scholarly journals Bone marrow transplantation in dogs after radio-ablation with a new Ho- 166 amino phosphonic acid bone-seeking agent (DOTMP)

Blood ◽  
1993 ◽  
Vol 82 (1) ◽  
pp. 318-325 ◽  
Author(s):  
NJ Parks ◽  
TG Kawakami ◽  
MJ Avila ◽  
R White ◽  
GR Cain ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Phosphonic Acid ◽  
Marrow Cell ◽  
Nuclear Imaging ◽  
Beta Particle ◽  
Skeletal Tissue ◽  
Red Marrow ◽  
Bone Biopsies ◽  
Total Body

beta-emitting 166Ho (t1/2 = 26.78 hours, E(beta)max = 1.8 MeV) complexed with the phosphonic acid chelator, 1,4,7,10 tetraazacyclododecane-1,4,7,10-tetra(methylene phosphonic acid) (DOTMP) at a ligand-to-metal ratio of 1.5:1 binds to bone. This radioactive complex is a marrow-ablating radiopharmaceutical that appears useful for preparation of bone marrow (BM) transplant recipients without the morbidity usually associated with total body irradiation preparatory regimens. We have found with seven splenectomized young adult beagle dogs that a 166Ho radiopharmaceutical dosage of 370 MBq/kg body weight provides an initial skeletal radioactivity burden of at least 1.5 GBq/kg skeleton and results in complete ablation of hematopoietic marrow cell populations within 7 days. The beta particle flux distribution in BM-forming skeletal tissue is not uniform. Red marrow radiation doses varied from 30 to 115 Gy as estimated by direct radioassay and autoradiographic analyses of both bone biopsies and postmortem samples; the median value of 61 Gy agreed with our theoretical expectations. In vivo radioactivity distribution was evaluated with nuclear imaging methods. Apparently, normal hematopoiesis was restored in three dogs with autologous BM transplants performed 5 to 6 days after administration of the marrow ablative radiopharmaceutical, 166Ho-DOTMP. BM biopsies at 7 to 10 months posttransplantation indicate continued normal hematopoietic activity.

Ly-A and Ly-B: two systems of lymphocyte isoantigens in the mouse

1968 ◽  
Vol 170 (1019) ◽  
pp. 175-193 ◽  
Keyword(s):  
Bone Marrow ◽  
Marrow Cell ◽  
Preliminary Evidence ◽  
Mouse Strains ◽  
Allogeneic Bone ◽  
High Concentration ◽  
Multiple Alleles ◽  
Two Systems ◽  
Total Body

Two systems of isoantigens confined to thym ocytes and lymphocytes have been defined in the mouse by cytotoxic isoantisera. The two genetic loci have been designated Ly-A and Ly-B . Typing of 25 mouse strains and sublines indicates that each system comprises only 2 alleles, determining alternative isoantigens Ly-A. 1 or Ly-A. 2, and Ly-B. 1 or Ly-B. 2, respectively. There is no evidence of multiple alleles or that either locus is compound. Tests for genetic linkage were performed by serological typing of mice from segregating generations. None of the four loci H -2 (group IX ), θ, Ly-A and Ly-B is closely linked to any other of the four. Ly antigens are found in high concentration on thymocytes and in lesser amounts on lymphocytes. The small absorptive capacity of bone marrow cell suspensions is probably due to the presence of mature lymphocytes rather than thymocyte-lymphocyte precursors, which according to preliminary evidence lack Ly antigens. Ly-B. 1 is exceptional in that the disparity between thymocytes and lymphocytes in content of antigen is greater than that of the three other antigens. When Ly antiserum is injected into mice of the relevant Ly type, under conditions which give complete absorption of H-2 antibody in vivo , Ly antibody is not extensively absorbed ; this is to be expected from the limited tissue distribution of Ly antigens. Absorption of Ly and θ iosantibodies in vivo is reduced by treatment of the recipients with cortisone or lethal total-body irradiation. The reduction in titre of Ly and θ antibodies in such mice may be no more than that resulting from dilution. Absorption of injected H-2 antibody also may be reduced by treatment of the recipients with cortisone but in this case the effect of corti­sone does not approach the virtual abolition of absorption that is seen with Ly and θ anti­bodies. The thymocytes and lymphocytes of chimeras formed by restoring lethally irradiated mice with allogeneic bone marrow have the Ly-A type, Ly-B type and θ type o f the donor. The content of Ly antigens on cells of different leukaemias varies widely and shows no correlation with presence or absence of TL (thymus-leukaemia) antigen; TL + leukaemias may be Ly — or Ly + and TL — leukaemias may be Ly — or Ly + . Five systems of isoantigens are now demonstrable on mouse thymocytes by means of cytotoxic isoantisera. Of these, TL is an exclusively thymic antigen. Ly-A and Ly-B antigens occur also on lymphocytes. θ occurs on thymocytes, on lymphocytes, and in brain. The fifth antigen, H-2. is still more widely distributed and differs from the other four in being repre­sented less strongly on thymocytes than on lymphocytes.

scholarly journals CD34+ human marrow cells that express low levels of Kit protein are enriched for long-term marrow-engrafting cells

Blood ◽  
1996 ◽  
Vol 87 (10) ◽  
pp. 4136-4142 ◽  
Author(s):  
I Kawashima ◽  
ED Zanjani ◽  
G Almaida-Porada ◽  
AW Flake ◽  
H Zeng ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Marrow Cell ◽  
In Utero ◽  
Fetal Sheep ◽  
Hematopoietic Stem ◽  
Show Evidence ◽  
Marrow Cells

Using in utero transplantation into fetal sheep, we examined the capability of human bone marrow CD34+ cells fractionated based on Kit protein expression to provide long-term in vivo engraftment. Twelve hundred to 5,000 CD34+ Kit-, CD34+ Kit(low), and CD34+ Kit(high) cells were injected into a total of 14 preimmune fetal sheep recipients using the amniotic bubble technique. Six fetuses were killed in utero 1.5 months after bone marrow cell transplantation. Two fetuses receiving CD34+ Kit(low) cells showed signs of engraftment according to analysis of CD45+ cells in their bone marrow cells and karyotype studies of the colonies grown in methylcellulose culture. In contrast, two fetuses receiving CD34+ Kit(high) cells and two fetuses receiving CD34+ Kit- cells failed to show evidence of significant engraftment. Two fetuses were absorbed. A total of six fetuses receiving different cell populations were allowed to proceed to term, and the newborn sheep were serially examined for the presence of chimerism. Again, only the two sheep receiving CD34+ Kit(low) cells exhibited signs of engraftment upon serial examination. Earlier in studies of murine hematopoiesis, we have shown stage-specific changes in Kit expression by the progenitors. The studies of human cells reported here are in agreement with observations in mice, and indicate that human hematopoietic stem cells are enriched in the Kit(low) population.

scholarly journals Bone Marrow and Peripheral Blood Cells Toxicity of a Single 2.0 Gy Cobalt60 Ionizing Radiation: An Animal Model

1970 ◽  
Vol 29 (2) ◽  
Author(s):  
Shittu Akeem ◽  
Olatunbosun Lukman ◽  
Khalil Eltahir ◽  
Olalere Fatai ◽  
Babatunde Abiola ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Marrow Cell ◽  
P Value ◽  
Peripheral Blood Cells ◽  
P Values ◽  
Cell Parameters ◽  
Post Irradiation ◽  
Total Body

BACKGROUND: Bone marrow is extremely vulnerable to damage caused by radiation therapy. Hence, bone marrow suppression is an important side effect of radiotherapy. Effective use of radiotherapy is therefore compromised by radiation-related injuries.MATERIAL AND METHODS: Six Guinea-pigs were recruited for the study of which three were subjected to total body irradiation with Co60 while the other three served as controls. Bone marrow and peripheral blood samples were collected before and at days 9, 14 and 21, post irradiation. Manual and automated counts were performed for bone marrow nucleated cells and peripheral blood cells respectively.RESULTS: Declining bone marrow cellularity was evident immediately post irradiation. Mean ± SD of marrow cell counted per mm3 were 121,924±281, 87,603±772, 121,367±375 and122,750±1000 pre-irradiation and days 9, 14 and 21, postirradiation (p-values 0.10, 0.27 and 0.29 respectively). Significant drops in counts were noticed on day 9 post-irradiation for all red cell parameters (p-values <0.05), for Total White Blood Cell Count and Neutrophil count (p-values <0.05) and also on days 14 and 21 for Lymphocytes (p-values <0.05) and on day 21 for Eosinophil/Basophil/Monocytes (p-value <0.05). A significant drop in platelets counts was also noticed on day 9 (p-value <0.05) which significantly increased above pre-irradiation value on day 21.CONCLUSION: Total body irrradiation with Co60 significantly affects the bone marrow with maximum reductions in marrow nucleated cells and peripheral blood cells counts on day 9 post irradiation. 

scholarly journals Dry Mass Distribution Changes in Mouse Bone Marrow Cell Population during the First 24 Hours after X—Irradiation as Determined by Interfereometry

Blood ◽  
1965 ◽  
Vol 25 (3) ◽  
pp. 299-309 ◽  
Author(s):  
HUN LEE ◽  
VICTOR RICHARDS ◽  
MARIA MAICHLE
Keyword(s):  
Bone Marrow ◽  
Mass Distribution ◽  
Bone Marrow Cells ◽  
Marrow Cell ◽  
Dry Mass ◽  
Steady Increase ◽  
Mouse Bone Marrow ◽  
Proliferating Cells ◽  
Mouse Bone Marrow Cell ◽  
Total Body

Abstract LAF1 mice were treated with a total-body dose of 800 r. x-ray. The dry mass distribution of the femur bone marrow cells was determined at different intervals postirradiation. The nonproliferating cells showed no significant dry mass change, whereas the proliferating cells of the myelocyte series had a steady increase in mean dry mass per cell. Few cells with the maximum dry mass increase survived at the end of 48 hours postirradiation. The dry mass distribution formed characteristic patterns for each postirradiation interval studied as the proliferating cells shifted to higher dry mass values with accompanied increase in cell sizes.

scholarly journals Observations on the binding and interaction of radioiodinated colony- stimulating factor with murine bone marrow cells in vivo

Blood ◽  
1982 ◽  
Vol 59 (2) ◽  
pp. 408-420 ◽  
Author(s):  
G Pigoli ◽  
A Waheed ◽  
RK Shadduck
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Marrow Cell ◽  
Cell Interaction ◽  
Peritoneal Macrophages ◽  
Colony Stimulating Factor ◽  
Murine Bone Marrow ◽  
Stimulating Factor ◽  
Marrow Cells

Abstract Radioiodinated L-cell-derived colony-stimulating factor (CSF) was used to characterize the binding reaction to murine bone marrow cells. The major increment in cell-associated radioactivity occurred over 24 hr incubation at 37 degrees C, but virtually no binding was observed at 4 degrees C. The reaction was saturable with approximately 1 ng/ml of purified CSF. Unlabeled CSF prevented the binding, whereas a number of other hormones and proteins did not compete for CSF uptake. Further specificity studies showed virtually no binding to human bone marrow, which is unresponsive to this form of murine CSF. Minimal CSF uptake was noted with murine peritoneal macrophages, but virtually no binding was detected with thymic, lymph node, liver, or kidney cells. The marrow cell interaction with tracer appeared to require a new protein synthesis, as the binding was prevented by cycloheximide or puromycin. Preincubation of marrow cells in medium devoid of CSF increased the degree of binding after 1 hr exposure to the tracer. This suggests that CSF binding sites may be occupied or perhaps decreased in response to ambient levels of CSF in vivo. Approximately 70% of the bound radioactivity was detected in the cytoplasm at 24 hr. This material was partially degraded as judged by a decrease in molecular weight from approximately 62,000 to 2 peaks of approximately 32,000 and approximately 49,000, but 72% of the binding activity was retained. After plateau binding was achieved, greater than 80% of the radioactivity released into the medium was degraded into biologically inactive peptides with molecular weights less than 10,000. These findings suggest that the interaction of CSF with marrow cells is characterized by binding with subsequent internalization and metabolic degradation into portions of the molecule that are devoid of biologic activity.

Live Attenuated Salmonella Carrying Platelet Factor 4 cDNAs as Radioprotection and Anti-Tumor Angiogenesis Agents.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3178-3178
Author(s):  
Zhong Chao Han ◽  
Bin Liu ◽  
Lihua Zhao
Keyword(s):  
Gene Therapy ◽  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Tumor Regression ◽  
Platelet Factor 4 ◽  
Platelet Factor ◽  
Delivery Vector ◽  
Total Body ◽  
Marrow Cells

Abstract In cancer therapy, specific radioprotection of normal tissue and antiangiogenesis are the ways to increase the therapeutic gain. Here we describe a novel gene therapy, which uses attenuated salmonella SL3261 as oral vectors carrying with cDNA of platelet factor 4 (PF4) or that of a truncated PF4. After oral administrations of attenuated salmonella carrying with cDNA of PF4 or truncated PF4, the survival rate of mice which received sublethal total body irradiation was improved by 50%, In comparison with the control mice, the bone marrow cells obtained from the mice of experimental group increased (13.2±8.3, 15.7±1.5 vs 4.1 ± 2.0 P<0.05) at day 7 after TBI, and the number of HPP-CFC of bone marrow cells also increased significantly (15.7±9, 11.7±5 vs 4.3±4.1 P<0.05) at day 7, suggesting a stimulating effect of PF4 on hematopoietic recovery. This gene therapy also caused significant tumor regression. The microvessel density (MVD) of tumors was significantly decreased in the group of treated mice compared to controls (4.25±0.96, 4.08±0.56 vs 11±0.83 P<0.05). Analysis TUNEL kit revealed an increase in the number of apoptosis cells in tumors of mice treated by SL3261 carrying with cDNA of PF4 or a truncated PF4. GFP expression and gene integration were detected in the liver, kidney, spleens, intestine, peripheral blood, bone marrow and tumors samples of the SL3261 treated mice, and the expression of GFP was higher in tumors than that in other tissues. These data demonstrate for the first time a dual biological function of PF4 against tumor growth and radiation injury. These results also demonstrate that attenuated salmonella can be used in vivo as a DNA delivery vector

Suppression of NK Cell-Mediated Bone Marrow Cell Rejection by CD4+CD25+ Regulatory T Cells: Linkage of Adaptive to Innate Responses.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2195-2195
Author(s):  
William J. Murphy ◽  
Isabel Bareo ◽  
Alan M. Hanash ◽  
Lisbeth A. Welniak ◽  
Kai Sun ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Regulatory T Cells ◽  
Cell Function ◽  
Nk Cell ◽  
Marrow Cell ◽  
Poly I:C ◽  
Hybrid Resistance

Abstract While a link between the innate to adaptive immune system has been established, studies demonstrating direct effects of T cells in regulating Natural Killer (NK) cell function have been lacking. Naturally occurring CD4+CD25+ regulatory T cells (Tregs) have been shown to potently inhibit adaptive responses by T cells. We therefore investigated whether Tregs could affect NK cell function in vivo. Using a bone marrow transplantation (BMT) model of hybrid resistance, in which parental (H2d) marrow grafts are rejected by the NK cells of the F1 recipients (H2bxd), we demonstrate that the in vivo removal of host Tregs significantly enhances NK-cell mediated BM rejection. This heightened rejection was mediated by the specific NK cell Ly-49+ subset previously demonstrated to reject the BMC in this donor/host pairing. The depletion of Tregs could also further increase rejection already enhanced by treating recipients with the NK cell activator, poly I:C. Although splenic NK cell numbers were not significantly altered, increased splenic NK in vitro cytotoxic activity was observed from the recovered cells. The regulatory role of Tregs was confirmed in adoptive transfer studies in which transferred CD4+CD25+ Tregs resulted in abrogation of NK cell-mediated hybrid resistance. Thus, Tregs can potently inhibit NK cell function in vivo and their depletion may have therapeutic ramifications with NK cell function in BMT and cancer therapy.

Induction of Donor-Type Chimerism and Transplantation Tolerance Across Major Histocompatibility Barriers in Sublethally Irradiated Mice by Sca-1+Lin− Bone Marrow Progenitor Cells: Synergism With Non-Alloreactive (Host × Donor)F1 T Cells

Blood ◽  
1999 ◽  
Vol 94 (9) ◽  
pp. 3212-3221 ◽  
Author(s):  
Esther Bachar-Lustig ◽  
Hong Wei Li ◽  
Hilit Gur ◽  
Rita Krauthgamer ◽  
Hadar Marcus ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Transplantation Tolerance ◽  
Major Histocompatibility ◽  
Hematopoietic Stem ◽  
Donor Type ◽  
Total Body ◽  
Veto Cells

Induction of transplantation tolerance by means of bone marrow (BM) transplantation could become a reality if it was possible to achieve engraftment of hematopoietic stem cells under nonlethal preparatory cytoreduction of the recipient. To that end, BM facilitating cells, veto cells, or other tolerance-inducing cells, have been extensively studied. In the present study, we show that BM cells within the Sca-1+Lin− cell fraction, previously shown to be enriched for early hematopoietic progenitors, are capable of reducing specifically antidonor CTL-p frequency in vitro and in vivo, and of inducing split chimerism in sublethally 7-Gy–irradiated recipient mice across major histocompatibility complex barriers. The immune tolerance induced by the Sca-1+Lin−cells was also associated with specific tolerance toward donor-type skin grafts. The minimal number of cells required to overcome the host immunity remaining after 7 Gy total body irradiation is very large and, therefore, it may be very difficult to harvest sufficient cells for patients. This challenge was further addressed in our study by demonstrating that non-alloreactive (host × donor)F1 T cells, previously shown to enhance T-cell–depleted BM allografts in lethally irradiated mice, synergize with Sca-1+Lin− cells in their capacity to overcome the major transplantation barrier presented by the sublethal mouse model.

Receptor-mediated clearance of G-CSF derivative nartograstim in bone marrow of rats

1995 ◽  
Vol 269 (1) ◽  
pp. E1-E9 ◽  
Author(s):  
T. Kuwabara ◽  
T. Uchimura ◽  
H. Kobayashi ◽  
S. Kobayashi ◽  
Y. Sugiyama
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Binding Capacity ◽  
Specific Binding ◽  
Maximal Velocity ◽  
Rate Dependent ◽  
Elimination Mechanism ◽  
Total Body

To clarify the role of the granulocyte colony-stimulating factor (G-CSF) receptor in the nonlinear elimination of a recombinant human G-CSF derivative, nartograstim (NTG), the accompanying changes in the in vivo NTG total body clearance at steady state (CLss) or the early-phase tissue uptake clearance (CLuptake) in rats were compared with the change in the number of G-CSF receptors in bone marrow. The infusion rate-dependent decrease in CLss in control rats confirmed the existence of a saturable elimination mechanism for NTG. The Michaelis-Menten constant (Km) and maximal velocity for this saturable process were estimated to be 107 pM and 15.5 pmol.h-1.kg-1, respectively. The Km for this saturable process was comparable with the dissociation constant (Kd) for the specific binding of NTG to bone marrow cells. After administration of excess NTG, the CLuptake of tracer amounts of 1251-NTG by bone marrow and spleen, which corresponds to the receptor density in the tissues, was reduced at 2 h but gradually recovered. This change in CLuptake corresponds well to the change in the in vitro NTG-binding capacity in each isolated cell. This reduction in CLuptake might be due to the downregulation of G-CSF receptors on the cell surface. On the other hand, the saturable CLss in cyclophosphamide-treated rats was 17% of that in control rats, whereas the saturable CLss in rats given NTG repeatedly was twofold greater than in controls, which is associated with the upregulation of G-CSF receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Ghrelin Therapy Improves Survival after Whole-Body Ionizing Irradiation or Combined with Burn or Wound: Amelioration of Leukocytopenia, Thrombocytopenia, Splenomegaly, and Bone Marrow Injury

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Juliann G. Kiang ◽  
Min Zhai ◽  
Pei-Jyun Liao ◽  
Thomas B. Elliott ◽  
Nikolai V. Gorbunov
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cell ◽  
Tissue Injury ◽  
Marrow Cell ◽  
Total Body Surface Area ◽  
Body Weight Loss ◽  
Cell Depletion ◽  
Photon Radiation ◽  
Whole Body ◽  
Total Body

Exposure to ionizing radiation alone (RI) or combined with traumatic tissue injury (CI) is a crucial life-threatening factor in nuclear and radiological events. In our laboratory, mice exposed to60Co-γ-photon radiation (9.5 Gy, 0.4 Gy/min, bilateral) followed by 15% total-body-surface-area skin wounds (R-W CI) or burns (R-B CI) experienced an increment of ≥18% higher mortality over a 30-day observation period compared to RI alone. CI was accompanied by severe leukocytopenia, thrombocytopenia, erythropenia, and anemia. At the 30th day after injury, numbers of WBC and platelets still remained very low in surviving RI and CI mice. In contrast, their RBC, hemoglobin, and hematocrit were recovered towards preirradiation levels. Only RI induced splenomegaly. RI and CI resulted in bone-marrow cell depletion. In R-W CI mice, ghrelin (a hunger-stimulating peptide) therapy increased survival, mitigated body-weight loss, accelerated wound healing, and increased hematocrit. In R-B CI mice, ghrelin therapy increased survival and numbers of neutrophils, lymphocytes, and platelets and ameliorated bone-marrow cell depletion. In RI mice, this treatment increased survival, hemoglobin, and hematocrit and inhibited splenomegaly. Our novel results are the first to suggest that ghrelin therapy effectively improved survival by mitigating CI-induced leukocytopenia, thrombocytopenia, and bone-marrow injury or the RI-induced decreased hemoglobin and hematocrit.

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