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Biomedical subjects

E Niskanen

Publications and source records attributed to E Niskanen.

At least 37 records · Page 2Linked to original sources
PubMed1986

Effect of lithium on stem cell and stromal cell proliferation in vitro.

Lithium is recognized as a potent stimulator of hematopoiesis both in vivo and in vitro. Previous work has suggested that this stimulation is mediated as an indirect, humoral effect by the action of lithium upon the stromal cell population. In the present study, the effects of lithium on the stromal population were investigated using a long-term liquid marrow culture model. These findings indicate that exposure of in vitro cultures to lithium results in an increase in the total cellularity and in the number of various hematopoietic progenitor cells residing within the stromal layer. A distinct morphologically recognizable cell has not been identified as the target cell responsible for the indirect stimulation of hematopoiesis by lithium. However, two candidate radioresistant stromal cells believed to be active in the production of humoral mediators of hematopoiesis did proliferate in response to lithium exposure.

Animals↗
PubMed1985

Treatment of advanced esthesioneuroblastoma with high-dose chemotherapy and autologous bone marrow transplantation. A case report.

A 46-year-old woman presented with an advanced unresectable esthesioneuroblastoma which failed to respond to radiation therapy and one course of chemotherapy. She underwent treatment with high-dose chemotherapy (cyclophosphamide, doxorubicin, and vinblastine) followed by autologous bone marrow transplantation. The major toxicity from the regimen was severe oropharyngeal mucositis. A complete remission was achieved and the patient is free of disease and asymptomatic 3.5 years after treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Separation by velocity sedimentation of human haemopoietic precursors forming colonies in vivo and in vitro cultures.

Cells which give rise to granulocyte-macrophage colonies under the influence of peripheral blood white cells (CFU-c (WBC] and Mo T cell conditioned medium (CFU-c (Mo] sedimented at a faster rate than the cells which form mixed erythroid-granulocytic colonies in methylcellulose in vitro (CFU-mix) and granulocytic (CFU-dg) and megakaryocytic (CFU-dm) colonies in diffusion chambers in mice. Despite identical peak sedimentation rate for the two CFU-c populations, sedimentation profiles suggest that they are heterogeneous with respect to size. A proportion of CFU-c (Mo) may be identical with CFU-dg and CFU-mix. Sedimentation profiles for cells which give rise to mixed colonies in vitro (CFU-mix) and to granulocytic colonies in diffusion chambers in cyclophosphamide pretreated mice (CFU-dg (CY] and in Mo conditioned medium treated mice (CFU-dg (Mo] were similar. On the average CFU-dm sedimented somewhat slower than CFU-dg. These and other observations suggesting a close relationship between CFU-dg and multipotential haemopoietic precursors are discussed.

Bone Marrow Cells↗
PubMed1985

Distinction of human T-cell line (HUT-102)-derived activity stimulating granulocytic colony formation in diffusion chambers in vivo from activities stimulating erythroid and mixed-colony formation in vitro.

Medium conditioned in the presence of human HUT-102 T-cell line cells contains activities stimulating human mixed (colony-forming unit, erythroid, granulocyte, macrophage, megakaryocyte) and erythroid (burst-forming unit, erythroid) colony formation in methylcellulose in vitro and granulocyte colony formation in diffusion chambers in mice. The stimulatory effect of HUT-102-conditioned medium on colony-forming unit, granulocyte diffusion chamber was also observed in diffusion chambers implanted in nude mice. The hemopoietic activities were heat stable and could be detected from serum-free conditioned medium. Chromatographically, it was possible to separate colony-forming unit, granulocyte diffusion chamber-stimulating activity from activities stimulating burst-forming unit, erythroid and colony-forming unit, erythroid, granulocyte, macrophage, megakaryocyte. On the other hand, the latter two activities were indistinguishable by the methodology used in this study. Failure to abolish the hemopoietic activities by boiling or by human T-lymphotropic retrovirus type 1 antibody indicates that human T-lymphotropic retrovirus type 1 or its components potentially present in the conditioned medium were not responsible for the stimulatory effects.

Cell Line↗
PubMed1985

Assessment of early hemopoiesis in in vivo diffusion chamber cultures.

Many studies have provided evidence that the cells which give rise to colonies containing granulocytes (CFU-DG) share several characteristics with other primitive hemopoietic precursors (CFU-S and CFU-MIX). Cell cycle status, sensitivity to hypotonic lysis, and velocity sedimentation rates are similar. On the other hand, CFU-DG can be distinguished from these precursors by difference in sensitivity to cryopreservation and hyperthermia. Uniqueness of the in vivo diffusion chamber culture system is accentuated by finding humoral activities produced by human HUT 102 and Mo T cell lines and murine BCL1 B cell line which seem to be different from the activities identifiable by CFU-C, BFU-E, and CFU-MIX assays in vitro.

Animals↗
PubMed1985

Potentiality of the murine colony-forming cells detected by an in vivo diffusion chamber culture system.

Culture of a mixture of bone marrow cells with and without T6 chromosome marker in diffusion chambers in mice yielded colonies (CFU-DG) containing cells of a single karyotype, suggesting clonality. Injection of individual CFU-DG colonies into lethally irradiated mice resulted in increased spleen colony formation on day 12 (CFU-S). The possibility of endogenous origin was excluded by demonstrating the presence of T6 marker in both CFU-DG and CFU-S colonies in karyotypically normal hosts. These findings suggest that the cells giving rise to granulocytic colonies in diffusion chambers also can give rise to multipotential hemopoietic cells.

Animals↗
PubMed1984

Granulopoietic precursors in chronic neutropenia.

11 patients with chronic neutropenia were evaluated. In 6 patients low numbers of CFU-DG were observed. Only 3 of these patients also had low CFU-C numbers, suggesting that these two precursors are not identical. Bone marrow samples from 2 patients were restudied a year later. The number of CFU-DG remained low while CFU-C numbers increased to control range in 1 patient. Studies for serum inhibitors were negative. No cytogenetic abnormalities were observed. This study suggests that abnormalities at different levels in the haemopoietic precursor cell hierarchy can be detected either simultaneously or independently in patients with chronic neutropenia.

Agranulocytosis↗
PubMed1983

Effect of cooling rate on human and murine hemopoietic precursor cell recovery.

The effect of cooling rate on recovery of human and murine hemopoietic precursor cells was studied. In the presence of 10% Me2SO, a cooling rate of 7 degrees C/min from -4 to -30 degrees C was optimal for recovery of both human and murine precursor cells which give rise to colonies in diffusion chambers implanted in mice (CFU-DG). Cooling of human marrow at a rate between 3 and 7 degrees C/min resulted in the best CFU-C recovery, although no good correlation between the cooling rate and murine CFU-C recovery was demonstrated. These data suggest that recovery of the primitive hemopoietic precursor cells can be improved by changing the standard cryopreservation programs used presently. However, improved recovery of CFU-DG does not necessarily translate into faster reconstitution of hemopoiesis. No significant difference was observed in overall recovery of bone marrow cellularity in lethally irradiated mice following injection of untreated marrow and marrow cooled at a rate of 1 and 7 degrees C/min.

Animals↗
PubMed1983

The role of polyamine biosynthesis in hematopoietic precursor cell proliferation in mice.

Under the influence of a selective irreversible inhibitor of ornithine decarboxylase (ODC), DL-alpha-difluoromethylornithine (DFMO), early hematopoiesis was enhanced. In the bone marrow, the absolute number of cells that give rise to spleen colonies in lethally irradiated mice (CFU-S), granulocytic colonies in diffusion chambers in mice (CFU-DG), and granulocyte-monocyte colonies in agar in vitro (CFU-C) was increased 2-4 fold. This could be abrogated by administration of putrescine, confirming the association of the stimulatory effect with polyamine biosynthesis most likely via depression of ornithine decarboxylase activity and subsequent synthesis of putrescine. Analysis of cell cycle characteristics by 3H-TdR suicide technique demonstrated that the proportion of CFU-S, CFU-DG, and CFU-C in S-phase was significantly increased. Additionally, the stimulatory effect was reflected by enhanced colony formation in diffusion chambers implanted intraperitoneally in mice receiving DFMO. This could also be eliminated by treatment of the host animal with putrescine, again suggesting that polyamine biosynthesis plays an important role at the early stages of hematopoiesis in vivo. Effect of DFMO on colony formation in vitro (CFU-C) was inhibitory and not reversible with putrescine. It could be partially eliminated by aminoguanidine, which neutralizes diamine oxidase present in fetal calf serum used in the CFU-C assay. These data suggest that the effect of DFMO in vitro was nonspecific.

Animals↗
PubMed1982

Humoral stimulation of hemopoietic progenitors from human fetal liver.

Hemopoietic cells from human fetal livers of 9-21 weeks gestation were cultured in semisolid media in vitro and in diffusion chambers implanted in mice. Myeloid colony formation in agar (CFU-C) was detected only in the presence of colony-stimulating factor. Formation of erythroid bursts in vitro was enhanced by addition of erythropoietin or erythroid-potentiating activity derived from a human T cell line (Mo). Fetal liver cells implanted in diffusion chambers gave rise to myeloid (CFU-DG) and occasionally to erythroid colonies. Administration of colony-stimulating factor derived from the T cell line to the host mice did not effect CFU-DG numbers. In contrast, a partially purified preparation containing erythroid-potentiating activity, caused a significant increase in the formation of CFU-DG. Similar stimulation was achieved by pretreatment of the diffusion chamber hosts with cyclophosphamide. None of these manipulations effected erythroid colony formation in diffusion chambers in mice.

Animals↗
PubMed1982

Human T-lymphocyte products stimulate human hemopoietic progenitor cell proliferation in diffusion chambers in vivo.

Human myeloid colony formation in diffusion chambers in mice (CFU-DG) was enhanced following administration of a human T-cell-line-derived conditioned medium (Mo). The Mo cell line also elaborates activities stimulating human myeloid colony formation in vitro in agar (CSF) and potentiating erythroid colony formation in vitro in methylcellulose (EPA). Depletion of CSF from Mo conditioned medium by heat inactivation or gel exclusion chromatography did not affect CFU-DG formation. EPA and CFU-DG stimulating activities are heat stable and have approximately the same molecular weight. Culture of human bone marrow cells in diffusion chambers in mice for 4 days under the influence of Mo conditioned medium resulted in significant increment of BFU-E and CFU-DG as judged by subculture of diffusion chamber contents. No effect on CFU-C could be detected.

Animals↗
PubMed1981

Corticosteroid effect on murine hemopoietic precursor cells in vivo.

The effect of methylprednisolone on murine hemopoietic colony formation in diffusion chambers implanted in mice was evaluated. A dose-dependent increase in granulocytic colony (CFU-DG) formation from murine marrow was observed. This effect could be abrogated by administration of progesterone. These studies suggest that the murine early granulocytic precursors (CFU-DG) have receptors that mediate proliferation-promoting signals triggered by glucocorticoids. Erythroid colony formation (CFU-DE) was not effected by methylprednisolone administration.

Animals↗
PubMed1980

Differentiation of subpopulations of human and murine hemopoietic stem cells by hypotonic lysis.

Both human and mouse bone marrow contain subpopulations of hemopoietic stem cells that greatly vary in their resistance to water exposure: The cells forming erythroid colonies or bursts in methyl cellulose in vitro are most sensitive to hypotonic conditions and are destroyed within 60 s in the hypotonic milieu. The murine pluripotent stem cells assayed by the spleen colony technique, as well as both murine and human myeloid stem cells assayed by the plasma clot diffusion chamber technique, displayed intermediate sensitivity and were nearly completely eliminated by 120 s of exposure to water. Both human and mouse bone marrow stem cells producing myeloid colonies in agar are most resistant to hypotonic conditions. The addition of monocyte-macrophages and lymphoid cells to water-exposed mouse bone marrow cell populations to compensate for losses did not restore either erythroid or myeloid colony formation.

Animals↗
PubMed1980

Enhancement of murine erythroid colony formation in the presence of activated T lymphocytes.

Erythroid colony formation was enhanced by treatment of mouse bone marrow cells with PHA prior to culture in diffusion chambers implanted into intact mice. Addition of PHA-pretreated thymocytes, lymph node lymphocytes, and spleen cells to untreated bone marrow cells also resulted in increased numbers of erythroid colonies in diffusion chambers but had no effect on myeloid colonies. PHA did not augment erythroid colony formation when bone marrow was depleted of Thy 1-bearing cells, although cells capable of erythroid differentiation were still present as judged by the response to erythropoietin. Furthermore, mixing of bone marrow depleted of Thy 1 + cells with PHA-treated thymocytes restored augmented erythroid colony formation. Lack of responsiveness of bone marrow cells to concanavalin A and pokeweed mitogen may indicate that a specific T cell subpopulation reacting with PHA is able to stimulate erythropoiesis. Note that addition of untreated thymocytes, lymph node lymphocytes, and spleen cells into cultures had no effect.

Animals↗
PubMed1979

Hemopoietic precursor cells in human peripheral blood.

Human peripheral blood contains two types of stem cells that differentiate along the granulocytic pathway. They are separable by their ability to form colonies in agar in vitro (CFU-C) and in plasma clots in diffusion chambers in vivo (CFU-DG). Kinetic studies suggest that CFU-DG represents an intermediate between the still hypothetical human pluripotent stem cell and CFU-C.

Animals↗