental conditioned media (HPCM) prepared from different placentas, six were found to be inactive (no colony formation at concentrations of 5% to 40% vol/vol), five were found to be a weak stimulator of colony formation (producing < 10 colonies/10(5) human marrow cells plated at a HPCM concentration of 30%) and three were found to be active (producing 30 or more colonies/10(5) cells plated at HPCM concentration of 30%). In six cases augmentation of CSF elaboration was attempted using endotoxin or BCG and in all a marked increase in CSF was achieved. The increased colony formation was found to be due to greater increase in neutrophil and macrophage colonies than eosinophil colonies. The method of augmenting CSF elaboration in HPCM could have important implications for producing large quantities of potent and standardized source of CSF for the use in clinical laboratories and for increasing the yield of colony-stimulating factor(s) for further purification.

Cells, Cultured↗
PubMed1980

Adherent cell-mediated inhibition of human leukemic myelopoiesis.

We investigated the possibility that the control of leukemic growth by autologous adherent marrow cells may explain the indolent behavior of oligoleukemia. Leukemic cluster growth was measured by in vitro agar culture. The following marrow fractions (Fr) were examined from 13 patients for leukemic growth: Fr I: ficollisopaque interface cells (density less than 1.077 g/ml); Fr II: adherent-cell depleted Fr I (4.8% +/- 2.1 (SE) monocytes); Fr III: adherent and phagocytic cell depleted Fr I (0.3% +/- 0.2 monocytes); and Fr IV: adherent cells removed from plastic surfaces by lidocaine plus EDTA (74% +/- 10.9 monocytes). Two patient groups were recognized: Group A showed cluster growth in Fr IV with no absolute increase in Fr III and no suppression of Fr III cluster growth with addition of Fr IV. In Group B, Fr III showed an absolute increase in cluster growth. Fr IV did not show cluster growth and addition of Fr IV to Fr III suppressed growth. This suggested that in Group B, monocytes may suppress leukemic growth, the failure to observe this in Group A indicated the possible leukemic nature of the adherent cell fraction and the absence of residual normal monocytes. Other possible explanations are discussed.

Bone Marrow↗
PubMed1980

The myeloid progenitor cell: a parallel study of subpopulations in human marrow and peripheral blood.

Ten persons who had no evident hematologic disorder or previous history of chemotherapy or irradiation were studied. Parallel in vitro agar cultures from marrow and peripheral blood were grown, colonies and clusters were scored and examined morphologically after 7 and 14 days of incubation. Mean marrow myeloid progenitor cell (CFUc) incidences after 7 and 14 days were 76 +/- 55.4 S.D. and 37.3 +/- 22.0 S.D. per 10(5)ficoll-hypaque interface cells respectively. Most of the colonies on day 7 were neutrophilic (median 86%). Eosinophil colonies made up only a minority (0%-2%) of the total number of colonies. By day 14 a decrease in neutrophil colonies (median 6%) and a rise in eosinophil colonies (median 37%) was observed. Most of the colonies on day 14 were mixed neutrophil-macrophage colonies (median 55%). Parallel studies from blood revealed no colony growth on day 7 except on one occasion. The mean cluster incidence was 1.1 +/- 0.9 S.D. per 10(5) mononuclear cells. Most of these colonies were identified as eosinophilic (median 83%). The relative incidence of various subpopulations of myeloid progenitor cells in marrow and blood is different. Cluster transplantation from peripheral blood cultures strongly suggests the possibility for separate eosinophil progenitor cells. However a possibility of a rare occurrence of bipotent neutrophil-eosinophil colony forming cell can not be completely excluded.

Adult↗