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Biomedical subjects

A R Zander

Publications and source records attributed to A R Zander.

At least 163 records · Page 9Linked to original sources
PubMed1984

Functional impairment of T-lymphocytes in mouse radiation chimeras by a nucleotide-free diet.

We examined the effect of a nucleotide-free diet on the immune function of mouse syngeneic bone marrow radiation chimeras. The graft-versus-host disease mortality assay revealed that GVH activity of spleen cells from radiation chimeras fed NFD (RCNFD) was reduced at 6-18 weeks after transplantation as compared with the radiation chimeras fed a control diet (RCCD). When tested 11-18 weeks after transplantation, the proliferative response of RCNFD spleen cells to phytohemagglutinin was significantly reduced at 11 and 13 weeks, the response to pokeweed mitogen (PWM) was significantly reduced at 11, 13, and 15 weeks, and the response to bacterial lipopolysaccharide remained virtually unaffected. At both six and eight weeks after transplantation, RCNFD and RCCD showed comparable numbers of CFUc/femur. RCNFD and RCCD did not differ significantly from each other in body weights or in spleen and bone marrow cellularity at 6-18 weeks after transplantation. These results suggest that dietary nucleotides are important for the normal function of mouse T-lymphocytes.

Animals↗
PubMed1984

Mobilization of canine hemopoietic stem cells by pyran copolymer (NSC 46015).

Pyran copolymer (NSC 46015), a divinyl ether maleic anhydride of broad spectrum molecular weight, was infused into six normal mongrel dogs. The effect on canine blood and bone marrow colony forming units in culture (CFU-C) was followed over an 11-day period. Significant elevation of circulating CFU-c was noted 2 days after pyran infusion; normalization occurred by day 7 postinfusion. Bone marrow CFU-C were decreased 2 days and 5 days after pyran administration. A further increase in circulating CFU-C was noted when pyran was administered twice, 5 days apart. The mobilizing effect of pyran copolymer appears promising enough to warrant further exploration of blood as a source of hemopoietic stem cells for transplantation purposes.

Animals↗
PubMed1983

Isolation of murine small bowel intraepithelial lymphocytes.

A method for the preparation of cellular suspensions of the epithelium of murine small bowel for the purpose of isolation and recovery of intraepithelial lymphocytes employing intraluminal hyaluronidase digestion is described. Discontinuous Percoll centrifugation of these suspensions yielded a 76-82% pure population of intraepithelial lymphocytes. Between 1.6 and 4.0 X 10(7) viable intraepithelial lymphocytes were obtained per gram of gut. The isolate contained approximately equal numbers of T, B and null lymphocytes.

Animals↗
PubMed1983

High-dose chemoradiotherapy and bone marrow transplantation in patients with refractory lymphoma.

Eight adult patients with refractory Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) were treated with high-dose combination chemotherapy (cyclophosphamide, BCNU and VP-16) or with cyclophosphamide and fractionated whole-body irradiation (TBI), followed by bone marrow transplant (BMT). Six patients received autologous and two patients allogeneic BMT. Five patients achieved complete remissions, and three of them (two with undifferentiated lymphoma, one with lymphoblastic lymphoma) are alive and free of disease 4-18+ months after BMT. The other two complete responders died of opportunistic infections 2 and 5 months, respectively, after BMT. One patient with HD achieved partial remission and is alive 18+ months after BMT. Two patients were considered failures: one developed leptomeningeal disease 24 days after BMT, and the other died of progressive lymphoma 7 months after BMT. Engraftment and prompt hematologic recovery occurred in all patients. The major toxicity included two fatal infections and one case of diffuse idiopathic interstitial pneumonitis. High-dose chemotherapy with or without TBI followed by BMT appears to produce a high response rate and, although associated with toxicity, it demonstrates the potential for salvaging patients with refractory lymphoma who otherwise would have a dismal prognosis.

Adult↗
PubMed1982

Human leukocyte interferon-mediated granulopoietic differentiation arrest and its abrogation by lithium carbonate.

Interferon has been shown to inhibit erythropoietic and granulopoietic differentiation. Since lithium carbonate (Li) elevates granulocyte levels in a variety of neutropenic disorders, we investigated the effect of Li on human leukocyte interferon (HLIF)-mediated inhibition of granulopoietic differentiation. Using an agar culture technique for cloning granulocyte-macrophage progenitor cells (GM-CFC), we demonstrated that Li blocks HLIF-induced granulopoietic differentiation arrest in a dose-dependent manner. Results of removal of T lymphocytes from marrow cells suggest that this Li effect is not mediated through marrow T lymphocytes.

Cell Differentiation↗
PubMed1982

Cyclic neutropenia and T lymphocyte suppression of granulopoiesis: abrogation of the neutropenic cycles by lithium carbonate.

To investigate the mechanisms of cyclic neutropenia, we studied the capacity of a patient's T lymphocytes (TLp) to interact with monocyte-macrophages from her normal HLA-identical sibling (MOb) in the elaboration of colony-stimulating activity (CSA). TLp obtained at the time of decreasing neutrophil counts, increased CSA elaboration (p less than 0.056) when incubated at a 1:1 ratio with MOb. Increasing the TLp to MOb ratios to 3:1 or 5:1 progressively decreased CSA. Also, lithium carbonate, which ordinarily prevents concanavalin A activation of suppressor TL, failed to do so, suggesting that preactivated suppressor TL were present in the patient while neutrophil levels were falling. In similar experiments performed while neutrophil levels were rising these activated suppressor TL were absent. These data suggest that some patients with cyclic neutropenia may have a cyclic increase in suppressor TL activity. As predicted by our in vitro experiments, lithium carbonate administration did not abrogate the first neutropenic cycle, but it did mitigate subsequent cycles.

Adult↗
PubMed1982

The mechanism of lithium carbonate-induced augmentation of colony-stimulating activity elaboration in man.

Lithium carbonate (Li) has been reported to elevate granulocyte counts in patients with certain neutropenic disorders and to improve chemotherapy-induced granulocytopenia. To investigate the mechanisms involved in the increase in myelopoiesis, the effect of Li on monocytemacrophage (M phi)- and T-lymphocyte (TL)-derived colony-stimulating activity (CSA) were studied in vitro. Li induced a dose-related increase in both M phi- and TL-derived CSA over that in non-Li-stimulated cell populations. However, the increase was significant (p less than 0.007) only at a higher concentration of Li (2 mEq/l). The results of co-incubating TL with M phi with or without Li indicated that Li significantly enhanced synergistic CSA production by the two cell populations (p less than 0.02). We further demonstrated the presence of a larger proportion of M phi with TL rosettes in the presence of Li (62%) than in its absence (21%). Further experiments with concanavalin A (Con-A)-inducible suppressor TL suggested that Li effectively blocks the suppressor TL-mediated suppression of CSA. These data suggest that Li enhances M phi and TL interaction which results in an augmented CSA elaboration. Further, Li would be more effective in those neutropenic disorders associated with enhanced suppressor TL activity. For an optimal effect, however, Li would require appropriately functioning M phi and non-suppressor subsets of TL and an intact stem cell pool.

Cell Division↗
PubMed1982

Monocyte-macrophage modulation of T-lymphocyte-derived colony-stimulating activity elaboration in man.

To investigate the source and the mechanisms of synergistically enhanced colony-stimulating activity elaboration by the coincubated monocyte-macrophages and T lymphocytes, we simultaneously prepared conditioned media both from the coincubated monocyte-macrophages and T lymphocytes (ratio 1:3) in the presence of phytohemagglutinin (1%) or methanol extraction residue of bacillus Calmette-Guerin (50 micrograms/ml) and from the isolated T lymphocytes that had been primed with monocyte-macrophages in the presence or absence of phytohemagglutinin or methanol extraction residue of bacillus Calmette-Guerin. Subsequently, colony-simulating activity in various conditioned media was assayed using light-density (less than 1.070 g/ml), nonadherent normal human marrow cells. Live monocyte-macrophages synergized with and significantly (P less than 0.01) agumented the T lymphocyte-derived colony-stimulating activity elaboration; while killed monocytes-macrophages had no such effect. Similarly, actinomycin D and cycloheximide not only diminished monocyte-macrophage colony-stimulating activity elaboration but also reduced their synergistic interaction with T lymphocytes and their ability to augment the T lymphocyte-derived colony-stimulating activity elaboration. In contrast, mitomycin C failed to diminish both - monocyte-macrophages' ability to synergise with T lymphocytes and also to augment T lymphocyte-derived colony-stimulating activity. These data suggest that monocyte-macrophages require an intact transcriptional and translational processes, but not DNA synthesis for synergising with T lymphocytes or for augmenting T lymphocyte colony-stimulating activity elaboration.

Cell Adhesion↗
PubMed1982

Premature chromosome condensation studies in human leukemia: 4. Characterization of albumin density fractionations of bone marrow at presentation, remission, and relapse.

Previous studies have suggested that the technique of premature chromosome condensation (PCC) is useful in the study of human leukemia, both as a predictive tool for course of disease and as a probe to better understand the biology of the disease process. The purpose of this study was to determine how the various subcomponents of bone marrow populations contribute to the overall PCC pattern. Thirty bone marrow aspirations from persons at various stages of disease (2 normal, 11 untreated, 12 in remission, and 5 n relapse) were fractionated according to density in albumin gradients, and the various fractions were characterized by determining the proliferative potential index (PPI, or the fraction of G1 cells in late G1) using the PCC technique. In general, normal bone marrow and marrow from patients In remission showed lower PPI values throughout the gradients, with the most dense and most mature cells yielding the lowest PPI values in the gradient. In contrast, bone marrow from newly presenting patients and from patients in relapse showed higher PPI values, with the highest PPI values found In the most dense fractions containing the most mature cells. Thus, residual mature cells from patients with active disease exhibit the malignant characteristic of accumulating in late G1 phase. It is postulated that these morphologically mature cells from patients with active disease either represent matured cells of malignant origin or represent residual normal cells pushed beyond the restriction point in early G1 phase by a putative tumor growth factor synthesized by the leukemic cell population.

Aged↗
PubMed1982

Human adherent cell contact-mediated modulation of normal myeloid colony formation.

The effects of coincubation of normal nonadherent bone marrow cells on adherent monolayers created from human peripheral blood mononuclear cells or marrow cells were investigated. Nonadherent marrow cells were coincubated for 4 hours with peripheral blood adherent cells at ratios of adherent cells to marrow cells of 2:1 to 5:1. This coincubation suppressed subsequent neutrophilic agar colony growth but not eosinophilic growth. Further studies suggested that this suppression was a cell-cell-mediated process and not secondary to soluble factors. However, coincubation on marrow adherent cells caused increased neutrophilic colony recovery. The possible in vivo relevance is discussed.

Agar↗
PubMed1982

High-dose AMSA and bone marrow rescue in patients with solid tumors.

The feasibility of high-dose AMSA followed by autologous bone marrow rescue was studied in seven patients with solid tumors. They received a total of 12 courses of treatment. Total doses ranged from 600 to 1000 mg/m2/course. Major toxic effects were myelosuppression, fever of unknown origin, and stomatitis. One patient with malignant melanoma had stable disease lasting 2 months; the other six had progressive disease.

Aminoacridines↗
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↗