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Biomedical subjects

A R Zander

Publications and source records attributed to A R Zander.

At least 181 records · Page 10Linked to original sources
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

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

Immunosuppressive effects of rabbit anti-canine brain serum.

Liver absorbed rabbit anticanine brain serum (ABS) was tested for its immunosuppressive capacities in dogs. Single intravenous injection of ABS led to significant decrease in lymphocyte counts and functions after 24 hours, as measured by phytohemagglutinin stimulation and mixed lymphocyte culture. The immunosuppressive effectiveness of ABS could further be documented by prolongation of skin graft survival in unrelated dogs which were treated daily for 12 days with intramuscular ABS injections. The ABS was generally well-tolerated. One dog died of pneumonia. All dogs showed moderate decrease in platelet counts after 10 days of ABS treatment. Autopsies showed normal cerebral histology, moderate lymphoid hypoplasia, and no changes in the bone marrow and liver. The results suggest that liver absorbed anti-canine brain serum is a potent immunosuppressant with limited toxicity.

Animals↗
PubMed1980

4'-(9-Acridinylamino) methanesulfon-m-anisidide (AMSA): a new drug effective in the treatment of adult acute leukemia.

Sixty-two adults with previously treated acute leukemia were treated with 4'-(9-acridinylamino) methanesulfon-m-anisidide (AMSA) with a total dose of 150 mg to 1320 mg/m2 of body surface area given over 3 to 14 days intravenously. Of the 56 patients who received an adequate trial, 13 achieved a complete remission and six had a partial remission. The best therapeutic results were observed when AMSA was used at a dose level of 75 to 90 mg/m2 per day for 7 days, which resulted in nine complete remissions among 30 patients. Eleven of 38 patients with myeloblastic leukemia achieved complete remission, and three of 13 with lymphoblastic disease achieved partial remission. Complete remissions were observed in nine of 39 patients who were refractory to cytarabine and anthracyclines, indicating a lack of cross-resistance between these drugs and AMSA. The median duration of remission was 12 weeks, and the median survival of responders was 28.5 weeks. The major toxicity of AMSA therapy was severe myelosuppression resulting in frequent infections during induction therapy. Our results indicate that AMSA has significant activity against refractory adult acute leukemia and deserves further evaluation.

Adolescent↗
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

Plasmapheresis as immunotherapeutic modality in the treatment of the canine venereal tumor.

Plasmapheresis was evaluated as a treatment modality for the transmissible venereal tumor (TVT) of the dog. The TVT is a unique tumor because of its capability for transplantation as a homograft between untreated randomly bred dogs and is characterized by the presence of dog leukocyte antigen (DLA) determinants on its tumor cells and reactivity in the mixed leukocyte tumor cell culture (MLTC). In the progressing phase, high titers of blocking antibodies measurable in the MLTC were noted. The purpose of this study was to evaluate the influence of plasmapheresis on the growth of established TVT and to correlate tumor response with the removal of blocking factors. Six pairs of DLA-identical dogs were used as experimental and control animals. Plasmapheresis was performed by discontinuous centrifugation using the Hemonetics model 30. An average of 1100 +/- 120 ml of plasma was exchanged on consecutive days during the third week after tumor injection. Consistently lower growth rates were observed in 2 experimental dogs, but there was no early rejection. Sera taken at day 14 of tumor growth contained significant blocking activity in all 12 dogs. Sera obtained post-plasmapheresis showed a decrease of blocking activity in all 6 experimental dogs, P less than 0.001. The TVT appears to be a suitable model for preclinical studies of plasmapheresis alone and in combination with other modalities.

Animals↗
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↗
PubMed1980

Enhancement of hemopoietic recovery after bone marrow transplantation with the addition of nucleated blood cells in mice.

Recovery of bone marrow cellularity, CFU-C, and CFU-S were studied sequentially over 90 days time after syngeneic bone marrow transplantation in mice. A minimal cell dose of 2 X 10(5) bone marrow cells was given. At day 28 after transplantation, CFU-C reached more than 50% of the normal range whereas the CFU-S concentration was less than 15%. Normalization of CFU-S occurred at day 90. The effect of the addition of peripheral blood nucleated cells on bone marrow hemopoietic recovery was studied at day 28. The augmentation of CFU-C and CFU-S recoverey were dose dependent. Optimal enhancement was seen with bone marrow to blood ratios of 1:1 and 1:2.5. This enhancement effect was lost when nucleated blood cells in a ratio of 1:10 were administered.

Animals↗
PubMed1980

Pyran copolymer: effect of molecular weight on stem cell mobilization in mice.

Maleic anhydride divinly ether copolymer polyanions (MVE) of well defined molecular weight ranging from 12,000 to 52,000 and Pyran Copolymer (NSC 46015), a MVE preparation with broader molecular weight range, were tested for their ability to mobilize murine stem cells, colony forming units spleen (CFU-S) and colony forming units in culture (CFU-C). Maximal mobilization of circulating stem cells was seen five days after Pyran Colopymer injection. This time point was chosen to determine the mobilization effect of different MVE preparations. It was found that the mobilization paralleled the molecular weight: the observed increase of circulation CFU-S by fractions MVE II, III, IV, and V and NSC 46015 were 3, 5, 14, and 20 fold.

Animals↗
PubMed1980

Effect of pyran copolymer on murine hemopoiesis.

Pyran Copolymer (NSC-46015), a divinyl-ether maleic anhydride leads to a significant shift in distribution of nucleated cells and CFUs in the bone marrow and spleen. The bone marrow cellularity and the CFUs content reach a nadir 4 to 6 days after Pyran injection, simultaneous rise in spleen cellularity and CFUs concentration of circulating pluripotent stem cells by a factor of 10 to 45 and a concomitant rise of CFUc is seen. the origin of the mobilized pluripotent stem cells is likely to be the bone marrow, not athe spleen.

Animals↗
PubMed1979

Oral complications of bone marrow transplantation in adults with acute leukemia.

In recent years bone marrow transplantation has become increasingly feasible for treating adult acute leukemia unresponsive to chemotherapy. However, the technique is not without significant intrinsic morbidity. The mouth is a singularly sensitive reflector of the cytotoxic, infectious, and hemorrhagic complications and of the graft-vs-host reactions associated with bone marrow transplantation in refractory acute leukemia.

Bacterial Infections↗
PubMed1979

Mobilization of murine hemopoietic stem cells (HSC) by Pyran Copolymer.

Pyran Copolymer, divinyl-ether maleic anhydride increases the concentration of circulating pluripotential stem cells in mice by a factor of 15 to 30. Maximal mobilization occurs five days after Pyran Copolymer injection with synchronous peaks of CFU-S and CFU-C. When Pyran fractions of defined molecular weight from 12,000 to 52,000 are injected into mice, mobilization of CFU-S and CFU-C parallels molecular weight. Hemopoietic stem cells are mobilized from bone marrow into peripheral blood and subsequently trapped in the spleen.

Animals↗