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Biomedical subjects

K Kase

Publications and source records attributed to K Kase.

53 records · Page 3Linked to original sources
PubMed1987

Engraftment of a clonal bone marrow stromal cell line in vivo stimulates hematopoietic recovery from total body irradiation.

Whether bone marrow stromal cells of donors contribute physiologically to hematopoietic stem cell reconstitution after marrow transplantation is unknown. To determine the transplantability of nonhematopoietic marrow stromal cells, stable clonal stromal cell line (GB1/6) expressing the a isoenzyme of glucose-6-phosphate isomerase (Glu6PI-a, D-glucose-6-phosphate ketol-isomerase; EC 5.3.1.9) was derived from murine long-term bone marrow cultures and made resistant to neomycin analogue G418 by retroviral gene transfer. GB1/6 cells were fibronectin+, laminin+, and collagen-type IV+ and collagen type I-; these GB1/6 cells supported in vitro growth of hematopoietic stem cells forming colony-forming units of spleen cells (CFU-S) and of granulocytes, erythrocytes, and macrophage/megakarocytes (CFU-GEMM) in the absence of detectable growth factors interleukin 3 (multi-colony-stimulating factor), granulocyte/macrophage colony-stimulating factor, granulocyte-stimulating factor, or their poly(A)+ mRNAs. The GB1/6 cells produced macrophage colony-stimulating factor constitutively. Recipient C57BL/6J (glucose-6-phosphate isomerase b) mice that received 3-Gy total-body irradiation and 13 Gy to the right hind limb were injected i.v. with GB1/6 cells. Engrafted mice demonstrated donor-originating Glu6PI-a+ stromal cells in marrow sinuses in situ 2 mo after transplantation and a significantly enhanced hematopoietic recovery compared with control irradiated nontransplanted mice. Continuous (over numerous passages) marrow cultures derived from transplanted mice demonstrated G418-resistant, Glu6PI-a+ stromal colony-forming cells and greater cumulative production of multipotential stem cells of recipient origin compared with cultures established from irradiated, nontransplanted control mice. These data are evidence for physiological function in vivo of a transplanted bone marrow stromal cell line.

Animals↗
PubMed1986

Effect of X-irradiation dose rate on the clonagenic survival of human and experimental animal hematopoietic tumor cell lines: evidence for heterogeneity.

It is a generally accepted principle of radiation biology that hematopoietic progenitor cells demonstrate dose rate independent killing by x-irradiation over the clinically relevant range for total body irradiation (TBI) (5-25 rad/min). To determine whether low dose rate (5 rad/min, or 20 rad/min) compared to conventional dose rate (200 rad/min) x-irradiation altered the clonagenic survival of leukemia and lymphoma cell lines, several permanent cell lines were studied. These included: bg/bg cl 1, mouse basophillic leukemia; LW12, [W/fu rat acute myelogenous leukemia (AML)]; and human cell lines: JY and Daudi (B-cell lymphomas); K45, (T-cell leukemia); K562, (erythroleukemia); HL60 and KG1 (monomyeloid leukemias), and U937 (human histiocytic/monocytic lymphoma). Dose rate independent killing was demonstrated at several plating densities with mouse and rat leukemia lines and all human leukemia lines tested except lines HL60 and U937. With HL60, increased plating density increased the D0 at each dose rate. This effect was not attributable to an increased plating efficiency. With line U937 there was a clear dose-rate effect with increase in D0 from 88 rad, n 4.6 at 200 rad/min, to D0 = 166, n 2.3 at 5 rad/min. The data demonstrate that some human hematopoietic tumor derived cell lines of myeloid/monocyte/macrophage lineage can exhibit atypical repair of irradiation damage in vitro. This repair may be enhanced by conditions relevant to clinical TBI including low irradiation dose-rate and cell to cell interactions by tumor cells in close proximity.

Animals↗
PubMed1986

Radiosensitivity of human bone marrow granulocyte-macrophage progenitor cells and stromal colony-forming cells: effect of dose rate.

Study of the radiation biology of human bone marrow hematopoietic cells has been difficult since unseparated bone marrow cell preparations also contain other nonhematopoietic stromal cells. We tested the clonogenic survival after 0.05 or 2 Gy/min X irradiation using as target cells either fresh human bone marrow or nonadherent hematopoietic cells separated from stromal cells by the method of long-term bone marrow culture (LTBMC). Sequential nonadherent cell populations removed from LTBMC were enriched for hematopoietic progenitors forming granulocyte-macrophage colony-forming unit culture (GM-CFUc) that form colonies at Day 7, termed GM-CFUc7, or Day 14 termed GM-CFUc14. The results demonstrated no effect of dose rate on the D0 or n of fresh marrow GM-CFUc (colonies greater than or equal to 50 cells) after plating in a source of their obligatory growth factor, colony-stimulating factor (CSF) (GM-CFUc7 irradiated at 2 Gy/min, D0 = 1.02 +/- 0.05, n = 1.59 +/- 0.21; at 0.05 Gy/min, D0 = 1.07 +/- 0.03, n = 1.50 +/- 0.04; GM-CFUc14 at 2 Gy/min, D0 = 1.13 +/- 0.03, n = 1.43 +/- 0.03; at 0.05 Gy/min, D0 = 1.16 +/- 0.04, n = 1.34 +/- 0.05). There was a decrease in the radiosensitivity of GM-CFUc7 and GM-CFUc14 derived from nonadherent cells of long-term bone marrow cultures compared to fresh marrow that was observed at both dose rates. In contrast, adherent stromal cells irradiated at low compared to high dose rate showed a significantly greater radioresistance (Day 19 colonies of greater than or equal to 50 cells; at 2 Gy/min, D0 = 0.99 Gy, n = 1.03; at 0.05 Gy/min D0 = 1.46 Gy, n = 2.00). These data provide strong evidence for a difference in the radiosensitivity of human marrow hematopoietic progenitor compared to adherent stromal cells.

Bone Marrow↗
PubMed1985

Activated human N-ras oncogene enhances x-irradiation repair of mammalian cells in vitro less effectively at low dose rate. Implications for increased therapeutic ratio of low dose rate irradiation.

The effect of x-irradiation dose rate on the clonagenic survival of mouse embryo fibroblast cell line NIH/3T3 and its N-ras human oncogene transformed subline was studied. Both control and N-ras transformed cell lines were maintained in Dulbecco's modified Eagle's medium at 37 degrees C with 5% CO2. These cell lines were passaged twice weekly and the cells were irradiated in log phase on a 250 kVp orthovoltage unit at 5 or 200 rad/min, adjusting filtration and FSD to account for each dose rate. After irradiation, the cells were replated and colonies of greater than or equal to 50 cells were scored on day 7. D0 and n were calculated via linear regression analysis. There was a significant increase in saturation density and plating efficiency of N-ras transformed cells with loss of contact inhibition. There was no significant difference in radiosensitivity between the two cell lines at 5 rad/min. For NIH/3T3 D0 = 336, n = 2.19; for N-ras transformant D0 = 314, n = 2.35 (p = 0.65); however, irradiation at 200 rad/min revealed a significant survival advantage for the transformed line. For NIH/3T3 D0 = 145, n = 9.1 and for the N-ras transformed line D0 = 208, n = 4.05 (p = 0.0018). The data provide evidence that repair factors which govern irradiation survival may differ for high and low dose rate irradiation and that repair of high dose rate irradiation damage is enhanced directly or indirectly by expression of the N-ras oncogene. The data support hyperfractionated (low dose rate) irradiation for improving the therapeutic ratio during control of rapidly proliferating tumors expressing an activated N-ras oncogene.

Animals↗
PubMed1985

Biologic effects of in vitro X-irradiation of murine long-term bone marrow cultures on the production of granulocyte-macrophage colony-stimulating factors.

The production of colony-stimulating factor (CSF) by murine long-term bone marrow culture (LTBMC) was studied by a technique involving measurement of colony formation in agar overlay by fresh marrow target cells. Colonies were removed and microscopically examined for morphology and histochemistry. LTBMCs were exposed to x-irradiation at 200 rad/min prior to the overlay. Nonirradiated control LTBMCs induced 51.5 +/- 11 granulocyte-macrophage colonies per 2 X 10(5) target cells. Irradiation of LTBMCs to 6000 rad revealed a six-fold plateau-maximum increase in the number of colonies. There was occasional appearance of macroscopic mixed colonies containing granulocytes, macrophages, and megakaryocytes over irradiated but not control LTBMCs. Irradiated cells in the adherent stromal layer of LTBMCs continuously produced CSF that was detectable in the cell-free supernatants for up to seven weeks after irradiation and after doses as high as 10,000 rad. Shielding of the x-ray beam over half of the culture surface by a 10-half-value-layer lead block produced increased colony formation by target cells near the exposed surface area. The data indicate that CSF production by adherent cells within LTBMC persists after supralethal doses of x-irradiation. The mechanism of the increased colony formation by target cells overlaid on irradiated stromal cells involves factors relative to the local microenvironment.

Animals↗
PubMed1984

Effects of low dose rate irradiation on plateau phase bone marrow stromal cells in vitro: demonstration of a new form of non-lethal, physiologic damage to support of hematopoietic stem cells.

The clinical use of low dose rate (LDR) (5-25 rad/min) total body irradiation in bone marrow transplantation patients is well established. We have developed an in vitro system for study of the effects of LDR irradiation on bone marrow stromal cells. Purified mouse bone marrow stromal cell cultures in plateau phase with no detectable hematopoiesis were prepared and were then "engrafted" in vitro by addition of purified nonadherent hematopoietic cells from continuous bone marrow cultures. Hematopoietic cells were added in liquid medium or suspended in an overlay of semisolid 0.4% agar-containing medium. Other agar overlays contained Interleukin-3-dependent cloned multipotential hematopoietic stem cell line B6SUtA. In parallel experiments, a cloned permanent bone marrow stromal cell line D2XRII was used in place of purified stromal cell cultures. Stromal cultures were irradiated at 5 rad/min, 20 rad/min, or 200 rad/min, 24 hours or 3 weeks prior to "engraftment." Two classes of irradiation damage were demonstrated following 1000 rad irradiation at 200 rad/min: 1) Decreased clonagenic survival of trypsinized replated marrow stromal cells (lethal effect); and 2) decreased production by marrow stromal cells or D2XRII cells of colony stimulating factors (CSF)s for granulocyte-macrophage progenitor cells and B6SUtA cells (physiologic effect). Holding the cultures in plateau phase for 3 weeks after irradiation was associated with significantly more repair of the lethal effect compared to the physiologic effect. Cultures irradiated at 5 rad/min or 20 rad/min to doses producing significantly less lethal effect showed a complex alteration of production of growth factors. Cumulative cell production by hemopoietic stem cells added in liquid culture was comparably decreased for all three dose rates. These data demonstrate a distinct physiologic expression of irradiation damage to bone marrow stromal cells that affects cell to cell interaction, responds differently to changes in dose rate, and is repaired with kinetics different from those of the lethal effect of irradiation. The present system should prove valuable for investigation of cellular interactions in hematopoietic stem cell engraftment that are altered by total body irradiation.

Animals↗
PubMedDate not supplied

Determination of nominal accelerating potential.

We present a simple linear relationship between the nominal accelerating potential (NAP) and the ratios of ionization measurements made with constant source-detector distance and at two different phantom thicknesses. This relationship can be used as a standard, unambiguous method for determining NAP for use in dosimetry and quality control.

Models, Structural↗
PubMedDate not supplied

Effects of ionization chamber construction on dose measurements in a heterogeneity.

Traditionally, measurements have been made in heterogeneous phantoms to determine the factors which should be applied to dose calculations, when calculating a dose to a heterogeneous medium. Almost all measurements have relied on relatively thin-walled ion chambers, with no attempt to match ion chamber wall material to the measuring medium. The recent AAPM dosimetry protocol has established that a mismatch between ion chamber wall and phantom material can have an effect on dose measurement. To investigate the affect of this mismatch of ion chamber wall material to phantom material, two parallel-plate ion chambers were constructed. One ion chamber from solid water, for measurements in a solid water phantom and the other from plastic lung material, for measurements in a plastic lung material phantom. Correction factors measured by matching ion chamber to media were compared to correction factors measured by using a thin-walled cavity ion chamber with no regard for matching wall and media for cobalt-60, 6-, 10- and 20-MV photon beams. The results demonstrated that the matching of ion chamber to measuring media can be ignored, provided that a small, approximately tissue-equivalent, thin-walled ion chamber is used for measuring the correction factors.

Humans↗
PubMedDate not supplied

A method of measuring the primary dose component in high-energy photon beams.

We present an approach for deriving the primary component of dose from measurements in a megavoltage gamma or x-ray beam. The theoretical development of the approach is discussed showing that primary dose can be obtained from four measurements of ionization in narrow beam geometry and two measurements of ionization in a large beam in a phantom. The uncertainty in the final result is analyzed and is about an order of magnitude greater than the uncertainty in an individual measurement.

Biophysical Phenomena↗