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Sample records for red marrow 131ina

  1. Marrow: red, yellow and bad.

    PubMed

    Guillerman, Robert Paul

    2013-03-01

    Bone marrow is one of the largest and most dynamic tissues in the body, and it is well-depicted on conventional MRI sequences. However, often only perfunctory attention is paid to the bone marrow on musculoskeletal imaging studies, raising the risk of delayed or missed diagnoses. To guide appropriate recognition of normal variants and pathological processes involving the marrow compartment, this article describes and depicts the physiological spatiotemporal pattern of conversion of hematopoietic red marrow to fatty yellow marrow during childhood and adolescence, and the characteristic imaging findings of disorders involving marrow hyperplasia/reconversion, marrow infiltration/deposition and marrow depletion/failure. PMID:23478934

  2. Investigation of effect of variations in bone fraction and red marrow cellularity on bone marrow dosimetry in radio-immunotherapy

    NASA Astrophysics Data System (ADS)

    Wilderman, S. J.; Roberson, P. L.; Bolch, W. E.; Dewaraja, Y. K.

    2013-07-01

    A method is described for computing patient-specific absorbed dose rates to active marrow which accounts for spatial variation in bone volume fraction and marrow cellularity. A module has been added to the 3D Monte Carlo dosimetry program DPM to treat energy deposition in the components of bone spongiosa distinctly. Homogeneous voxels in regions containing bone spongiosa (as defined on CT images) are assumed to be comprised only of bone, active (red) marrow and inactive (yellow) marrow. Cellularities are determined from biopsy, and bone volume fractions are computed from cellularities and CT-derived voxel densities. Electrons are assumed to deposit energy locally in the three constituent components in proportions determined by electron energy absorption fractions which depend on energy, cellularity, and bone volume fraction, and which are either taken from the literature or are derived from Monte Carlo simulations using EGS5. Separate algorithms are used to model primary β particles and secondary electrons generated after photon interactions. Treating energy deposition distinctly in bone spongiosa constituents leads to marrow dosimetry results which differ from homogeneous spongiosa dosimetry by up to 20%. Dose rates in active marrow regions with cellularities of 20, 50, and 80% can vary by up to 20%, and can differ by up to 10% as a function of bone volume fraction. Dose to bone marrow exhibits a strong dependence on marrow cellularity and a potentially significant dependence on bone volume fraction.

  3. Investigation of effect of variations in bone fraction and red marrow cellularity on bone marrow dosimetry in radio-immunotherapy.

    PubMed

    Wilderman, S J; Roberson, P L; Bolch, W E; Dewaraja, Y K

    2013-07-21

    A method is described for computing patient-specific absorbed dose rates to active marrow which accounts for spatial variation in bone volume fraction and marrow cellularity. A module has been added to the 3D Monte Carlo dosimetry program DPM to treat energy deposition in the components of bone spongiosa distinctly. Homogeneous voxels in regions containing bone spongiosa (as defined on CT images) are assumed to be comprised only of bone, active (red) marrow and inactive (yellow) marrow. Cellularities are determined from biopsy, and bone volume fractions are computed from cellularities and CT-derived voxel densities. Electrons are assumed to deposit energy locally in the three constituent components in proportions determined by electron energy absorption fractions which depend on energy, cellularity, and bone volume fraction, and which are either taken from the literature or are derived from Monte Carlo simulations using EGS5. Separate algorithms are used to model primary ? particles and secondary electrons generated after photon interactions. Treating energy deposition distinctly in bone spongiosa constituents leads to marrow dosimetry results which differ from homogeneous spongiosa dosimetry by up to 20%. Dose rates in active marrow regions with cellularities of 20, 50, and 80% can vary by up to 20%, and can differ by up to 10% as a function of bone volume fraction. Dose to bone marrow exhibits a strong dependence on marrow cellularity and a potentially significant dependence on bone volume fraction. PMID:23780474

  4. Development and evaluation of a new algorithm for determining radiation dose to the red bone marrow

    NASA Astrophysics Data System (ADS)

    Caracappa, Peter F.

    Red bone marrow is among the tissues of the human body that are most sensitive to ionizing radiation. Red bone marrow cannot be easily modeled because it is distributed heterogeneously throughout the skeleton and cannot be distinguished from yellow or inactive bone marrow by radiographic means, so dosimetry models must apply algorithms to estimate the dose to the red bone marrow. The current methods for deriving red bone marrow distribution from CT data are based on assumptions that may not be anatomically realistic and the uncertainty of such calculations has been difficult to estimate. This dissertation describes a new algorithm for calculating the distribution of red bone marrow and the applications of the algorithm. The CT data and red bone marrow distribution algorithms are incorporated into an EGS4 user code to assess the effects of the red bone marrow distribution on the computed dose to the red bone marrow for three irradiation scenarios. Parallel beams of monoenergetic photons have been modeled from the Anterior-Posterior, Posterior-Anterior, Left Lateral and Right Lateral directions in the energy range of 30 keV to 6 MeV. Monoenergetic photons in the range of 30 keV to 1 MeV have been modeled in geometries representing head and abdominal CT examinations. A so-called "whole body irradiation" procedure for a 6-direction 3.9 MeV electron protocol has also been studied. Comparing the whole body red bone marrow doses for these irradiations demonstrates a discrepancy between the two different methods for parallel beams of photons below about 200 keV as high as 25%. At higher energies, the disparity in red bone marrow dose is less than 5%. For non-uniform irradiations, however, a greater improvement is realized with the proposed new method. An improvement in red bone marrow dose of 25% to 35% was found for the CT examinations, and nearly 40% for the whole body electron skin treatment protocol. The data presented here justify the need to better understand the uncertainty in existing dosimetry methodologies for radiation protection. This dissertation also presents recommendations for incorporating the new algorithm into other models and for future work.

  5. Estimation of radiation absorbed doses to the red marrow in radioimmunotherapy

    SciTech Connect

    Macey, D.J.; DeNardo, S.J.; DeNardo, G.L.; DeNardo, D.A.; Sui Shen

    1995-02-01

    Myelotoxicity is the dose-limiting factor in radioimmunotherapy. Traditional methods most commonly used to estimate the radiation adsorbed dose to the bone marrow of patients consider contribution from radionuclide in the blood and/or total body. Targeted therapies, such as radioimmunotherapy, add a third potential source for radiation to the bone marrow because the radiolabeled targeting molecules can accumulate specifically on malignant target cells infiltrating the bone marrow. A non-invasive method for estimating the radiation absorbed dose to the red marrow of patients who have received radiolabeled monoclonal antibodies (MoAb) has been developed and explored. The method depends on determining the cumulated activity in three contributing sources: (1) marrow; (2) blood; and (3) total body. The novel aspect of this method for estimating marrow radiation dose is derivation of the radiation dose for the entire red marrow from radiation dose estimates obtained by detection of cumulated activity in three lumbar vertebrae using a gamma camera. Contributions to the marrow radiation dose form marrow, blood, and total body cumulated activity were determined for patients who received an I-131 labeled MoAb, Lym-1, that reacts with malignant B-lymphocytes of chronic lymphocytic leukemia and nonHodgkin`s lymphoma. Six patients were selected for illustrative purposes because their vertebrae were readily visualized on lumbar images. 32 refs., 6 figs., 1 tab.

  6. Preparation of red-blood-cell-depleted marrow for ABO-incompatible marrow transplantation by density-gradient separation using the IBM 2991 blood cell processor.

    PubMed

    Jin, N R; Hill, R; Segal, G; Still, B; Petersen, F B; Amos, D; Buckner, C D; Clift, R; Bensinger, W; Martin, P

    1987-01-01

    Thirty patients who had major ABO blood group incompatibility with their HLA-matched donors underwent allogeneic marrow transplantation after removal of red blood cells (RBC) from donor marrow by Ficoll-Diatrazoate (F-D) separation using the IBM 2991 blood cell processor. We selected the IBM 2991 because we were interested in obtaining information about RBC-depleted mononuclear cells for monoclonal antibody and complement incubation of marrow. The median residual marrow RBC volume was 2.6 ml (1.2% of the original volume) and marrow infusion was well tolerated in every instance. The median doses of nucleated and mononuclear cells were 8.7 X 10(7)/kg and 2.2 X 10(7)/kg recipient weight, respectively, representing median marrow total nucleated and mononuclear cell losses of 63.4% and 52.9%, respectively. The median CFU-GM loss was 52.4%. Four patients died 13-21 days after marrow infusion and were unevaluable for engraftment. One patient failed to achieve engraftment and received a second transplant on day 36 from a second donor. One patient with myelofibrosis had poor engraftment and died on day 177 with low peripheral blood counts. For evaluable patients, no significant differences were observed in the rate of recovery of peripheral blood granulocyte or platelet counts between those receiving RBC-depleted marrow or ABO-matched unprocessed marrow. However, posttransplant red cell transfusion requirements were increased and transfusion independence delayed in patients receiving RBC-depleted marrow as compared to patients receiving unprocessed marrow. We concluded that red cell depletion using the IBM 2991 was effective in removing red cell, but resulted in significant and variable hematopoietic cell losses which may have contributed to graft failure in at least one patient. Such cell losses appear to be inherent in both manual and semiautomated methods for F-D cell separation. PMID:3536547

  7. MRI of Residual Red Bone Marrow in the Distal Femur of Healthy Subjects

    PubMed Central

    Arslan, Gozde; Ozmen, Evrim; Soyturk, Mehmet

    2015-01-01

    Summary Backround The purpose of our study is to examine the correlation of the residual red bone marrow areas of distal femoral metaphysis with the age, gender, weight and hemoglobin (hgb) values; evaluate the results, and comprehend the importance of these residual areas in the light of the results. Material/Methods 140 nonsmoking patients between the ages of 26 and 72 (92 women, 48 men) who had knee MR examinations were included in the study. The residual red bone marrow areas in the distal femoral metaphysis in MR images were examined by a radiologist. The areas were separated into grades according to their sizes. The hemoglobin values of the cases were measured. The size of the residual red bone marrow area and the age, gender, weight and hemoglobin values of the cases were compared by using the Tukey and Chi-Square Tests. Results Although no significant differences were observed between the mean ages, weights and hemoglobin values of the grades, a significant difference was detected between the gender distribution The male group had less residual red bone marrow in the distal femoral metaphysis than the female group (p=0.003). Conclusions We observed that the hypointensities due to residual red bone marrow observed in the T1WS of the distal femoral metaphysis are not related with the age, weight and hemoglobin values. No grade 2 and grade 3 patient was detected in male group. We observed that these hypointense areas showed difference according to the gender variable; however, were not affected by the hemoglobin values over certain levels. PMID:26124901

  8. Hyperemic peripheral red marrow in a patient with sickle cell anemia demonstrated on Tc-99m labeled red blood cell venography

    SciTech Connect

    Heiden, R.A.; Locko, R.C.; Stent, T.R. )

    1991-03-01

    A 25-year-old gravid woman, homozygous for sickle cell anemia, with a history of recent deep venous thrombosis, was examined using Tc-99m labeled red blood cell venography for recurrent thrombosis. Although negative for thrombus, the study presented an unusual incidental finding: the patient's peripheral bone marrow was hyperemic in a distribution consistent with peripheral red bone marrow expansion. Such a pattern has not been documented before using this technique. This report supports other literature that has demonstrated hyperemia of peripheral red bone marrow in other hemolytic anemias. This finding may ultimately define an additional role of scintigraphy in assessing the pathophysiologic status of the sickle cell patient.

  9. 660 nm red light-enhanced bone marrow mesenchymal stem cell transplantation for hypoxic-ischemic brain damage treatment

    PubMed Central

    Li, Xianchao; Hou, Wensheng; Wu, Xiaoying; Jiang, Wei; Chen, Haiyan; Xiao, Nong; Zhou, Ping

    2014-01-01

    Bone marrow mesenchymal stem cell transplantation is an effective treatment for neonatal hypoxic-ischemic brain damage. However, the in vivo transplantation effects are poor and their survival, colonization and differentiation efficiencies are relatively low. Red or near-infrared light from 6001,000 nm promotes cellular migration and prevents apoptosis. Thus, we hypothesized that the combination of red light with bone marrow mesenchymal stem cell transplantation would be effective for the treatment of hypoxic-ischemic brain damage. In this study, the migration and colonization of cultured bone marrow mesenchymal stem cells on primary neurons after oxygen-glucose deprivation were detected using Transwell assay. The results showed that, after a 40-hour irradiation under red light-emitting diodes at 660 nm and 60 mW/cm2, an increasing number of green fluorescence-labeled bone marrow mesenchymal stem cells migrated towards hypoxic-ischemic damaged primary neurons. Meanwhile, neonatal rats with hypoxic-ischemic brain damage were given an intraperitoneal injection of 1 106 bone marrow mesenchymal stem cells, followed by irradiation under red light-emitting diodes at 660 nm and 60 mW/cm2 for 7 successive days. Shuttle box test results showed that, after phototherapy and bone marrow mesenchymal stem cell transplantation, the active avoidance response rate of hypoxic-ischemic brain damage rats was significantly increased, which was higher than that after bone marrow mesenchymal stem cell transplantation alone. Experimental findings indicate that 660 nm red light emitting diode irradiation promotes the migration of bone marrow mesenchymal stem cells, thereby enhancing the contribution of cell transplantation in the treatment of hypoxic-ischemic brain damage. PMID:25206807

  10. Visible red and infrared light alters gene expression in human marrow stromal fibroblast cells

    PubMed Central

    Guo, Jie; Wang, Qing; Wai, Daniel; Zhou, Qunzhou; Shi, Shihong; Le, Anh D; Shi, Songtao; Yen, Stephen L-K

    2015-01-01

    Objectives This study tested whether or not gene expression in human marrow stromal fibroblast (MSF) cells depends on light wavelength and energy density. Material and Methods Primary cultures of isolated human bone marrow stem cells (hBMSC) were exposed to visible red (VR, 633 nm) and infrared (IR, 830) radiation wavelengths from a light emitting diode (LED) over a range of energy densities (0.5, 1.0, 1.5, 2.0 Joules/cm2) Cultured cells were assayed for cell proliferation, osteogenic potential, adipogenesis, mRNA and protein content. mRNA was analyzed by microarray, and compared among different wavelengths and energy densities. Mesenchymal and epithelial cell responses were compared to determine whether responses were cell-type specific. Protein array analysis was used to further analyze key pathways identified by microarrays. Result Different wavelengths and energy densities produced unique sets of genes identified by microarray analysis. Pathway analysis pointed to TGF beta 1 in the visible red and Akt 1 in the infrared wavelengths as key pathways to study. TGF beta protein arrays suggested switching from canonical to non-canonical TGF beta pathways with increases to longer IR wavelengths. Microarrays suggest RANKL and TIMP 10 followed IR energy density dose response curves. Epithelial and mesenchymal cells respond differently to stimulation by light suggesting cell-type specific response is possible. Conclusions These studies demonstrate differential gene expression with different wavelengths, energy densities and cell types. These differences in gene expression have the potential to be exploited for therapeutic purposes and can help explain contradictory results in the literature when wavelengths, energy densities and cell types differ. PMID:25865533

  11. Resolution enhancement in MR spectroscopy of red bone marrow fat via intermolecular double-quantum coherences

    NASA Astrophysics Data System (ADS)

    Bao, Jianfeng; Cui, Xiaohong; Huang, Yuqing; Zhong, Jianhui; Chen, Zhong

    2015-08-01

    High-resolution 1H magnetic resonance spectroscopy (MRS) is generally inaccessible in red bone marrow (RBM) tissues using conventional MRS techniques. This is because signal from these tissues suffers from severe inhomogeneity in the main static B0 field originated from the intrinsic honeycomb structures in trabecular bone. One way to reduce effects of B0 field inhomogeneity is by using the intermolecular double quantum coherence (iDQC) technique, which has been shown in other systems to obtain signals insensitive to B0 field inhomogeneity. In the present study, we employed an iDQC approach to enhance the spectral resolution of RBM. The feasibility and performance of this method for achieving high resolution MRS was verified by experiments on phantoms and pig vertebral bone samples. Unsaturated fatty acid peaks which overlap in the conventional MRS were well resolved and identified in the iDQC spectrum. Quantitative comparison of fractions of three types of fatty acids was performed between iDQC spectra on the in situ RMB and conventional MRS on the extracted fat from the same RBM. Observations of unsaturated fatty acids with iDQC MRS may provide valuable information and may hold potential in diagnosis of diseases such as obesity, diabetes, and leukemia.

  12. Monte Carlo estimation of radiation doses in red bone marrow and breast in common pediatric x-ray examinations.

    PubMed

    Gialousis, George I; Yakoumakis, Emmanuel N; Dimitriadis, Anastasios I; Papouli, Zografia K; Yakoumakis, Nikolaos E; Tsalafoutas, Ioannis A; Papadopoulou, Despoina I; Georgiou, Evangelos K

    2008-09-01

    Radiation exposure was investigated for children undergoing various common radiographies in three dedicated pediatric hospitals in Greece. Kerma in air at the entrance of the beam (Ka,e) was measured with thermoluminescent dosimeters. Ka,e values ranged from 0.09 mGy to 5.52 mGy and were found to be greater in Hospital C, because of the increased high voltage and time-current product used by the radiation technologists. Equivalent doses in red bone marrow and breast were estimated with Monte Carlo simulation by PCXMC code. Values ranged from 2 microSv to 204 microSv for red bone marrow and from 0 to 817 muSv for breast. Variation in doses occurred due to field size, high voltage setting, and Ka,e. PMID:18695414

  13. Red bone marrow doses, integral absorbed doses, and somatically effective dose equivalent from four maxillary occlusal projections

    SciTech Connect

    Berge, T.I.; Wohni, T.

    1984-02-01

    Phantom measurements of red bone marrow (RBM) doses, integral absorbed doses, and somatically effective dose equivalent (SEDE) from four different maxillary occlusal projections are presented. For each projection, different combinations of focus-skin distances and tube potentials were compared with regard to the patient's radiation load. The axial incisal view produced the highest patient exposures, with a maximum red bone marrow dose of 122.5 microGy/exposure, integral absorbed dose of 8.6 mJ/exposure, and SEDE values of 39.6 microSv/exposure. The corresponding values from the frontal, lateral occlusal, and tuber views ranged between 4% and 44% of the axial incisal view values for the integral absorbed dose and SEDE values, and between 0.3% and 3% for the red bone marrow doses. Increasing the focus-skin distance from 17.5 cm to 27 cm is accompanied by a 24% to 30% reduction in integral absorbed dose. Increasing the tube potential from 50 kV to 65 kV likewise results in a 23% reduction in absorbed energy.

  14. Comparison of a restrictive versus liberal red cell transfusion policy for patients with myelodysplasia, aplastic anaemia, and other congenital bone marrow failure disorders

    PubMed Central

    Gu, Yisu; Estcourt, Lise J; Doree, Carolyn; Trivella, Marialena; Hopewell, Sally; Vyas, Paresh

    2015-01-01

    This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the efficacy and safety of a restrictive versus liberal red cell transfusion strategy for patients with long-term bone marrow failure. These include myelodysplasia, acquired aplastic anaemia, and other inherited bone marrow failure disorders. PMID:25983657

  15. Total extract of Korean red ginseng facilitates human bone marrow hematopoietic colony formation in vitro

    PubMed Central

    Kim, Sang-Gyung; Bae, Sung Hwa; Kim, Seong-Mo; Lee, Ji-Hye; Kim, Min Ji; Jang, Hae-Bong

    2014-01-01

    Background The number of CD34+ cells in a peripheral blood stem cell collection is the key factor in predicting successful treatment of hematologic malignancies. Korean Red Ginseng (KRG) (Panax ginseng C.A. Meyer) is the most popular medicinal herb in Korea. The objective of this study was to determine the effect of KRG on hematopoietic colony formation. Methods Bone marrow (BM) samples were obtained from 8 human donors after acquiring informed consent. BM mononuclear cells (MNCs) were isolated, and CD34+ cells were sorted using magnetic beads. The sorted CD34+ cells were incubated with or without total extract of KRG (50 g/mL, 100 g/mL) or Ginsenoside Rg1 (100 g/mL), and the hematopoietic colony assay was performed using methylcellulose semisolid medium. The CD34+ cell counts were measured by a single platform assay using flow cytometry. Results The numbers of human BM-MNCs and CD34+ cells obtained after purification were variable among donors (5.6107 and 1.3-48107 and 8.9104 and 1.8-80104, respectively). The cells expanded 1,944 times after incubation for 12 d. Total extract of KRG added to the hematopoietic stem cell (HSC)-specific medium increased CD34+ cell counts 3.6 times compared to 2.6 times when using HSC medium alone. Total numbers of hematopoietic colonies in KRG medium were more than those observed in conventional medium, especially that of erythroid colonies such as burst forming unit-erythroid. Conclusion Total extract of KRG facilitated CD34+ cell expansion and hematopoietic colony formation, especially of the erythroid lineage. PMID:25325037

  16. Red bone marrow dose calculations in radiotherapy of prostate cancer based on the updated VCH adult male phantom.

    PubMed

    Ai, Jinqin; Xie, Tianwu; Sun, Wenjuan; Liu, Qian

    2014-04-01

    Red bone marrow (RBM) is an important dose-limiting tissue that has high radiosensitivity but is difficult to identify on clinical medical images. In this study, we investigated dose distribution in RBM for prostate cancer radiotherapy. Four suborgans were identified in the skeleton of the visible Chinese human phantom: cortical bone (CB), trabecular bone (TB), RBM, and yellow bone marrow (YBM). Dose distributions in the phantom were evaluated by the Monte Carlo method. When the left os coxae was taken as the organ-at-risk (OAR), the difference in absorbed dose between RBM and each CB and TB was up to 20%, but was much less (?3.1%) between RBM and YBM. When the left os coxae and entire bone were both taken as OARs, RBM dose also increased with increasing planning target volume size. The results indicate the validity of using dose to homogeneous bone marrow mixture for estimating dose to RBM when RBM is not available in computational phantoms. In addition, the human skeletal system developed in this study provides a model for considering RBM dose in radiotherapy planning. PMID:24625466

  17. Red bone marrow dose calculations in radiotherapy of prostate cancer based on the updated VCH adult male phantom

    NASA Astrophysics Data System (ADS)

    Ai, Jinqin; Xie, Tianwu; Sun, Wenjuan; Liu, Qian

    2014-04-01

    Red bone marrow (RBM) is an important dose-limiting tissue that has high radiosensitivity but is difficult to identify on clinical medical images. In this study, we investigated dose distribution in RBM for prostate cancer radiotherapy. Four suborgans were identified in the skeleton of the visible Chinese human phantom: cortical bone (CB), trabecular bone (TB), RBM, and yellow bone marrow (YBM). Dose distributions in the phantom were evaluated by the Monte Carlo method. When the left os coxae was taken as the organ-at-risk (OAR), the difference in absorbed dose between RBM and each CB and TB was up to 20%, but was much less (≤3.1%) between RBM and YBM. When the left os coxae and entire bone were both taken as OARs, RBM dose also increased with increasing planning target volume size. The results indicate the validity of using dose to homogeneous bone marrow mixture for estimating dose to RBM when RBM is not available in computational phantoms. In addition, the human skeletal system developed in this study provides a model for considering RBM dose in radiotherapy planning.

  18. Fluorescence microscopy is superior to polarized microscopy for detecting amyloid deposits in Congo red-stained trephine bone marrow biopsy specimens.

    PubMed

    Marcus, Alan; Sadimin, Evita; Richardson, Maurice; Goodell, Lauri; Fyfe, Billie

    2012-10-01

    The classic gold standard for detecting amyloid deposits is Congo red-stained bright field and polarized microscopy (CRPM). A prior study showed that Congo red fluorescence (CRF) microscopy had increased sensitivity compared with traditional CRPM when analyzing fat pad specimens. The purpose of the current study was to determine the sensitivity of CRF for evaluating Congo red-stained bone marrow biopsy specimens, and to compare these results with those of CRPM. We compared the CRPM and the CRF analyses of 33 trephine bone marrow biopsy specimens with clinical or morphologic suspicion of amyloid deposits. These results were verified against immunohistochemical staining with anti-amyloid P antibody. CRF achieved 100% sensitivity, and CRPM achieved 75% sensitivity. Both groups showed 100% specificity compared with amyloid P immunohistochemical staining. The results show that CRF is a sensitive method to analyze trephine bone marrow biopsy specimens for amyloid deposits. PMID:23010714

  19. [MR imaging patterns of bone marrow].

    PubMed

    Boulet, B; Caramella, C; Couanet, D; Balleyguier, C; Bidault, F; Dromain, C

    2010-09-01

    The marrow contains a variable amount of yellow or fatty marrow and red or cellular marrow creating the signal intensity observed on MRI. Marrow replacement (by cells not normally present in bone marrow) typically is T1W hypointense. Marrow proliferation (by cells normally present in bone marrow) may be T1W hypointense (pseudo marrow replacement) or show intermediate T1W signal intensity due to red marrow redistribution. Marrow edema (reaction to an external process) show intermediate T1W hypointensity (mixture of water and marrow). Location will allow correct diagnosis. Bone marrow ischemia usually results in a necrotic fragment surrounded by a thin T1W hypointense rim. PMID:20814387

  20. Can blood group O red cells of donor origin acquire weak group A reactivity through serum A transferase of the recipient after bone marrow transplantation?

    PubMed

    Wichmann, M G; Haferlach, T; Suttorp, M; Zhang, Y; Neppert, J

    1994-01-01

    Blood group A substance was detected on red cells of a patient who had received a bone marrow transplant from a blood group 0 donor 3 1/2 years ago. All peripheral blood cells are of donor origin. Anti-A but not anti-A,B of blood group 0 individuals can be absorbed to the group 0 red cells of the patient. We suppose that the patient's residual serum A transferase attaches the appropriate sugar to H substance on the red cell membrane to form A substance. PMID:9422108

  1. The relative roles of MHC and non-MHC antigens in bone marrow transplantation in rats. Graft acceptance and antigenic expression on donor red blood cells

    SciTech Connect

    Pinto, M.; Gill, T.J.; Kunz, H.W.; Dixon-McCarthy, B.D.

    1983-06-01

    In order to investigate the influence of MHC and non-MHC genes in bone marrow transplantation, various combinations of congenic and inbred strains of rats were used as donors and recipients. A standard regimen of busulfan and cyclophosphamide treatment was used to condition the recipients. The resultant survival patterns of the animals indicated that: (1) a difference across the entire RT1 (MHC) complex is sufficient for the induction of fatal graft-versus-host disease (GVHD) in 100% of the engrafted animals; and (2) the blood group antigens RT2 and RT3, which are controlled by non-MHC genes, do not cause bone marrow graft rejection or GVHD. There were sequential changes of expression in surface alloantigens on the red cells in different donor-recipient combinations without other hematologic changes in the busulfan-cyclophosphamide conditioned bone marrow chimeras.

  2. Evaluation of dual energy quantitative CT for determining the spatial distributions of red marrow and bone for dosimetry in internal emitter radiation therapy

    SciTech Connect

    Goodsitt, Mitchell M. Shenoy, Apeksha; Howard, David; Christodoulou, Emmanuel; Dewaraja, Yuni K.; Shen, Jincheng; Schipper, Matthew J.; Wilderman, Scott; Chun, Se Young

    2014-05-15

    Purpose: To evaluate a three-equation three-unknown dual-energy quantitative CT (DEQCT) technique for determining region specific variations in bone spongiosa composition for improved red marrow dose estimation in radionuclide therapy. Methods: The DEQCT method was applied to 80/140 kVp images of patient-simulating lumbar sectional body phantoms of three sizes (small, medium, and large). External calibration rods of bone, red marrow, and fat-simulating materials were placed beneath the body phantoms. Similar internal calibration inserts were placed at vertebral locations within the body phantoms. Six test inserts of known volume fractions of bone, fat, and red marrow were also scanned. External-to-internal calibration correction factors were derived. The effects of body phantom size, radiation dose, spongiosa region segmentation granularity [single (∼17 × 17 mm) region of interest (ROI), 2 × 2, and 3 × 3 segmentation of that single ROI], and calibration method on the accuracy of the calculated volume fractions of red marrow (cellularity) and trabecular bone were evaluated. Results: For standard low dose DEQCT x-ray technique factors and the internal calibration method, the RMS errors of the estimated volume fractions of red marrow of the test inserts were 1.2–1.3 times greater in the medium body than in the small body phantom and 1.3–1.5 times greater in the large body than in the small body phantom. RMS errors of the calculated volume fractions of red marrow within 2 × 2 segmented subregions of the ROIs were 1.6–1.9 times greater than for no segmentation, and RMS errors for 3 × 3 segmented subregions were 2.3–2.7 times greater than those for no segmentation. Increasing the dose by a factor of 2 reduced the RMS errors of all constituent volume fractions by an average factor of 1.40 ± 0.29 for all segmentation schemes and body phantom sizes; increasing the dose by a factor of 4 reduced those RMS errors by an average factor of 1.71 ± 0.25. Results for external calibrations exhibited much larger RMS errors than size matched internal calibration. Use of an average body size external-to-internal calibration correction factor reduced the errors to closer to those for internal calibration. RMS errors of less than 30% or about 0.01 for the bone and 0.1 for the red marrow volume fractions would likely be satisfactory for human studies. Such accuracies were achieved for 3 × 3 segmentation of 5 mm slice images for: (a) internal calibration with 4 times dose for all size body phantoms, (b) internal calibration with 2 times dose for the small and medium size body phantoms, and (c) corrected external calibration with 4 times dose and all size body phantoms. Conclusions: Phantom studies are promising and demonstrate the potential to use dual energy quantitative CT to estimate the spatial distributions of red marrow and bone within the vertebral spongiosa.

  3. Evaluation of dual energy quantitative CT for determining the spatial distributions of red marrow and bone for dosimetry in internal emitter radiation therapy

    PubMed Central

    Goodsitt, Mitchell M.; Shenoy, Apeksha; Shen, Jincheng; Howard, David; Schipper, Matthew J.; Wilderman, Scott; Christodoulou, Emmanuel; Chun, Se Young; Dewaraja, Yuni K.

    2014-01-01

    Purpose: To evaluate a three-equation three-unknown dual-energy quantitative CT (DEQCT) technique for determining region specific variations in bone spongiosa composition for improved red marrow dose estimation in radionuclide therapy. Methods: The DEQCT method was applied to 80/140 kVp images of patient-simulating lumbar sectional body phantoms of three sizes (small, medium, and large). External calibration rods of bone, red marrow, and fat-simulating materials were placed beneath the body phantoms. Similar internal calibration inserts were placed at vertebral locations within the body phantoms. Six test inserts of known volume fractions of bone, fat, and red marrow were also scanned. External-to-internal calibration correction factors were derived. The effects of body phantom size, radiation dose, spongiosa region segmentation granularity [single (?17 17 mm) region of interest (ROI), 2 2, and 3 3 segmentation of that single ROI], and calibration method on the accuracy of the calculated volume fractions of red marrow (cellularity) and trabecular bone were evaluated. Results: For standard low dose DEQCT x-ray technique factors and the internal calibration method, the RMS errors of the estimated volume fractions of red marrow of the test inserts were 1.21.3 times greater in the medium body than in the small body phantom and 1.31.5 times greater in the large body than in the small body phantom. RMS errors of the calculated volume fractions of red marrow within 2 2 segmented subregions of the ROIs were 1.61.9 times greater than for no segmentation, and RMS errors for 3 3 segmented subregions were 2.32.7 times greater than those for no segmentation. Increasing the dose by a factor of 2 reduced the RMS errors of all constituent volume fractions by an average factor of 1.40 0.29 for all segmentation schemes and body phantom sizes; increasing the dose by a factor of 4 reduced those RMS errors by an average factor of 1.71 0.25. Results for external calibrations exhibited much larger RMS errors than size matched internal calibration. Use of an average body size external-to-internal calibration correction factor reduced the errors to closer to those for internal calibration. RMS errors of less than 30% or about 0.01 for the bone and 0.1 for the red marrow volume fractions would likely be satisfactory for human studies. Such accuracies were achieved for 3 3 segmentation of 5 mm slice images for: (a) internal calibration with 4 times dose for all size body phantoms, (b) internal calibration with 2 times dose for the small and medium size body phantoms, and (c) corrected external calibration with 4 times dose and all size body phantoms. Conclusions: Phantom studies are promising and demonstrate the potential to use dual energy quantitative CT to estimate the spatial distributions of red marrow and bone within the vertebral spongiosa. PMID:24784380

  4. Influence of total-body mass on the scaling of S-factors for patient-specific, blood-based red-marrow dosimetry

    NASA Astrophysics Data System (ADS)

    Traino, A. C.; Ferrari, M.; Cremonesi, M.; Stabin, M. G.

    2007-09-01

    To perform patient-specific, blood-based red-marrow dosimetry, dose conversion factors (the S factors in the MIRD formalism) have to be scaled by patients' organ masses. The dose to red marrow includes both self-dose and cross-irradiation contributions. Linear mass scaling for the self-irradiation term only is usually applied as a first approximation, whereas the cross-irradiation term is considered to be mass independent. Recently, the need of a mass scaling correction on both terms, not necessarily linear and dependent on the radionuclide, has been highlighted in the literature. S-factors taking into account different mass adjustments of organs are available in the OLINDA/EXM code. In this paper, a general algorithm able to fit the mass-dependent factors Srm<--tb and Srm<--rm is suggested and included in a more general equation for red-marrow dose calculation. Moreover, parameters to be considered specifically for therapeutic radionuclides such as 131I, 90Y and 177Lu are reported. The red-marrow doses calculated by the traditional and new algorithms are compared for 131I in ablation therapy (14 pts), 177Lu- (13 pts) and 90Y- (11 pts) peptide therapy for neuroendocrine tumours, and 90Y-Zevalin therapy for NHL (21 pts). The range of differences observed is as follows: -36% to -10% for 131I ablation, -22% to 5% for 177Lu-DOTATATE, -9% to 11% for 90Y-DOTATOC and -8% to 6% for 90Y-Zevalin. All differences are mostly due to the activity in the remainder of the body contributing to cross-irradiation. This paper quantifies the influence of mass scaling adjustment on usually applied therapies and shows how to derive the appropriate parameters for other radionuclides and radiopharmaceuticals.

  5. Bone-marrow transplant - series (image)

    MedlinePLUS

    Bone-marrow is a soft, fatty tissue found inside of bones that produces blood cells (red blood cells, ... Bone-marrow transplants are performed for: deficiencies in red blood cells (aplastic anemia) and white blood cells (leukemia ...

  6. Factors affecting the relationship between the red marrow dose and myelotoxicity in patients receiving radioimmunotherapy with {sup 131}I-labeled anti-CEA monoclonal antibodies

    SciTech Connect

    Juweid, M.; Behr, T.M.; Sharkey, R.M.

    1996-05-01

    This study examined the relationship between the red marrow dose (RMD) and myelotoxicity in patients with CEA-producing tumors who received radioimmunotherapy (RAIT) with {sup 131}I-NP-4 and MN-14 anti-CEA MAbs. Eligibility criteria included no chemotherapy in the last 4 weeks prior to RAIT, no X-irradiation (XT) to >25% of marrow, WBC >3,000, platelets > 100,000, and Hg > 10.0. The RMD was estimated based on blood by assuming a red marrow-to-blood activity concentration ratio of 1.0. Myelotoxicity was evaluated based on standard RTOG criteria. Leukopenia or thrombocytopenia {ge} grade 3 was considered dose-limiting toxicity (DLT). A total of 109 eligible patients were assessed for myelotoxicity. Overall, reversible DLT occurred in 0/14 (0%), 1/25 (4%), 4/26 (15%), 6/25 (24%), 5/9 (55%), 3/6 (50%), and 3/4 (75%) patients receiving a mean RMD of 75, 150, 250, 350, 450, 550, and 650 cGy, respectively. Patients were further stratified into those who had chemotherapy (CHT) in the last 1-6 months prior to RAIT, and/or had XT or tumor metastases to 11-25% of their marrow (group 1), and those who had no CHT in the last 6 months and/or XT or metastases to {ge} 10% of the marrow (group 2). At 250, 350, 450, and 550 cGy, the incidence of DLT in group 1 was 4/17 (23%), 5/11 (45%), 4/4 (100%), and 3/3 (100%), respectively, compared to 0/9 (0%), 1/14 (7%), 1/5 (20%), and 0/3 (0%) in group 2. In conclusion, these data indicate that recent CHT, XT, and marrow metastases are important factors determining myelotoxicity after RAIT. Further, the relatively low incidence of myelotoxicity in group 2 (1/8, 12/5%) DLT at a RMD of 450-550cGy suggests that these patients may be able to tolerate an almost 2-fold higher dose than those in group 1. Although further refinement in identifying risk-factors for myelotoxicity are necessary, these results provide important insights for future planning of phase II trials.

  7. Bone marrow reconversion - imaging of physiological changes in bone marrow.

    PubMed

    Ma?kiewicz, Agata; Dziedzic, Magdalena

    2012-10-01

    Reconversion of bone marrow is a reverse process of natural replacement of red marrow by yellow marrow. The occurrence of reconversion can be misleading and challenging in interpretation of musculoskeletal system imaging. Changes of signal intensity in bone marrow are frequently observed in radiological routine and its diversity can cause a suspicion of pathologic findings. Therefore, the knowledge about distribution of red and yellow bone marrow depending on age, concomitant diseases and presentation of the patient are essential for MR image interpretation. PMID:23269936

  8. Comparison of a restrictive versus liberal red cell transfusion policy for patients with myelodysplasia, aplastic anaemia, and other congenital bone marrow failure disorders

    PubMed Central

    Gu, Yisu; Estcourt, Lise J; Doree, Carolyn; Hopewell, Sally; Vyas, Paresh

    2015-01-01

    Background Bone marrow failure disorders include a heterogenous group of disorders, of which myelodysplastic syndrome (MDS), forms the largest subgroup. MDS is predominantly a disease of the elderly, with many elderly people managed conservatively with regular allogeneic red blood cell (RBC) transfusions to treat their anaemia. However, RBC transfusions are not without risk. Despite regular transfusions playing a central role in treating such patients, the optimal RBC transfusion strategy (restrictive versus liberal) is currently unclear. Objectives To assess the efficacy and safety of a restrictive versus liberal red blood cell transfusion strategy for patients with myelodysplasia, acquired aplastic anaemia, and other inherited bone marrow failure disorders. Search methods We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2015, Issue 4), Ovid MEDLINE (from 1946), Ovid EMBASE (from 1974), EBSCO CINAHL (from 1937), the Transfusion Evidence Library (from 1980) and ongoing trial databases to 26th May 2015. Selection criteria RCTs including patients with long-term bone marrow failure disorders that require allogeneic blood transfusion, who are not being actively treated with a haematopoietic stem cell transplant, or intensive chemotherapy. Data collection and analysis We used standard Cochrane review methodology. One author initially screened all references, and excluded any that were clearly irrelevant or duplicates. Two authors then independently screened all abstracts of articles, identified by the review search strategy, for relevancy. Two authors independently assessed the full text of all potentially relevant articles for eligibility, completed the data extraction and assessed the studies for risk of bias using The Cochrane Collaboration’s ’Risk of bias’ tool. Main results We included one trial (13 participants) and identified three ongoing trials that assess RBC transfusion strategies in people with MDS. The quality of the evidence was very low across different outcomes according to GRADE methodology. The one included study randomised participants to a restrictive [haemoglobin (Hb) transfusion trigger < 72 g/L, 8 participants] or liberal [Hb trigger < 96 g/L, 5 participants] transfusion policy. There was insufficient evidence to determine a difference in all-cause mortality (1 RCT; 13 participants; RR 0.13, 95% CI 0.01 to 2.32; very low quality evidence). There was insufficient evidence to determine a difference in the number of red blood cell transfusions (1 RCT; 13 participants; 1.8 units per patient per month in the liberal group, compared to 0.8 in the restrictive arm, no standard deviation was reported; very low quality evidence). There were no anaemia-related complications reported (cardiac failure) and no reported effect on activity levels (no statistics provided). The study did not report: mortality due to bleeding/infection/transfusion reactions or iron overload, quality of life, frequency and length of hospital admissions, serious infections (requiring admission to hospital), or serious bleeding (e.g. WHO/CTCAE grade 3 (or equivalent) or above). Authors’ conclusions This review indicates that there is currently a lack of evidence for the recommendation of a particular transfusion strategy for bone marrow failure patients undergoing supportive treatment only. The one RCT included in this review was only published as an abstract and contained only 13 participants. Further randomised trials with robust methodology are required to develop the optimal transfusion strategy for such patients, particularly as the incidence of the main group of bone marrow failure disorders, MDS, rises with an ageing population. PMID:26436602

  9. Comparison of mathematical models for red marrow and blood absorbed dose estimation in the radioiodine treatment of advanced differentiated thyroid carcinoma

    NASA Astrophysics Data System (ADS)

    Miranti, A.; Giostra, A.; Richetta, E.; Gino, E.; Pellerito, R. E.; Stasi, M.

    2015-02-01

    Metastatic and recurrent differentiated thyroid carcinoma is preferably treated with 131I, whose administered activity is limited by red marrow (RM) toxicity, originally correlated by Benua to a blood absorbed dose higher than 2?Gy. Afterward a variety of dosimetric approaches has been proposed. The aim of this work is to compare the results of the Benua formula with the ones of other three blood and RM absorbed dose formulae. Materials and methods have been borrowed by the dosimetric protocol of the Italian Internal Dosimetry group and adapted to the routine of our centre. Wilcoxon t-tests and percentage differences have been applied for comparison purposes. Results are significantly different (p < 0.05) from each other, with an average percentage difference between Benua versus other results of -22%. The dosimetric formula applied to determine blood or RM absorbed dose may contribute significantly to increase heterogeneity in absorbed dose and dose-response results. Standardization should be a major objective.

  10. Red blood cell production

    MedlinePLUS

    ... Red blood cells are formed in the red bone marrow of bones. Stem cells in the red bone marrow called hemocytoblasts give rise to all of ... in a centrifuge, the formed elements and fluid matrix of blood can be separated from each other. ...

  11. Bone marrow transplant

    MedlinePLUS

    Transplant - bone marrow; Stem cell transplant; Hematopoietic stem cell transplant; Reduced intensity, nonmyeloablative transplant; Mini transplant; Allogenic bone marrow transplant; Autologous bone marrow transplant; ...

  12. Bone marrow biopsy

    MedlinePLUS

    Biopsy - bone marrow ... A bone marrow biopsy may be done in the health care provider's office or in a hospital. The sample may be taken from the pelvic or breast bone. Sometimes, other areas are used. Marrow is removed ...

  13. Personalized estimation of dose to red bone marrow and the associated leukaemia risk attributable to pelvic kilo-voltage cone beam computed tomography scans in image-guided radiotherapy

    NASA Astrophysics Data System (ADS)

    Zhang, Yibao; Yan, Yulong; Nath, Ravinder; Bao, Shanglian; Deng, Jun

    2012-07-01

    The aim of this study is to investigate the imaging dose to red bone marrow (RBM) and the associated leukaemia risks attributable to pelvic kilo-voltage cone beam computed tomography (kVCBCT) scans in image-guided radiation therapy (IGRT). The RBM doses of 42 patients (age 2.7-86.4 years) were calculated using Monte Carlo simulations. The trabecular spongiosa was segmented to substitute RBM rather than the whole bone. Quantitative correlations between anthropometric variables such as age, physical bone density (PBD) and RBM dose were established. Personalized leukaemia risk was evaluated using an improved Boice model which included the age-associated RBM involvement. An incremental leukaemia risk of 29%-82% (mean = 45%) was found to be associated with 40 pelvic kVCBCT scans in the subject group used in a typical external beam radiation therapy course. Higher risks were observed in children. Due to the enhanced photoelectric effect in high atomic number materials, PBD was observed to strongly affect the RBM dose. Considerable overestimations (9%-42%, mean = 28%) were observed if the whole bone doses were used as surrogates of RBM doses. The personalized estimation of RBM dose and associated leukaemia risk caused by pelvic kVCBCT scans is clinically feasible with the proposed empirical models. Higher radiogenic cancer risks are associated with repeated kVCBCT scans in IGRT of cancer patients, especially children.

  14. Bone marrow transplant - discharge

    MedlinePLUS

    Transplant - bone marrow - discharge; Stem cell transplant - discharge; Hematopoietic stem cell transplant - discharge; Reduced intensity, non-myeloablative transplant - discharge; Mini transplant - discharge; Allogenic bone marrow transplant - ...

  15. Bone marrow dosimetry: Regional variability of marrow-localizing antibody

    SciTech Connect

    Sgouros, G.; Jureidini, I.M.; Scott, A.M.

    1996-04-01

    In radiolabeled antibody therapy, imaging and biopsy-based methods are used to estimate marrow activity concentration when the administered antibody localizes to the marrow. Absorbed dose estimates obtained using such measurements may be subject to large variability due to the potential for regional differences in marrow activity concentration. This variability was examined in ten patients with leukemia after administration of {sup 131}I-labeled HuM195 antibody. Regions of interest were drawn around the head and neck of the numerus and femur (both sides) and around lumbar vertebra 3 (L3) and 4 (L4) on a series of planar images collected at multiple times postadministration of the antibody. A single exponential fit to each attenuation-corrected, time-activity curve was obtained to estimate clearance half-life and the back-extrapolated percent injected activity. The activity concentration in the femoral head and neck (mean and s.d. = 0.04 {plus_minus} 0.02 %ID/g) was not significantly different than that measured in L3 and L4 (0.06 {plus_minus} 0.02% ID/g) but was significantly lower than the concentrations measure din the humeral head and neck regions (0.07 {plus_minus} 0.03 %ID/g, p {le} 0.05). Although half-life estimates differing by more than a factor of 2 were observed among different regions for individual patients, no systematic difference was observed in half-life between regions overall. S-factors were used for individual marrow regions to determine the mean absorbed dose to marrow in the femoral and humeral heads and the lumbar vertebrae (L3 and L4) which were 0.66 {plus_minus} 0.3, 1.0 {plus_minus} 0.3 and 2.2 {plus_minus} 0.5 mGy/MBq (2.4, 3.8 and 8.3 rad/mCi), respectively. A single value is generally quoted for the absorbed dose delivered to the red marrow following marrow-localizing radiolabeled antibody administration. These results suggest that the regional marrow dose may differ significantly from the mean. 32 refs., 5 figs., 1 tab.

  16. Use of Monte Carlo simulations with a realistic rat phantom for examining the correlation between hematopoietic system response and red marrow absorbed dose in Brown Norway rats undergoing radionuclide therapy with {sup 177}Lu- and {sup 90}Y-BR96 mAbs

    SciTech Connect

    Larsson, Erik; Ljungberg, Michael; Martensson, Linda; Nilsson, Rune; Tennvall, Jan; Strand, Sven-Erik; Joensson, Bo-Anders

    2012-07-15

    Purpose: Biokinetic and dosimetry studies in laboratory animals often precede clinical radionuclide therapies in humans. A reliable evaluation of therapeutic efficacy is essential and should be based on accurate dosimetry data from a realistic dosimetry model. The aim of this study was to develop an anatomically realistic dosimetry model for Brown Norway rats to calculate S factors for use in evaluating correlations between absorbed dose and biological effects in a preclinical therapy study. Methods: A realistic rat phantom (Roby) was used, which has some flexibility that allows for a redefinition of organ sizes. The phantom was modified to represent the anatomic geometry of a Brown Norway rat, which was used for Monte Carlo calculations of S factors. Kinetic data for radiolabeled BR96 monoclonal antibodies were used to calculate the absorbed dose. Biological data were gathered from an activity escalation study with {sup 90}Y- and {sup 177}Lu-labeled BR96 monoclonal antibodies, in which blood cell counts and bodyweight were examined up to 2 months follow-up after injection. Reductions in white blood cell and platelet counts and declines in bodyweight were quantified by four methods and compared to the calculated absorbed dose to the bone marrow or the total body. Results: A red marrow absorbed dose-dependent effect on hematological parameters was observed, which could be evaluated by a decrease in blood cell counts. The absorbed dose to the bone marrow, corresponding to the maximal tolerable activity that could safely be administered, was determined to 8.3 Gy for {sup 177}Lu and 12.5 Gy for {sup 90}Y. Conclusions: There was a clear correlation between the hematological effects, quantified with some of the studied parameters, and the calculated red marrow absorbed doses. The decline in body weight was stronger correlated to the total body absorbed dose, rather than the red marrow absorbed dose. Finally, when considering a constant activity concentration, the phantom weight, ranging from 225 g to 300 g, appeared to have no substantial effect for the estimated absorbed dose.

  17. Relationship of bone marrow type and microvasculature of the microdistribution and local dosimetry of plutonium in the adult skeleton. [Beagles

    SciTech Connect

    Smith, J.M.; Miller, S.C.; Jee, W.S.S.

    1984-08-01

    Most plutonium-induced bone tumors in beagles arise in trabecular bone sites surrounded by hematopoietic tissue. The microvasculature and the relative incorporation of /sup 241/Pu (a low energy ..beta.. emitter) on trabecular bone surfaces from red and fatty marrow sites were studied in the adult beagle. The vascular volume, as determined by India ink perfusion, was about 16% in the red marrow and about 2% in the fatty marrow. Plutonium concentrations on bone surfaces of red marrow sites are about 0.43 pCi/cm/sup 2//nCi/kg of injected dosage, a factor of eight greater than at fatty marrow sites. The differences in the bone marrow microvasculature between red and fatty marrow help to explain differences in plutonium incorporation and local bone physiology in these skeletal sites. These observations may relate to the nonuniform distribution of plutonium-induced osteosarcomas observed in adult, long-lived mammals.

  18. [Status of hemapoiesis in residents of the Techa riverside villages in the period of maximum radiation exposure. Report 2. Influence of exposure dose and dose rate of red bone marrow as well as modifying factors on the frequency of cytopenia and cytosis].

    PubMed

    Akleev, A V; Dimov, G P; Varfolomeeva, T A

    2012-01-01

    The purpose of this study is a retrospective estimation of the influence of dose and dose rate of the red bone marrow chronic radiation exposure in combination with various modifying factors (gender, age, comorbidity) on the frequency of deviations from normal values of the results of peripheral blood investigation in humans exposed on the Techa River. The results of investigation show that humans chronically exposed to radiation can develop marked changes in the cellular composition of peripheral blood characterized by a tendency to cytopenia (signs of the decompensation of hemopoiesis). The tendency to cytopenia can be identified earlier in the lymphoid germ, and later in platelet and erythroid lines. A high lability of granulocytes under the influence of various, often infectious, factors is the cause of the lack of statistically significant differences in terms of frequency of neutropenia. Several non-radiation factors (gender, age, health status) in combination with radiation exposure could have a modifying influence on hematopoiesis, which contributed to the disruption of adaptation processes and the development of conditions characterized by a tendency to cytopenias in exposed individuals. The red bone marrow dose rate reduction resulted in a gradual decrease in the frequency of erythrocytopenia, thrombocytopenia, neutropenia and lymphocytopenia in the group of exposed population. Increased frequencies of erythrocytosis, thrombocytosis, lymphocytosis, monocytosis and neutrophilia were observed when the median dose rate was reduced to the level of 0.024 Gy/year (in the year 1956), which could be regarded as activation of regenerative processes in hematopoiesis. PMID:22690575

  19. Bone marrow (stem cell) donation

    MedlinePLUS

    Bone marrow is the soft, fatty tissue inside your bones. Bone marrow contains stem cells, which are immature cells that ... lymphoma , and myeloma can be treated with a bone marrow transplant . This is now often called a stem ...

  20. Bone Marrow Diseases

    MedlinePLUS

    Bone marrow is the spongy tissue inside some of your bones, such as your hip and thigh bones. It contains stem cells. The stem cells can ... the platelets that help with blood clotting. With bone marrow disease, there are problems with the stem ...

  1. Bone Marrow Transplantation

    MedlinePLUS

    Bone marrow is the spongy tissue inside some of your bones, such as your hip and thigh bones. It contains immature cells, called stem cells. The ... platelets, which help the blood to clot. A bone marrow transplant is a procedure that replaces a ...

  2. Aspiration and Biopsy: Bone Marrow

    MedlinePLUS

    ... Bullies Pregnant? What to Expect Aspiration and Biopsy: Bone Marrow KidsHealth > Parents > Doctors & Hospitals > Medical Tests & Exams > Aspiration and Biopsy: Bone Marrow Print A A A Text Size What's in ...

  3. Aspiration and Biopsy: Bone Marrow

    MedlinePLUS

    ... Smart Snacking Losing Weight Safely Aspiration and Biopsy: Bone Marrow KidsHealth > Teens > Cancer Center > Diagnostic Tests > Aspiration and Biopsy: Bone Marrow Print A A A Text Size What's in ...

  4. Aspiration and Biopsy: Bone Marrow

    MedlinePLUS

    ... Help a Friend Who Cuts? Aspiration and Biopsy: Bone Marrow KidsHealth > For Teens > Aspiration and Biopsy: Bone Marrow Print A A A Text Size What's in ... Risks If You Have Questions What It Is Bone marrow aspirations and biopsies are performed to examine bone ...

  5. Overview of marrow transplantation

    SciTech Connect

    Thomas, E.D.

    1985-12-01

    Bone marrow transplantation is now an accepted form of therapy for many hematologic disorders including aplastic anemia, genetically determined diseases and malignant diseases, particularly leukemia, and for rescue of patients given intensive chemoradiotherapy for malignant disease. The donor may be a healthy identical twin, a family member or even an unrelated person. Selection is made on the basis of human leukocyte antigen tissue typing. Intensive chemoradiotherapy is used to suppress patients' immune systems to facilitate engraftment and destroy diseased marrow. Transfusion of platelets, erythrocytes and granulocytes (or all of these), antibiotic coverage and protection from infection are necessary during the pancytopenic period. Survival rates vary considerably depending on a patient's disease, clinical state and age. Patients with aplastic anemia transplanted early in the course of their disease have a survival rate of approximately 80%. Patients with acute lymphoblastic leukemia are usually transplanted in a second or subsequent remission and have a survival rate of 25% to 40%. Patients with acute nonlymphoblastic leukemia in remission have survivals ranging from 45% to 70%. More than 200 patients in the chronic phase of chronic granulocytic leukemia have been transplanted with survival ranging from 50% to 70%. Complications of marrow transplantation include marrow graft rejection, graft-versus-host disease, immunologic insufficiency and the possibility of recurrence of the leukemia. 14 references.

  6. Phase I/II study of Holmium-166-DOTMP for bone marrow ablation in multiple myeloma prior to bone marrow transplantation (BMT)

    SciTech Connect

    Podoloff, D.A.; Bhadkamkar, V.H.; Kasi, L.P.

    1994-05-01

    We evaluated a bone seeking radionuclide, Ho-166 DOTMP (which has both beta and gamma energies) as an agent for bone marrow ablation prior to bone marrow transplant. Six men and 1 woman in the age range 42-59 yrs. who had previously failed conventional chemotherapy using VAD (Vincristine, Adriamycin, Dexamethasone) were treated. Each patient received a diagnostic dose (Dx) of 30 mCi of Ho-166 DOTMP and underwent serial total body images using photopeak and scatter windows. Transmission images were obtained on day O. Transmission, scatter and photopeak images were used to calculate marrow dose and skeletal uptake. Therapy dose (Tx) was established to deliver a prescribed absorbed dose to the marrow. Bone marrow biopsy samples from lilac crest were obtained to determine activity concentration and to calculate marrow dose. The Dx was followed by a Tx of 25 Gy (3 pts.), 40 Gy (3 pts.) and 50 Gy (1 pt.). Additional total body imaging was accomplished prior to each Tx and SPECT after the final Tx. Bone retention varied from 26-33%. The calculated red marrow dose varied from 11 to 48 Gy. Toxicity was minimal and included: myalgia (1), nausea (2), increased BUN (1), sore throat (1), fever (1x1 day). Bone marrow ablation was achieved in 3/7 pts. The last pt. treated at the highest dose level had greater than 75% reduction in myeloma protein. We conclude that at doses as high as 31.8 mCi/Kg no significant toxicity has been observed. Diagnostic pretherapy imaging and derived dosimetry is helpful in prescribing a red marrow dose prior to radionuclide therapy. The MTD has not yet been reached. However, thus far Ho-166 DOTMP has safely ablated bone marrow prior to BMT.

  7. Autoimmune Lymphoproliferative Syndrome with Red Cell Aplasia.

    PubMed

    Meena, K R; Bisht, Supriya; Tamaria, K C

    2015-12-01

    Autoimmune Lymphoproliferative Syndrome (ALPS) is a rare inherited disorder of abnormal lymphocyte apoptosis, leading to chronic lymphoproliferation. It presents as lymphadenopathy, hepatosplenomegaly and autoimmune phenomena. Pure red cell aplasia is characterized by normochromic normocytic anemia, reticulocytopenia, and absence of erythroblasts from a normal bone marrow. Only few lymphoproliferative disorders have been associated with erythroid aplasia. The authors are reporting a case of ALPS associated with red cell aplasia in a 7-y-old girl. PMID:25972287

  8. Blood and Marrow Stem Cell Transplant

    MedlinePLUS

    ... on Twitter. What Is a Blood and Marrow Stem Cell Transplant? A blood and marrow stem cell transplant ... NEXT >> Updated: November 15, 2011 Blood and Marrow Stem Cell Transplant in the News May 19, 2015 New ...

  9. Red Clover

    MedlinePLUS

    ... common names, what the science says, potential side effects and cautions, and resources for more information. Like peas and beans, red clover belongs to the family of plants called legumes. Red clover contains phytoestrogens—compounds similar ...

  10. Red clover

    MedlinePLUS

    ... have protein S deficiency. Surgery: Red clover might slow blood clotting. It might increase the chance of extra bleeding ... Talk with your health provider.Medications that slow blood clotting (Anticoagulant / Antiplatelet drugs)Large amounts of red clover ...

  11. Fat cotent of ectopic marrow implants and cellularity of resulting ossicles. [Rabbits

    SciTech Connect

    Maloney, M.A.; Flannery, M.L.; Patt, H.M.

    1980-11-01

    The capacity of marrow stroma to transfer a microenvironment conducive to hematopoiesis was studied in rabbits by means of subcutaneous implants of autologous marrow with variable hematopoietic cellularity and fat content as determined by histologic analysis. Cellularity of marrow in ossicles present at the implantation site 3 months later was found to be sigmoidally related to cellularity of the implant. Hypocellular marrow with fat content in excess of 50% was associated with onset of a sharp increase in saturated lipids as revealed by histochemistry. These results, which confirm and extend earlier qualitative observations of a difference in potential of red and yellow marrow upon ectopic implantation, are consistent with the putative regulatory role of stromal elements in hematopoiesis.

  12. High-fidelity organic preservation of bone marrow in ca. 10 Ma amphibians

    NASA Astrophysics Data System (ADS)

    McNamara, Maria E.; Orr, Patrick J.; Kearns, Stuart L.; Alcal, Luis; Anadn, Pere; Pealver-Moll, Enrique

    2006-08-01

    Bone marrow in ca. 10 Ma frogs and salamanders from the Miocene of Libros, Spain, represents the first fossilized example of this extremely decay-prone tissue. The bone marrow, preserved in three dimensions as an organic residue, retains the original texture and red and yellow color of hematopoietic and fatty marrow, respectively; moldic osteoclasts and vascular structures are also present. We attribute exceptional preservation of the fossilized bone marrow to cryptic preservation: the bones of the amphibians formed protective microenvironments, and inhibited microbial infiltration. Specimens in which bone marrow is preserved vary in their completeness and articulation and in the extent to which the body outline is preserved as a thin film of organically preserved bacteria. Cryptic preservation of these labile tissues is thus to a large extent independent of, and cannot be predicted by, the taphonomic history of the remainder of the specimen.

  13. Red clover

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Red clover (Trifolium pratense L.) is an important forage legume grown on approximately 4 million hectares worldwide. An estimated 2.8 million kg of red clover seed per year was produced worldwide in 2005-2007. This amount of seed would be enough to maintain approximately 4 million hectares of red...

  14. KSC CENTER DIRECTOR ACCEPTS PLAQUE FOR RECORD-SETTING BONE MARROW DONOR REGISTRATION DRIVE

    NASA Technical Reports Server (NTRS)

    1996-01-01

    Kennedy Space Center's Bone Marrow Donor Registration Drive Chairman Dr. George A. Martin and Center Director Jay Honeycutt (left to right) accept a plaque from the Leukemia Society of America's Associate Executive Director Martin Bernstine and the American Red Cross' Southeast Regional Director Jeff Koenreich. Representatives from the American Red Cross and the Leukemia Society of America came to KSC to honor those involved in the record-setting Bone Marrow Donor Registration Drive held here earlier this year. Over 900 potential donors were added to the National Bone Marrow Registry as a result of the KSC drive. The drive established a new record for the most people registered in a single day for the American Red Cross in the three state region of which Florida is a part.

  15. Bone-marrow imaging with indium-111 chloride in aplastic anemia and myelofibrosis: concise communication

    SciTech Connect

    Sayle, B.A.; Helmer, R.E.; Birdsong, B.A.; Balachandran, S.; Gardner, F.H.

    1982-02-01

    Twenty-nine patients with aplastic anemia and 11 patients with myelofibrosis were evaluated with indium-111 chloride bone-marrow imaging, ferrokinetics, and bone-marrow core biopsies. There was good correlation between the erythrocyte cellularity of the marrow and the In-111 bone-marrow scan grades in most patients. In some, the overall scan grade tended to underestimate the erythroid elements because the core biopsy had been taken from the area of the greatest radionuclide concentration on the scan. In patients with aplastic anemia, there was good correlation between the plasma iron clearance t1/2 and the scan grade. Less agreement was found in the comparison between the Fe-59 sacral and organ counts and the red-cell iron utilization. In patients with myelofibrosis, there was poor correlation between the surface counts over the sacrum and the red-cell iron utilization. Plasma iron clearances were abnormally short and were unrelated to the transferrin saturation levels. Eighteen patients were studied several times to evaluate their responses to steroid therapy. In all, there was good correlation between the bone-marrow imaging, the erythrocyte cellularity, ferrokinetics, and the patient's response to therapy. Indium-111 bone-marrow imaging is useful both in evaluating marrow erythroid activity and in following the response to therapy in patients with these diseases.

  16. Effect of syngeneic marrow injection upon recovery in sub- and near-lethally irradiated mice

    SciTech Connect

    Boggs, S.S.; Boggs, D.R.; Patrene, K.D.

    1989-06-01

    Mice were given sub-lethal (200-600 cGy) or near-lethal (800 cGy) whole body irradiation and the effect of injecting syngeneic marrow on subsequent hematopoietic recovery was studied. Marrow cell injection enhanced erythropoietic recovery after sub-lethal irradiation as reflected in hematocrit values and rate of appearance of /sup 59/Fe-labeled red cells in blood. However, this enhanced erythropoiesis was only seen in the spleen, and /sup 59/Fe uptake in marrow was reduced. When the irradiation dose was kept constant and the marrow dose increased from 10(5) to 10(6) to 10(7) cells, there was a somewhat erratic increase in spleen /sup 59/Fe and a decrease in marrow /sup 59/Fe uptake. When marrow cell number was kept constant and the dose of irradiation was increased from 200 to 400 to 600 to 800 cGy, there was an exponential increase in spleen /sup 59/Fe uptake but the marrow /sup 59/Fe uptake changed from depressed after lower doses to increased after 800 cGy. Cell injection after sub-lethal irradiation did not increase or decrease granulocytopoiesis. Injection of irradiated marrow cells also reduced marrow erythropoiesis and this was evident after both sub- and near-lethal irradiation. However, injection of irradiated cells did not increase splenic erythropoiesis. Following splenectomy, the depressed marrow erythropoiesis attending injection of viable cells was virtually eliminated but no increase was seen. These data suggest that the injection of autologous or syngeneic marrow may not be effective as a means of accelerating hematopoietic recovery after irradiation unless near-lethal or lethal dose have been received.

  17. High-gradient magnetic separation in blood and bone marrow processing

    NASA Astrophysics Data System (ADS)

    Roath, S.; Smith, A. Richards; Watson, J. H. P.

    1990-04-01

    High-gradient magnetic separation (HGMS) has been succesful in capturing red blood cells from whole blood. This is due to the paramagnetic property of the haemoglobin contained in red blood cells when it is in the deoxygenated state. The captured red blood cells and the processed white blood cells and platelets appear to be functionally undamaged by separation. The capture depends on field gradient, flow rate, dilution of the blood, size of filter and a number of other factors. Malarial parasite-containing red cells have been captured using this technique and elsewhere lymphocyte/red cell rosettes have been retained in the filter of a system using a field gradient produced by a superconducting magnet. The ex vivo processing of human bone marrow is currently under study. Removal of targetted cells from bone marrow, such as tumour cells or T-lymphocytes prior to reinfusion is currently practiced. Positive cell rescue, however, is not practicable as the present techniques mostly damage the targetted cells. We are applying high-gradient magnetic separation, using an antibody complex linked to the surface of red blood cells, which should recognise target cells within bone marrow. The whole complex is then liable to retention in a sufficiently high-gradient magnetic field and the target cell made available by red-blood-cell lysis.

  18. Bone marrow granulomas in mononucleosis.

    PubMed Central

    Fiala, M.; Colodro, I.; Talbert, W.; Ellis, R.; Chatterjee, S.

    1987-01-01

    Two patients with mononucleosis, one due to cytomegalovirus (CMV), and the other due to Epstein-Barr virus (EBV), presenting with high fever, malaise and hepatitis, had granulomas in the bone marrow but not in the liver. In patients who have unexplained fever, bone marrow granulomas may be a clue to CMV or EBV infection and need not initially raise the fear of prognostically more severe illness. Images Figure 1 Figure 2 PMID:2825152

  19. Internal dose to active marrow and endosteum from radioactive iodine.

    PubMed

    Hoseinian-Azghadi, E; Rafat-Motavalli, L; Miri-Hakimabad, H

    2015-04-01

    This study analyses the active marrow and endosteum dose differences between the new International Commission on Radiological Protection (ICRP) male and female reference computational phantoms and the stylised phantom for two thyroid agents. The active marrow and endosteum doses from (131)I and (123)I were calculated for 0-55 % maximum thyroid uptakes using the MCNP-4C Monte Carlo code. The biokinetic models were taken from ICRP Publication 53. To evaluate the absorbed doses to red marrow and endosteum, the deposited energy was determined for the 19 spongiosa regions and 6 medullary cavities and was mass weighted using the mass fractions available in ICRP Publication 116. The results were then compared with the published values given in ICRP Publication 53. The poor anatomic realism of the stylised phantom used in ICRP Publication 53 leads to important dose differences between the ICRP voxel phantoms and the stylised phantom. The influence of the use of different bone material was also investigated. Underestimations of ∼60% were observed for active marrow doses of the stylised phantom compared with reference voxel phantoms. The results highlight the importance of the accuracy of the shape and inter-organ distances of the anthropomorphic model used. PMID:25157198

  20. Functional hyposplenism following allogeneic bone marrow transplantation.

    PubMed Central

    Cuthbert, R J; Iqbal, A; Gates, A; Toghill, P J; Russell, N H

    1995-01-01

    AIMS--To investigate the incidence of functional hyposplenism in a group of patients who had undergone allogeneic bone marrow transplantation (BMT). METHODS--Splenic function was assessed by counting the number of gluteraldehyde fixed red blood cells containing pits or indentations as examined by interference phase microscopy. Normal values are < 2% whereas splenectomy patients have values of 25 to 40%. RESULTS--Twenty eight BMT recipients (17 men, 11 women) were studied at varying periods post-transplant and the results compared with 20 healthy volunteers and 10 patients who had undergone splenectomy or had splenic atrophy because of haematological conditions. Of the 28 BMT recipients, one had undergone a prior splenectomy; of the remaining 27 patients, four (15%) had evidence of functional hyposplenism with between 5.0 and 34.0% pitted cells. Of these four patients, one had active extensive chronic graft versus host disease (GvHD) which has been previously reported to be associated with functional hyposplenism following transplantation. Only one of the four patients had peripheral blood red cell changes typical of hyposplenism. CONCLUSION--These results confirm that extensive chronic GvHD is associated with hyposplenism. Intermediate degrees of functional hyposplenism may also occur following BMT in the absence of chronic GvHD and in the absence of haematological features of hyposplenism on routine blood films. This may be of significance in mediating the susceptibility to infection with encapsulating bacteria seen following allogeneic BMT. PMID:7730489

  1. Fragment filtration: a method for the accurate determination of flow cytometric kinetic data from bone marrow aspirates

    SciTech Connect

    Zbroja, R.A.; Wass, J.; Vincent, P.C.; Young, G.A.

    1986-02-01

    The extent to which bone marrow obtained by conventional aspiration is contaminated by peripheral blood has been confirmed and quantitated. In marrow aspirates from normal subjects the median percentage of nucleated cells that had originated from the peripheral blood was 32% (range 2.5%-64%), in patients with acute leukemia 23% (range 0.5%-96.5%), in patients with chronic leukemia 59% (range 17%-76%), and in patients with lymphoma 31% (range 0.5%-74%). Flow cytometric (FCM) DNA analysis of conventional marrow aspirates from a range of subjects significantly underestimated the proportions of S-phase cells present, when compared with results from trephines obtained at the same time. Having shown, using 51Cr-labeled red cells in mice, that circulating red cells do not reenter the marrow parenchyma, a mathematical correction for contaminating blood similar to that described by Holdrinet et al. was devised. This correction improved the S-phase cell estimate from aspirated marrows, and the corrected values were not significantly different from values from paired trephine samples. A previously described technique for collecting fragments by filtration of aspirated marrow has been adapted for FCM analysis as a more direct way of overcoming problems due to blood contamination. This method was shown to yield estimates of S-phase cells not significantly different from those in paired marrow trephines and offers an alternative to routine trephine biopsies for FCM analysis of marrow cell kinetics.

  2. Red blood cell decreases of microgravity

    NASA Technical Reports Server (NTRS)

    Johnson, P. C.

    1985-01-01

    Postflight decreases in red blood cell mass (RBCM) have regularly been recorded after exposure to microgravity. These 5-25 percent decreases do not relate to the mission duration, workload, caloric intake or to the type of spacecraft used. The decrease is accompanied by normal red cell survivals, increased ferritin levels, normal radioactive iron studies, and increases in mean red blood cell volume. Comparable decreases in red blood cell mass are not found after bed rest, a commonly used simulation of the microgravity state. Inhibited bone marrow erythropoiesis has not been proven to date, although reticulocyte numbers in the peripheral circulation are decreased about 50 percent. To date, the cause of the microgravity induced decreases in RBCM is unknown. Increased splenic trapping of circulating red blood cells seem the most logical way to explain the results obtained.

  3. Evaluation of the invivo genotoxicity of Allura Red AC (Food Red No. 40).

    PubMed

    Honma, Masamitsu

    2015-10-01

    Allura Red AC (Food Red No. 40) is a red azo dye that is used for food coloring in beverage and confectionary products. However, its genotoxic properties remain controversial. To clarify the in vivo genotoxicity, we treated mice with Allura Red AC and investigated the induction of DNA damage (liver, glandular stomach), clastogenicity/anuegenicity (bone marrow), and mutagenicity (liver, glandular stomach) using Comet assays, micronucleus tests, and transgenic gene mutation assays, respectively. All studies were conducted in accordance with the Organization for Economic Co-operation and Development (OECD) guideline. Although Allura Red AC was administered up to the maximum doses recommended by the OECD guideline, no genotoxic effect was observed in any of the genotoxic endpoints. These data clearly show no evidence of in vivo genotoxic potential of Allura Red AC administered up to the maximum doses in mice. PMID:26364875

  4. Red Sky with Red Mesa

    ScienceCinema

    None

    2014-06-23

    The Red Sky/Red Mesa supercomputing platform dramatically reduces the time required to simulate complex fuel models, from 4-6 months to just 4 weeks, allowing researchers to accelerate the pace at which they can address these complex problems. Its speed also reduces the need for laboratory and field testing, allowing for energy reduction far beyond data center walls.

  5. Red Sky with Red Mesa

    SciTech Connect

    2011-04-14

    The Red Sky/Red Mesa supercomputing platform dramatically reduces the time required to simulate complex fuel models, from 4-6 months to just 4 weeks, allowing researchers to accelerate the pace at which they can address these complex problems. Its speed also reduces the need for laboratory and field testing, allowing for energy reduction far beyond data center walls.

  6. Mechanics of intact bone marrow.

    PubMed

    Jansen, Lauren E; Birch, Nathan P; Schiffman, Jessica D; Crosby, Alfred J; Peyton, Shelly R

    2015-10-01

    The current knowledge of bone marrow mechanics is limited to its viscous properties, neglecting the elastic contribution of the extracellular matrix. To get a more complete view of the mechanics of marrow, we characterized intact yellow porcine bone marrow using three different, but complementary techniques: rheology, indentation, and cavitation. Our analysis shows that bone marrow is elastic, and has a large amount of intra- and inter-sample heterogeneity, with an effective Young?s modulus ranging from 0.25 to 24.7 kPa at physiological temperature. Each testing method was consistent across matched tissue samples, and each provided unique benefits depending on user needs. We recommend bulk rheology to capture the effects of temperature on tissue elasticity and moduli, indentation for quantifying local tissue heterogeneity, and cavitation rheology for mitigating destructive sample preparation. We anticipate the knowledge of bone marrow elastic properties for building in vitro models will elucidate mechanisms involved in disease progression and regenerative medicine. PMID:26189198

  7. A stochastic model of radiation-induced bone marrow damage

    SciTech Connect

    Cotlet, G.; Blue, T.E.

    2000-03-01

    A stochastic model, based on consensus principles from radiation biology, is used to estimate bone-marrow stem cell pool survival (CFU-S and stroma cells) after irradiation. The dose response model consists of three coupled first order linear differential equations which quantitatively describe time dependent cellular damage, repair, and killing of red bone marrow cells. This system of differential equations is solved analytically through the use of a matrix approach for continuous and fractionated irradiations. The analytic solutions are confirmed through the dynamical solution of the model equations using SIMULINK. Rate coefficients describing the cellular processes of radiation damage and repair, extrapolated to humans from animal data sets and adjusted for neutron-gamma mixed fields, are employed in a SIMULINK analysis of criticality accidents. The results show that, for the time structures which may occur in criticality accidents, cell survival is established mainly by the average dose and dose rate.

  8. The distribution of Thorotrast in human bone marrow: a case report.

    PubMed

    Priest, N D; Humphreys, J A; Kathren, R L; Mays, C W

    1992-07-01

    Samples of bone containing cellular and fatty bone marrow were removed at autopsy from the body of a woman who, following an automobile accident, had been injected with approximately 25 mL of the radiographic contrast medium Thorotrast. The woman survived for 36 y after the accident and died at age 72 y following bone marrow failure. The samples were analyzed to determine their thorium content by x-ray fluorescence and by image analysis. In addition, Thorotrast was visualized in the different bones examined by light microscopy and by backscattered electron imaging with a scanning electron microscope. The results showed Thorotrast to be largely restricted to areas of cellular bone marrow. In such regions, Thorotrast was present throughout the marrow tissue and was also concentrated within cells that were commonly aggregated within focalized areas of the marrow. Overall the results suggest a rather uniform pattern of Thorotrast uptake by the red bone marrow at different skeletal sites. Significant deposits of Thorotrast were not found in fatty yellow marrow. We conclude that Thorotrast-derived risk estimates for human leukemia following high LET, alpha irradiation may be used for calculating the risks of alpha exposure, but with caution. PMID:1522010

  9. Red yeast

    MedlinePLUS

    ... cholesterol levels and triglycerides. However, this specific product contains large amounts of a chemical similar to "statin" ... this product and other red yeast products that contain statins to be illegal unapproved drugs. However, outside ...

  10. Red Sea

    Atmospheric Science Data Center

    2013-04-16

    ... and is surrounded by hot, dry deserts and steppes. More fish species (over 1000) live in the Red Sea than in any other body of water the same size. Data: August 13, 2000; MISR Level 1B2 Ellipsoid ...

  11. Inherited bone marrow failure syndromes.

    PubMed

    Okuno, Yusuke

    2016-01-01

    Inherited bone marrow failure syndromes comprise a series of disorders caused by various gene mutations. Genetic tests were formerly difficult to perform because of the large size and number of causative genes. However, recent advances in next-generation sequencing has enabled simultaneous testing of all causative genes to be performed at an acceptable cost. We collaboratively conducted a series of whole-exome sequencing studies of patients with inherited bone marrow failure syndromes and discovered RPS27/RPL27 and FANCT as causative genes of Diamond-Blackfan anemia and Fanconi anemia, respectively. Furthermore, we established a target gene sequencing system to cover 189 genes associated with pediatric blood diseases to assist genetic diagnoses in clinical practice. In this review, discovery of new causative genes and possible roles of next-generation sequencing in the genetic diagnosis of inherited bone marrow failure syndromes are discussed. PMID:26935625

  12. Bone marrow processing and cryopreservation.

    PubMed

    Linch, D C; Knott, L J; Patterson, K G; Cowan, D A; Harper, P G

    1982-02-01

    Three different closed procedures for concentrating bone marrow progenitor cells prior to cryopreservation have been compared. These were by a manual double centrifugation method, a Hemonetics 30 cell separator and an Aminco Celltrifuge. The best results were achieved using the paediatric pheresis set on the Hemonetics model 30. Marrow was frozen in 120 ml aliquots in a programmed freezer with rapid cooling of the freezing chamber during the phase change from the liquid to the solid state. After freeze-thawing the average nucleated cell recovery was approximately 50% and the progenitor cell recovery 80%. PMID:7068909

  13. Bone marrow and splenic histology in hairy cell leukaemia.

    PubMed

    Wotherspoon, Andrew; Attygalle, Ayoma; Mendes, Larissa Sena Teixeira

    2015-12-01

    Hairy cell leukaemia is a rare chronic neoplastic B-cell lymphoproliferation that characteristically involves blood, bone marrow and spleen with liver, lymph node and skin less commonly involved. Histologically, the cells have a characteristic appearance with pale/clear cytoplasm and round or reniform nuclei. In the spleen, the infiltrate involves the red pulp and is frequently associated with areas of haemorrhage (blood lakes). The cells stain for B-cell related antigens as well as with antibodies against tartrate-resistant acid phosphatase, DBA44 (CD72), CD11c, CD25, CD103, CD123, cyclin D1 and annexin A1. Mutation of BRAF -V600E is present and antibody to the mutant protein can be used as a specific marker. Bone marrow biopsy is essential in the initial assessment of disease as the bone marrow may be inaspirable or unrepresentative of degree of marrow infiltration as a result of the tumour associated fibrosis preventing aspiration of the tumour cell component. Bone marrow biopsy is important in the assessment of therapy response but in this context staining for CD11c and Annexin A1 is not helpful as they are also markers of myeloid lineage and identification of low level infiltration may be obscured. In this context staining for CD20 may be used in conjunction with morphological assessment and staining of serial sections for cyclin D1 and DBA44 to identify subtle residual infiltration. Staining for CD79a and CD19 is not recommended as these antibodies will identify plasma cells and can lead to over-estimation of disease. Staining for CD20 should not be used in patients following with anti-CD20 based treatments. Down regulation of cyclin D1 and CD25 has been reported in patients following BRAF inhibitor therapy and assessment of these antigens should not be used in this context. Histologically, hairy cell leukaemia needs to be distinguished from other B-cell lymphoproliferations associated with splenomegaly including splenic marginal zone lymphoma, splenic diffuse red pulp small B-cell lymphoma and hairy cell leukaemia variant. This can be done by assessment of the spleen but as this is now rarely performed in this disorder distinction is almost always possible by a combination of morphological and immunophenotypic studies on bone marrow trephine biopsy, which can be supplemented by assessment of BRAF-V600E mutation assessment in borderline cases. PMID:26614898

  14. Blood volume and red cell life span (M113), part C

    NASA Technical Reports Server (NTRS)

    Johnson, P. C., Jr.

    1973-01-01

    Prechamber, in-chamber, and postchamber blood samples taken from Skylab simulation crewmembers did not indicate significant shortening of the red cell life span during the mission. This does not suggest that the space simulation environment could not be associated with red cell enzyme changes. It does show that any changes in enzymes were not sufficiently great to significantly shorten red cell survival. There was no evidence of bone marrow erythropoetic suppression nor was there any evidence of increased red cell destruction.

  15. Transplant Outcomes (Bone Marrow and Cord Blood)

    MedlinePLUS

    ... reports show patient survival and transplant data of bone marrow and umbilical cord blood transplants in the transplant ... Data by Center Report —View the number of bone marrow and cord blood transplants performed at a specific ...

  16. Planning for a Bone Marrow Transplant (BMT)

    MedlinePLUS

    ... us Digg Facebook Google Bookmarks Planning for a Bone Marrow Transplant (BMT) When a bone marrow transplant (also called a BMT) or umbilical cord ... to a friend or family member undergoing a bone marrow or cord blood transplant. Help Your Loved One ...

  17. A bone marrow toxicity model for 223Ra alpha-emitter radiopharmaceutical therapy

    NASA Astrophysics Data System (ADS)

    Hobbs, Robert F.; Song, Hong; Watchman, Christopher J.; Bolch, Wesley E.; Aksnes, Anne-Kirsti; Ramdahl, Thomas; Flux, Glenn D.; Sgouros, George

    2012-05-01

    Ra-223, an ?-particle emitting bone-seeking radionuclide, has recently been used in clinical trials for osseous metastases of prostate cancer. We investigated the relationship between absorbed fraction-based red marrow dosimetry and cell level-dosimetry using a model that accounts for the expected localization of this agent relative to marrow cavity architecture. We show that cell level-based dosimetry is essential to understanding potential marrow toxicity. The GEANT4 software package was used to create simple spheres representing marrow cavities. Ra-223 was positioned on the trabecular bone surface or in the endosteal layer and simulated for decay, along with the descendants. The interior of the sphere was divided into cell-size voxels and the energy was collected in each voxel and interpreted as dose cell histograms. The average absorbed dose values and absorbed fractions were also calculated in order to compare those results with previously published values. The absorbed dose was predominantly deposited near the trabecular surface. The dose cell histogram results were used to plot the percentage of cells that received a potentially toxic absorbed dose (2 or 4 Gy) as a function of the average absorbed dose over the marrow cavity. The results show (1) a heterogeneous distribution of cellular absorbed dose, strongly dependent on the position of the cell within the marrow cavity; and (2) that increasing the average marrow cavity absorbed dose, or equivalently, increasing the administered activity resulted in only a small increase in potential marrow toxicity (i.e. the number of cells receiving more than 4 or 2 Gy), for a range of average marrow cavity absorbed doses from 1 to 20 Gy. The results from the trabecular model differ markedly from a standard absorbed fraction method while presenting comparable average dose values. These suggest that increasing the amount of radioactivity may not substantially increase the risk of toxicity, a result unavailable to the absorbed fraction method of dose calculation.

  18. A bone marrow toxicity model for 223Ra alpha-emitter radiopharmaceutical therapy

    PubMed Central

    Hobbs, Robert F; Song, Hong; Watchman, Christopher J; Bolch, Wesley E; Aksnes, Anne-Kirsti; Ramdahl, Thomas; Flux, Glenn D; Sgouros, George

    2012-01-01

    Purpose Ra-223, an ?-particle emitting bone-seeking radionuclide, has recently been used in clinical trials for osseous metasteses of prostate cancer. We investigated the relationship between absorbed fraction-based red marrow dosimetry and cell level-dosimetry using a model that accounts for the expected localization of this agent relative to marrow cavity architecture. We show that cell level-based dosimetry is essential to understanding potential marrow toxicity. Methods The GEANT4 software package was used to create simple spheres representing marrow cavities. Ra-223 was positioned on the trabecular bone surface or in the endosteal layer and simulated for decay, along with the descendants. The interior of the sphere was divided into cell-size voxels and the energy was collected in each voxel and interpreted as dose cell histograms. The average absorbed dose values and absorbed fractions were also calculated in order to compare those results with previously published values. Results The absorbed dose was predominantly deposited near the trabecular surface. The dose cell histograms results were used to plot the percentage of cells that received a potentially toxic absorbed dose (2 or 4 Gy) as a function of the average absorbed dose over the marrow cavity. The results show (1) a heterogeneous distribution of cellular absorbed dose, strongly dependent on the position of the cell within the marrow cavity; and (2) that increasing the average marrow cavity absorbed dose, or equivalently, increasing the administered activity resulted in only a small increase in potential marrow toxicity (i.e., the number of cells receiving more than 4 or 2 Gy), for a range of average marrow cavity absorbed doses from 1 Gy to 20 Gy. Conclusion The results from the trabecular model differ markedly from a standard absorbed fraction method while presenting comparable average dose values. These suggest that increasing the amount of radioactivity may not substantially increase the risk of toxicity, a result unavailable to the absorbed fraction method of dose calculation. PMID:22546715

  19. Neocytolysis: physiological down-regulator of red-cell mass

    NASA Technical Reports Server (NTRS)

    Alfrey, C. P.; Rice, L.; Udden, M. M.; Driscoll, T. B.

    1997-01-01

    It is usually considered that red-cell mass is controlled by erythropoietin-driven bone marrow red-cell production, and no physiological mechanisms can shorten survival of circulating red cells. In adapting to acute plethora in microgravity, astronauts' red-cell mass falls too rapidly to be explained by diminished red-cell production. Ferrokinetics show no early decline in erythropolesis, but red cells radiolabelled 12 days before launch survive normally. Selective destruction of the youngest circulating red cells-a process we call neocytolysis-is the only plausible explanation. A fall in erythropoietin below a threshold is likely to initiate neocytolysis, probably by influencing surface-adhesion molecules. Recognition of neocytolysis will require re-examination of the pathophysiology and treatment of several blood disorders, including the anaemia of renal disease.

  20. Bone marrow necrosis in acute leukemia.

    PubMed

    Navari, R M; Carter, J; Hillman, R S

    1983-01-01

    2 patients with premortem marrow necrosis in acute leukemia are discussed. A review of the course of each patient plus those in the literature suggests that premortem marrow necrosis may not be a poor prognostic sign in acute lymphoblastic leukemia but generally precedes a prolonged and fatal pancytopenia in acute myelogenous leukemia. The technetium-99m rhenium sulfur colloid marrow scan was found to be of value in assessing the extent and degree of necrosis of the marrow as well as in documenting and predicting marrow recovery following chemotherapy. PMID:6404098

  1. Bone marrow and the control of immunity

    PubMed Central

    Zhao, Ende; Xu, Huanbin; Wang, Lin; Kryczek, Ilona; Wu, Ke; Hu, Yu; Wang, Guobin; Zou, Weiping

    2012-01-01

    Bone marrow is thought to be a primary hematopoietic organ. However, accumulated evidences demonstrate that active function and trafficking of immune cells, including regulatory T cells, conventional T cells, B cells, dendritic cells, natural killer T (NKT) cells, neutrophils, myeloid-derived suppressor cells and mesenchymal stem cells, are observed in the bone marrow. Furthermore, bone marrow is a predetermined metastatic location for multiple human tumors. In this review, we discuss the immune network in the bone marrow. We suggest that bone marrow is an immune regulatory organ capable of fine tuning immunity and may be a potential therapeutic target for immunotherapy and immune vaccination. PMID:22020068

  2. [Bone Marrow Microenvironment and Myelodysplastic Syndromes].

    PubMed

    Zhang, Gao-Chao; Wang, Hua-Quan; Shao, Zong-Hong

    2016-02-01

    Myelodysplastic syndromes (MDS) are a group of bone marrow failure diseases. The bone marrow microenvironment consists of bone marrow stromal cells (BMSC), growth factors and cytokines. The BMSC supporting haemopoiesis include mesenchymal stem cells (MSC), osteoblasts, endothelial cells and macrophages, but the adipocytes play a role in the suppression of hematopoiesis. Recently more and more researches indicate that the abnormality of bone marrow microenvironment involves in the pathogenesis and progression of MDS. In this review the abnormality of MDS bone marrow microenvironment is summarized briefly. PMID:26913439

  3. Cellular complexity of the bone marrow hematopoietic stem cell niche.

    PubMed

    Calvi, Laura M; Link, Daniel C

    2014-01-01

    The skeleton serves as the principal site for hematopoiesis in adult terrestrial vertebrates. The function of the hematopoietic system is to maintain homeostatic levels of all circulating blood cells, including myeloid cells, lymphoid cells, red blood cells, and platelets. This action requires the daily production of more than 500billion blood cells. The vast majority of these cells are synthesized in the bone marrow, where they arise from a limited number of hematopoietic stem cells (HSCs) that are multipotent and capable of extensive self-renewal. These attributes of HSCs are best demonstrated by marrow transplantation, where even a single HSC can repopulate the entire hematopoietic system. HSCs are therefore adult stem cells capable of multilineage repopulation, poised between cell fate choices which include quiescence, self-renewal, differentiation, and apoptosis. While HSC fate choices are in part determined by multiple stochastic fluctuations of cell autonomous processes, according to the niche hypothesis, signals from the microenvironment are also likely to determine stem cell fate. While it had long been postulated that signals within the bone marrow could provide regulation of hematopoietic cells, it is only in the past decade that advances in flow cytometry and genetic models have allowed for a deeper understanding of the microenvironmental regulation of HSCs. In this review, we will highlight the cellular regulatory components of the HSC niche. PMID:24101231

  4. Cellular complexity of the bone marrow hematopoietic stem cell niche

    PubMed Central

    Calvi, Laura M.; Link, Daniel C.

    2013-01-01

    The skeleton serves as the principal site for hematopoiesis in adult terrestrial vertebrates. The function of the hematopoietic system is to maintain homeostatic levels of all circulating blood cells, including myeloid cells, lymphoid cells, red blood cells, and platelets. This action requires the daily production of more than 500 billion blood cells every day. The vast majority of these cells are synthesized in the bone marrow, where they arise from a limited number of hematopoietic stem cells (HSCs) that are multipotent and capable of extensive self-renewal. These attributes of HSCs are best demonstrated by marrow transplantation, where even a single HSC can repopulate the entire hematopoietic system. HSCs are therefore adult stem cells capable of multilineage repopulation, poised between cell fate choices, which include quiescence, self-renewal, differentiation and apoptosis. While HSC fate choices are in part determined by multiple stochastic fluctuations of cell autonomous processes, according to the niche hypothesis, signals from the microenvironment are also likely to determine stem cell fate. While it had long been postulated that signals within the bone marrow could provide regulation of hematopoietic cells, it is only in the past decade that advances in flow cytometry and genetic models have allowed for a deeper understanding of microenvironmental regulation of HSCs. In this review, we will highlight the cellular regulatory components of the HSC niche. PMID:24101231

  5. Baby marrow: ethicists and privacy.

    PubMed Central

    Zucker, A

    1992-01-01

    A family had a child in large part to use its marrow in the hopes of saving the life of an older child afflicted with leukaemia. Public response from medical ethicists was negative. This paper argues that what the family did was not clearly wrong and that the ethicists should not have made public pronouncements calling the morals of the family into question. PMID:1404278

  6. Immune transfer studies in canine allogeneic marrow graft donor-recipient pairs

    SciTech Connect

    Grosse-Wilde, H.; Krumbacher, K.; Schuening, F.D.; Doxiadis, I.; Mahmoud, H.K.; Emde, C.; Schmidt-Weinmar, A.; Schaefer, U.W.

    1986-07-01

    Transfer of immunity occurring with bone marrow grafting was studied using the dog as a preclinical model. Allogeneic bone marrow transplantation (BMT) was performed between DLA-identical beagle litter-mates. The donors were immunized with tetanus toxoid (TT) or sheep red blood cells (SRBC), and their humoral response was monitored by hemagglutination. The recipients of bone marrow from TT-immunized donors showed a marked increase of antibody titer one week posttransplantation, while in the recipients of marrow from SRBC immunized donors the antibody titers were considerably lower. Within the following 60 days the antibody titers in both groups diminished gradually to pregrafting levels. Control experiments in which cell-free plasma from donors immunized with TT and SRBC respectively was transfused indicated that the initial rise of specific antibody titers after marrow grafting is likely to be due to a passive transfer of humoral immunity. A single challenge of these marrow graft recipients with the respective antigen 15-18 weeks posttransplantation led to a secondary type of humoral immune response. It could be demonstrated that transfer of memory against TT or SRBC was independent from the actual antibody titer and the time of vaccination of the donor. One dog was immunized with TT after serving as marrow donor. When the donor had shown an antibody response, a peripheral blood leukocytes (PBL) transfusion was given to his chimera. Subsequent challenge of the latter resulted in a secondary type of specific antibody response. This indicates that specific cellular-bound immunological memory can be transferred after BMT from the donor to his allogeneic bone marrow chimera by transfusion of peripheral blood leukocytes. The data may be of importance in clinical BMT to protect patients during the phase of reduced immune reactivity by transfer of memory cells.

  7. Bone Marrow Therapies for Chronic Heart Disease.

    PubMed

    Behbahan, Iman Saramipoor; Keating, Armand; Gale, Robert Peter

    2015-11-01

    Chronic heart failure is a leading cause of death. The demand for new therapies and the potential regenerative capacity of bone marrow-derived cells has led to numerous clinical trials. We critically discuss current knowledge of the biology and clinical application of bone marrow cells. It appears unlikely that bone marrow cells can develop into functional cardiomyocyte after infusion but may have favorable paracrine effects. Most, but not all, clinical trials report a modest short- but not long-term benefit of infusing bone marrow-derived cells. Effect size appears to correlate with stringency of study-design: the most stringent trials report the smallest effect-sizes. We conclude there may be short- but not substantial long-term benefit of infusing bone marrow-derived cells into persons with chronic heart failure and any benefit observed is unlikely to result from trans-differentiation of bone marrow-derived cells into functioning cardiomyocytes. PMID:26086629

  8. Cure of murine thalassemia by bone marrow transplantation without eradication of endogenous stem cells

    SciTech Connect

    Wagemaker, G.; Visser, T.P.; van Bekkum, D.W.

    1986-09-01

    alpha-Thalassemic heterozygous (Hbath/+) mice were used to investigate the possible selective advantage of transplanted normal (+/+) hemopoietic cells. Without conditioning by total-body irradiation (TBI), infusion of large numbers of normal bone marrow cells failed to correct the thalassemic peripheral blood phenotype. Since the recipients' stem cells are normal with respect to number and differentiation capacity, it was thought that the transplanted stem cells were not able to lodge, or that they were not stimulated to proliferate. Therefore, a nonlethal dose of TBI was given to temporarily reduce endogenous stem cell numbers and hemopoiesis. TBI doses of 2 or 3 Gy followed by infusion of normal bone marrow cells proved to be effective in replacing the thalassemic red cells by normal red cells, whereas a dose of 1 Gy was ineffective. It is concluded that cure of thalassemia by bone marrow transplantation does not necessarily require eradication of thalassemic stem cells. Consequently, the objectives of conditioning regimens for bone marrow transplantation of thalassemic patients (and possibly other nonmalignant hemopoietic disorders) should be reconsidered.

  9. Adult 'fetal-like' erythropoiesis characterizes recovery from bone marrow transplantation.

    PubMed

    Weinberg, R S; Schofield, J M; Lenes, A L; Brochstein, J; Alter, B P

    1986-07-01

    The transient fetal-like erythropoiesis which appears during recovery from bone marrow transplantation has now been examined at the level of erythroid progenitor cells. A 7-year-old boy with beta +-thalassaemia major was studied during engraftment from his beta-thalassaemia trait sister. Hb F and i antigen rose as expected. Macrocytosis never developed, but red cell size distribution became very heterogeneous. Bone marrow CFU-E and BFU-E were detected by 30 d, prior to the appearance of reticulocytes. Marrow erythroid progenitor cell numbers were normal by 146 d, while those in the blood became normal by 360 d. After transplantation globin synthesis ratios in erythroid colonies were diagnostic of thalassaemia trait, indicating engraftment. Individual erythroid colonies derived from both blood and marrow at all times during reconstitution showed no correlation of G gamma and gamma. Thus the fetal-like stress erythropoiesis of marrow expansion following transplantation was derived from adult and not fetal progenitor cells. PMID:3524655

  10. Inherited Bone Marrow Failure Syndromes (IBMFS)

    Cancer.gov

    The NCI IBMFS Cohort Study consists of affected individuals and their immediate families in North America who have an inherited bone marrow failure syndrome (IBMFS)-either one that has been specifically identified and defined, or bone marrow failure that appears to be inherited but has not yet been clearly identified as having a genetic basis.

  11. Differential diagnoses of bone marrow granuloma.

    PubMed Central

    Eid, A; Carion, W; Nystrom, J S

    1996-01-01

    The finding of a granuloma on a bone marrow biopsy is not common. The etiologic spectrum encompasses a wide variety of disorders. We present the case of a young woman with a bone marrow granuloma and discuss the differential diagnosis, emphasizing the most common causes. This disorder can be associated with serious diseases. Images Figure 1. Figure 2. PMID:8764626

  12. Bone marrow necrosis complicating chronic myeloid leukaemia.

    PubMed

    Macheta, A T; Cinkotai, K I; Love, E M; Geary, C G; Liu Yin, J A

    1991-01-01

    Two women with chronic myeloid leukaemia in chronic phase were found to have bone marrow necrosis when severe bone pains and falling blood counts prompted a marrow examination to exclude blast transformation. One patient survived for 12 months following the event without transforming. The second patient died soon after and was found to have widespread extramedullary disease. PMID:1934927

  13. Question of bone marrow stromal fibroblast traffic

    SciTech Connect

    Maloney, M.A.; Lamela, R.A.; Patt, H.M.

    1985-01-01

    Bone marrow stromal fibroblasts (CFU-F) normally do not exchange bone marrow sites in vivo. Restitution of the CFU-F after radiation damage is primarily recovery by the local fibroblasts from potentially lethal damage. Migration of stromal fibroblasts from shielded sites to an irradiated site makes a minimal contribution, if any, to CFU-F recovery. Determination of the relative contribution of donor stromal cells in bone marrow transplants by karyotyping the proliferating bone marrow stromal cells in vitro may not reflect the relative distribution of fibroblasts in the marrow. If there is residual damage to the host stromal fibroblasts from treatment before transplantation, these cells may not be able to proliferate in vitro. Therefore, an occasional transplanted fibroblast may contribute most of the metaphase figures scored for karyotype.

  14. Performance of a gravitational marrow separator, multidirectional bone marrow aspiration needle, and repeated bone marrow collections on the production of concentrated bone marrow and separation of mesenchymal stem cells in horses.

    PubMed

    Ishihara, Akikazu; Helbig, Holly J; Sanchez-Hodge, Rebekah B; Wellman, Maxey L; Landrigan, Matthew D; Bertone, Alicia L

    2013-06-01

    Objective-To determine the efficiency of a novel point-of-care gravitational marrow separator and bone marrow aspiration needle for concentrated bone marrow production and bone marrow-derived mesenchymal stem cell (MSC) separation and assess the effect of repeated bone marrow collections in horses. Animals-8 healthy adult horses. Procedures-Bone marrow aspiration was performed twice (1 month apart) from sternebral bodies with a standard or prototype multidirectional needle. Concentrated bone marrow was obtained by gravitational marrow separation and evaluated for WBC and platelet counts, automated and cytomorphologic cell differential counts, MSCs, and cell viability. Results-Concentrated bone marrow samples obtained with the marrow separator had 5- to 19-fold bone marrow-derived MSC, WBC, and platelet counts, compared with original bone marrow samples. Use of a multidirectional needle increased the frequency of obtaining MSC-richer concentrated bone marrow. Repeating bone marrow aspiration at 1 month yielded greater MSC numbers but slightly lower cell viability after processing. Conclusions and Clinical Relevance-The gravitational bone marrow separator and multidirectional needle were used to effectively harvest bone marrow and improve the quality of concentrated bone marrow. Comparable, or even greater, numbers of bone marrow-derived MSCs were collected by repeated bone marrow aspiration after a 1-month interval from the same aspiration sites. Use of the marrow separator and multidirectional bone marrow aspiration needle can facilitate a 1-step, point-of-care, nonlaboratory method to obtain concentrated bone marrow as a mixture of bone marrow-derived MSCs and growth factors from platelets and plasma. PMID:23718653

  15. Seeing Red

    NASA Technical Reports Server (NTRS)

    2008-01-01

    This New Horizons image of Jupiter's volcanic moon Io was taken at 13:05 Universal Time during the spacecraft's Jupiter flyby on February 28, 2007. It shows the reddish color of the deposits from the giant volcanic eruption at the volcano Tvashtar, near the top of the sunlit crescent, as well as the bluish plume itself and the orange glow of the hot lava at its source. The relatively unprocessed image on the left provides the best view of the volcanic glow and the plume deposits, while the version on the right has been brightened to show the much fainter plume, and the Jupiter-lit night side of Io.

    New Horizons' color imaging of Io's sunlit side was generally overexposed because the spacecraft's color camera, the super-sensitive Multispectral Visible Imaging Camera (MVIC), was designed for the much dimmer illumination at Pluto. However, two of MVIC's four color filters, the blue and 'methane' filter (a special filter designed to map methane frost on the surface of Pluto at an infrared wavelength of 0.89 microns), are less sensitive than the others, and thus obtained some well-exposed views of the surface when illumination conditions were favorable. Because only two color filters are used, rather than the usual three, and because one filter uses infrared light, the color is only a rough approximation to what the human eye would see.

    The red color of the Tvashtar plume fallout is typical of Io's largest volcanic plumes, including the previous eruption of Tvashtar seen by the Galileo and Cassini spacecraft in 2000, and the long-lived Pele plume on the opposite side of Io. The color likely results from the creation of reddish three-atom and four-atom sulfur molecules (S3 and S4) from plume gases rich in two-atom sulfur molecules (S2 After a few months or years, the S3 and S4 molecules recombine into the more stable and familiar yellowish form of sulfur consisting of eight-atom molecules (S8), so these red deposits are only seen around recently-active Io volcanos. Though the plume deposits are red, the plume itself is blue, because it is composed of very tiny particles that preferentially scatter blue light, like smoke. Also faintly visible in the left image is the pale-colored Prometheus plume, almost on the edge of the disk on the equator at the 9 o'clock position.

    Io was 2.4 million kilometers from the spacecraft when the picture was taken, and the center of Io's disk is at 77 degrees West longitude, 5 degrees South latitude. The solar phase angle was 107 degrees.

  16. Rosiglitazone Promotes Bone Marrow Adipogenesis to Impair Myelopoiesis under Stress

    PubMed Central

    Lu, Wenyi; Wang, Weimin; Wang, Shujuan; Feng, Yonghuai; Liu, Kaiyan

    2016-01-01

    Objective The therapeutic use of thiazolidinediones (TZDs) causes unwanted hematological side effects, although the underlying mechanisms of these effects are poorly understood. This study tests the hypothesis that rosiglitazone impairs the maintenance and differentiation of hematopoietic stem/progenitor cells, which ultimately leads to hematological abnormalities. Methods Mice were fed a rosiglitazone-supplemented diet or a normal diet for 6 weeks. To induce hematopoietic stress, all mice were injected once with 250 mg/kg 5-fluorouracil (5-Fu) intraperitoneally. Next, hematopoietic recovery, hematopoietic stem/progenitor cells (HSPCs) subsets, and myeloid differentiation after 5-Fu treatment were evaluated. The adipogenesis induced by rosiglitazone was assessed by histopathology and oil red O staining. The effect of adipocytes on HSPCs was studied with an in vitro co-culture system. Results Rosiglitazone significantly enhanced bone marrow adipogenesis and delayed hematopoietic recovery after 5-Fu treatment. Moreover, rosiglitazone inhibited proliferation of a granulocyte/monocyte progenitor (GMP) cell population and granulocyte/macrophage colony-stimulating factor (GM-CSF) colonies, although the proliferation and mobilization of Lin-c-kit+Sca-1+ cells (LSK) was maintained following hematopoietic stress. These effects could be partially reversed by the selective PPARγ antagonist BADGE. Finally, we demonstrated in a co-culture system that differentiated adipocytes actively suppressed the myeloid differentiation of HSPCs. Conclusion Taken together, our results demonstrate that rosiglitazone inhibits myeloid differentiation of HSPCs after stress partially by inducing bone marrow adipogenesis. Targeting the bone marrow microenvironment might be one mechanism by which rosiglitazone impairs stress-induced hematopoiesis. PMID:26895498

  17. Analyzing the cellular contribution of bone marrow to fracture healing using bone marrow transplantation in mice

    SciTech Connect

    Colnot, C. . E-mail: colnotc@orthosurg.ucsf.edu; Huang, S.; Helms, J.

    2006-11-24

    The bone marrow is believed to play important roles during fracture healing such as providing progenitor cells for inflammation, matrix remodeling, and cartilage and bone formation. Given the complex nature of bone repair, it remains difficult to distinguish the contributions of various cell types. Here we describe a mouse model based on bone marrow transplantation and genetic labeling to track cells originating from bone marrow during fracture healing. Following lethal irradiation and engraftment of bone marrow expressing the LacZ transgene constitutively, wild type mice underwent tibial fracture. Donor bone marrow-derived cells, which originated from the hematopoietic compartment, did not participate in the chondrogenic and osteogenic lineages during fracture healing. Instead, the donor bone marrow contributed to inflammatory and bone resorbing cells. This model can be exploited in the future to investigate the role of inflammation and matrix remodeling during bone repair, independent from osteogenesis and chondrogenesis.

  18. Inherited Bone Marrow Failure Syndromes (IBMFS)

    Cancer.gov

    A study of inherited bone marrow failure syndromes (IBMFS), a group of rare genetic blood disorders that include Fanconi Anemia, Dyskeratosis Congenita, Diamond-Blackfan Anemia, Shwachman-Diamond Syndrome, Severe Congenital Neutropenia, Amegakaryocytic Thrombocytopenia, and Thrombocytopenia Absent Radii.

  19. Induction of marrow hypoxia by radioprotective agents

    SciTech Connect

    Allalunis-Turner, M.J.; Walden, T.L.; Sawich, C.

    1989-01-01

    Many compounds that possess sulfhydryl groups have been shown to protect bone marrow from radiation injury. The most effective thiol radioprotective agent is ethiofos (S-2-(3-aminopropylamino)ethylphosphorothoic acid or WR-2721). The ability of thiol and non-thiol radioprotectors to induce hypoxia was determined using binding of ({sup 3}H)misonidazole by bone marrow cells as a measure of hypoxia. When administered at maximally radioprotective doses, four drugs (WR-2721, cysteamine, 5-hydroxytryptamine, and 16,16-dimethyl prostaglandin E2) significantly increased the amount of ({sup 3}H)misonidazole bound by marrow cells, while no significant increase in binding was observed with three other agents (endotoxin, AET, superoxide dimutase). Doses of WR-2721 previously shown to provide suboptimal radioprotection did not significantly increase {sup 3}H-misonidazole binding. These results suggest that the physiological effects of some radioprotectors, that is, their ability to induce marrow hypoxia, may contribute to their efficacy in vivo.

  20. Bone and bone marrow involvement in sarcoidosis.

    PubMed

    Yachoui, Ralph; Parker, Brian J; Nguyen, Thanhcuong T

    2015-11-01

    Bone and bone marrow involvement in sarcoidosis have been infrequently reported. We aimed to describe the clinical features, radiological descriptions, pathological examinations, and outcomes of three patients with osseous sarcoidosis and one patient with bone marrow sarcoidosis seen at our institution. Our case series included fluorodeoxyglucose positron emission tomography descriptions in assessing the whole-body extent of sarcoidosis. In the era of advanced imaging, large bone and axial skeleton sarcoidosis lesions are more common than previously reported. PMID:26248533

  1. Bone Marrow and Fetal Liver Radiation Chimeras.

    PubMed

    Flomerfelt, Francis A; Gress, Ronald E

    2016-01-01

    Radiation chimeras are prepared by subjecting recipient mice to sublethal or lethal dose of irradiation and injecting them with hematopoietic stem cells (HSC) from untreated donor mice. HSC can be obtained from bone marrow or fetal liver. This technique is a powerful tool when coupled with gene targeting strategies to investigate function of HSCs, thymocyte development, and T cell function. This protocol describes how to produce bone marrow or fetal liver chimeras. PMID:26294402

  2. MRI of bone marrow abnormalities in hematological malignancies.

    PubMed

    Silva, Jose Roberto; Hayashi, Daichi; Yonenaga, Takenori; Fukuda, Kunihiko; Genant, Harry K; Lin, Chieh; Rahmouni, Alain; Guermazi, Ali

    2013-01-01

    Magnetic resonance imaging (MRI) is essential for evaluating bone marrow. Bone marrow undergoes constant modification and its appearance on MRI changes in response. Knowledge of the types of changes and their origins is essential for analysis of MRI findings of bone marrow infiltration with hematological malignancies. This pictorial review describes the MRI pulse sequences used for imaging of bone marrow, and illustrates bone marrow changes due hematological malignancies, including changes following treatment. PMID:23748035

  3. The bone marrow aspirate and biopsy in the diagnosis of unsuspected nonhematologic malignancy: A clinical study of 19 cases

    PubMed Central

    Ozkalemkas, Fahir; Ali, R?dvan; Ozkocaman, Vildan; Ozcelik, Tulay; Ozan, Ulku; Ozturk, Hulya; Kurt, Ender; Evrensel, Turkkan; Yerci, Omer; Tunali, Ahmet

    2005-01-01

    Background Although bone marrow metastases can be found commonly in some malignant tumors, diagnosing a nonhematologic malignancy from marrow is not a usual event. Methods To underscore the value of bone marrow aspiration and biopsy as a short cut in establishing a diagnosis for disseminated tumors, we reviewed 19 patients with nonhematologic malignancies who initially had diagnosis from bone marrow. Results The main indications for bone marrow examination were microangiopathic hemolytic anemia (MAHA), leukoerythroblastosis (LEB) and unexplained cytopenias. Bone marrow aspiration was not diagnostic due to dry tap or inadequate material in 6 cases. Biopsy results were parallel to the cytological ones in all cases except one; however a meticulous second examination of the biopsy confirmed the cytologic diagnosis in this patient too. The most common histologic subtype was adenocarcinoma, and after all the clinical and laboratory evaluations, the primary focus was disclosed definitively in ten patients (5 stomach, 3 prostate, 1 lung, 1 muscle) and probably in four patients (3 gastrointestinal tract, 1 lung). All work up failed in five patients and these cases were classified as tumor of unknown origin (TUO). Conclusion Our series showed that anemia, thrombocytopenia, elevated red cell distribution width (RDW) and hypoproteinemia formed a uniform tetrad in patients with disseminated tumors that were diagnosed via bone marrow examination. The prognosis of patients was very poor and survivals were only a few days or weeks (except for 4 patients whose survivals were longer). We concluded that MAHA, LEB and unexplained cytopenias are strong indicators of the necessity of bone marrow examination. Because of the very short survival of many patients, all investigational procedures should be judged in view of their rationality, and should be focused on treatable primary tumors. PMID:16262899

  4. Computerized quantification of bone tissue and marrow in stained microscopic images.

    PubMed

    Shi, Lin; Liu, Shangping; Wang, Defeng; Wong, Hing-Lok; Huang, Wen-Hua; Wang, Yi-Xiang J; Griffith, James F; Leung, Ping-Chung; Ahuja, Anil T

    2012-10-01

    Stained histological images assist physicians to identify different types of tissues or cells and their architectures. They can be applied on the diagnosis of various diseases and the assessment of treatment effects. Osteoporosis is an aging disease that reduces the density of bones and increases the risk of bone fracture. Literatures indicate that osteoporosis is associated with the ratio of trabecular bone tissues and bone marrow cells, and bones in osteoporosis patients consist of a significantly higher marrow fat content. Interactive segmentation of bone tissue and different types of bone marrow cells in high-resolution histological images, however, is a very tedious and labor-intensive process. The aim of this study is to develop an automatic algorithm to quantify the areas of different tissues such as the trabecular bones and yellow and red marrow cells. This image segmentation method consists of a series of mathematical morphological operation steps based on both the color and morphology features of tissues and was implemented in Matlab. The results obtained from the proposed method have been verified by comparing with those obtained interactively from an experienced histotechnician (Pearson correlation coefficient > 0.94, P < 0.001). The result suggests that the proposed algorithm can effectively assist physicians to quantify stained bone histological images. PMID:22899564

  5. Calcitriol modulates the effects of bone marrow-derived mesenchymal stem cells on macrophage functions

    PubMed Central

    Motlagh, Bahman Mansouri; Ahangaran, Nahideh Afzale; Froushani, Seyyed Meysam Abtahi

    2015-01-01

    Objective(s): Some evidence showed that calcitriol has an important role in regulating growth and differentiation of mesenchymal stem cells (MSCs). However, the interaction between mesenchymal stem cells and macrophage is not clear yet. The current study was done to investigate the in vitro effects of calcitriol on the interactions between bone marrow-derived MSCs and rat macrophages. Materials and Methods: MSCs were isolated from rat bone marrow and pulsed with different concentrations of calcitriol (50, 100 and 200 nanomolar) for 24, 48 and 72 hr. Then, mesenchymal stem cells were co-cultured with macrophages for 4 hr. Finally, macrophages were evaluated for ability to uptake neutral red, phagocytosis activity against opsonized yeast, respiratory burst and viability. Results: Our data showed that bone marrow-derived MSCs pulsed with calcitriol may cause a significant increase in uptake of neutral red and phagocytic activity of opsonized heat killed bakers yeast. Moreover, treatment of MSCs with calcitriol enhanced macrophage viability. Nevertheless, the respiratory burst of macrophages was significantly reduced in macrophages co-cultured with calcitriol-treated MSCs compared to control group. Conclusion: Calcitriol may accelerate and potentiate anti-inflammatory M2 macrophage polarization by MSCs. PMID:26351558

  6. Tracking mouse bone marrow monocytes in vivo.

    PubMed

    Hamon, Pauline; Rodero, Mathieu Paul; Combadire, Christophe; Boissonnas, Alexandre

    2015-01-01

    Real time multiphoton imaging provides a great opportunity to study cell trafficking and cell-to-cell interactions in their physiological 3-dimensionnal environment. Biological activities of immune cells mainly rely on their motility capacities. Blood monocytes have short half-life in the bloodstream; they originate in the bone marrow and are constitutively released from it. In inflammatory condition, this process is enhanced, leading to blood monocytosis and subsequent infiltration of the peripheral inflammatory tissues. Identifying the biomechanical events controlling monocyte trafficking from the bone marrow towards the vascular network is an important step to understand monocyte physiopathological relevance. We performed in vivo time-lapse imaging by two-photon microscopy of the skull bone marrow of the Csf1r-Gal4VP16/UAS-ECFP (MacBlue) mouse. The MacBlue mouse expresses the fluorescent reporters enhanced cyan fluorescent protein (ECFP) under the control of a myeloid specific promoter, in combination with vascular network labelling. We describe how this approach enables the tracking of individual medullar monocytes in real time to further quantify the migratory behaviour within the bone marrow parenchyma and the vasculature, as well as cell-to-cell interactions. This approach provides novel insights into the biology of the bone marrow monocyte subsets and allows to further address how these cells can be influenced in specific pathological conditions. PMID:25867540

  7. Abnormal bone marrow histopathology in paediatric mastocytosis.

    PubMed

    Carter, Melody C; Metcalfe, Dean D; Clark, Alicia S; Wayne, Alan S; Maric, Irina

    2015-03-01

    The diagnostic criteria for paediatric mastocytosis are largely based on adult studies and bone marrow findings are not well described in children. We evaluated use of the World Health Organization (WHO) criteria for the diagnosis of systemic disease in paediatric mastocytosis. In addition, we identified unique clinico-histopathological features within the biopsies. One hundred and thirteen children with paediatric mastocytosis were evaluated at the National Institutes of Health between 1986 and 2013. Complete bone marrow evaluations were performed in 50 cases. Seven children had repeat procedures. Bone marrows were analysed by histopathology, flow cytometry and for KIT D816V. Bone marrow biopsies displayed mild atypical haematopoietic maturation, increased haematogones and hypocellularity in a sub-set of patients with urticaria pigmentosa, diffuse cutaneous mastocytosis and indolent systemic mastocytosis. Hypocellularity was most pronounced in those with urticaria pigmentosa. Haematogones were highest, on average, in patients with diffuse cutaneous mastocytosis or mastocytomas. There was no evidence of peripheral blood cytopenias, myelodysplastic syndrome, myeloproliferative neoplasm or leukaemia within this cohort. The WHO criteria are applicable for the diagnosis of systemic mastocytosis in paediatrics. Although unsuspected bone marrow findings typically seen in myeloproliferative disorders are frequent in paediatric mastocytosis, patients within this study remained clinically stable without progression to a more aggressive variant. PMID:25429914

  8. Hyperuricemia and bone marrow transplantation.

    PubMed

    Deliliers, Giorgio Lambertenghi; Annaloro, Claudio

    2005-01-01

    Blood uric acid levels and purine metabolism are affected in many ways after bone marrow transplantation (BMT). Although BMT is usually performed when patients have a low residual disease burden, a proportion of them are still at risk of tumor lysis syndrome, even with limited disease or after nonmyeloablative conditioning regimens; moreover, an alteration in uric acid turnover can also be observed in patients with persistently normal uric acid blood levels. Apart from this obvious complication, multiple physiopathological events occurring after transplantation may derange uric acid homeostasis. Although there is only indirect evidence (derived from obstetric eclampsia and experimental gout arthritis), a transplant-related increase in cytokine production (particularly TNF, IL-1 and IL-6) may activate xanthine oxidase which, in turn, may be responsible for a further cytokine bout: deranged cytokine homeostasis is involved in the pathogenesis of some of the main acute post-BMT complications, such as hepatic veno-occlusive disease (VOD) and acute graft-versus-host disease (aGVHD). Hyperuricemia is also a well-known side effect of cyclosporine A, the reference drug for the prevention of post-BMT GVHD, which may affect uric acid turnover by reducing glomerular filtration and/or affecting tubular handling; the available evidence favors the former explanation. Hyperuricemia is found in long-term transplanted patients as part of a metabolic pattern reminiscent of the so-called 'X' or 'metabolic'syndrome related to insulin resistance: there is still no precise interpretation of this post-transplant complication nor any definite data concerning its real incidence and outcome. Hyperuricemia is frequently regarded as a marginal finding in the context of X syndrome, but it is pathogenetically linked to the other component of the syndrome and has proved to be autonomously responsible for tissue and vessel damage. Finally, BMT is a possible therapeutic strategy for some inherited forms of hyperuricemia, particularly Lesch- Nyhan disease, although there is still some perplexity concerning the possibility of preventing the development of neurological impairment. PMID:15604610

  9. Induction of marrow hypoxia by radioprotective agents

    SciTech Connect

    Allalunis-Turner, M.J.; Walden, T.L. Jr.; Sawich, C.

    1989-06-01

    The ability of thiol and non-thiol radioprotectors to induce hypoxia was determined using the binding of (/sup 3/H)misonidazole by bone marrow cells as a measure of hypoxia. When administered at maximally radioprotective doses, four drugs (WR-2721, cysteamine, 5-hydroxytryptamine, and 16,16-dimethyl prostaglandin E2) significantly increased the amount of (/sup 3/H)misonidazole bound by marrow cells, while no significant increase in binding was observed with three other agents (endotoxin, AET, superoxide dimutase). Doses of WR-2721 previously shown to provide suboptimal radioprotection did not significantly increase /sup 3/H-misonidazole binding. These results suggest that the physiological effects of some radioprotectors, that is, their ability to induce marrow hypoxia, may contribute to their efficacy in vivo.

  10. Treatment with a sclerostin antibody increases cancellous bone formation and bone mass regardless of marrow composition in adult female rats.

    PubMed

    Tian, XiaoYan; Setterberg, Rebecca B; Li, Xiaodong; Paszty, Chris; Ke, Hua Zhu; Jee, Webster S S

    2010-09-01

    The current report describes the skeletal effects of a sclerostin monoclonal antibody (Scl-AbIII) treatment at a yellow (fatty) marrow skeletal site in adult female rats. Ten-month-old female Sprague-Dawley rats were treated with vehicle or Scl-AbIII at 5 or 25 mg/kg, twice per week by s.c. injection for 4 weeks. Trabecular bone from a yellow (fatty) marrow site, the 5th caudal vertebral body (CVB), was processed undecalcified for quantitative bone histomorphometric analysis. Compared to vehicle controls, Scl-AbIII at both doses significantly increased bone formation parameters and trabecular bone volume and thickness and decreased bone resorption parameter in the trabecular bone of the CVB. As a reference, we also found that the Scl-AbIII at both doses significantly decreased bone resorption and increased bone formation and bone volume in a red (hematopoietic) marrow site, the 4th lumber vertebral body (LVB). It appears that the percentage of increase in trabecular bone volume induced by Scl-AbIII treatment was slightly larger in the LVB than in the CVB. In summary, these preclinical findings show that antibody-mediated sclerostin inhibition has significant bone anabolic effects at both red and yellow marrow skeletal sites. PMID:20561907

  11. Cell survival kinetics in peripheral blood and bone marrow during total body irradiation for marrow transplantation

    SciTech Connect

    Shank, B.; Andreeff, M.; Li, D.

    1983-11-01

    Cell survival kinetics in both peripheral blood and in bone marrow have been studied over the time course of hyperfractionated total body irradiation (TBI) for bone marrow transplantation. Our unique TBI regimen allows the study of the in vivo radiation effect uncomplicated by prior cyclophosphamide, since this agent is given after TBI in our cytoreduction scheme. Peripheral blood cell concentrations were monitored with conventional laboratory cell counts and differentials. Absolute bone marrow cell concentrations were monitored by measuring cell concentrations in an aspirate sample and correcting for dilution with blood by a cell cycle kinetic method using cytofluorometry. For lymphocytes in peripheral blood in patients in remission, the effective D/sub 0/ ranged from 373 rad in 10 children less than or equal to 10 y old, to 536 rad in the four patients between 11 to 17 y old, while n = 1.0 in all groups. There was no trend observed according to age. Granulocytes had a much higher effective D/sub 0/, approximately 1000 rad in vivo. Absolute nucleated cell concentration in marrow dropped slowly initially, due to an increased lymphocyte concentration in marrow during a concurrent drop in lymphocyte concentration in peripheral blood, but eventually fell on the last day of TBI ranging from 7 to 44% of the initial marrow nucleated cell concentration. Marrow myeloid elements, however, dropped continuously throughout the course of TBI.

  12. Bone Marrow Stress Decreases Osteogenic Progenitors.

    PubMed

    Ng, Adeline H; Baht, Gurpreet S; Alman, Benjamin A; Grynpas, Marc D

    2015-11-01

    Age-related bone loss may be a result of declining levels of stem cells in the bone marrow. Using the Col2.3?tk (DTK) transgenic mouse, osteoblast depletion was used as a source of marrow stress in order to investigate the effects of aging on osteogenic progenitors which reside in the marrow space. Five-month-old DTK mice were treated with one or two cycles of ganciclovir to conditionally ablate differentiated osteoblasts, whereas controls were saline-treated. Treatment cycles were two weeks in length followed by four weeks of recovery. All animals were sacrificed at 8 months of age; bone marrow stromal cells (BMSCs) were harvested for cell culture and whole bones were excised for bone quality assessment. Colony-forming unit (CFU) assays were conducted to investigate the osteogenic potential of BMSC in vitro, and RNA was extracted to assess the expression of osteoblastic genes. Bone quality assessments included bone histomorphometry, TRAP staining, microcomputed tomography, and biomechanical testing. Osteoblast depletion decreased CFU-F (fibroblast), CFU-ALP (alkaline phosphatase), and CFU-VK (von Kossa) counts and BMSC osteogenic capacity in cell culture. Ex vivo, there were no differences in bone mineral density of vertebrae or femurs between treatment groups. Histology showed a decrease in bone volume and bone connectivity with repeated osteoblast depletion; however, this was accompanied by an increase in bone formation rate. There were no notable differences in osteoclast parameters or observed bone marrow adiposity. We have developed a model that uses bone marrow stress to mimic age-related decrease in osteogenic progenitors. Our data suggest that the number of healthy BMSCs and their osteogenic potential decline with repeated osteoblast depletion. However, activity of the remaining osteoblasts increases to compensate for this loss in progenitor osteogenic potential. PMID:26220824

  13. Allogeneic marrow grafts from donors with congenital chromosomal abnormalities in marrow cells.

    PubMed

    Barquinero, J; Witherspoon, R; Sanders, J; Horowitz, M M; Montuoro, A; Patton, D F; Bacigalupo, A; Abecasis, M M; Miale, T; Rozman, C

    1995-07-01

    To determine whether siblings with chromosomal abnormalities in marrow cells which are associated with cellular defects (e.g. Down syndrome or heterozygosity for Fanconi syndrome) are suitable donors for allogeneic bone marrow transplants, we have reviewed the patient files at the Fred Hutchinson Cancer Research Center (FHCRC) and carried out a survey among member centres of the International Bone Marrow Transplant Registry (IBMTR). The 57 of 253 (23%) member centres which responded to the survey reported seven transplants from donors with the following conditions: Down syndrome (n = 2), suspected heterozygotes for Fanconi syndrome (n = 3), and 47,XXX syndrome (n = 2), among a total of 5,561 allogeneic transplants from HLA-identical siblings. Adding the three cases seen at the Fed Hutchinson Cancer Research Center among 2,927 HLA-identical sibling transplants during 1992 resulted in 10 transplants among 8,488 cases transplanted overall: four with Down syndrome, four suspected of being heterozygous for Fanconi syndrome, and two trisomy X. Three out of four grafts from siblings with Down syndrome had complications, including poor graft function (n = 2) and graft failure (n = 1). Two of four recipients of marrow from presumed Fanconi syndrome heterozygotes presented with poor graft function and a third recipient developed graft failure after initial evidence of engraftment. The two patients given marrow from siblings with 47,XXX syndrome engrafted uneventfully. The experience reported here shows a low frequency of encountering an HLA-identical sibling donor who has chromosomal abnormalities in marrow cells consistent with Down syndrome or heterozygosity for Fanconi syndrome, about one case among 1,000 transplants. The much higher than expected incidence of graft problems with marrow from such a donor would make it reasonable to look either for an alternative marrow donor or consider an autologous transplant, in case a sibling marrow donor with Down syndrome or heterozygosity for Fanconi syndrome is encountered, although a donor with trisomy X seems acceptable. PMID:7646999

  14. [Prolonged acute pancreatitis after bone marrow transplantation].

    PubMed

    De Singly, B; Simon, M; Bennani, J; Wittnebel, S; Zagadanski, A-M; Pacault, V; Gornet, J-M; Allez, M; Lmann, M

    2008-04-01

    Acute pancreatitis is not infrequent after allogenic marrow transplantation. Several causes can predispose to pancreatitis, including Graft-Versus-Host Disease (GVHD), a condition which is probably underestimated. In the literature, few description of pancreatic GVHD can be found. Pancreatic GVHD diagnosis can be difficult if pancreatic involvement occurs without other typical manifestations of GVHD. We report the case of a woman, 54 years old, suffering from prolonged, painful pancreatitis two months after allogenic bone marrow transplantation for acute myeloid leucemia. Pancreatic GVHD diagnosis was performed after five weeks on duodenal biopsies despite the absence of diarrheoa. The patient dramatically improved within few days on corticosteroids. PMID:18378104

  15. Bone Marrow Injury Induced via Oxidative Stress in Mice by Inhalation Exposure to Formaldehyde

    PubMed Central

    McHale, Cliona; Li, Rui; Zhang, Luoping; Wu, Yang; Ye, Xin; Yang, Xu; Ding, Shumao

    2013-01-01

    Objective Formaldehyde, a ubiquitous environmental pollutant has been classified as a human leukemogen. However, toxicity of formaldehyde in bone marrow, the target site of leukemia induction, is still poorly understood. Methodology/Principal Findings To investigate bone marrow toxicity (bone marrow pathology, hematotoxicity) and underlying mechanisms (oxidative stress, inflammation, apoptosis) in formaldehyde-exposed mice. Male Balb/c mice were exposed to formaldehyde (0, 0.5, and 3.0 mg/m3) by nose-only inhalation for 8 hours/day, over a two week period designed to simulate a factory work schedule, with an exposure-free weekend on days 6 and 7, and were sacrificed on the morning of day 13. Counts of white blood cells, red blood cells and lymphocytes were significantly (p<0.05) decreased at 0.5 mg/m3 (43%, 7%, and 39%, respectively) and 3.0 mg/m3 (52%, 27%, and 43%, respectively) formaldehyde exposure, while platelet counts were significantly increased by 109% (0.5 mg/m3) and 67% (3.0 mg/m3). Biomarkers of oxidative stress (reactive oxygen species, glutathione depletion, cytochrome P450 1A1 and glutathione s-transferase theta 1 expression), inflammation (nuclear factor kappa-B, tomour necrosis factor alpha, interleukin-1 beta), and apoptosis (activity of cysteine-aspartic acid protease 3) in bone marrow tissues were induced at one or both formaldehyde doses mentioned above. Conclusions/Significance Exposure of mice to formaldehyde by inhalation induced bone marrow toxicity, and that oxidative stress, inflammation and the consequential apoptosis jointly constitute potential mechanisms of such induced toxicity. PMID:24040369

  16. Bone Marrow Blood Vessel Ossification and Microvascular Dead Space in Rat and Human Long Bone

    PubMed Central

    Prisby, Rhonda D.

    2014-01-01

    Severe calcification of the bone microvascular network was observed in rats, whereby the bone marrow blood vessels appeared ossified. This study sought to characterize the magnitude of ossification in relation to patent blood vessels and adipocyte content in femoral diaphyses. Additionally, this study confirmed the presence of ossified vessels in patients with arteriosclerotic vascular disease and peripheral vascular disease and cellulitis. Young (46 mon; n=8) and old (2224 mon; n=8) male Fischer-344 rats were perfused with barium sulfate to visualize patent bone marrow blood vessels. Femoral shafts were processed for bone histomorphometry to quantify ossified (Goldners Trichrome) and calcified (Alizarin Red) vessels. Adipocyte content was also determined. Additional femora (n=5/age group) were scanned via CT to quantify microvascular ossification. Bone marrow blood vessels from rats and the human patients were also isolated and examined via microscopy. Ossified vessels (rats and humans) had osteocyte lacunae on the vessel surfaces and normal vessels were transitioning into bone. The volume of ossified vessels was 4800% higher (p <0.05) in old vs. young rats. Calcified and ossified vessel volumes per tissue volume and calcified vessel volume per patent vessel volume were augmented (p <0.05) 262%, 375% and 263%, respectively, in old vs. young rats. Ossified and patent vessel number was higher (171%) and lower (40%), respectively, in old vs. young rats. Finally, adipocyte volume per patent vessel volume was higher (86%) with age. This study is the first to report ossification of bone marrow blood vessels in rats and humans. Ossification presumably results in microvascular dead space in regards to loss of patency and vasomotor function as opposed to necrosis. The progression of bone microvascular ossification may provide the common link associated with age-related changes in bone and bone marrow. The clinical implications may be evident in the difficulties treating bone disease in the elderly. PMID:24680721

  17. Marrow-tumor interactions: the role of the bone marrow in controlling chemically induced tumors

    SciTech Connect

    Rosse, C

    1980-01-01

    This report summarizes work done to evaluate the role of the bone marrow in tumor growth regulation. Work done with the MCA tumor showed that several subclasses of mononuclear bone marrow cells (e.g. natural regulatory cell, NRC) play a major role in the regulation of tumor growth. Experiments with the spontaneous CE mammary carcinoma system illustrate that a rapid growth of certain neoplasms may be due to the fact that through some as yet undefined mechanism the tumor eliminates mononuclear cells in the bone marrow of the host and stops their production. (KRM)

  18. RED-LETTER DAYS

    EPA Science Inventory

    The word "red-letter" is an adjective meaning "of special significance." It's origin is from the practice of marking Christian holy days in red letters on calendars. The "red-letter days" to which I refer occurred while I was a graduate student of ...

  19. [Proton MR spectroscopy of hyperplastic hematopoietic marrow in aplastic anemia].

    PubMed

    Amano, Y; Kumazaki, T; Arai, N

    1997-04-01

    The purpose of this study was to compare the findings of magnetic resonance (MR) spectroscopy of hyperplastic hematopoietic marrow with those of normal bone marrow. Twenty-four samples of normal marrow from eight control subjects and 19 samples of hyperplastic marrow in aplastic anemia were examined with a 1.5T MR unit. The former showed low intensity on opposed-phase T1-weighted images, while the latter showed high intensity on both fast STIR and opposed-phase T1-weighted images. MR spectroscopy quantitatively confirmed that the water: fat ratio was increased and the transverse relaxation time of water was changed in hyperplastic bone marrow, compared with normal bone marrow. In summary, MR imaging is able to detect hematopoietic regions among a wide range of bone marrow of aplastic anemia, while MR spectroscopy allowed us to quantitatively analyze the cell population of hyperplastic hematopoietic marrow in aplastic anemia. PMID:9164114

  20. Chronic axial compression of the mouse tail segment induces MRI bone marrow edema changes that correlate with increased marrow vasculature and cellularity.

    PubMed

    Papuga, M Owen; Proulx, Steven T; Kwok, Edmund; You, Zhigang; Rubery, Paul T; Dougherty, Paul E; Hilton, Matthew J; Awad, Hani A; Schwarz, Edward M

    2010-09-01

    Magnetic resonance imaging (MRI) of bone marrow edema (BME) has been found to be helpful in the diagnosis of back pain attributed to degenerative disk disease (DDD) and spondyloarthropathy (SA), but its interpretation is limited by a lack of knowledge of its nature and natural history. We assessed effects of compressive forces to mouse tail segments of WT and TNF-Tg mice with SA, via contrast enhanced-MRI and histology. Normalized marrow contrast enhancement (NMCE) of uninstrumented WT vertebrae significantly decrease, threefold (p < 0.01) from 8 to 12 weeks of age, while the NMCE of TNF-Tg vertebrae remained elevated. Compressive loading (6x body weight) increased NMCE twofold (p < 0.02) within 2 weeks in WT tails, which was equal to 6x loaded TNF-Tg tails within 4 weeks. Histology confirmed degenerative changes and that load-induced NMCE corresponded to increased vascular sinus tissue (35 +/- 3% vs. 19 +/- 3%; p < 0.01) and cellularity (4,235 +/- 886 vs.1,468 +/- 320 cells/mm(2); p < 0.01) for the loaded versus unloaded WT, respectively. However, micro-computed tomography (CT) analyses failed to detect significant load-induced changes to bone. While the bone marrow of loaded WT and TNF-Tg vertebrae were similar, histology demonstrated mild cellular infiltrate and increased osteoclastic resorption in the WT tails versus severe inflammatory-erosive arthritis in TNF-Tg joints. Significant (p < 0.05) decreases in cortical and trabecular bone volume in uninstrumented TNF-Tg versus WT vertebrae were confirmed by micro-CT. Thus, chronic load-induced DDD causes BME signals in vertebrae similar to those observed from SA, and both DDD and SA signals correlate with a conversion from yellow to red marrow, with increased vascularity. PMID:20187115

  1. The Starfield Pattern of Cerebral Fat Embolism From Bone Marrow Necrosis in Sickle Cell Crisis

    PubMed Central

    Dhakal, Laxmi P.; Bourgeois, Kirk; Barrett, Kevin M.

    2015-01-01

    Sickle cell disease may manifest with cerebrovascular and systemic complications. Sickle crisis that results in avascular necrosis of long bones with resultant cerebral fat embolism syndrome is rare and has a characteristic starfield pattern on MRI. This starfield MRI pattern should raise suspicion for sickle cell crisis in patients without a known history of the disease, which can lead to earlier sickle cell red blood cell exchange transfusion and treatment. We present a case of a male who presented emergently with acute seizure, coma with a characteristic MRI pattern, which lead to the diagnosis of avascular bone marrow necrosis and cerebral fat embolism syndrome from sickle cell crisis PMID:25829988

  2. [Genetic diversity and bone marrow transplantation].

    PubMed

    Marry, E

    2012-05-01

    The genetic origin of the patients, for whom a bone marrow transplantation has been proposed, is a key determinant in the possibility of identifying or not a compatible unrelated donor, and consequently in the possibility of performing the bone marrow transplantation. The required strict HLA compatibility, in the context of a bone marrow transplantation, increases the difficulty. A patient has one chance over four to have a compatible donor within his brothers and sisters, if any. This chance becomes one over a million, as an average, in the context of unrelated donor search. Taking into consideration the genetic history of the populations, their evolution and the large actual HLA diversity, the probability of finding an unrelated donor for a defined patient varies according to the frequency and the combination of the patient's HLA antigens, genetic markers inherited not only from his parents, but also from his ancestries. In the unrelated context, the HLA compatible donor most probably shares the same genetic history than the patient, and consequently belongs to the same population group. The study of the genetic of populations explains the difficulties in finding an unrelated compatible donor in the migrant populations, particularly those originated from Africa and from the middle east, due to their HLA specificities and to the small number of donors sharing the same origins registered on a volunteer bone marrow donors' file worldwide. PMID:22454281

  3. Bone marrow manifestations in multicentric Castleman disease.

    PubMed

    Ibrahim, Hazem A H; Balachandran, Kirsty; Bower, Mark; Naresh, Kikkeri N

    2016-03-01

    This study aimed to document the morphological and immunophenotypic features, and describe the diagnostic features of bone marrow (BM) involvement in human herpes virus 8 Multicentric Castleman disease (HHV8-MCD). BM trephine biopsy (BMTB) specimens from 28 patients were revisited. Samples were evaluated for expression of CD3, CD20, CD138, CD68R, glycophorin C, CD42b, HHV8-latency-associated nuclear antigen (LANA1), Epstein-Barr virus-encoded small RNA and light chains. Presence of significant numbers of HHV8-LANA1(+) lymphoid/plasmacytic cells, noted in 10/28 cases, was indicative of BM involvement and was associated with low CD4 and CD8 counts in peripheral blood. The characteristic morphological appearance of MCD seen in lymph nodes is a rare finding in BMTB. 4/5 cases with lymphoid aggregates were involved by MCD, whereas 6/23 cases without lymphoid aggregates were involved by MCD (P = 0·023). 9/18 cases with hypercellular marrow were involved by MCD, whilst only 1/8 cases with normo/hypocellular marrow showed involvement by MCD (P = 0·070). While 9/21 cases with increased marrow reticulin were involved by MCD, none of the cases with no increase in reticulin were involved by MCD (P = 0·080). Reactive plasmacytosis is a frequent finding. We conclude that bone marrow is involved in a significant proportion of patients with MCD (36%), and involvement can be identified by HHV8-LANA1 immunohistochemistry. PMID:26817834

  4. Bone marrow biopsy from the flipper of a dolphin.

    PubMed

    Itou, Takuya; Koie, Hiroshi; Segawa, Takao; Kato, Masako; Yanagisawa, Makio; Ueda, Keiichi; Kuwano, Ryo; Suzuki, Miwa; Moritomo, Tadaaki; Sakai, Takeo

    2010-08-01

    To find macroscopically palpable bone marrow cavities in dolphins is difficult because of their extremely retrogressive limbs and pelvis and because they do not contain abundant modular cavities (as in terrestrial mammals) that can serve as sites for bone marrow biopsies. Three-dimensional computed tomography analysis of dolphin skeletons suggests that bone marrow could be harvested from the humerus and radius. In this report, post-mortem paracentesis of the humerus from a captive rough-toothed dolphin using a biopsy needle provided a marrow preparation containing myelocytes, erythroblasts and megakaryocytes. This type of bone marrow collection from the flipper might be useful for clinical diagnostic work in cetaceans. PMID:19553147

  5. Participation of bone marrow derived cells in cutaneous wound healing.

    PubMed

    Badiavas, Evangelos V; Abedi, Mehrdad; Butmarc, Janet; Falanga, Vincent; Quesenberry, Peter

    2003-08-01

    Bone marrow has long been known to be a source of stem cells capable of regeneration of the hematopoeitic system. Recent reports, however, have indicated that bone marrow might also contain early stem cells that can differentiate into other organ tissues such as skin. While these studies have illustrated that bone marrow stem cells could find their way to the skin, they have not addressed the dynamics of how bone marrow stem cells might participate in the homeostatis and regeneration of skin. In this report we followed green fluorescent protein (GFP) labeled bone marrow transplanted into non-GFP mice in order to determine the participation of bone marrow stem cells in cutaneous wounds. Our results indicate that there are a significant number of bone marrow cells that traffic through both wounded and non-wounded skin. Wounding stimulated the engraftment of bone marrow cells to the skin and induced bone marrow derived cells to incorporate into and differentiate into non-hematopoietic skin structures. This report thus illustrates that bone marrow might be a valuable source of stem cells for the skin and possibly other organs. Wounding could be a stimulus for bone marrow derived stem cells to travel to organs and aid in the regeneration of damaged tissue. PMID:12811816

  6. Thymus dependency of antigen-binding cells in the bone marrow and spleen of chicks.

    PubMed Central

    Sato, K

    1977-01-01

    The bone marrow and spleen of normal unimmunized chicks contain lymphoid cells which form rosettes with quail red blood cells (QRBC), but not with sheep red blood cells. The number of these antigen binding cells (QRBC-ABC) were restored to their original level 2-3 weeks after whole body X-irradiation following a temporary but drastic decrease in the number of QRBC-ABC. This recovery is not observed in chicks which have been thymectomized or thymectomized and bursectomized. However, QRBC-ABC numbers were restored in bursectomized chicks comparable with those levels in control chicks. Anti-thymic serum effectively blocked rosette formation and it seems that QRBC-ABC are a thymus-dependent population. Possibly, the thymus exerts an influence on the genesis of QRBC-ABC through a humoral mechanism. Images Figure 1 Figure 2 Figure 3 PMID:300356

  7. Bone marrow evaluation in small cell carcinoma of the lung.

    PubMed

    Giaccone, G; Ciuffreda, L; Donadio, M; Ferrati, P; Risio, M; Leria, G; Bonardi, G; Calciati, A

    1987-01-01

    Bone marrow examination is commonly included in the staging of small cell lung carcinoma (SCLC). We reviewed marrow samples of 103 patients. Marrow examination was mainly performed by unilateral or bilateral biopsy of iliac crests, using a Jamshidi needle. Only 6 of 97 evaluable cases (6.2 per cent) were positive for marrow metastases at staging, and in 3 cases (3 per cent) bone marrow was the only metastatic site. No focal metastases were found in additional sections made from the blocks of negative samples. In our experience bone marrow biopsy was of little value in staging SCLC. Bilateral biopsy plus aspirate, with the addition of more sophisticated staining techniques might, however, provide a higher yield of positive marrow involvement. PMID:2820447

  8. Biology of Marrow Failure Syndromes: Role of Microenvironment and Niches

    PubMed Central

    Balderman, Sophia R.; Calvi, Laura M.

    2015-01-01

    The marrow microenvironment and its components regulate hematopoietic stem and progenitor cell (HSC) fate. An abnormality in the marrow microenvironment and specific dysfunction of the HSC niche could play a critical role in initiation, disease progression and response to therapy of marrow failure syndromes. Therefore, the identification of changes in the HSC niche in marrow failure syndromes should lead to further knowledge of the signals that disrupt the normal microenvironment. In turn, niche disruption may contribute to disease morbidity resulting in pancytopenia and clonal evolution, and its understanding could point to new therapeutic targets for these conditions. We briefly (a) review evidence for the importance of the marrow microenvironment as a regulator of normal hematopoiesis, (b) summarize the current knowledge regarding the role of dysfunctions in the marrow microenvironment in marrow failure syndromes, and (c) propose a strategy through which niche stimulation can complement current treatment for MDS. PMID:25696837

  9. Facilitation of allogeneic bone marrow transplantation by a T cell-specific immunotoxin containing daunomycin

    SciTech Connect

    Xie, S.S.; Inazawa, M.; Sinha, N.; Sawada, S.; Vergidis, R.; Diener, E.

    1987-12-01

    Daunomycin coupled via an acid-sensitive spacer to monoclonal Thy-1.2-specific antibody was used to purge T lymphocytes from a 1:1 mixture of murine C57BL/6J bone marrow and spleen cells prior to engraftment in fully allogeneic, irradiated BALB/c recipients. Treatment of bone marrow with the immunotoxin at a concentration used for purging had no effect on the viability of committed hematopoietic progenitor or multipotent stem cells. All of the recipients of purged bone marrow were at least 80% chimeric for donor peripheral blood cells and none developed graft-versus-host disease. Out of 50 chimeras, 49 were still alive more than 200 days posttransplantation. The chimeras were shown to be tolerant to donor tissue as tested by mixed lymphocyte reactivity, cell-mediated cytotoxicity, and skin grafting. The same tests revealed full immunocompetence of chimeras to third-party alloantigens. In vivo IgM and IgG antibody responses to sheep red blood cells were similar in magnitude in allogeneically and syngeneically reconstituted mice.

  10. Frequency of Micronucleated Erythrocytes in Rat Bone Marrow Exposed to 2.45 GHz Radiation

    NASA Astrophysics Data System (ADS)

    Trosic, I.; Busljeta, I.

    2005-01-01

    Wistar rats were exposed to 2.45 GHz continuous, radiofrequency microwave (RF/MW) field 2 hours daily, 7 days weekly, at power density 5 10 mW/cm2. Four subgroups were created in order to be irradiated 4, 16, 30 and 60 hours. Sham-exposed controls were included in the study. Animals were euthanized on the final irradiation day of each treated subgroup. Bone marrow smears were examined to determine the extent of genotoxicity after the particular treatment time. Mann-Whitney test was used for statistical evaluation of data. In comparison to the sham-exposed subgroups, the findings of polychromatic erythrocytes revealed significant differences for the 8th and 15th experimental day. Bone marrow erythrocyte maturation and/or proliferation initiated by subthermogenic RF/MW irradiation showed temporary disturbance. Thereafter, the frequency of micronucleated bone marrow red cells was significantly increased after 15 irradiation treatments. Comparison of micronucleus frequency data obtained after 2, 8 and 30 irradiation treatments did not reveal statistically significant differences between sham and treated subgroups. Under the applied experimental conditions, RF/MW irradiation initiates transitory cytogenetic effect manifested with micronucleus formation in erythropoietic cells.

  11. Magnetic resonance imaging of the spinal marrow: Basic understanding of the normal marrow pattern and its variant

    PubMed Central

    Nouh, Mohamed Ragab; Eid, Ahmed Fathi

    2015-01-01

    For now, magnetic resonance (MR) is the best noninvasive imaging modality to evaluate vertebral bone marrow thanks to its inherent soft-tissue contrast and non-ionizing nature. A daily challenging scenario for every radiologist interpreting MR of the vertebral column is discerning the diseased from normal marrow. This requires the radiologist to be acquainted with the used MR techniques to judge the spinal marrow as well as its normal MR variants. Conventional sequences used basically to image marrow include T1W, fat-suppressed T2W and short tau inversion recovery (STIR) imaging provides gross morphological data. Interestingly, using non-routine MR sequences; such as opposed phase, diffusion weighted, MR spectroscopy and contrasted-enhanced imaging; may elucidate the nature of bone marrow heterogeneities; by inferring cellular and chemical composition; and adding new functional prospects. Recalling the normal composition of bone marrow elements and the physiologic processes of spinal marrow conversion and reconversion eases basic understanding of spinal marrow imaging. Additionally, orientation with some common variants seen during spinal marrow MR imaging as hemangiomas and bone islands is a must. Moreover, awareness of the age-associated bone marrow changes as well as changes accompanying different variations of the subject’s health state is essential for radiologists to avoid overrating normal MR marrow patterns as pathologic states and metigate unnecessary further work-up. PMID:26753060

  12. Magnetic resonance imaging of the spinal marrow: Basic understanding of the normal marrow pattern and its variant.

    PubMed

    Nouh, Mohamed Ragab; Eid, Ahmed Fathi

    2015-12-28

    For now, magnetic resonance (MR) is the best noninvasive imaging modality to evaluate vertebral bone marrow thanks to its inherent soft-tissue contrast and non-ionizing nature. A daily challenging scenario for every radiologist interpreting MR of the vertebral column is discerning the diseased from normal marrow. This requires the radiologist to be acquainted with the used MR techniques to judge the spinal marrow as well as its normal MR variants. Conventional sequences used basically to image marrow include T1W, fat-suppressed T2W and short tau inversion recovery (STIR) imaging provides gross morphological data. Interestingly, using non-routine MR sequences; such as opposed phase, diffusion weighted, MR spectroscopy and contrasted-enhanced imaging; may elucidate the nature of bone marrow heterogeneities; by inferring cellular and chemical composition; and adding new functional prospects. Recalling the normal composition of bone marrow elements and the physiologic processes of spinal marrow conversion and reconversion eases basic understanding of spinal marrow imaging. Additionally, orientation with some common variants seen during spinal marrow MR imaging as hemangiomas and bone islands is a must. Moreover, awareness of the age-associated bone marrow changes as well as changes accompanying different variations of the subject's health state is essential for radiologists to avoid overrating normal MR marrow patterns as pathologic states and metigate unnecessary further work-up. PMID:26753060

  13. [Q fever: bone marrow characteristic granuloma].

    PubMed

    Szablewski, Vanessa; Costes, Valrie; Rousset, Thrse; Mania, Emile; El Aoufi, Nasreddine

    2012-08-01

    Q fever is a worldwise zoonosis, caused by an obligate intracellular bacterium, Coxiella burnetii. In humans, acute disease, when symptomatic, can manifest by a flu-like illness, pneumonia or hepatitis. Patients with predisposing conditions can evolve with chronic disease, which major clinical presentation is endocarditis with negative routine blood cultures. Histological studies of Q fever based on infected organs biopsies (liver and bone marrow) have demonstrated a distinctive type of granuloma, typically appearing as a "doughnut" granuloma, characterized by a central clean space surrounded by inflammatory cells and rimmed with an eosinophilic fibrinoid material. We describe a 37-year-old man, admitted to hospital for persistent fever. Bone marrow biopsy showed the characteristic "doughnut" granuloma, suggesting a Q fever. Diagnosis was then confirmed by serological tests for C.burnetii. PMID:23010400

  14. Myelodysplastic syndrome associated with bone marrow fibrosis.

    PubMed

    Lambertenghi-Deliliers, G; Annaloro, C; Oriani, A; Soligo, D

    1992-09-01

    Bone marrow biopsy (BMB) in myelodysplastic syndrome (MDS) frequently reveals a slight alteration in the reticulin stroma which does not have any clinical significance. However, in a minority of cases, full-blown bone marrow fibrosis (BMF) can be found. Primary MDS patients with BMF show distinct clinico-pathological features and an unfavourable prognosis mainly attributable to complications deriving from pancytopenia and continuous transfusions, while leukemic transformation occurs only rarely. Since BMF may characterize other hematological disorders, primary MDS with BMF should be included in the differential diagnosis particularly with malignant myelofibrosis (MM) and idiopathic myelofibrosis (IMF). Secondary MDS with BMF represent a variety of preleukemic conditions in subjects treated for previous neoplasias. Unlike the primary forms, they do not form a clearcut clinico-pathological entity. PMID:1493471

  15. Post-bone marrow transplant patient management.

    PubMed Central

    Poliquin, C. M.

    1990-01-01

    Increasingly, bone marrow transplant (BMT) is the treatment of choice for certain hematologic diseases. BMT is, however, a risky procedure with many potentially serious complications. Some complications are the result of the conditioning regimen, a stage of transplantation that includes large doses of chemotherapy and/or radiation therapy. Conditioning-induced neutropenia and thrombocytopenia often result in infection, bleeding, and mucositis. Veno-occlusive disease (VOD), a chemotherapy-induced hepatotoxicity, can cause a mild to severe form of liver disease. Other complications are directly attributable to the engrafted new marrow. Graft-versus-host disease, a rejection process initiated by immunocompetent donor T lymphocytes, is a complication frequently observed in allogeneic BMT. Approximately 14-28 days after the day of transplant, signs of engraftment begin to appear. When specific discharge criteria are met, the BMT patient is discharged from the hospital. Specific follow-up medical care is ongoing for about one year after BMT. PMID:2293508

  16. [MR images of bone marrow in aplastic anemia and correlation between MR findings and age].

    PubMed

    Amano, Y; Kumazaki, T; Amano, M

    1996-07-01

    We observed 125 lumbar vertebrae in 25 patients with aplastic anemia using a 0.5-T MR imager. Bone marrow patterns of aplastic anemia on STIR images were classified into five types: 1) homogeneously low intensity fatty marrow, 2) fatty marrow with scattered hematopoietic nodules, 3) fatty marrow with marginal hematopoietic regions, 4) fatty marrow surrounded by bandlike hematopoietic regions, and 5) homogeneously high-signal-intensity hematopoietic marrow. STIR images defined the fatty marrow as a markedly hypointense region and the hematopoietic marrow as a high signal intense area. Many cases included the homogeneously fatty marrow and fatty marrow with marginal hematopoietic areas, whereas marrow with a broad range of hematopoiesis was detected in patients younger than 40 years. MR images also demonstrated that fatty marrow could shift to hematopoietic marrow following therapy. MR images were useful for detection of the bone marrow distribution of aplastic anemia, related to aging and treatment. PMID:8797344

  17. Total body irradiation in bone marrow transplantation: the influence of fractionation and delay of marrow infusion

    SciTech Connect

    Lichter, A.S.; Tracy, D.; Lam, W.C.; Order, S.E.

    1980-03-01

    Bone marrow transplantation (BMT) after total body irradiation (TBI) and cyclophosphamide is being employed increasingly in the therapy of end stage leukemia. Interstitial pneumonitis (IP) represents a major acute toxicity after allogeneic transplantation. A more rapid reconstitution of lymphoid organs and bone marrow post transplant may result in increased immune competence and hence fewer opportunistic pulmonary infections and IP. By delaying the infusion of marrow to 72 hr after TBI (1250 rad at 7.5 rad/min) instead of the customary 24 hr, we can demonstrate an increase in initial repopulation of thymus, spleen and bone marrow, with syngeneic transplants in Lewis rats. Interstitial pneumonitis may also be caused, in part, by the pulmonary toxicity of large single exposures of TBI. Clinical and laboratory data suggest that fractionated TBI may be less toxic to the lung. When fractionated TBI (625 rad x 2, 7.5 rad/min) is compared to single dose TBI (1250 rad, 7.5 rad/min), and increased initial repopulation of lymphoid organs is observed when fractionated therapy is employed. Delay in marrow infusion and fractionation of TBI exposure may have clinical advantages in patients who receive BMT.

  18. Knee cartilage defect: marrow stimulating techniques.

    PubMed

    Mirza, M Zain; Swenson, Richard D; Lynch, Scott A

    2015-12-01

    Painful chondral defects of the knee are very difficult problems. The incidence of these lesions in the general population is not known since there is likely a high rate of asymptomatic lesions. The rate of lesions found during arthroscopic exam is highly variable, with reports ranging from 11 to 72% Aroen (Aroen Am J Sports Med 32: 211-5, 2004); Curl(Arthroscopy13: 456-60, 1997); Figueroa(Arthroscopy 23(3):312-5, 2007;); Hjelle(Arthroscopy 18: 730-4, 2002). Examples of current attempts at cartilage restoration include marrow stimulating techniques, ostochondral autografts, osteochondral allografts, and autologous chondrocyte transplantation. Current research in marrow stimulating techniques has been focused on enhancing and guiding the biology of microfracture and other traditional techniques. Modern advances in stem cell biology and biotechnology have provided many avenues for exploration. The purpose of this work is to review current techniques in marrow stimulating techniques as it relates to chondral damage of the knee. PMID:26411978

  19. Osteoclast derivation from mouse bone marrow.

    PubMed

    Tevlin, Ruth; McArdle, Adrian; Chan, Charles K F; Pluvinage, John; Walmsley, Graham G; Wearda, Taylor; Marecic, Owen; Hu, Michael S; Paik, Kevin J; Senarath-Yapa, Kshemendra; Atashroo, David A; Zielins, Elizabeth R; Wan, Derrick C; Weissman, Irving L; Longaker, Michael T

    2014-01-01

    Osteoclasts are highly specialized cells that are derived from the monocyte/macrophage lineage of the bone marrow. Their unique ability to resorb both the organic and inorganic matrices of bone means that they play a key role in regulating skeletal remodeling. Together, osteoblasts and osteoclasts are responsible for the dynamic coupling process that involves both bone resorption and bone formation acting together to maintain the normal skeleton during health and disease. As the principal bone-resorbing cell in the body, changes in osteoclast differentiation or function can result in profound effects in the body. Diseases associated with altered osteoclast function can range in severity from lethal neonatal disease due to failure to form a marrow space for hematopoiesis, to more commonly observed pathologies such as osteoporosis, in which excessive osteoclastic bone resorption predisposes to fracture formation. An ability to isolate osteoclasts in high numbers in vitro has allowed for significant advances in the understanding of the bone remodeling cycle and has paved the way for the discovery of novel therapeutic strategies that combat these diseases. Here, we describe a protocol to isolate and cultivate osteoclasts from mouse bone marrow that will yield large numbers of osteoclasts. PMID:25407120

  20. The effect of autologous bone marrow stromal cells differentiated on scaffolds for canine tibial bone reconstruction.

    PubMed

    zdal-Kurt, F; Tu?lu, I; Vatansever, H S; Tong, S; Delilo?lu-Grhan, S I

    2015-10-01

    Bone marrow contains mesenchymal stem cells that form many tissues. Various scaffolds are available for bone reconstruction by tissue engineering. Osteoblastic differentiated bone marrow stromal cells (BMSC) promote osteogenesis on scaffolds and stimulate bone regeneration. We investigated the use of cultured autologous BMSC on different scaffolds for healing defects in tibias of adult male canines. BMSC were isolated from canine humerus bone marrow, differentiated into osteoblasts in culture and loaded onto porous ceramic scaffolds including hydroxyapatite 1, hydroxyapatite gel and calcium phosphate. Osteoblast differentiation was verified by osteonectine and osteocalcine immunocytochemistry. The scaffolds with stromal cells were implanted in the tibial defect. Scaffolds without stromal cells were used as controls. Sections from the defects were processed for histological, ultrastructural, immunohistochemical and histomorphometric analyses to analyze the healing of the defects. BMSC were spread, allowed to proliferate and differentiate to osteoblasts as shown by alizarin red histochemistry, and osteocalcine and osteonectine immunostaining. Scanning electron microscopy showed that BMSC on the scaffolds were more active and adhesive to the calcium phosphate scaffold compared to the others. Macroscopic bone formation was observed in all groups, but scaffolds with stromal cells produced significantly better results. Bone healing occurred earlier and faster with stromal cells on the calcium phosphate scaffold and produced more callus compared to other scaffolds. Tissue healing and osteoblastic marker expression also were better with stromal cells on the scaffolds. Increased trabecula formation, cell density and decreased fibrosis were observed in the calcium phosphate scaffold with stromal cells. Autologous cultured stromal cells on the scaffolds were useful for healing of canine tibial bone defects. The calcium phosphate scaffold was the best for both cell differentiation in vitro and bone regeneration in vivo. It may be possible to improve healing of bone defects in humans using stem cells from bone marrow. PMID:25994048

  1. Persistent genetic damage in blood and bone marrow cells following radioiodine therapy

    SciTech Connect

    Livingston, G.K.; Schumfann, B.L.; Bigbee, W.L.

    1995-11-01

    Patients treated with medical isotopes provide opportunity for prospective study of radiation effects induced by internally-deposited radionuclides. We analyzed serial blood samples of a thyroid cancer patient treated with {sup 131}I for changes in micronuclei (MN) and chromosome aberrations (CA) in lymphocytes and glycophorin A (GPA) locus mutations in erythrocytes. Initial treatment (48 mCi) induced a 6-fold increase in MN frequency (from 6 to 36/1000). Dose response studies of the patient`s lymphocytes X-irradiated in vitro before diagnosis of cancer showed the increase corresponds to an in vivo blood dose of 11.4 cGy compared to an NCRP red marrow dose estimate of 9.6 cGy (0.2 cGy/mCi {sup 131}I). A second treatment (390 mCi), given 26 months after the first, further increased the MN frequency to 17-fold over background (101/1000). Analysis of 80 MN for kinetochores using the CREST anti-kinetochore antibody showed that 90% contained acentric chromosomal fragments. Analysis of 100 G-banded metaphases revealed 20 with structural CAs including rings, deletions, translocations and a dicentric. The frequency of GPA allele-loss variant erythrocytes increased from 11.4 to 10.8 and 17.8 x 10{sup {minus}6} in samples obtained at 2, 4 and 6 months, respectively, after the second treatment. This response is consistent with radiation-induced GPA mutations in long-lived erythroid marrow stem cells as previously reported for A-bomb survivors. The induced frequency of GPA variant cells corresponds to a red marrow dose of 60 cGy based on the persistent linear dose response of 25 x 10{sup {minus}6} per Gy from previous studies. We conclude that exposure to {sup 131}I induces persistent genetic damage and that these biodosimetric methods are useful in reconstructing radiation doses in exposed individuals.

  2. Red Clover Breeding Progress

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Red clover (Trifolium pratense L.) is an important forage legume grown on approximately 4 million hectares worldwide. It has a long and varied history in agriculture. Active breeding efforts began at the end of the 19th century. Since this time significant improvement in red clover cultivar for a...

  3. Grapevine red blotch

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Grapevine red blotch disease was first recognized in 2008 in vineyards in Napa County in California. The name ‘red blotch' was given to distinguish disease symptoms from those caused by leafroll viruses and other graft-transmissible agents involved in graft union disorders (see pages… this compendi...

  4. Cobb's Red Cabbage Indicator.

    ERIC Educational Resources Information Center

    Cobb, Vicki

    1998-01-01

    Describes the use of an indicator made from the pigment in red cabbage. Cabbage is grated then soaked in water. When the water is a strong red, the cabbage is strained out. The cabbage-juice indicator is then used to test for acids and bases. Includes a list of good foods to test for acidity and alkalinity. (PVD)

  5. Intractable diseases treated with intra-bone marrow-bone marrow transplantation

    PubMed Central

    Li, Ming; Guo, Kuquan; Ikehara, Susumu

    2014-01-01

    Bone marrow transplantation (BMT) is used to treat hematological disorders, autoimmune diseases (ADs) and lymphoid cancers. Intra bone marrow-BMT (IBM-BMT) has been proven to be a powerful strategy for allogeneic BMT due to the rapid hematopoietic recovery and the complete restoration of T cell functions. IBM-BMT not only replaces hematopoietic stem cells (HSCs) but also mesenchymal stromal cells (MSCs). MSCs are multi-potent stem cells that can be isolated from bone marrow (BM), umbilical cord blood (UCB), and adipose tissue. MSCs play an important role in the support of hematopoiesis, and modify and influence the innate and adaptive immune systems. MSCs also differentiate into mesodermal, endodermal and ectodermal lineage cells to repair tissues. This review aims to summarize the functions of BM-derived-MSCs, and the treatment of intractable diseases such as rheumatoid arthritis (RA) and malignant tumors with IBM-BMT. PMID:25364755

  6. Bone marrow findings in patients with pulmonary tuberculosis.

    PubMed

    Olaniyi, J A; Aken'Ova, Y A

    2003-06-01

    The cytology and culture of bone marrow aspirate in sixty-two newly diagnosed patients with pulmonary tuberculosis were studied. The findings were depressed erythroid activity in 69% of the patients, micronormoblastic changes in 18% and megaloblastic changes in 16.6%. Myeloid activity was increased in 65% of the patients. Normal looking plasma cells above 5% was found in 17.7% of the bone marrow aspirates while 12.9% had eosinophilic precursors above 5% in the marrow. None of the marrow smears showed granuloma formation or caseation necrosis. The bone marrow cultures yielded no growth of Mycobaterium tuberculosis while stainable iron in the marrow was found to be low or negative in 88.8% of the patients. PMID:15032462

  7. Pathophysiological role of enhanced bone marrow adipogenesis in diabetic complications

    PubMed Central

    Piccinin, Meghan A; Khan, Zia A

    2014-01-01

    Diabetes leads to complications in select organ systems primarily by disrupting the vasculature of the target organs. These complications include both micro- (cardiomyopathy, retinopathy, nephropathy, and neuropathy) and macro-(atherosclerosis) angiopathies. Bone marrow angiopathy is also evident in both experimental models of the disease as well as in human diabetes. In addition to vascular disruption, bone loss and increased marrow adiposity have become hallmarks of the diabetic bone phenotype. Emerging evidence now implicates enhanced marrow adipogenesis and changes to cellular makeup of the marrow in a novel mechanistic link between various secondary complications of diabetes. In this review, we explore the mechanisms of enhanced marrow adipogenesis in diabetes and the link between changes to marrow cellular composition, and disruption and depletion of reparative stem cells. PMID:26317050

  8. Vertebral hyperemia associated with bone marrow insult and recovery

    SciTech Connect

    Klein, H.A.; Bolden, R.O.; Simone, F.J.

    1984-06-01

    A 15-year-old boy with rhabdoid sarcoma received chemotherapy, which was followed by bone marrow depression, massive nosebleeds and, finally, hematologic recovery. On both hepatobiliary and renal scintigraphy, prominent vertebral activity was present in early images. Correlation with his clinical course suggests that the findings reflect hyperemia due to marrow insult and recovery. Radionuclide imaging to detect hyperemia may be a useful probe for drug effects on hematopoietic bone marrow.

  9. A multiscale model of the bone marrow and hematopoiesis

    PubMed Central

    Silva, Ariosto S; Anderson, Alexander R.A.

    2013-01-01

    The bone marrow is necessary for renewal of all hematopoietic cells and critical for maintenance of a wide range of physiologic functions. Multiple human diseases result from bone marrow dysfunction. It is also the site in which liquid tumors, including leukemia and multiple myeloma, develop as well as a frequent site of metastases. Understanding the complex cellular and microenvironmental interactions that govern normal bone marrow function as well as diseases and cancers of the bone marrow would be a valuable medical advance. Our goal is the development of a spatially-explicit in silico model of the bone marrow to understand both its normal function and the evolutionary dynamics that govern the emergence of bone marrow malignancy. Here we introduce a multiscale computational model of the bone marrow that incorporates three distinct spatial scales, cell, hematopoietic subunit, whole marrow. Implemented as a fixed lattice 3D cellular automaton, it reproduces the spatial characteristics of the normal bone marrow and is validated against data from the daily production of mature blood cells and response of hematopoiesis after irradiation. The major mechanisms modeled in this work are: (1) replication, specialization and migration of hematopoietic cells, (2) optimized spatial configuration of sinuses and hematopoietic compartments and, (3) intravasation of mature hematopoietic cells into sinuses. Our results, using parameter estimates from literature, recapitulates normal bone marrow function and suggest an explanation for the fractal-like structure of trabeculae and sinuses in the marrow, which would be an optimization of the hematopoietic function in order to maximize the number of mature blood cells produced daily within the volumetric restrictions of the marrow. PMID:21631151

  10. Marrow Fat and Bone: Review of Clinical Findings

    PubMed Central

    Schwartz, Ann V.

    2015-01-01

    With growing interest in the connection between fat and bone, there has been increased investigation of the relationship with marrow fat in particular. Clinical research has been facilitated by the development of non-invasive methods to measure bone marrow fat content and composition. Studies in different populations using different measurement techniques have established that higher marrow fat is associated with lower bone density and prevalent vertebral fracture. The degree of unsaturation in marrow fat may also affect bone health. Although other fat depots tend to be strongly correlated, marrow fat has a distinct pattern, suggesting separate mechanisms of control. Longitudinal studies are limited, but are crucial to understand the direct and indirect roles of marrow fat as an influence on skeletal health. With greater appreciation of the links between bone and energy metabolism, there has been growing interest in understanding the relationship between marrow fat and bone. It is well established that levels of marrow fat are higher in older adults with osteoporosis, defined by either low bone density or vertebral fracture. However, the reasons for and implications of this association are not clear. This review focuses on clinical studies of marrow fat and its relationship to bone. PMID:25870585

  11. The inherited bone marrow failure syndromes.

    PubMed

    Chirnomas, S Deborah; Kupfer, Gary M

    2013-12-01

    Molecular pathogenesis may be elucidated for inherited bone marrow failure syndromes (IBMFS). The study and presentation of the details of their molecular biology and biochemistry is warranted for appropriate diagnosis and management of afflicted patients and to identify the physiology of the normal hematopoiesis and mechanisms of carcinogenesis. Several themes have emerged within each subsection of IBMFS, including the ribosomopathies, which include ribosome assembly and ribosomal RNA processing. The Fanconi anemia pathway has become interdigitated with the familial breast cancer syndromes. In this article, the diseases that account for most IBMFS diagnoses are analyzed. PMID:24237972

  12. Metastatic thymoma involving the bone marrow

    PubMed Central

    Wenceslao, Stella; Krause, John R.

    2016-01-01

    Although relatively rare, thymomas can be involved in a considerable variety of clinical presentations. Clinicians should be mindful of the breadth of associations with other diseases, including autoimmune disorders and many secondary nonthymic malignancies. For the pathologist, knowledge of the extremely varied histopathologic presentation of thymoma is vital to formulate a proper differential, workup, and diagnosis. The presented case illustrates the finding of very rare metastatic thymoma involvement of bone marrow, identified during evaluation for pancytopenia. The history of prior prostate cancer and an uncharacterized pancreatic lesion, as well as the familial presentation, also suggests a possible underlying hereditary syndrome. PMID:26722174

  13. [Bone marrow pathology of myeloproliferative neoplasms].

    PubMed

    Ito, Masafumi

    2015-08-01

    Myeloproliferative neoplasms (MPN) have been characterized by their clinical and histological patterns and have also been accordingly subclassified. Several specific genomic abnormalities are identifiable, raising the possibility of introducing a new era of genotype classification for an updated MPN classification. MPN classified by clinical and hematological data have specific histopathological characteristics of JAK2, MPL, and CALR abnormalities. Herein, the author will endeavor to devise an algorithm for MPN diagnosis based on bone marrow histology. Cellularity, erythroid islet formation, size, nuclear morphology, and the distribution pattern of megakaryocytes are the specific findings indicative of differences in genotype abnormalities. PMID:26345553

  14. Histological alterations in bone marrow in patients with late engraftment after autologous bone marrow transplantation.

    PubMed

    Annaloro, C; Oriani, A; Pozzoli, E; Deliliers, D L; Bertolli, V G; Volpe, A D; Soligo, D; Deliliers, G L

    2000-04-01

    Bone marrow histology after bone marrow transplantation has rarely been studied. Here, we reviewed the pre- and post-transplant bone marrow biopsies (BMB) of 40 acute myelogenous leukemia (AML) patients autografted in our center, 28 with normal and 12 with delayed peripheral recovery. The two groups were comparable in terms of previous therapy, disease phase and the number of infused cells, and received the same conditioning regimen. In the former group, reduced bone marrow cellularity and mild reticulin abnormalities were usual histological findings; in the latter, five patients had the same pattern, but the other seven had an almost undetectable hematopoietic parenchyma and severe reticulin derangement. One of these seven patients died of reactivated hepatitis B virus infection; the others eventually achieved peripheral recovery, with none of them experiencing a relapse. Autografted AML patients are excellent subjects for histological investigations. They account for the majority of delayed engraftments, the contribution of extramedullary components to the timing of engraftment is minimal, and leukemia relapse cannot be ruled out. These results suggest that BMB is a useful investigation in the work-up of late engraftment. A high degree of reticulin derangement with an almost undetectable hematopoietic parenchyma appear to be the morphological hallmarks of late engraftment. PMID:10808204

  15. Bone marrow and bone marrow derived mononuclear stem cells therapy for the chronically ischemic myocardium

    SciTech Connect

    Waksman, Ron; Baffour, Richard

    2003-09-01

    Bone marrow stem cells have been shown to differentiate into various phenotypes including cardiomyocytes, vascular endothelial cells and smooth muscle. Bone marrow stem cells are mobilized and home in to areas of injured myocardium where they are involved in tissue repair. In addition, bone marrow secretes multiple growth factors, which are essential for angiogenesis and arteriogenesis. In some patients, these processes are not enough to avert clinical symptoms of ischemic disease. Therefore, in vivo administration of an adequate number of stem cells would be a significant therapeutic advance. Unfractionated bone marrow derived mononuclear stem cells, which contain both hematopoietic and nonhematopoietic cells may be more appropriate for cell therapy. Studies in animal models suggest that implantation of different types of stem cells improve angiogenesis and arteriogenesis, tissue perfusion as well as left ventricular function. Several unanswered questions remain. For example, the optimal delivery approach, dosage and timing of the administration of cell therapy as well as durability of improvements need to be studied. Early clinical studies have demonstrated safety and feasibility of various cell therapies in ischemic disease. Randomized, double blind and placebo-controlled clinical trials need to be completed to determine the effectiveness of stem cell.

  16. American Red Cross

    MedlinePLUS

    ... the site correctly, please enable cookies. Latest News Music, Dancing and Mobilizing for Health Red Cross SAF ... Supporting Nation’s Military For More Than A Century Music, Dancing and Mobilizing for Health Sign Up for ...

  17. Jupiter's Great Red Spot

    NASA Technical Reports Server (NTRS)

    1996-01-01

    This view of Jupiter's Great Red Spot is a mosaic of two images taken by the Galileo spacecraft. The image was created using two filters, violet and near-infrared, at each of two camera positions. The Great Red Spot is a storm in Jupiter's atmosphere and is at least 300 years-old. Winds blow counterclockwise around the Great Red Spot at about 400 kilometers per hour (250 miles per hour). The size of the storm is more than one Earth diameter (13,000 kilometers or 8,000 miles) in the north-south direction and more than two Earth diameters in the east-west direction. In this oblique view, where the Great Red Spot is shown on the planet's limb, it appears longer in the north-south direction. The image was taken on June 26, 1996.

    The Galileo mission is managed by NASA's Jet Propulsion Laboratory.

  18. Splenocytes Seed Bone Marrow of Myeloablated Mice: Implication for Atherosclerosis

    PubMed Central

    Wang, Lai; Yang, Mingjie; Arias, Ana; Song, Lei; Li, Fuqiang; Tian, Fang; Qin, Minghui; Yukht, Ada; Williamson, Ian K.; Shah, Prediman K.; Sharifi, Behrooz G.

    2015-01-01

    Extramedullary hematopoiesis has been shown to contribute to the pathogenesis of a variety of diseases including cardiovascular diseases. In this process, the spleen is seeded with mobilized bone marrow cells that augment its hematopoietic ability. It is unclear whether these immigrant cells that are produced/reprogrammed in spleen are similar or different from those found in the bone marrow. To begin to understand this, we investigated the relative potency of adult splenocytes per se to repopulate bone marrow of lethally-irradiated mice and its functional consequences in atherosclerosis. The splenocytes were harvested from GFP donor mice and transplanted into myeloablated wild type recipient mice without the inclusion of any bone marrow helper cells. We found that adult splenocytes repopulated bone marrow of myeloablated mice and the transplanted cells differentiated into a full repertoire of myeloid cell lineages. The level of monocytes/macrophages in the bone marrow of recipient mice was dependent on the cell origin, i.e., the donor splenocytes gave rise to significantly more monocytes/macrophages than the donor bone marrow cells. This occurred despite a significantly lower number of hematopoietic stem cells being present in the donor splenocytes when compared with donor bone marrow cells. Atherosclerosis studies revealed that donor splenocytes displayed a similar level of atherogenic and atheroprotective activities to those of donor bone marrow cells. Cell culture studies showed that the phenotype of macrophages derived from spleen is different from those of bone marrow. Together, these results demonstrate that splenocytes can seed bone marrow of myeloablated mice and modulate atherosclerosis. In addition, our study shows the potential of splenocytes for therapeutic interventions in inflammatory disease. PMID:26038819

  19. Glutamine supplementation in bone marrow transplantation.

    PubMed

    Ziegler, Thomas R

    2002-01-01

    An increasing number of clinical investigations have focused on supplementation of specialized enteral and parenteral nutrition with the amino acid glutamine. This interest derives from strong evidence in animal models and emerging clinical data on the efficacy of glutamine administration following chemotherapy, trauma, sepsis and other catabolic conditions. Glutamine has protein-anabolic effects in stressed patients and, among many key metabolic functions, is used as a major fuel/substrate by cells of the gastrointestinal epithelium and the immune system. These effects may be particularly advantageous in patients undergoing bone marrow transplantation (BMT), who exhibit post-transplant body protein wasting, gut mucosal injury and immunodeficiency. Studies to date indicate that enteral and parenteral glutamine supplementation is well tolerated and potentially efficacious after high-dose chemotherapy or BMT for cancer treatment. Although not all studies demonstrate benefits, sufficient positive data have been published to suggest that this nutrient should be considered as adjunctive metabolic support of some individuals undergoing marrow transplant. However, BMT is a rapidly evolving clinical procedure with regard to the conditioning and supportive protocols utilized. Thus, additional randomized, double-blind, controlled clinical trials are indicated to define the efficacy of glutamine with current BMT regimens. PMID:11895159

  20. Simultaneous development of antibody-dependent cellular cytotoxicity (ADCC) and natural killer (NK) activity in irradiated mice reconstituted with bone marrow cells

    SciTech Connect

    Sihvola, M.; Hurme, M.

    1987-10-01

    Spleen cells from irradiated, bone marrow-reconstituted mice were tested for their ability to mediate antibody-dependent cellular cytotoxicity against P815 target (ADCC-P815), ADCC against sheep red blood cells (ADCC-SRBC), and natural killer (NK) activity judged as YAC-1 lysis at different times after bone marrow reconstitution. Donor-derived ADCC-P815 effectors were found to appear in the spleens 10-12 days after bone marrow reconstitution simultaneously with the appearance of donor-derived NK cells. NK cells recently derived from bone marrow are known to express the Thy-1 antigen; the phenotype of the ''early'' ADCC-P815 effectors was found to be the same as that of NK cells, i.e., Thy-1+, asialo-GM1+. These data suggest that ADCC-P815 effector cells belong to the NK cell population. ADCC-SRBC, in contrast to ADCC-P815 and NK activity, was already high on Day 7 after bone marrow reconstitution. However, it was mediated partly by recipient-derived effectors. ADCC-SRBC effectors were characterized to be different from ADCC-P815 effectors.

  1. The study of indicators of bone marrow and peripheral blood of rats with diabetes and transplanted liver tumor after intravenous injection of gold nanorods

    NASA Astrophysics Data System (ADS)

    Dikht, Nataliya I.; Bucharskaya, Alla B.; Maslyakova, Galina N.; Terentyuk, Georgy S.; Matveeva, Olga V.; Navolokin, Nikita A.; Khlebtsov, Boris N.; Khlebtsov, Nikolai G.

    2015-03-01

    In study the evaluation of the influence of gold nanorods on morphological indicators of red bone marrow and peripheral blood of rats with diabetes and transplanted liver tumor after intravenous administration of gold nanorods was conducted. We used gold nanorods with length 41 ± 8 nm and diameter of 10.2±2 nm, synthesized in the laboratory of nanobiotechnology IBPPM RAS (Saratov). After intravenous administration of gold nanorods the decrease of leukocytes, platelets and lymphocytes was observed in animals of control group in blood. It was marked the decrease of the number of mature cellular elements of the leukocyte germ in bone marrow - stab neutrophils and segmented leukocytes, and the increase of immature elements- metamyelocytes, indicating the activation of leukocyte germ after nanoparticle administration. The decrease of leukocyte amount was noted in blood and the increase of cellular elements of the leukocyte germ was revealed in bone marrow, indicating the activation of leukocyte germ in rats with alloxan diabetes and transplanted tumors. The changes of morphological indicators of blood and bone marrow testify about stimulation of myelocytic sprouts of hemopoiesis in bone marrow as a result of reduction of mature cells in peripheral blood after gold nanoparticle administration.

  2. First reported case of Ehrlichia ewingii involving human bone marrow.

    PubMed

    Allen, M Brandon; Pritt, Bobbi S; Sloan, Lynne M; Paddock, Christopher D; Musham, Chaitanya K; Ramos, Jeanette M; Cetin, Neslihan; Rosenbaum, Eric R

    2014-11-01

    A 65-year-old female with a history of multiple tick bites presented with fever and pancytopenia. Intracytoplasmic rickettsial morulae were detected on peripheral smear and bone marrow biopsy specimens, and PCR amplified Ehrlichia ewingii DNA from both specimens. To our knowledge, this is the first report of E. ewingii infection of human bone marrow. PMID:25187638

  3. First Reported Case of Ehrlichia ewingii Involving Human Bone Marrow

    PubMed Central

    Allen, M. Brandon; Pritt, Bobbi S.; Sloan, Lynne M.; Paddock, Christopher D.; Musham, Chaitanya K.; Ramos, Jeanette M.; Cetin, Neslihan

    2014-01-01

    A 65-year-old female with a history of multiple tick bites presented with fever and pancytopenia. Intracytoplasmic rickettsial morulae were detected on peripheral smear and bone marrow biopsy specimens, and PCR amplified Ehrlichia ewingii DNA from both specimens. To our knowledge, this is the first report of E. ewingii infection of human bone marrow. PMID:25187638

  4. Painless transient bone marrow edema syndrome in a pediatric patient.

    PubMed

    Joshi, Vivek; Hermann, George; Balwani, Manisha; Simpson, William L

    2014-11-01

    Transient regional migratory osteoporosis, considered to be part of the spectrum of bone marrow edema syndrome, is a rare condition with an unknown etiology. Patients usually present with lower extremity pain, most commonly in the 4th-5th decades of life. We describe a 15-year-old male patient with type 1 Gaucher disease who presented with transient bone marrow edema syndrome with features most closely resembling regional migratory osteoporosis. The patient presented with bone marrow edema of the lateral tibial epiphysis of his right knee that was incidentally seen on routine surveillance MRI that was performed as protocol for patients with type 1 Gaucher disease on enzyme replacement therapy. At this time, the patient had no pain and physical examination was normal. Follow-up MRI of the right knee 4 months afterward showed complete resolution of the signal abnormality in the right tibial epiphysis, and repeat study 8 months later displayed a new focus of painless migratory edema of the medial tibial epiphysis of the same knee. These changes completely resolved as well. Marrow signal abnormalities in children with Gaucher disease can have a broad differential, including infection, marrow infiltration, trauma, osteonecrosis, and bone marrow edema syndrome, amongst others. Correct diagnosis of bone marrow edema syndrome is critical, as this disease process most often resolves on conservative measures. The unusual presentation of transient bone marrow edema syndrome with regional migratory osteoporosis features in a young patient with Gaucher disease is described. PMID:24893724

  5. Pure red cell aplasia caused by Parvo B19 virus in a kidney transplant recipient.

    PubMed

    Baral, A; Poudel, B; Agrawal, R K; Hada, R; Gurung, S

    2012-01-01

    Parvo B19 is a single stranded DNA virus, which typically has affinity for erythroid progenitor cells in the bone marrow and produces a severe form of anemia known as pure red cell aplasia. This condition is particularly worse in immunocompromised individuals. We herein report a young Nepali male who developed severe and persistent anaemia after kidney transplantation while being on immunosuppressive therapy. His bone marrow examination revealed morphological changes of pure red cell aplasia, caused by parvovirus B19. The IgM antibody against the virus was positive and the virus was detected by polymerase chain reaction in the blood. He was managed with intravenous immunoglobulin. He responded well to the treatment and has normal hemoglobin levels three months post treatment. To the best of our knowledge, this is the first such case report from Nepal. PMID:23478734

  6. Proliferative and Glycolytic Assessment of the Whole-Body Bone Marrow Compartment

    PubMed Central

    Goryawala, Mohammed; Adjoua, Malek; Gle, Seza

    2015-01-01

    Objective: Quantitative assessment of active bone marrow (BM) in vivo is yet to be well-defined. This study aims to compare total body BM volume estimations obtained from use of both18F-FLT PET/CT and 18F-FDG PET/CT in order to consolidate higher cellular proliferation rates with imaging the highly active red BM in pancreatic cancer. Methods: This phase I pilot study includes seven patients with pancreatic cancers who underwent both 18F-FLT and 18F-FDG imaging each acquired within a weeks duration. A CT-based classifier is used for segmenting bone into cortical and trabecular regions. The total BM volume is determined through statistical thresholding on PET activity found within the trabecular bone. Results: Results showed that 18F-FLT measures of red BM volume (RBV) were higher than those obtained from 18F-FDG (?=89.21 ml). RBV obtained using 18F-FLT in males were found to have high correlation with measured weight (R2=0.61) and BMI (R2=0.70). The red BM fraction obtained from 18F-FLT was significantly different between males and females, with females showing much higher red bone matter within the trabecular bone (p<0.05). In contrast to 18F-FLT, 18F-FDG BM measurements showed that RBV was significantly different between males and females (p<0.05). Results also show that spinal activity SUV threshold for red BM segmentation is significantly different between 18F-FLT PET and 18F-FDG PET (p<0.05). Conclusion: By combining 18F-FLT-PET and 18F-FDG-PET, this study provides useful insights for in vivo BM estimation through its proliferative and glycolytic activities. PMID:26316472

  7. Autologous bone marrow transplantation using marrow incubated with Asta Z 7557 in adult acute leukemia.

    PubMed

    Gorin, N C; Douay, L; Laporte, J P; Lopez, M; Mary, J Y; Najman, A; Salmon, C; Aegerter, P; Stachowiak, J; David, R

    1986-05-01

    The sensitivity of human myeloblastic leukemic (CFU-L) and normal hemopoietic stem cells (CFU-GM and BFU-e) to Asta Z 7557 (INN Mafosfamide) was studied with regard to autologous bone marrow transplantation (ABMT) with cleansed marrow for consolidation therapy in adult patients with acute leukemia (AL) in remission. Establishment of the dose-response curves for CFU-GM (n = 37), BFUe (n = 11), and myeloblastic CFU-L (n = 9) demonstrated a wide range of sensitivity from patient to patient for all three progenitors. Whereas CFU-L, CFU-GM, and BFU-e grown in semisolid cultures disclosed similar sensitivities to Asta Z 7557, long-term culture (LTC) studies (n = 41) indicated a higher resistance of early progenitors. In an effort to achieve a maximum tumor cell kill and yet spare a sufficient amount of normal stem cells to ensure consistent engraftment, we defined the optimal dose for marrow cleansing as the dose sparing 5% CFU-GM (LD95). This dose was established from a preincubation test (PIT) realized on a 10-mL marrow aspirate taken 15 days before marrow collection in each individual patient. Twenty-four adult patients while in remission of AL (20 in complete remission, four in partial remission) were consolidated by cyclophosphamide 60 mg/kg X 2 and total body irradiation at 10 Gy followed by ABMT with marrow cleansed by Asta Z 7557 according to the specification described above. Patients were divided in two groups: group 1, unfavorable prognosis (11 patients); group 2, standard prognosis [13 patients in first complete remission (CR)]. All patients engrafted on leukocytes (median day for recovery to 10(9)/L: day 30), patients with ALL recovered faster than patients with ANL (median day 19 v 34). Similarly, recovery of platelets to 50.10(9)/L occurred sooner in patients with ALL (median day 67, range day 23 through 90) whereas three patients with acute nonlymphoblastic leukemia (ANLL) in group 2 had to be supported with platelet transfusions for more than one year. In group 1, six patients had recurrent tumor within six months; three patients died from toxicity with no evidence of tumor. Two patients are still disease-free with a short follow-up (nine and ten months). In group 2, two patients died from toxicity with no evidence of leukemia three and 16 months post-ABMT. One patient with a M5 ANLL and one patient with ALL relapsed at six and 15 months, respectively. Nine patients have remained in CR or are disease-free with a median follow-up of 22 months.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:3516254

  8. The bone marrow microenvironment and leukemia: biology and therapeutic targeting

    PubMed Central

    Sison, Edward Allan R; Brown, Patrick

    2011-01-01

    Multiple studies have demonstrated that interaction with the bone marrow stromal microenvironment contributes to the survival of leukemia cells. One explanation for this phenomenon is the interaction between the cell surface receptors CXCR4 and CXCL12. Through CXCL12/CXCR4-mediated chemotaxis, leukemia cells migrate to microscopic niches within the bone marrow, which leads to increased proliferation and survival. Several studies have suggested that increased CXCR4 expression may portend a poor prognosis in various types of leukemia, possibly due to increased protection of leukemia cells by bone marrow stroma. A potential therapeutic strategy to overcome this stromal-mediated survival advantage is to target CXCR4. Inhibition of CXCR4 may allow leukemia cells to be released from bone marrow niches that confer resistance to chemotherapy and negate the survival benefit imparted by bone marrow stroma. PMID:21668393

  9. Caffeine inhibits adipogenic differentiation of primary adipose-derived stem cells and bone marrow stromal cells.

    PubMed

    Su, Shu-Hui; Shyu, Huey-Wen; Yeh, Yao-Tsung; Chen, Kuan-Ming; Yeh, Hua; Su, Shu-Jem

    2013-09-01

    Caffeine consumption has been related to loss of body weight and modulates lipid metabolism. However, impacts of caffeine on adipogenic differentiation have not been well determined yet. The present study evaluated the effects of caffeine on adipogenesis using primary rat adipose-derived stem cells (ADSCs) and a mouse bone marrow stromal cell line (M2-10B4) in vitro. ADSCs and M2-10B4 were continuously exposed to caffeine (0.1-1mM) during adipogenic differentiation for 7 and 12 days, respectively. Oil red O and Nile red staining showed that caffeine reduced lipid droplet and adipocyte levels in both cell types. In addition, Nile red staining and FACScan flow cytometry showed that caffeine dose-dependently decreased adipocyte differentiation from 20% to 50% of the control ADSCs and M2-10B4 cells. Caffeine decreased the expression of adipogenesis-related genes including peroxisome proliferator-activated receptor-γ, CCAAT/enhancer-binding protein-α, adipocyte lipid binding protein, lipoprotein lipase, leptin, and TNFα in a dose-dependent manner. Rather, low concentration of caffeine (0.1mM) significantly increased IL-6 expression, but unexpectedly inhibited that at a concentration more than 0.3mM. Taken together, caffeine was able to effectively inhibit adipogenic differentiation of ADSCs and M2-10B4 cells partly through its inhibition of adipogenesis-related factors. PMID:23727198

  10. [A case of pure red cell aplasia with hypogammaglobulinemia appearing after thymo-thymectomy].

    PubMed

    Kokubo, M; Shirohashi, Y; Inaba, K; Sato, H; Tateyama, K

    1999-06-01

    We present a case of 83-year-old woman with pure red cell aplasia appearing eight months after thymo-thymectomy for an invasive thymoma. She underwent thymo-thymectomy for an invasive thymoma in July 1996. Preoperative examination revealed neither anemia nor hypogammaglobulinemia. About eight months after the operation, she was readmitted because of anemia and hypogammaglobulinemia. Bone marrow aspiration revealed absence of erythroblasts and chest CT revealed norecurrence of thymoma. Her anemia had responded to ciclosporin. PMID:10380482

  11. Reviving red snapper.

    PubMed

    Estabrook, Barry

    2010-01-01

    Red snappers in the Gulf of Mexico once hovered on the brink of extinction, their population having dropped to 2 percent of what had historically swum in the Gulf. But thanks to a recently introduced plan that turns the conventional wisdom of fisheries management on its head, the picture has begun to change. Called Individual Fishing Quotas (IFQs), the new regulations, which give a guaranteed allotment of fish to each participant instead of applying industry-wide quotas, went into effect for Gulf of Mexico Red Snapper (Lutjanus campechanus) in early 2007. The results were immediate and so profound that the Gulf Fishery Management Council voted earlier this year to increase the annual limit on red snapper to nearly 7 million pounds from 5 million. PMID:21542214

  12. Mouse Models of Bone Marrow Transplantation

    PubMed Central

    Reddy, Pavan; Negrin, Robert; Hill, Geoffrey R.

    2010-01-01

    Over the last 50 years, mouse models of bone marrow transplantation have provided the critical links between graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) pathophysiology and clinical practice. The initial insight from mouse models that GVHD and GVL were T cell dependent has long been confirmed clinically. More recent translations from mouse models have included the important role of inflammatory cytokines in GVHD. Newly developed concepts relating to the ability of antigen presenting cell (APC) and T cell subsets to mediate GVHD now promise significant clinical advances. The ability to use knockout and transgenic approaches to dissect mechanisms of GVHD and GVL mean that mouse systems will continue as the predominant preclinical platform. The basic transplant approach in these models, coupled with modern real-time immunologic imaging of GVHD and GVL is discussed. PMID:18162233

  13. Lung function after bone marrow grafting

    SciTech Connect

    Depledge, M.H.; Barrett, A.; Powles, R.L.

    1983-02-01

    Results of a prospective lung function study are presented for 48 patients with acute myeloid leukemia (AML) treated with total body irradiation (TBI) and bone marrow transplantation (BMT) at the Royal Marsden Hospital between 1978 and 1980. Patients with active disease or who were in remission following cytoreductive chemotherapy had mildly impaired gas exchange prior to grafting. After TBI and BMT all patients studied developed progressive deterioration of lung function during the first 100 days, although these changes were subclinical. Infection and graft-versus-host disease (GvHD) were associated with further worsening of restrictive ventilatory defects and diffusing capacity (D/sub L/CO). Beyond 100 days, ventilatory ability returned to normal and gas transfer improved, although it failed to reach pre-transplant levels. There was no evidence of progressive pulmonary fibrosis during the first year after grafting.

  14. Marrow failure: a window into ribosome biology

    PubMed Central

    Ruggero, Davide

    2014-01-01

    Diamond-Blackfan anemia, Shwachman-Diamond syndrome, and dyskeratosis congenita are inherited syndromes characterized by marrow failure, congenital anomalies, and cancer predisposition. Genetic and molecular studies have uncovered distinct abnormalities in ribosome biogenesis underlying each of these 3 disorders. How defects in ribosomes, the essential organelles required for protein biosynthesis in all cells, cause tissue-specific abnormalities in human disease remains a question of fundamental scientific and medical importance. Here we review the overlapping and distinct clinical features of these 3 syndromes and discuss current knowledge regarding the ribosomal pathways disrupted in each of these disorders. We also explore the increasing complexity of ribosome biology and how this informs our understanding of developmental biology and human disease. PMID:25237201

  15. Heme oxygenase-1 deficiency alters erythroblastic island formation, steady-state erythropoiesis and red blood cell lifespan in mice

    PubMed Central

    Fraser, Stuart T.; Midwinter, Robyn G.; Coupland, Lucy A.; Kong, Stephanie; Berger, Birgit S.; Yeo, Jia Hao; Andrade, Osvaldo Cooley; Cromer, Deborah; Suarna, Cacang; Lam, Magda; Maghzal, Ghassan J.; Chong, Beng H.; Parish, Christopher R.; Stocker, Roland

    2015-01-01

    Heme oxygenase-1 is critical for iron recycling during red blood cell turnover, whereas its impact on steady-state erythropoiesis and red blood cell lifespan is not known. We show here that in 8- to 14-week old mice, heme oxygenase-1 deficiency adversely affects steady-state erythropoiesis in the bone marrow. This is manifested by a decrease in Ter-119+-erythroid cells, abnormal adhesion molecule expression on macrophages and erythroid cells, and a greatly diminished ability to form erythroblastic islands. Compared with wild-type animals, red blood cell size and hemoglobin content are decreased, while the number of circulating red blood cells is increased in heme oxygenase-1 deficient mice, overall leading to microcytic anemia. Heme oxygenase-1 deficiency increases oxidative stress in circulating red blood cells and greatly decreases the frequency of macrophages expressing the phosphatidylserine receptor Tim4 in bone marrow, spleen and liver. Heme oxygenase-1 deficiency increases spleen weight and Ter119+-erythroid cells in the spleen, although ?4?1-integrin expression by these cells and splenic macrophages positive for vascular cell adhesion molecule 1 are both decreased. Red blood cell lifespan is prolonged in heme oxygenase-1 deficient mice compared with wild-type mice. Our findings suggest that while macrophages and relevant receptors required for red blood cell formation and removal are substantially depleted in heme oxygenase-1 deficient mice, the extent of anemia in these mice may be ameliorated by the prolonged lifespan of their oxidatively stressed erythrocytes. PMID:25682599

  16. Influenza virus infects bone marrow mesenchymal stromal cells in vitro: implications for bone marrow transplantation.

    PubMed

    Khatri, Mahesh; Saif, Yehia M

    2013-01-01

    Mesenchymal stromal cells (MSCs) have differentiation, immunomodulatory, and self-renewal properties and are, therefore, an attractive tool for regenerative medicine and autoimmune diseases. MSCs may be of great value to treat graft-versus-host disease. Influenza virus causes highly contagious seasonal infection and occasional pandemics. The infection is severe in children, elderly, and immunocompromised hosts including hematopoietic stem cell transplant patients. The objective of this study was to determine if MSCs are permissive to influenza virus replication. We isolated MSCs from the bone marrow of 4- to 6-week-old germ-free pigs. Swine and human influenza virus strains were used to infect MSCs in vitro. MSCs expressed known influenza virus ?-2,3 and ?-2,6 sialic acid receptors and supported replication of swine and human influenza viruses. Viral infection of MSCs resulted in cell lysis and proinflammatory cytokine production. These findings demonstrate that bone marrow-derived MSCs are susceptible to influenza virus. The data also suggest that transplantation of bone marrow MSCs from influenza virus-infected donors may transmit infection to recipients. Also, MSCs may get infected if infused into a patient with an ongoing influenza virus infection. PMID:23006541

  17. A Method for Generation of Bone Marrow-Derived Macrophages from Cryopreserved Mouse Bone Marrow Cells

    PubMed Central

    Lima, Djalma S.; Zamboni, Dario S.

    2010-01-01

    The broad use of transgenic and gene-targeted mice has established bone marrow-derived macrophages (BMDM) as important mammalian host cells for investigation of the macrophages biology. Over the last decade, extensive research has been done to determine how to freeze and store viable hematopoietic human cells; however, there is no information regarding generation of BMDM from frozen murine bone marrow (BM) cells. Here, we establish a highly efficient protocol to freeze murine BM cells and further generate BMDM. Cryopreserved murine BM cells maintain their potential for BMDM differentiation for more than 6 years. We compared BMDM obtained from fresh and frozen BM cells and found that both are similarly able to trigger the expression of CD80 and CD86 in response to LPS or infection with the intracellular bacteria Legionella pneumophila. Additionally, BMDM obtained from fresh or frozen BM cells equally restrict or support the intracellular multiplication of pathogens such as L. pneumophila and the protozoan parasite Leishmania (L.) amazonensis. Although further investigation are required to support the use of the method for generation of dendritic cells, preliminary experiments indicate that bone marrow-derived dendritic cells can also be generated from cryopreserved BM cells. Overall, the method described and validated herein represents a technical advance as it allows ready and easy generation of BMDM from a stock of frozen BM cells. PMID:21179419

  18. Lustre on Red Sky.

    SciTech Connect

    Monk, Stephen Todd; Mervini, Joe

    2010-04-01

    The goals of Lustre on Red Sky are: (1) provide home/projects/scratch Lustre file systems; (2) adhere to the Sun HPC stack; (3) implement software RAID on Sun provided JBODs; and (4) design for easy administration. Conclusions are: (1) software RAID includes additional risks and administration vs. hardware RAID solutions; (2) limited testing of hardware in these configurations make it ill-suited for rapid deployment in a production environment; and (3) Lustre has been a shining star on this machine, Red Sky users are pleased with its performance.

  19. Isolation of a preadipocyte cell line from rat bone marrow and differentiation to adipocytes.

    PubMed

    Marko, O; Cascieri, M A; Ayad, N; Strader, C D; Candelore, M R

    1995-10-01

    A unique population of rat adipocyte precursor cells was derived from normal rat bone marrow. The epitheloid-like preadipocytes were isolated from a mixed culture of bone marrow cells by a combination of differential trypsinization, enrichment by Ficoll gradient centrifugation, and differential seeding. This cell line, designated RBM-Ad, can be fully differentiated into multilocular adipocytes morphologically resembling brown adipose tissue. No changes in the differentiation pattern are observed during propagation of these cells, and they have been successfully carried and differentiated up to passage 49. Histological staining of differentiated cells with Sudan black, Sudan IV, and oil red O indicates the presence of lipids in intracellular vesicles. The nonselective beta-adrenergic agonist isoproterenol stimulates adenylyl cyclase activity in both preadipocytes and differentiated adipocytes. In contrast, BRL-37344, a beta 3-adrenergic receptor-specific agonist, stimulates adenylyl cyclase activity and glycerol release in differentiated adipocytes, but not preadipocytes. In addition, differentiated adipocytes contain messenger RNA encoding the brown adipose-specific protein, thermogenin. Thus, this rat preadipocyte cell line can be differentiated into adipocytes that histologically and functionally resemble brown adipose tissue. PMID:7545105

  20. The effects of bone marrow stromal cell transplants on tendon healing in vitro

    PubMed Central

    Zhao, Chunfeng; Chieh, Hsiao-Feng; Bakri, Karim; Ikeda, Jun; Sun, Yu-Long; Moran, Steven L.; An, Kai-Nan; Amadio, Peter C.

    2014-01-01

    The purpose of this study was to investigate the effect of bone marrow stromal cells (BMSCs) on tendon healing in a canine ex vivo model. Bone marrow was harvested and BMSCs were isolated and cultured according to established protocols. Cells were seeded into 0.5 mg/ml collagen gels and cultured for 24 h to allow gel contraction, and then implanted between the lacerated ends of repaired flexor digitorum profundus tendons. Tendons repaired with a gel patch alone and without a gel patch served as control groups. After 2 and 4 weeks in culture, the repaired tendons were evaluated for breaking strength and stiffness. Cell viability was assessed by labeling the cells with PKH26 red fluorescent cell linker. The maximal strength and stiffness of repaired tendons with the BMSC-seeded patch were significantly higher than the repaired tendons without a patch or with a patch without cells, at both 2 and 4 weeks (p < 0.05). Viable BMSC were present between the cut tendon ends at both 2 and 4 weeks. We conclude that BMSC-seeded gel patch transplantation has the potential to enhance flexor tendon healing, and we plan to investigate this effect in vivo. PMID:19736035

  1. Bone marrow replacement in the treatment of hemolytic disease in mice

    SciTech Connect

    Bernstein, S.E.; Deveau, S.A. )

    1989-11-01

    Bone marrow replacement therapy following whole-body x- or gamma-irradiation has until now proven to be of limited value in the treatment of individuals with hemolytic disease. The large doses of radiation required for destruction of defective erythropoietic tissues coupled with their resultant high mortality appears to limit its usefulness. Techniques have been developed by the authors to limit the extent of exposure and to improve survival following irradiation. These techniques include shielding of all parts of the body except the hind limbs, prophylactic use of antibiotics, and preparatory blood transfusion to suppress the development of indigenous defective erythrocytes. Using these combined techniques we were able to establish high rates of survival, successful engraftment, and long-term clinical improvement in mice with several hemolytic disorders emanating from hereditary defects in spectrin production and incorporation. Evidence is presented indicating that complete bone marrow replacement occurs even in nonirradiated portions of the erythron and that only donor type red blood cells appear in the circulation.

  2. Daily variation in radiosensitivity of circulating blood cells and bone marrow cell density in mice

    SciTech Connect

    Tabatabai, R.N.

    1984-01-01

    Mice on a 12/12 light/dark cycle were bled during a twenty-four hour period each week for eight weeks to establish daily values of circulating blood cells. No significant daily variation was found in total red blood cells, hematocrit, or percentage of reticulocytes. A significant (P < 0.001) daily variation was found in total white blood cells, with the minimum occurring at 8 PM and the maximum occurring during the daylight hours from 8 a.m. to 2 p.m. Mice were then exposed to 0 R, 20 R, 50 R, or 100 R of x-radiation to determine what dose significantly reduces the total white cell count in circulating blood. It was found that 100 R significantly (P < .05) reduces the total white cell count over a four week period post-exposure. To determine if circulating blood cells and bone marrow cells show a diurnal radiosensitivity, mice were exposed to 100 R or 200 R of x-radiation at noon or midnight. Hematocrits, reticulocyte and white blood cell counts, daily white blood cell rhythm, and bone marrow cell density indicate that these mice were more radiosensitive at night.

  3. PRIMARY MARROW DERIVED STROMAL CELLS: ISOLATION AND MANIPULATION

    PubMed Central

    Ramakrishnan, Aravind; Torok-Storb, Beverly; Pillai, Manoj M

    2013-01-01

    Marrow Stromal Cells (MSCs) are relatively rare cells difficult to visualize in marrow biopsies or detect in aspirated marrow. Under specific conditions MSC can be expanded in vitro and the population can give rise to several mesenchymal lineages. MSC also refers to mesenchymal stem cells which implies that all cells in the population are multipotent. It is generally agreed that while there may be a few multipotent stem cells in an MSC population the majority are not stem cells. In either case MSC do not produce hematopoietic cells. Although MSCs have been isolated and characterized from several tissues, bone marrow is their most common source for research and clinical use. Primary MSC populations can be derived from bone marrow mononuclear cells with relative ease, but it is important to recognize the cellular heterogeneity within a culture and how this may vary from donor to donor. In this chapter, we will describe methodology to derive primary MSCs from bone marrow screens, an otherwise discarded byproduct of bone marrow harvests used for clinical transplantation. We will also describe some useful techniques to characterize and manipulate MSCs both primary and immortalized cell lines. PMID:23959984

  4. Clover, Red (Trifolium pretense)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genetic modification of plants by the insertion of transgenes can be a powerful experimental approach to answer basic questions about gene product function. This technology can also be used to make improved crop varieties for use in the field. To apply this powerful tool to red clover, an important ...

  5. Red Cross Swimming Update.

    ERIC Educational Resources Information Center

    Vlasich, Cynthia

    1989-01-01

    Six new aquatic courses, developed by the Red Cross, are described. They are: Infant and Preschool Aquatics, Longfellow's Whale Tales (classroom water safety lessons for K-Six), Basic Water Safety, Emergency Water Safety, Lifeguard Training, and Safety Training for Swim Coaches. (IAH)

  6. CHINOOK RED RASPBERRY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    'Chinook' is a new primocane fruiting red raspberry (Rubus idaeus L.) from the U.S. Department of Agriculture- Agricultural Research Service (USDA-ARS) breeding program in Corvallis, Ore. released in cooperation with the Oregon State Agricultural Experiment Station, the Washington State University A...

  7. Red sea drillings.

    PubMed

    Ross, D A; Whitmarsh, R B; Ali, S A; Boudreaux, J E; Coleman, R; Fleisher, R L; Girdler, R; Manheim, F; Matter, A; Nigrini, C; Stoffers, P; Supko, P R

    1973-01-26

    Recent drilling in the Red Sea has shown that much of the basin is underlain by evaporites of a similar age to that of evaporites found in the Mediterranean Sea. These evaporites and their structural positions indicate that other brine areas are present-and, indeed, several others have been discovered. PMID:17843766

  8. 'Saanich' Red Raspberry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    'Saanich' is a new floricane-fruiting red raspberry (Rubus idaeus) cultivar from the breeding program at the Pacific Agri-Food Research Centre (PARC) of Agriculture and Agri-Food Canada, Agassiz, British Columbia. 'Saanich', tested as BC 89-34-41, was selected from a 1989 cross of BC 82-5-161 and BC...

  9. 'Valley Red' Strawberry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    'Valley Red' is a new June-bearing (short-day) strawberry (Fragaria ×ananassa Duchesne ex Rozier) cultivar from the U.S. Department of Agriculture-Agricultural Research Service (USDA-ARS) breeding program in Corvallis, Ore., released in cooperation with the Oregon Agricultural Experiment Station, Th...

  10. 'Vintage' Red Raspberry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    'Vintage' is a new primocane-fruiting red raspberry (Rubus idaeus L.) from the U.S. Dept. of Agriculture–Agricultural Research Service (USDA–ARS) breeding program in Corvallis, OR released in cooperation with the Oregon State Agricultural Experiment Station and the Washington State University Agricu...

  11. RED2TEX: A TRIX RED to LATEX converter

    SciTech Connect

    Chase, L.; Langdon, A.B.

    1987-05-20

    A summary of RED2TEX is presented. RED2TEX converts standard TRIX RED format commands to TEX or LATEX commands for subsequent LATEX formatting. LATEX is a special version of the TEX document preparation system. LATEX adds to TEX a collection of commands that simplifies formatting. LATEX runs on the J-Vax and the LLL-LCC Pyramid machines. RED2TEX resides in Unix directory CHASE/TEX.

  12. Bone marrow suppression and severe anaemia associated with persistent Plasmodium falciparum infection in African children with microscopically undetectable parasitaemia

    PubMed Central

    Helleberg, Marie; Goka, Bamenla Q; Akanmori, Bartholomew D; Obeng-Adjei, George; Rodriques, Onike; Kurtzhals, Jorgen AL

    2005-01-01

    Background Severe anaemia can develop in the aftermath of Plasmodium falciparum malaria because of protracted bone marrow suppression, possibly due to residual subpatent parasites. Materials and methods Blood was collected from patients with recent malaria and negative malaria microscopy. Detection of the Plasmodium antigens, lactate dehydrogenase (Optimal®), aldolase and histidine rich protein 2 (Now malaria®) were used to differentiate between patients with (1) no malaria, (2) recent cleared malaria, (3) persistent P. falciparum infection. Red cell distribution width (RDW), plasma levels of soluble transferrin receptor (sTfR) and erythropoietin (EPO) were measured as markers of erythropoiesis. Interleukin (IL) 10 and tumour necrosis factor (TNF)α were used as inflammation markers. Results EPO was correlated with haemoglobin, irrespective of malaria (R = -0.36, P < 0.001). Persistent P. falciparum infection, but not recent malaria without residual parasites, was associated with bone marrow suppression i.e., low RDW (P < 0.001 vs. P = 0.56) and sTfR (P = 0.02 vs. P = 0.36). TNF-α and IL-10 levels were not associated with bone marrow suppression. Conclusion In the treatment of malaria, complete eradication of parasites may prevent subsequent development of anaemia. Severely anaemic children may benefit from antimalarial treatment if antigen tests are positive, even when no parasites can be demonstrated by microscopy. PMID:16321150

  13. Engraftment of allogeneic bone marrow without graft-versus-host disease in mongrel dogs using total lymphoid irradiation

    SciTech Connect

    Gottlieb, M.; Strober, S.; Hoppe, R.T.; Grumet, F.C.; Kaplan, H.S.

    1980-06-01

    We achieved long-term engraftment of unmatched bone marrow (BM) in dogs without graft-versus-host disease (GVHD) using a regimen of total lymphoid irradiation (TLI) which could be applied clinically. Twelve normal adult mongrel dogs were given TLI in 18 fractions of 100 rad each (total dose, 1800 rad) over 4 weeks to mantle and abdominal fields in continuity. Nine of the 12 were transfused with one or two random donor whole blood transfusions during the irradiation regimen to determine the risk of sensitization after the onset of immunosuppression. A mean (+- SD) of 0.71 +- 0.54 x 10/sup 9/ BM cells/kg of recipient body weight from unrelated sex-mismatched donors was infused within 24 h of the 18th irradiation fraction. Engraftment was assessed by demonstration of donor-type sex chromosomes in spontaneous metaphase spreads of recipient marrow aspirates, and by the appearance of donor-type red blood cells antigens (DEA) in the recipients' blood. Three untransfused and nine transfused recipients were shown to be stable mixed BM chimeras during a followup period of 2 to 11 months after transplantation. Blood transfusion during TLI did not result in graft rejection. We observed no clinical signs of acute or chronic GVHD. TLI has minimal toxicity when compared with conditioning regimens currently used in BM transplantation for aplastic anemia. Potential advantages of the TLI regimen include the opportunity to use unmatched marrow donors and protection from GVHD.

  14. Evaluation of the silicon phthalocyanine Pc 4 for photodynamic bone marrow purging

    NASA Astrophysics Data System (ADS)

    Keij, Jan F.; Jiang, Yajuan; Sotiropoulos, Damianos A.; Ben-Hur, Ehud; Visser, Jan W.

    1998-07-01

    The silicon phthalocyanine Pc 4 was tested as a photosensitizer for the selective photoinactivation of malignant cells in bone marrow transplantation samples. Using a murine model system, incubation of 1.5 X 107 cells/mL with 15 nM Pc 4 followed by exposure to red light ((lambda) > 600 nm, fluence of 18 J/cm2) was shown to result in a greater than 6 log10 reduction of the clonogenic growth for the murine cell lines ABE-8.1/2, BC3A and L1210. The clonogenic growth of WEHI-3 and P815 cells was reduced by more than 5 log10 and more than 3 log10, respectively. Late murine hematopoietic progenitor cells were less sensitive than cancer cells; the surviving fractions were 0.084 for the colony forming unit, megakaryocyte (CFU-Mk); 0.038 for the colony forming unit, granulocyte macrophage (CFU-GM); 0.0018 for the colony forming unit, mix (CFU-mix) and < 0.003 for burst forming units, erythroid (BFU-E). Early hematopoietic progenitor cells, assayed in the in vitro cobble stone area forming cell assay, were not affected by the photodynamic treatment. Likewise, in vivo assays of early hematopoietic progenitor cells showed no reduction of their ability to repopulate the bone marrow. Irradiation of the samples following incubation of 1.5 X 106 cells/mL with Pc 4 resulted in increased photosensitivity of all cell types, including the early and late hematopoietic progenitor cells. Flow cytometric analysis of Pc 4 uptake by the cells revealed that the increased photosensitivity could be traced to increased Pc 4 uptake; however, Pc 4 uptake among cell types did not correlate with photosensitivity. When mixed with bone marrow (BM) cells, Pc 4 uptake in the cell lines increased as the fraction of BM increased from 0.5 to 0.95. These observations suggest that Pc 4 may be a suitable photosensitizer for bone marrow purging.

  15. Bone marrow osteoma of the tibia: A case report

    PubMed Central

    ZHOU, BEN-GEN; LIU, MEI-YUAN; LV, LI-CHUN; XIA, HONG

    2014-01-01

    In this study, an unusual case of osteoma is presented, whereby a bone marrow osteoma was identified in the tibia. No previous cases of bone marrow osteoma have been reported. In this case, an eight-year-old male presented with discontinuous discomfort in the right distal calf for six months. Radiological examination and computed tomography revealed a radiopaque lesion within the affected bone. A technetium-99m bone scan revealed focally increased uptake in the same region. Together, these observations prior to surgery indicated that the patient may suffer from bone disease. Subsequently, a surgical excision was performed and the biopsy specimen was identified as bone marrow osteoma. Following surgery, the symptoms were eradicated and the prognosis was positive during the 24-month follow-up period. Bone marrow osteoma should be considered when a patient suffers from discontinuous and unexplained limb discomfort. PMID:25364463

  16. Technetium-99m antimony colloid for bone-marrow imaging

    SciTech Connect

    Martindale, A.A.; Papadimitriou, J.M.; Turner, J.H.

    1980-11-01

    Technetium-99m antimony colloid was prepared in our laboratory for bone-marrow imaging. Optimal production of colloid particles of size range 1 to 13 nm was achieved by the use of polyvinylpyrrolidone of mol. wt. 44,000. Electron microscopy was used to size the particles. Studies in rabbits showed exclusive concentration in the subendothelial dendritic phagocytes of the bone marrow. Pseudopods from these cells were found to traverse interendothelial junctions and concentrate colloid from the sinusoids. Imaging studies of bone marrow in rabbits showed the superiority of the Tc-99m antimony colloid over the much larger colloidal particle of Tc-99m sulfur colloid. Tissue distribution studies in the rat confirmed that bone-marrow uptake of Tc-99m antimony colloid was greater than that of Tc-99m sulfur colloid, although blood clearance was much slower.

  17. NIH Blood and Marrow Transplant Late Effects Consensus Conference

    Cancer.gov

    This day and a half symposium will bring together experts in blood and marrow transplantation, late effects, and health care delivery to discuss current evidence and knowledge gaps, develop consensus guidelines, and inform future research in the BMT survivor population.

  18. Understanding Bone Marrow Transplantation as a Treatment Option

    MedlinePLUS

    ... icio.us Digg Facebook Google Bookmarks Understanding Transplantation as a Treatment Option When you are diagnosed with a ... Transplant Talking with Your Doctor Diseases Treatable with a Bone Marrow Transplant or Cord Blood Transplant A ...

  19. Genetics Home Reference: Pearson marrow-pancreas syndrome

    MedlinePLUS

    ... Handbook Glossary Resources Pearson marrow-pancreas syndrome Mitochondrial DNA Related Condition(s) References Quick links to this topic ... This process is called oxidative phosphorylation. Although most DNA is packaged in chromosomes within the nucleus (nuclear ...

  20. Who Needs a Blood and Marrow Stem Cell Transplant?

    MedlinePLUS

    ... Aplastic Anemia Bone Marrow Tests Sickle Cell Disease Thalassemias Send a link to NHLBI to someone by ... and breast cancer Severe blood diseases, such as thalassemias , aplastic anemia , and sickle cell anemia Certain immune- ...

  1. Clonal analysis of bone marrow and macrophage cultures

    SciTech Connect

    Stewart, C.C.; Walker, E.B.; Johnson, C.; Little, R.

    1984-01-01

    To establish lineages that can be used to study their functional heterogeneity, the proliferation and differentiation of bone marrow derived mononuclear phagocytes and the lineages derived from them were studied. 28 references, 7 figures, 5 tables. (ACR)

  2. Registration of 'Red Ruby' Wheat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Red Ruby’ soft red winter wheat (Triticum aestivum L.) was developed by the Michigan Agricultural Experiment Station and released in 2007 via an exclusive licensing agreement through Michigan State University (MSU) Technologies. Red Ruby was selected from the cross Pioneer ‘2552’/Pioneer ‘2737W’ ma...

  3. Red Knots at Delaware Bay

    USGS Multimedia Gallery

    Red knots, an at-risk shorebird, at Delaware Bay. Red knots like to feed on horseshoe crab eggs to refuel after their marathon migrations of some 10,000 miles. Declines of horseshoe crabs and red knots seem to be related....

  4. Pathophysiology and Management of Inherited Bone Marrow Failure Syndromes

    PubMed Central

    Shimamura, Akiko; Alter, Blanche P.

    2012-01-01

    The inherited marrow failure syndromes are a diverse set of genetic disorders characterized by hematopoietic aplasia and cancer predisposition. The clinical phenotypes are highly variable and much broader than previously recognized. The medical management of the inherited marrow failure syndromes differs from that of acquired aplastic anemia or malignancies arising in the general population. Diagnostic workup, molecular pathogenesis, and clinical treatment are reviewed. PMID:20417588

  5. Bone marrow niche in the myelodysplastic syndromes.

    PubMed

    Cogle, Christopher R; Saki, Najmaldin; Khodadi, Elahe; Li, June; Shahjahani, Mohammad; Azizidoost, Shirin

    2015-10-01

    The myelodysplastic syndromes (MDS) are a diverse group of clonal hematopoietic malignancies characterized by ineffective hematopoiesis, progressive bone marrow (BM) failure, cytogenetic and molecular abnormalities, and variable risk of progression to acute myeloid leukemia (AML). The BM microenvironment in MDS plays an important role in the development of this disorder. The BM stromal cells of MDS patients often harbor distinct chromosomal aberrations than the hematopoietic elements, suggesting different genetic origins. Perturbed cytokine secretions from BM stromal cells such as multipotent mesenchymal stem cells (MSCs) and endothelial cells are associated with increased proliferation and survival of malignant hematopoietic cells. Within the MDS BM there are also alterations in stromal cell composition, signaling and angiogenesis between Low- and High-risk MDS patients. Several open lines of investigation into the MDS niche remain, including the timing of stromal defects in context to dysplastic hematopoiesis. Another important, unanswered question is the impact of age on BM stroma function and regulation (or dysregulation) or hematopoietic stem/progenitor cells. With a better understanding of the MDS niche, new therapeutic strategies will emerge. PMID:26276090

  6. Clover, red (Trifolium pratense).

    PubMed

    Sullivan, Michael L; Quesenberry, Kenneth H

    2015-01-01

    Genetic modification of plants by the insertion of transgenes can be a powerful experimental approach to answer basic questions about gene product function. This technology can also be used to make improved crop varieties for use in the field. To apply this powerful tool to red clover, an important forage legume, a population of red clover with high potential for regeneration in tissue culture has been developed. Here we provide a detailed procedure for Agrobacterium-mediated transformation of genotypes derived from this regenerable population. We have successfully used this methodology to express ?-glucuronidase (GUS) reporter genes as well as for hairpin RNA-mediated silencing of endogenous genes for polyphenol oxidase and a transferase crucial in phaselic acid accumulation. PMID:25300845

  7. Red lead: understanding red lead in lead-acid batteries

    NASA Astrophysics Data System (ADS)

    McKinley, J. P.; Dlaska, M. K.; Batson, R.

    The use of red lead in battery plates is not very well known to a large segment of the lead-acid battery industry. Historically, it was used in pasted and tubular positive plates in order to improve their formation time and enhance deep-cycle performance. Although the use of red lead has diminished over the last few decades, many companies are again considering the use of red lead in their plates. This article aims to give manufacturers a solid knowledge of the properties of red lead, including production and handling methods. Further, it presents an understanding of the influence in battery production, battery performance, and the cost-saving potential of red lead usage. The first part of the article is intended to explain the chemical and physical properties and fields of usage of red lead. The most widely used red lead product specifications for the battery industry are presented and explained. In the second part, the typical equipment for the production of red lead is reviewed. Raw material requirements, material handling equipment, a red lead furnace and milling are presented and discussed. The reader is taken through the production of a typical batch of red lead. Operating charts, process control data and system photos will help to understand the production process. The final part outlines an overall view of process requirements and identifies stages in lead-acid battery production that will be influenced by the use of red lead.

  8. Religious red herrings.

    PubMed

    Sheehan, Mark

    2013-09-01

    Brierley et al take big polarised political debates deep into the context of paediatric intensive care. They are concerned that 'deeply held belief in religion leads to children being potentially subjected to burdensome care'. However, it can be argued that they make a mistake in categorising this as a problem derived from religion, religious belief or the depth of religious conviction. Religion here is a red herring. PMID:22893531

  9. Bone marrow transplantation: economic, ethical, and social issues.

    PubMed

    Durbin, M

    1988-11-01

    Bone marrow transplantation is a useful model for the controversies surrounding medical technologies that involve high cost, mortality, and complications. This essay first delineates the economic circumstances of bone marrow transplantation, comparing it with other organ transplantations. Although children represent a significant proportion of bone marrow transplantation patients, little research has focused on the economic impact for this population. Next, the financial, social, and ethical motivations and controversies that surround bone marrow transplantation are explored, along with current allocation mechanisms. Finally, recommendations are offered for guiding discussions regarding the appropriate use of bone marrow transplantation. In making transplantation decisions, physicians must consider the costs and benefits of bone marrow transplantation for each patient. Such analyses, whether based on medical or socioeconomic criteria, are insufficient to resolve the fundamental cultural dilemmas posed by this procedure and other expensive medical technologies, however. The goal is to foster broader discussion of these issues to achieve more candid decisions in allocating resources among competing health priorities. PMID:3054784

  10. Evaluation of radiation effects on hematopoetic bone marrow by immunoscintigraphy

    SciTech Connect

    Dohmen, B.M.; Bares, R.; Buell, U.

    1994-05-01

    Radiotherapy is known to cause dose-dependent damage to the hematopoetic bone marrow (HBM) within the portal. It was the aim of the present study to evaluate acute suppression and long term recovery of HBM by use of bone marrow immunoscintigraphy (BMI) with monoclonal antibodies (1 mg of intact BW 250/183 labelled with 350-400 MBq Tc-99m) against NCA-95, expressed on granulocytes and their precursor cells. Ninety-five planar scintigrams covering 114 portals were analyzed. Antibody uptake of irradiated bone marrow was quantified by ROI-technique and expressed as percentage of uptake in corresponding areas outside the portal. During irradiation a marked drop of marrow uptake significantly correlating with the already received dose was observed. Scans obtained after completion of radiotherapy revealed a reduced uptake ({approximately}40% of the reference region) for about 4 years. Afterwards bone marrow normalized in portals with doses <35 Gy while following >35 Gy diminished uptake (70{plus_minus}25%) persisted indicating irreversible damage to HBM. We conclude that BMI is suitable for evaluation of acute damage and long time recovery of functional bone marrow after therapeutic irradiation and may be used for optimized planning of repeated radiotherapy.

  11. The bone marrow in aplastic anaemia: Diagnostic and prognostic features

    PubMed Central

    Frisch, B.; Lewis, S. M.

    1974-01-01

    Bone marrow preparations were examined from 80 patients with aplastic anaemia. The degree of cellularity varied greatly and in a third of the cases it was normal or even hypercellular at one site of aspiration. In the severely hypoplastic marrows lymphoid cells were predominant and this situation was associated with a worse prognosis. There was no correlation between marrow lymphoid cell content and blood lymphocyte count but there was an inverse relationship between blood lymphocyte count and marrow erythroblasts and a close direct relationship between the blood neutrophil count and marrow myeloid cell content. In all cases a proportion of the erythroblasts showed morphological abnormalities. These included especially megaloblastic changes and asynchrony of nuclear-cytoplasmic maturation. There were also binucleated cells, internuclear chromatin bridges, intercellular cytoplasmic connexions, nuclear degenerative changes, namely, blurred outlines, irregular shapes, budding and fragmentation, and atypical mitotic figures. These appearances illustrate the extent to which a qualitative defect of erythropoiesis occurs as part of the haematological pattern in aplastic anaemia, and in some cases dominates the bone marrow picture. Similar cytological features were found in all cases, including five patients with Fanconi's anaemia. Images PMID:4832303

  12. Clinical use of bone marrow, bone marrow concentrate, and expanded bone marrow mesenchymal stem cells in cartilage disease.

    PubMed

    Veronesi, Francesca; Giavaresi, Gianluca; Tschon, Matilde; Borsari, Veronica; Nicoli Aldini, Nicol; Fini, Milena

    2013-01-15

    Mesenchymal stem cells (MSCs) from bone marrow (BM) are widely used for bone and less for cartilage tissue regeneration due to their self-renewal and differentiating properties into osteogenic or chondrogenic lineages. This review considers the last decade of clinical trials involving a two-step procedure, by expanding in vitro MSCs from BM, or the so called "one-step" procedure, using BM in toto or BM concentrate, for the regeneration of cartilage and osteochondral tissue defects. The following conclusions were drawn: (1) Cartilage defects that can be repaired by the two-step technique are about twice the size as those where the one-step method is used; (2) the two-step procedure is especially used for the treatment of osteoarthritic lesions, whereas the one-step procedure is used for osteochondral defects; (3) the number of transplanted cells ranges between 3.810(6) and 11.210(6) cells/mL, and the period of cell culture expansion of implanted MSCs varies widely with regard to the two-step procedure; (4) hyaluronic or collagenic scaffolds are used in all the clinical studies analyzed for both techniques; (5) the follow-up of the two-step procedure is longer than that of the one-step method, despite having a lower number of patients; and, finally, (6) the mean age of the patients (about 39 years old) is similar in both procedures. Clinical results underline the safety and good and encouraging outcomes for the use of MSCs in clinics. Although more standardized procedures are required, the length of follow-up and the number of patients observed should be augmented, and the design of trials should be implemented to achieve evidence-based results. PMID:23030230

  13. Long-term survival of murine allogeneic bone marrow chimeras: effect of anti-lymphocyte serum and bone marrow dose

    SciTech Connect

    Norin, A.J.; Emeson, E.E.; Veith, F.J.

    1981-02-01

    Graft-vs-host disease (GVHD) and failure of donor stem cells to engraft permanently are two major obstacles to successful bone marrow transplantation. The effect of a single large dose of anti-lymphocyte serum (ALS) on mice receiving various numbers of H-2 incompatible bone marrow cells was evaluated. Most animals receiving lethal total body irradiation (TBI) and allogeneic marrow died within 45 days due to GVHD. Mice that were given ALS 6 to 24 h before TBI and bone marrow 24 h after irradiation survived in good health for more than 200 days. These cell preparations caused lethal GVHD in third party mice indicating that the lack of alloreactivity was specific to the strain in which the unresponsiveness was originally induced.

  14. Mars: simply red?

    NASA Astrophysics Data System (ADS)

    Hauber, Ernst; Neukum, Gerhard

    2006-04-01

    Mars has been known as the Red Planet since ancient times, and the small flotilla of spacecraft that has visited our solar system neighbour over the past few years could only confirm this basic observation from those ancient civilizations. However, the enormous amount of data returned from the varied instruments has significantly increased our knowledge of almost every aspect of the planet's evolution. Three orbiters and two rovers are currently operating there, and NASA's Mars Reconnaissance Orbiter is on its way. One of the three orbiters is Mars Express, ESA's first spacecraft to another planet. It is considered a major success of ESA's science programme, and one of the highlights of the agency's increasing efforts in planetary exploration. A wealth of scientific results has been published in journals and presented at conferences. The instrument on Mars Express that probably has the largest appeal to the public is the High Resolution Stereo Camera (HRSC). Two years ago we gave a description of its scientific goals and presented the first images obtained from orbit (Hauber and Neukum 2004). Here we give an overview of the technical and scientific achievements of HRSC made over the two years of the nominal mission, and show some of the most appealing images. But don't be fooled: despite the spectacular false-colour images shown here to enhance the subtle colour variations of the martian surface, HRSC's multispectral images have shown that Mars is red in varying tones everywhere, except at small parts of its ice-covered poles. Many other aspects of the data are harder to understand. Mars may still be red, but it is by no means simple!

  15. Red Spot Movie

    NASA Technical Reports Server (NTRS)

    2000-01-01

    This brief movie shows counterclockwise atmospheric motion around Jupiter's Great Red Spot. The clip was made from blue-filter images taken with the narrow-angle camera on NASA's Cassini spacecraft during seven separate rotations of Jupiter between Oct. 1 and Oct. 5, 2000.

    The clip also shows the eastward and westward motion of the zonal jets, seen as the horizontal stripes flowing in opposite directions. The zonal jets circle the planet. As far as can be determined from both Earth-based and spacecraft measurements, the positions and speeds of the jets have not changed for 100 years. Since Jupiter is a fluid planet without a solid boundary, the jet speeds are measured relative to Jupiter's magnetic field, which rotates, wobbling like a top because of its tilt, every 9 hours 55.5 minutes. The movie shows motions in the magnetic reference frame, so winds to the west correspond to features that are rotating a little slower than the magnetic field, and eastward winds correspond to features rotating a little faster.

    Because the Red Spot is in the southern hemisphere, the direction of motion indicates it is a high-pressure center. Small bright clouds appear suddenly to the west of the Great Red Spot. Scientists suspect these small white features are lightning storms. The storms eventually merge with the Red Spot and surrounding jets, and may be the main energy source for the large-scale features.

    The smallest features in the movie are about 500 kilometers (about 300 miles) across. The spacing of the movie frames in time is not uniform; some consecutive images are separated by two Jupiter rotations, and some by one. The images have been re-projected using a simple cylindrical map projection. They show an area from 50 degrees north of Jupiter's equator to 50 degrees south, extending 100 degrees east-west, about one quarter of Jupiter's circumference.

    Cassini is a cooperative project of NASA, the European Space Agency and the Italian Space Agency. The Jet Propulsion Laboratory, a division of the California Institute of Technology in Pasadena, manages the Cassini mission for NASA's Office of Space Science, Washington, D.C.

  16. Irradiation alters the differentiation potential of bone marrow mesenchymal stem cells.

    PubMed

    Wang, Yu; Zhu, Guoying; Wang, Jianping; Chen, Junxiang

    2016-01-01

    Bone injury following radiotherapy has been confirmed by epidemiological and animal studies. However, the underlying mechanism remains to be elucidated and no preventive or curative solution has been identified for this bone loss. The present study aimed to investigate the irradiation?altered osteogenesis and adipogenesis of bone marrow mesenchymal stem cells (BMSCs). BMSCs were derived and exposed to ??irradiation at doses of 0, 0.25, 0.5, 1, 2, 5 and 10Gy. Cell viability was assessed using a 3?(4,5?dimethylthiazol?2?yl)?2,5 diphenyl tetrazolium bromide assay, and clonal expansion invitro was detected by colony forming unit assessment. The osteogenic differentiation ability was demonstrated by alkaline phosphatase (ALP) activity, ALP staining and mineralization alizarin red staining, and the adipogenic differentiation ability was determined using OilOred staining. The osteogenesis?associated genes, RUNX2, ALP, osteocalcin (OCN) and adipogenesis?associated genes, PPAR?? and C/EBP?, were detected using reverse transcription?quantitative polymerase chain reaction analyses. The protein expression levels of RUNX2, ALP and PPAR?? were detected using western blotting. Compared with the control, significant decreases in the proliferation, ALP activity and mineralization ability of the BMSCs were observed in the ??irradiation group, with a high level of correlation with the exposure dose. However, no significant changes were observed in the area of OilredO positive staining. The mRNA levels of RUNX2, ALP and OCN were decreased (P<0.05), however, no significant changes were observed in the levels of C/EBP? and PPAR??. The protein expression levels of RUNX2 and ALP were decreased in the irradiated BMSCs, however, no significant difference was observed in the protein expression of PPAR??. Irradiation inhibited the osteogenic and adipogenic ability of the BMSCs, and the osteogenic differentiation was decreased. The results of the present study provided evidence to assist in further elucidating radiotherapy?associated side effects on the skeleton. PMID:26572960

  17. Lasting engraftment of histoincompatible bone marrow cells in dogs

    SciTech Connect

    Vriesendorp, H.M.; Klapwijk, W.M.; van Kessel, A.M.C.; Zurcher, C.; van Bekkum, D.W.

    1981-05-01

    Conditioning protocols were tested for their efficacy in increasng the incidence of engraftment of histoincompatible dog bone marrow cells. Cyclophosphamide and total body irradiation (TBI), Corynebacterium parvum and TBI, a 3- or 5-day delayed transfusion of bone marrow cells after TBI, or an increase in the number of donor bone marrow cells or lymphocytes appeared to be ineffective. These protocols were previously reported to promote recovery of splenic hemopoiesis in mice in short-term assays. The noted discrepancy between studies with mice and dogs invalidated allogeneic resistance as measured in the mouse spleen assay as a model for bone marrow allograft rejection. Intravenous treatment with silica particles or L-asparaginase did improve the engraftment rate after 7.5 Gy TBI. Low efficiency and significant extra toxicity restrict the applicability of these procedures. The most promising conditioning schedule found appeared to be two fractions of 6.0 Gy TBI separated by a 72-h interval. Prolonged survival was noted after transplantation of bone marrow cells from a one-DLA haplotype-mismatched donor. Possibilities for further improvement of this protocol are discussed.

  18. Lasting engraftment of histoincompatible bone marrow cells in dogs

    SciTech Connect

    Vriesendorp, H.M.; Klapwijk, W.M.; van Kessel, A.M.; Zurcher, C.; van Bekkum, D.W.

    1981-05-01

    Conditioning protocols were tested for their efficacy in increasing the incidence of engraftment of histoincompatible dog bone marrow cells. Cyclophosphamide and total body irradation (TBI), Corynebacterium parvum and TBI, a 3- or 5-day delayed transfusion of bone marrow cells after TBI, or an increase in the number of donor bone marrow cells or lymphocytes appeared to be ineffective. These protocols were previously reported to promote recovery of splenic hemopoiesis in mice in short-term assays. The noted discrepancy between studies with mice and dogs invalidated allogeneic resistance as measured in the mouse spleen assay as a model for bone marrow allograft rejection. Intravenous treatment with silica particles or L-asparaginase did improve the engraftment rate after 7.5 Gy TBI. Low efficiency and significant extra toxicity restrict the applicability of these procedures. The most promising conditioning schedule found appeared to be two fractions of 6.0 Gy TBI separated by a 72-hr interval. Prolonged survival was noted after transplantation of bone marrow cells from a one-DLA haplo-type-mismatched donor. Possibilities for further improvement of this protocol are discussed.

  19. Biological characteristics of micrometastatic cancer cells in bone marrow.

    PubMed

    Braun, S; Pantel, K

    1999-01-01

    There is emerging evidence that epithelial tumor cells are able to disseminate to secondary organs at an early stage of primary tumor development. One of the most prominent secondary organs screened for this type of dissemination is bone marrow. Even in cancer entities where overt skeletal metastases are rare (e.g., colorectal and ovarian cancer), bone marrow is a prognostically relevant indicator organ for the presence of hematogenous micrometastases. The currently available data suggest that bone marrow micrometastases represent a selected population of dormant cancer cells which still express a considerable degree of heterogeneity. The analysis of micrometastatic cells will open a new avenue to assess the molecular determinants of early tumor cell dissemination and subsequent outgrowth into overt metastases. Moreover, monitoring the elimination of bone marrow micrometastases and identification of treatment-resistant tumor cell clones may help to increase the efficacy of adjuvant therapy. This review summarizes the current knowledge on the biological characteristics of micrometastatic cancer cells in bone marrow of patients with solid epithelial malignancies. PMID:10505547

  20. Bone marrow-derived T lymphocytes responsible for allograft rejection

    SciTech Connect

    Senjanovic, M.; Marusic, M.

    1984-08-01

    Lethally irradiated mice reconstituted with syngeneic bone marrow cells were grafted with allogeneic skin grafts 6-7 weeks after irradiation and reconstitution. Mice with intact thymuses rejected the grafts whereas the mice thymectomized before irradiation and reconstitution did not. Thymectomized irradiated mice (TIR mice) reconstituted with bone marrow cells from donors immune to the allografts rejected the grafts. Bone marrow cells from immunized donors, pretreated with Thy 1.2 antibody and C', did not confer immunity to TIR recipients. To determine the number of T lymphocytes necessary for the transfer of immunity by bone marrow cells from immunized donors, thymectomized irradiated mice were reconstituted with nonimmune bone marrow cells treated with Thy 1.2 antibody and C' and with various numbers of splenic T lymphocytes from nonimmune and immune donors. Allogeneic skin graft rejection was obtained with 10(6) nonimmune or 10(4) immune T cells. The effect of immune T cells was specific: i.e., immune T cells accelerated only rejection of the relevant skin grafts whereas against a third-party skin grafts acted as normal T lymphocytes.

  1. Red face revisited: Flushing.

    PubMed

    ?kizo?lu, Gliz

    2014-01-01

    The term red face is reserved for lesions located exclusively or very predominantly on the face that result from changes in cutaneous blood flow triggered by multiple different conditions. Facial erythema may not only present clinically as a distinct entity, but can also be a sign of other diseases. Patients with a red face challenge clinicians to consider a broad differential diagnosis. Diagnosis is based on date and mode of appearance, characteristics of the erythema, functional signs, and associated systemic manifestations. In most cases, the cause is a benign disease such as rosacea, contact dermatitis, photodermatosis, and climacterium, and a thorough history and physical examination is enough to make a diagnosis; facial erythema may also present as a symptom of drug allergies, cardiac disease, carcinoid syndrome, pheochromocytoma, mastocytosis, and anaphylaxis, as well as some rare causes such as medullary carcinoma of the thyroid, pancreatic cell tumor, and renal carcinoma where further laboratory, radiologic, or histopathologic studies are required. In this review, the mechanisms of flushing, its clinical differential diagnosis, and management of various conditions that cause flushing are discussed. PMID:25441473

  2. Effects of Focused Extracorporeal Shock Waves on Bone Marrow Mesenchymal Stem Cells in Patients with Avascular Necrosis of the Femoral Head.

    PubMed

    Zhai, Lei; Sun, Nan; Zhang, Bo; Liu, Shui-Tao; Zhao, Zhe; Jin, Hai-Chao; Ma, Xin-Long; Xing, Geng-Yan

    2016-03-01

    To observe the effect of extracorporeal shock waves (ESWs) on bone marrow mesenchymal stem cells (MSCs) in patients with avascular necrosis of the femoral head, we collected bone marrow donated by patients and then cultivated and passaged MSCs in vitro using density gradient centrifugation combined with adherence screening methods. The P3 generation MSCs were divided into the ESW group and the control group. The cell counting kit for MSCs detected some proliferation differences. Cytochemistry, alkaline phosphatase staining and Alizarin red staining were used to determine alkaline phosphatase content. Simultaneously, real-time polymerase factor α1, osteocalcin and peroxisome proliferator-activated receptor γ. Together, the results of our study first indicate that moderate ESW intensity, which is instrumental in enhancing MSC proliferation, inducing conversion of MSCs into osteoblasts, and inhibiting differentiation of MSCs into adipocytes from MSCs, is one of the effective mechanisms for treating avascular necrosis of the femoral head. PMID:26674675

  3. Red - Take a Closer Look

    PubMed Central

    Buechner, Vanessa L.; Maier, Markus A.; Lichtenfeld, Stephanie; Schwarz, Sascha

    2014-01-01

    Color research has shown that red is associated with avoidance of threat (e.g., failure) or approach of reward (e.g., mating) depending on the context in which it is perceived. In the present study we explored one central cognitive process that might be involved in the context dependency of red associations. According to our theory, red is supposed to highlight the relevance (importance) of a goal-related stimulus and correspondingly intensifies the perceivers attentional reaction to it. Angry and happy human compared to non-human facial expressions were used as goal-relevant stimuli. The data indicate that the color red leads to enhanced attentional engagement to angry and happy human facial expressions (compared to neutral ones) - the use of non-human facial expressions does not bias attention. The results are discussed with regard to the idea that red induced attentional biases might explain the red-context effects on motivation. PMID:25254380

  4. [Diagnosis and management of pure red cell aplasia].

    PubMed

    Hirokawa, Makoto

    2015-10-01

    Pure red cell aplasia (PRCA) is a type of bone marrow failure syndrome (stem cell failure) and is characterized by severe normocytic, normochromic anemia associated with reticulocytopenia, and the absence of erythroblasts in otherwise normal bone marrow. PRCA may be congenital or acquired, and the acquired form of chronic PRCA may present as a primary hematological disease in the absence of any other diseases or secondary to thymoma, lymphoproliferative disorders, infections, and collagen vascular diseases or after exposure to various drugs or chemicals. The most common types of acquired chronic PRCA in Japan are idiopathic, thymoma-associated and lymphoid neoplasm-associated PRCA. Initial treatment of PRCA includes the cessation of potentially deleterious drugs and careful observation for one month while making efforts to identify the cause of PRCA. Idiopathic PRCA and secondary PRCA refractory to treatment of the underlying diseases are generally treated as immune-mediated disorders. Most chronic PRCA patients successfully treated with immunosuppressants require maintenance immunosuppressive therapy. Thus, identifying the cause of PRCA is crucial for the optimal management of this disorder. PMID:26458430

  5. Seeing red on the road.

    PubMed

    Daz-Romnn, Amparo; Megas, Alberto; Daz-Piedra, Carolina; Catena, Andrs; Di Stasi, Leandro L

    2015-01-01

    Human and animal research has found that red perception is associated with specific behavioral reactions, generally characterized by intense responses. Here, we explored whether red cars are perceived as more dangerous than other colored cars. One hundred Spanish drivers examined several road scenarios which involved hazardous cars with different colors: red, green, yellow, black, gray, and white. Driver's behavior (response time and probability of braking) and the perceived level of risk for each scenario were analyzed. Although car color affected participants' response times, contrary to expectations, red cars did not elicit faster responses or higher perceived levels of risk. PMID:26489219

  6. Red cell filterability in diabetes.

    PubMed

    Isogai, Y; Mochzuki, K; Maeda, T

    1981-01-01

    A negative pressure red cell filteration technique using polycarbonate sieve (Nuclepore) was devised for the observation of red cell filterability (RCF) in diabetes. A significant increase of HbA1 was suggested to be closely correlated to the decrease of RCF. A greater decrease of RCF was observed in diabetics with advanced retinopathy. The increased 2,3-DPG of red cells has been observed in diabetes, but P50 changed much less than might be expected. Improved RCF was observed when Pentoxifylline was added into red cell suspensions. This suggests that Pentoxifylline will have a good effect on microcirculation where impared circulation is observed. PMID:6948379

  7. Urothelial Cancer With Occult Bone Marrow Metastases and Isolated Thrombocytopenia

    PubMed Central

    Alva, Ajjai; Davis, Elizabeth; Chinnaiyan, Arul M.; Dhanasekaran, Saravana; Mehra, Rohit

    2015-01-01

    Bladder cancer rarely presents clinically with a myelophthisic picture from diffuse bone marrow infiltration especially in the absence of detectable skeletal metastases. A 75-year old man presented with newly diagnosed urothelial cell carcinoma of the bladder. Pathology from transurethral resection of bladder tumor demonstrated muscle-invasive disease. Pre-therapy imaging including CT abdomen/pelvis, CXR and bone scan demonstrated liver lesions concerning for metastatic disease but no skeletal metastases. Labs were notable for isolated thrombocytopenia, hypercalcemia and acute kidney injury prompting hospitalization. Hematologic work-up including bone marrow aspiration and biopsy revealed diffuse infiltration of the bone marrow by urothelial cancer. The case illustrates the importance of fully investigating otherwise unexplained clinical findings in patients with clinically localized urothelial cancer prior to curative intent surgery.

  8. Whole bone marrow irradiation for the treatment of multiple myeloma

    SciTech Connect

    Coleman, M.; Saletan, S.; Wolf, D.; Nisce, L.; Wasser, J.; McIntyre, O.R.; Tulloh, M.

    1982-04-01

    Nine patients with multiple myeloma were treated with whole bone marrow irradiation. Six had heavily pretreated disease refractory to chemotherapy. Three had stable disease lightly pretreated by chemotherapy. A modification of the ''three and two'' total nodal radiation technique was employed. Although varying and often severe treatment related cytopenia occurred, infectious complications, clinical bleeding, and nonhematalogic complications were minimal. Five of nine patients showed a decrease in monoclonal protein components, and one showed an increase during treatment. These preliminary results indicate that a reduction of tumor cell burden may occur in patients following whole bone marrow irradiation and that the technique is feasible. Whole bone marrow irradiation combined with chemotherapy represents a new conceptual therapeutic approach for multiple myeloma.

  9. Modeling Selective Elimination of Quiescent Cancer Cells from Bone Marrow

    PubMed Central

    Cavnar, Stephen P.; Rickelmann, Andrew D.; Meguiar, Kaille F.; Xiao, Annie; Dosch, Joseph; Leung, Brendan M.; Cai Lesher-Perez, Sasha; Chitta, Shashank; Luker, Kathryn E.; Takayama, Shuichi; Luker, Gary D.

    2015-01-01

    Patients with many types of malignancy commonly harbor quiescent disseminated tumor cells in bone marrow. These cells frequently resist chemotherapy and may persist for years before proliferating as recurrent metastases. To test for compounds that eliminate quiescent cancer cells, we established a new 384-well 3D spheroid model in which small numbers of cancer cells reversibly arrest in G1/G0 phase of the cell cycle when cultured with bone marrow stromal cells. Using dual-color bioluminescence imaging to selectively quantify viability of cancer and stromal cells in the same spheroid, we identified single compounds and combination treatments that preferentially eliminated quiescent breast cancer cells but not stromal cells. A treatment combination effective against malignant cells in spheroids also eliminated breast cancer cells from bone marrow in a mouse xenograft model. This research establishes a novel screening platform for therapies that selectively target quiescent tumor cells, facilitating identification of new drugs to prevent recurrent cancer. PMID:26408255

  10. Bones of contention: marrow-derived cells in myocardial regeneration.

    PubMed

    Sussman, Mark A; Murry, Charles E

    2008-06-01

    Almost 7 years have passed since the initial publication reporting that bone marrow cells regenerate infarcted myocardium. The subsequent years produced hundreds of investigations that ran the gamut of findings from validation to disproof. Undeterred by the concurrent debate, clinical trials ensued to test the safety and efficacy of bone marrow-derived cell population for autologous therapy in clinical treatment of myocardial disease. In the following conversational exchange, two scientists with distinct perspectives weigh the pros and cons of pursuing bone marrow stem cell therapy and look toward finding a consensus of where the future lies for regenerative medicine and the heart. The conclusion is that the two camps may not be as far apart as it may seem from the rancor in literature and at meetings, and the potential of one day achieving regenerative therapy is indeed a vision that both parties enthusiastically share. PMID:18440020

  11. Bone marrow edema syndrome in postpartal women: treatment with iloprost.

    PubMed

    Aigner, Nicholas; Meizer, Roland; Meraner, Dominik; Becker, Stephan; Meizer, Elizabeth; Landsiedl, Franz

    2009-04-01

    Bone marrow edema syndrome of the femoral head in pregnant women is a rare disease resulting in disabling coxalgia, beginning in the last 3 months of pregnancy and persisting for several months after parturition. The parenteral administration of the vasoactive drug iloprost constitutes a new approach to the treatment of painful bone marrow edema syndrome of the hip of pregnant women. Six postpartal women (8 hips) with bone marrow edema syndrome of the femoral head were treated with iloprost followed by 3 weeks of partial weight-bearing. Relief from pain, restoration of functional capacity, and normalization of the MRI signal pattern were rapidly achieved, thus avoiding the need for surgical intervention. As the substance is contraindicated in pregnancy, therapy may begin only some days after parturition, with a short discontinuation in breastfeeding. PMID:19358909

  12. Biology of the bone marrow microenvironment and myelodysplastic syndromes.

    PubMed

    Rankin, Erinn B; Narla, Anupama; Park, Joseph K; Lin, Shuo; Sakamoto, Kathleen M

    2015-01-01

    Myelodysplastic syndromes (MDS) are characterized by cytopenias resulting from ineffective hematopoiesis with a predisposition to transform to acute myeloid leukemia (AML). Recent evidence suggests that the hematopoietic stem cell microenvironment contributes to the pathogenesis of MDS. Inflammation and hypoxia within the bone marrow are key regulators of hematopoietic stem and progenitor cells that can lead to several bone marrow failure syndromes, including MDS. In this brief review, we provide an overview of the clinical and molecular features of MDS, the bone marrow microenvironment, and specific pathways that lead to abnormal blood cell development in MDS. Characterization of key steps in the pathogenesis of MDS will lead to new approaches to treat patients with this disease. PMID:26210353

  13. Molecular and histopathological detection of Hepatozoon canis in red foxes (Vulpes vulpes) from Portugal

    PubMed Central

    2014-01-01

    Background Hepatozoon canis is a protozoan tick-borne pathogen of dogs and wild canids. Hepatozoon spp. have been reported to infect foxes in different continents and recent studies have mostly used the polymerase chain reaction (PCR) for the detection and characterization of the infecting species. Surveying red foxes (Vulpes vulpes) may contribute to better understanding the epidemiology of canine vector-borne diseases, including hepatozoonosis caused by H. canis in domestic dogs. The present study investigated the prevalence of Hepatozoon spp. by means of histopathology and molecular analysis of different tissues in red foxes from different parts of Portugal. Methods Blood and tissues including bone marrow, heart, hind leg muscle, jejunum, kidney, liver, lung, popliteal or axillary lymph nodes, spleen and/or tongue were collected from 91 red foxes from eight districts in northern, central and southern Portugal. Tissues were formalin-fixed, paraffin-embedded, cut and stained with hematoxylin and eosin. Polymerase chain reaction (PCR) amplified a ~650bp fragment of the 18S rRNA gene of Hepatozoon spp. and the DNA products were sequenced. Results Hepatozoon canis was detected in 68 out of 90 foxes (75.6%) from all the sampled areas by PCR and sequencing. Histopathology revealed H. canis meronts similar in shape to those found in dogs in the bone marrow of 11 (23.4%) and in the spleen of two (4.3%) out of 47 foxes (p?=?0.007). All the 11 foxes found positive by histopathology were also positive by PCR of bone marrow and/or blood. Positivity by PCR (83.0%) was significantly higher (p?marrow samples from the same 47 foxes. Sequences of the 18S rRNA gene of H. canis were 9899% identical to those in GenBank. Conclusions Hepatozoon canis was found to be highly prevalent in red fox populations from northern, central and southern Portugal. Detection of the parasite by histopathology was significantly less sensitive than by PCR. Red foxes are a presumptive reservoir of H. canis infection for domestic dogs. PMID:24655375

  14. Robust conversion of marrow cells to skeletal muscle with formation of marrow-derived muscle cell colonies: A multifactorial process

    SciTech Connect

    Abedi, Mehrdad; Greer, Deborah A.; Colvin, Gerald A.; Demers, Delia A.; Dooner, Mark S.; Harpel, Jasha A.; Weier, Heinz-Ulrich G.; Lambert, Jean-Francois; Quesenberry, Peter J.

    2004-01-10

    Murine marrow cells are capable of repopulating skeletal muscle fibers. A point of concern has been the robustness of such conversions. We have investigated the impact of type of cell delivery, muscle injury, nature of delivered cell, and stem cell mobilizations on marrow to muscle conversion. We transplanted GFP transgenic marrow into irradiated C57BL/6 mice and then injured anterior tibialis muscle by cardiotoxin. One month after injury, sections were analyzed by standard and deconvolutional microscopy for expression of muscle and hematopietic markers. Irradiation was essential to conversion although whether by injury or induction of chimerism is not clear. Cardiotoxin and to a lesser extent PBS injected muscles showed significant number of GFP+ muscle fibers while uninjected muscles showed only rare GFP+ cells. Marrow conversion to muscle was increased by two cycles of G-CSF mobilization and to a lesser extent with G-CSF and steel or GM-CSF. Transplantation of female GFP to male C57 BL/6 and GFP to Rosa26 mice showed fusion of donor cells to recipient muscle. High numbers of donor derived muscle colonies and up to12 percent GFP positive muscle cells were seen after mobilization or direct injection. These levels of donor muscle chimerism approach levels which could be clinically significant in developing strategies for the treatment of muscular dystrophies. In summary, the conversion of marrow to skeletal muscle cells is based on cell fusion and is critically dependent on injury. This conversion is also numerically significant and increases with mobilization.

  15. Combination of bone marrow concentrate and PGA scaffolds enhance bone marrow stimulation in rabbit articular cartilage repair.

    PubMed

    Zhao, Qinghua; Wang, Shouguo; Tian, Jiwei; Wang, Lei; Dong, Shuanghai; Xia, Tian; Wu, Zhenkai

    2013-03-01

    Bone marrow stimulation (BMS) has been regarded as a first-line procedure for the repair of articular cartilage. However, cartilage repair using BMS alone has so far not been ideal because cell homing to the required area has not been sufficient. The aim of this study was to investigate the feasibility of autologous bone marrow concentrate transplantation for the repair of large, full-thickness cartilage defects. Thirty rabbits were divided into five groups: untreated (control); BMS only (BMS); BMS followed by PGA implantation (PGA); BMS followed by a combination of PGA and autologous bone marrow concentrate (BMC); and BMS together with a composite of PGA and cultured bone marrow stem cells (BME). The animals were sacrificed at week 8 after operation, and HE staining, toluidine blue staining and immunohistochemistry were used to assess the repair of defects. The results showed that improved repair, including more newly formed cartilage tissue and hyaline cartilage-specific extracellular matrix, was observed in BMC group relative to the first three groups, in addition similar results were found between BMC and BME groups, however it took longer time for in vitro cell expansion in the BME group. This study demonstrates that the transplantation of autologous bone marrow concentrate is an easy, safe and potentially viable method to contribute to articular cartilage repair. PMID:23274630

  16. Fade to Red

    NASA Technical Reports Server (NTRS)

    2006-01-01

    [figure removed for brevity, see original site] Infrared Andromeda Galaxy (M31) Poster [figure removed for brevity, see original site] [figure removed for brevity, see original site] Stars Dust

    This animation shows the Andromeda galaxy, first as seen in visible light by the National Optical Astronomy Observatory, then as seen in infrared by NASA's Spitzer Space Telescope.

    The visible-light image highlights the galaxy's population of about one trillion stars. The stars are so crammed into its core that this region blazes with bright starlight.

    In contrast, the false-colored Spitzer view reveals red waves of dust against a more tranquil sea of blue stars. The dust lanes can be seen twirling all the way into the galaxy's center. This dust is warmed by young stars and shines at infrared wavelengths , which are represented in red. The blue color signifies shorter-wavelength infrared light primarily from older stars.

    The Andromeda galaxy, also known affectionately by astronomers as Messier 31, is located 2.5 million light-years away in the constellation Andromeda. It is the closest major galaxy to the Milky Way, making it the ideal specimen for carefully examining the nature of galaxies. On a clear, dark night, the galaxy can be spotted with the naked eye as a fuzzy blob.

    Andromeda's entire disk spans about 260,000 light-years, which means that a light beam would take 260,000 years to travel from one end of the galaxy to the other. By comparison, the Milky Way is about 100,000 light-years across. When viewed from Earth, Andromeda occupies a portion of the sky equivalent to seven full moons.

    Because this galaxy is so large, the infrared images had to be stitched together out of about 3,000 separate Spitzer exposures. The light detected by Spitzer's infrared array camera at 3.6 and 4.5 microns is sensitive mostly to starlight and is shown in blue and green, respectively. The 8-micron light shows warm dust and is shown in red. The contribution from starlight has been subtracted from the 8-micron image to better highlight the dust structures.

    Note: The size of the Full-Res TIFF for the still image is 14772 samples x 4953 lines.

  17. International red meat trade.

    PubMed

    Brester, Gary W; Marsh, John M; Plain, Ronald L

    2003-07-01

    The maturation of the US beef and pork markets and increasing consumer demands for convenience, safety, and nutrition suggests that the beef and pork industries must focus on product development and promotion. New marketing arrangements are developing that help coordinate production with consumer demands. The relative high levels of incomes in the United States are likely to increase the demands for branded products rather than increase total per capita consumption. Foreign markets represent the greatest opportunity for increased demand for commodity beef and pork products. Increasing incomes in developing countries will likely allow consumers to increase consumption of animal-source proteins. Real prices of beef and pork have declined substantially because of sagging domestic demand and increasing farm-level production technologies. Increasing US beef and pork exports have obviated some of the price declines. Pork attained a net export position from a quantity perspective in 1995. The United States continues to be a net importer of beef on a quantity basis but is close to becoming a net exporter in terms of value. By-products continue to play a critical role in determining the red meat trade balance and producer prices. The United States, however, must continue to become cost, price, and quality competitive with other suppliers and must secure additional market access if it is to sustain recent trade trends. Several trade tensions remain in the red meat industry. For example, mandated COOL will undoubtedly have domestic and international effects on the beef and pork sectors. Domestically, uncertainty regarding consumer demand responses or quality perceptions regarding product origin, as well as added processor-retailer costs will be nontrivial. How these factors balance out in terms of benefits versus costs to the industry is uncertain. From an international perspective, some beef and pork export suppliers to the United States could view required labeling as a trade restriction, which could ultimately impact future US red meat exports. Conversely, some countries may view such labeling requirements as an opportunity to brand high-quality products. The US lamb meat industry has experienced declining real prices, domestic production, and demand. The cessation of wool incentive payments, increased environmental regulations, and competition by imports have significantly affected the industry. Import suppliers have capitalized on product quality in this niche market. Trade restrictions initially imposed in 1999 by the US Government were ruled illegal by the WTO. The US Government responded by providing financial assistance to lamb producers. Product quality improvements and promotion aimed at the domestic market, however, will be critical factors in shaping the economic viability of the US lamb meat industry. PMID:12951744

  18. Acquired pure red cell aplasia in a patient of rheumatoid arthritis.

    PubMed

    Parida, Prasant Kumar; Shukla, Shilin N; Talati, Shailesh S; Parikh, Sonia K

    2014-09-01

    Pure red cell aplasia (PRCA) is characterized as a normocytic anemia associated with reticulocytopenia and the absence of erythroblasts in the bone marrow. PRCA can be induced by various causes such as thymoma, connective tissue disease, viral infection, lymphoma, and adverse drug reactions. There have been only a few reports of PRCA associated with rheumatoid arthritis (RA). We report a 45year old female presented with symptomatic anemia of several months duration on a background of long standing seropositive deforming RA. Bone marrow examination revealed marked suppression of erythroid precursors with normal myeloid and megakaryocytic series, thereby confirming PRCA. Anemia improved following therapy with prednisolone 1mg/kg/day. This article also reviews the current status of therapy in acquired PRCA. PMID:25332592

  19. P-glycoprotein expression in normal and reactive bone marrows.

    PubMed Central

    Hegewisch-Becker, S.; Fliegner, M.; Tsuruo, T.; Zander, A.; Zeller, W.; Hossfeld, D. K.

    1993-01-01

    The expression of mdr1 gene product P-glycoprotein (P-gp) was investigated in 53 normal and reactive bone marrows by means of immunocytochemistry, using the monoclonal antibody (mAb) C219 and the alkaline phosphatase anti-alkaline phosphatase method. In a limited number of patients, data were confirmed by using the mAb MRK16 or a polymerase chain reaction assay for mdr1 gene expression. There was no history of prior chemotherapy or any malignancy in this group. Bone marrow aspirates were obtained as part of a routine diagnostic programme in bone marrow donors or in patients presenting with a variety of diagnoses such as unexplained gammopathy, fever, anaemia, other changes in peripheral blood smear, rheumatoid arthritis, vasculitis, or urticaria pigmentosa. Morphologically the bone marrow was normal in 23 patients, a megaloblastic erythropoiesis was seen in two patients and unspecific changes were seen in 28 patients. Twenty-seven of 53 samples were found to be positive for P-gp expression with the percentage of positive cells ranging from 2%-80% (mean = 24%). With a cutoff point of 10%, five of 23 normal (22%) and 13 of 28 reactive bone marrows (46%) were considered positive for P-gp expression. There was no obvious correlation between diagnosis or age and P-gp expression. Additional staining for the early surface marker CD-34 was performed in 12 samples, with none of them revealing more than 1% positivity. Since P-gp expression has so far been described only in CD-34 positive bone marrow cells, data suggest that P-gp expression may be reinduced in CD-34 negative cells under conditions which remain to be determined. Images Figure 1 Figure 2 PMID:8094974

  20. Spatial mapping of functional pelvic bone marrow using FLT PET

    PubMed Central

    McGuire, Sarah M.; Menda, Yusuf; Boles Ponto, Laura L.; Gross, Brandie; TenNapel, Mindi; Smith, Brian; Bayouth, John E.

    2014-01-01

    The purpose of this study was to determine the ability of regions identified with bony landmarks on CT imaging to accurately represent active bone marrow when compared to FLT PET imaging. These surrogate regions could then be used to create a bone marrow sparing radiation therapy plan when FLT PET imaging is not available. WB FLT PET images were obtained of 18 subjects prior to chemoradiation therapy. The FLT image of each subject was registered to a CT image acquired for that subject to obtain anatomic information of the pelvis. Seventeen regions were identified based on features of the pelvic bones, sacrum, and femoral heads. The probability of FLT uptake being located in each of 17 different CT-based regions of the bony pelvis was calculated using Tukeys multiple comparison test. Statistical analysis of FLT uptake in the pelvis indicated 4 distinct groups within the 17 regions that had similar levels of activity. Regions located in the central part of the pelvis including the superior part of the sacrum, the inner halves of the iliac crests and the L5 vertebral body had greater FLT uptake than those in the peripheral regions (p < 0.05). We have developed a method to use CT defined pelvic bone regions to represent FLT PET identified functional bone marrow. Individual regions that have a statistically significant probability of containing functional bone marrow can be used as avoidance regions to reduce radiation dose to functional bone marrow in radiation therapy planning. However, because likely active bone marrow regions and pelvic targets typically overlap, patient specific spatial detail may be advantageous in IMRT planning scenarios and may best be provided using FLT PET imaging. PMID:25207403

  1. Classification of red variables

    NASA Technical Reports Server (NTRS)

    Mattei, Janet A.; Foster, Grant; Hurwitz, Leora A.; Malatesta, Kerriann H.; Willson, Lee Anne; Mennessier, Marie-Odile

    1997-01-01

    Red variables are traditionally classified into Mira, semiregular (SR), and slow irregular (L) variables. The Mira variables are the best defined subgroup, whereas SR and L stars are more numerous. The SR subgroup is additionally subdivided into: SRa variables, which feature regular variability with smaller pulsation amplitudes than Miras; SRb variables, which are less regular; SRc variables, which are more luminous; and SRd variables, which are warmer. Relationships within each group are not clear. An analysis of long-term American Association of Variable Star Observers (AAVSP) light curves is reported on. It is found that Mira-type variables are clearly different and distinguishable from SR variables. Similarly, M-type Miras and C-type Miras feature different light curve properties. The M-Miras form a homogeneous group. The pulsations of SR variables are unstable.

  2. Inherited bone marrow failure syndromes in adolescents and young adults

    PubMed Central

    Wilson, David B.; Link, Daniel C.; Mason, Philip J.; Bessler, Monica

    2015-01-01

    The inherited bone marrow failure syndromes are a diverse group of genetic diseases associated with inadequate production of one or more blood cell lineages. Examples include Fanconi anemia, dyskeratosis congenita, Diamond-Blackfan anemia, thrombocytopenia absent radii syndrome, severe congenital neutropenia, and Shwachman-Diamond syndrome. The management of these disorders was once the exclusive domain of pediatric subspecialists, but increasingly physicians who care for adults are being called upon to diagnose or treat these conditions. Through a series of patient vignettes, we highlight the clinical manifestations of inherited bone marrow failure syndromes in adolescents and young adults. The diagnostic and therapeutic challenges posed by these diseases are discussed. PMID:24888387

  3. Marrow fat deposition and skeletal growth in caribou calves

    USGS Publications Warehouse

    Adams, L.

    2003-01-01

    I evaluated rates of marrow fat deposition and skeletal growth of caribou (Rangifer tarandus granti) calves through 20 days of age at Denali National Park, Alaska, USA. Both were negatively correlated with late winter snowfall, indicating the prolonged effects of maternal undernutrition following severe winters. Using regression analyses, I found that the rates of marrow fat deposition and hindfoot growth during the 20 days following birth declined 46% and 68%, respectively, over the range of winter severity during this study. These measures of development may indicate a broader array of effects of maternal undernutrition, influencing the vulnerability of caribou calves to predation.

  4. Purification of hematopoietic stem cells from bone marrow.

    PubMed

    Tian, Chen; Zhang, Yizhuo

    2016-03-01

    Lifelong production of blood cells is sustained by hematopoietic stem cells (HSC) which reside at a very low frequency within the bone marrow (BM). The use of flow cytometry has been critical in establishing methods to isolate and characterize HSCs and their progenitors. For more than 30 years, researchers have uncovered many novel markers that when used in combination significantly enhance the purification of HSCs from murine and human bone marrow. Here, we review the phenotypic markers and strategies used to purify HSCs. PMID:26858027

  5. Zinc toxicity: denture adhesives, bone marrow failure and polyneuropathy.

    PubMed

    Crown, Loren A; May, Jeffery A

    2012-02-01

    A 36-year-old female developed bone marrow failure diagnosed as myelodysplastic syndrome (MDS) (Sidebar), followed shortly by a peripheral neuropathy and a gait disturbance. While waiting for a bone marrow transplant, she reported to us that she had seen attorney-generated, televised advertisements concerning the role of denture adhesives relating to her malady. Labs were then obtained demonstrating she had dramatic and unsuspected hypocupremia and hyperzincemia. Administration of copper and cessation of denture adhesives resulted in recovery of her hematopoietic system and partial resolution of the neurological sequela. PMID:22375440

  6. Advancement of Pediatric Blood and Marrow Transplantation Research in North America: Priorities of the Pediatric Blood and Marrow Transplant Consortium

    PubMed Central

    Pulsipher, Michael A.; Horwitz, Edwin M.; Haight, Ann E.; Kadota, Richard; Chen, Allen R.; Frangoul, Haydar; Cooper, Laurence J.N.; Jacobsohn, David A.; Goyal, Rakesh K.; Mitchell, David; Nieder, Michael L.; Yanik, Gregory; Cowan, Morton J.; Soni, Sandeep; Gardner, Sharon; Shenoy, Shalini; Taylor, Douglas; Cairo, Mitchell; Schultz, Kirk R.

    2010-01-01

    Advances in pediatric blood and marrow transplantation (BMT) are slowed by the small number of patients with a given disease transplanted, a lack of sufficient infrastructure to run early phase oncology protocols and studies of rare non-malignant disorders, and challenges associated with funding multi-institutional trials. Leadership of the Pediatric Blood and Marrow Transplant Consortium (PBMTC), a large pediatric BMT clinical trials network representing 77 active and 45 affiliated centers worldwide, met in April 2009 to develop strategic plans to address these issues. Key barriers including infrastructure development and funding, along with scientific initiatives in malignant and non-malignant disorders, cellular therapeutics, graft versus host disease, and supportive care were discussed. The PBMTC agenda for approaching these issues will result in infrastructure and trials specific to pediatrics that will run through the PBMTC or its partners, the Blood and Marrow Transplant Clinical Trials Network and the Children’s Oncology Group. PMID:20079865

  7. What to Expect After a Blood and Marrow Stem Cell Transplant

    MedlinePLUS

    ... What To Expect After a Blood and Marrow Stem Cell Transplant You’ll stay in the hospital for ... or even months after your blood and marrow stem cell transplant. Your doctors will want to be sure ...

  8. Bone Marrow Transplantation and Peripheral Blood Stem Cell Transplantation: Questions and Answers

    MedlinePLUS

    ... to Ask about Your Treatment Research Blood-Forming Stem Cell Transplants On This Page What are bone marrow ... Considering becoming a bone marrow or a blood stem cell donor? View this video on YouTube. Follow a ...

  9. Characteristics of human bone marrow mesenchymal stem cells isolated by immunomagnetic selection.

    PubMed

    Lagar'kova, M A; Lyakisheva, A V; Filonenko, E S; Volchkov, P Yu; Rubtsova, K V; Gerasimov, Yu V; Chailakhyan, R K; Kiselev, S L

    2006-01-01

    Immunophenotype of human bone marrow mesenchymal stem cells was studied after several culturing passages and after cryopreservation. Immunocytochemical analysis showed that bone marrow mesenchymal stem cells acquired homogeneity during in vitro culturing, but initially contained heterogeneous populations. PMID:16929980

  10. Blockage of caspase-1 activation ameliorates bone marrow inflammation in mice after hematopoietic stem cell transplantation.

    PubMed

    Qiao, Jianlin; Wu, Jinyan; Li, Yuanyuan; Xia, Yuan; Chu, Peipei; Qi, Kunming; Yan, Zhiling; Yao, Haina; Liu, Yun; Xu, Kailin; Zeng, Lingyu

    2016-01-01

    Conditioning regimens before hematopoietic stem cell transplantation (HSCT), cause damage to bone marrow and inflammation. Whether inflammasomes are involved in bone marrow inflammation remains unclear. The study aims to evaluate the role of inflammasomes in bone marrow inflammation after HSCT. On days 7, 14, 21 and 28 after HSCT, mice were sacrificed for analysis of bone marrow inflammation, pro-inflammatory cytokines secretion, inflammasomes expression and caspase-1 activation. Bone marrow inflammation with neutrophils and macrophages infiltration was observed after HSCT. Secretion of IL-1?, IL-18, TNF-? and IL-6 were elevated, with increased caspase-1 activation and inflammasomes expression. Caspase-1 inhibitor administration after HSCT significantly reduced infiltration of neutrophils and macrophages into bone marrow and increased the numbers of megakaryocytes and platelets. In conclusion, inflammasomes activation is involved in bone marrow inflammation after HSCT and caspase-1 inhibition attenuates bone marrow inflammation and promoted hematopoietic reconstitution, suggesting targeting caspase-1 might be beneficial for improving HSCT outcomes. PMID:26639193

  11. Red yeast rice for dysipidemia.

    PubMed

    Shamim, Shariq; Al Badarin, Firas J; DiNicolantonio, James J; Lavie, Carl J; O'Keefe, James H

    2013-01-01

    Red yeast rice is an ancient Chinese food product that contains monacolins, chemical substances that are similar to statins in their mechanisms of action and lipid lowering properties. Several studies have found red yeast rice to be moderately effective at improving the lipid profile, particularly for lowering the low-density lipoprotein cholesterol levels. One large randomized controlled study from China found that red yeast rice significantly improved risk of major adverse cardiovascular events and overall survival in patients following myocardial infarction. Thus, red yeast rice is a potentially useful over-the-counter cholesterol-lowering agent. However, many red yeast rice formulations are non-standardized and unregulated food supplements, and there is a need for further research and regulation of production. PMID:24003656

  12. Evidence that the expression of transferrin receptor 1 on erythroid marrow cells mediates hepcidin suppression in the liver

    PubMed Central

    Keel, Siobn B.; Doty, Raymond; Liu, Li; Nemeth, Elizabeta; Cherian, Sindhu; Ganz, Tomas; Abkowitz, Janis L.

    2015-01-01

    Hepcidin is the key regulator of iron absorption and recycling, and its expression is suppressed by red blood cell production. When erythropoiesis is expanded, hepcidin expression decreases. To gain insight into the stage of erythroid differentiation at which the regulation might originate, we measured serum hepcidin levels in archived pure red cell aplasia samples from patients whose block in erythroid differentiation was well defined by hematopoietic colony assays and marrow morphologic review. Hepcidin values are high or high normal in pure red cell aplasia patients in whom erythropoiesis is inhibited prior to the proerythroblast stage, but are suppressed in patients with excess proerythroblasts and few later erythroid cells. These data suggest that the suppressive effect of erythropoietic activity on hepcidin expression can arise from proerythroblasts, the stage at which transferrin receptor 1 expression peaks, prompting the hypothesis that transferrin receptor 1 expression on erythroid precursors is a proximal mediator of the erythroid regulator of hepcidin expression. Our characterization of erythropoiesis, iron status, and hepcidin expression in mice with global or hematopoietic cell-specific haploinsufficiency of transferrin receptor 1 provides initial supporting data for this model. The regulation appears independent of erythroferrone and growth differentiation factor 15, supporting the concept that several mechanisms signal iron need in response to an expanded erythron. PMID:25782630

  13. The role of marrow transplantation in the eradication of malignant disease. [Dogs; /sup 60/Co

    SciTech Connect

    Thomas, E.D.

    1982-05-05

    This Kettering award lecture describes the history of bone marrow transplantation for treatment of disseminated malignant disease, leukemia, carried out at the University of Washington. A major problem after marrow grafting is the recurrence of leukemia and display of profound immunologic incompetence. Presently, marrow transplantation has become an accepted form of therapy for several types of human disease including malignant disease as well as hereditory diseases of the bone marrow.

  14. Red Marks the Spot

    NASA Technical Reports Server (NTRS)

    2004-01-01

    This hematite abundance index map helps geologists choose hematite-rich locations to visit around Opportunity's landing site. Blue dots equal areas low in hematite and red dots equal areas high in hematite.

    Why Hematite Geologists are eager to reach the hematite-rich area in the upper left to closely examine the soil, which may reveal secrets about how the hematite got to this location. Knowing how the hematite on Mars was formed may help scientists characterize the past environment and determine whether that environment provided favorable conditions for life.

    The Plan Over the next few sols, engineers and scientists plan to drive Opportunity to the hematite-rich area then attempt a 'pre-trench' sequence, taking measurements with the Moessbauer spectrometer, alpha particle X-ray spectrometer and microscopic imager. Next, the plan is to trench the hematite rich area by spinning one wheel in place to 'dig' a shallow hole. Finally, scientists will aim the instrument arm back at the same area where it pre-trenched to get post-trench data with the same instruments to compare and contrast the levels of hematite and revel how deep the hematite lays in the dirt.

    Index Map Details The hematite abundance index map was created using data from the miniature thermal emission instrument. The first layer is a mosaic of panoramic camera images taken prior to egress, when Opportunity was still on the lander. The colored dots represent data collected by the miniature thermal emission spectrometer on sol 11, after Opportunity had rolled off of the lander and the rover was located at the center of the blue semi-circle.

    The spectrometer is located on the panoramic camera mast. On sol 11, it took a low-angle 180-degree panorama of the area in front of the rover, indicated by the blue shaded dots. The instrument then raised the angle of its field of view a few degrees higher to sweep around behind the rover, indicated by the red and yellow dots offset at the far sides of the image.

    JPL, a division of the California Institute of Technology in Pasadena, manages the Mars Exploration Rover project for NASA's Office of Space Science, Washington, D.C.

  15. Effect of Rosiglitazone on Radiation Damage in Bone Marrow Hemopoiesis

    SciTech Connect

    Benko', Klara; Pintye, Eva; Szabo, Boglarka; Geresi, Krisztina; Megyeri, Attila; Benko, Ilona

    2008-12-08

    To study radiobiological effects and drugs, which can modify radiation injury, has an importance if we would like to avoid harmful effects of radiation due to emergency situations or treat patients with malignant diseases by radiotherapy. During the long treatment schedules patients may be treated by not only anticancer but many other drugs because of accompanying diseases. These drugs may also modify radiobiological effects. Rosiglitazone pre-treatment proved to be myeloprotective and accelerated recovery of 5-fluorouracil-damaged bone marrow in our previous experiments. Our new studies are designed to evaluate whether rosiglitazone has similar beneficial effects in radiation-damaged hemopoiesis. Bone marrow damage was precipitated by total body irradiation (TBI) using single increasing doses (2-10 Gy) of {gamma}--irradiation in groups of mice. Lethality was well correlated with damage in hemopoiesis measured by cellularity of bone marrow (LD{sub 50} values were 4.8 and 5.3 gray respectively). Rosiglitazone, an insulin-sensitizing drug, had no significant effect on bone marrow cellularity. Insulin resistance associated with obesity or diabetes mellitus type 2 is intensively growing among cancer patients requiring some kind of radiotherapy. Therefore it is important to know whether drugs used for their therapy can modify radiation effects.

  16. Thorotrast-Associated Anemia and Bone Marrow Hypoplasia

    PubMed Central

    Summers, Diane E.; Chung, E. B.

    1986-01-01

    Two patients with chronic anemia and bone marrow hypoplasia secondary to Thorotrast deposition are described. In one case thorium dioxide was identified by histoautoradiography, scanning electron microscopy, and x-ray spectrometry. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6Figure 7Figure 8 PMID:3806691

  17. Anaplasma platys in bone marrow megakaryocytes of young dogs.

    PubMed

    De Tommasi, A Sara; Baneth, Gad; Breitschwerdt, Edward B; Stanneck, Dorothee; Dantas-Torres, Filipe; Otranto, Domenico; de Caprariis, Donato

    2014-06-01

    Anaplasma platys is an obligate intracellular rickettsial pathogen that infects platelets of dogs, forming basophilic intracellular morulae. In the present report, cellular inclusions were documented in bone marrow thrombocyte precursors of two young naturally infected dogs, indicating that A. platys can infect megakaryocytes and promegakaryocytes. PMID:24622106

  18. Treating Families of Bone Marrow Recipients and Donors

    ERIC Educational Resources Information Center

    Cohen, Marie; And Others

    1977-01-01

    Luekemia and aplastic anemia are beginning to be treated by bone marrow transplants, involving donors and recipients from the same family. Such intimate involvement in the patient's life and death struggles typically produces a family crisis and frequent maladaptive responses by various family members. (Author)

  19. Effect of Rosiglitazone on Radiation Damage in Bone Marrow Hemopoiesis

    NASA Astrophysics Data System (ADS)

    Benk?, Klra; Pintye, va; Szab, Boglrka; Gresi, Krisztina; Megyeri, Attila; Benk?, Ilona

    2008-12-01

    To study radiobiological effects and drugs, which can modify radiation injury, has an importance if we would like to avoid harmful effects of radiation due to emergency situations or treat patients with malignant diseases by radiotherapy. During the long treatment schedules patients may be treated by not only anticancer but many other drugs because of accompanying diseases. These drugs may also modify radiobiological effects. Rosiglitazone pre-treatment proved to be myeloprotective and accelerated recovery of 5-fluorouracil-damaged bone marrow in our previous experiments. Our new studies are designed to evaluate whether rosiglitazone has similar beneficial effects in radiation-damaged hemopoiesis. Bone marrow damage was precipitated by total body irradiation (TBI) using single increasing doses (2-10 Gy) of ?irradiation in groups of mice. Lethality was well correlated with damage in hemopoiesis measured by cellularity of bone marrow (LD50 values were 4.8 and 5.3 gray respectively). Rosiglitazone, an insulin-sensitizing drug, had no significant effect on bone marrow cellularity. Insulin resistance associated with obesity or diabetes mellitus type 2 is intensively growing among cancer patients requiring some kind of radiotherapy. Therefore it is important to know whether drugs used for their therapy can modify radiation effects.

  20. Generation of Eosinophils from Cryopreserved Murine Bone Marrow Cells

    PubMed Central

    Schollaert, Kaila L.; Stephens, Michael R.; Gray, Jerilyn K.; Fulkerson, Patricia C.

    2014-01-01

    Eosinophils are produced in the bone marrow from CD34+ eosinophil lineagecommitted progenitors, whose levels in the bone marrow are elevated in a variety of human diseases. These findings suggest that increased eosinophil lineagecommitted progenitor production is an important process in disease-associated eosinophilia. The pathways central to the biology of the eosinophil lineagecommitted progenitor remain largely unknown. Thus, developing new methods to investigate the regulators of eosinophil lineagecommitted progenitor differentiation is needed to identify potential therapeutic targets to specifically inhibit eosinophil production. We tested cytokine regimens to optimize liquid cultures for the study of eosinophil lineagecommitted progenitor and eosinophil precursor differentiation into mature eosinophils. Stem cell factor (but not fms-related tyrosine kinase 3 ligand) was required for optimal yield of eosinophils. Furthermore, we evaluated the effects of cell preservation and scale on the culture, successfully culturing functional eosinophils from fresh and frozen murine bone marrow cells and in a standard-sized and 96-well culture format. In summary, we have developed an adaptable culture system that yields functionally competent eosinophils from murine low-density bone marrow cells and whose cytokine regime includes expansion of progenitors with stem cell factor alone with subsequent differentiation with interleukin 5. PMID:25551463

  1. A Role For Photodynamic Therapy In Autologous Bone Marrow Transplantation

    NASA Astrophysics Data System (ADS)

    Sieber, Fritz

    1988-02-01

    Simultaneous exposure to the amphipathic fluorescent dye merocyanine 540 (MC 540) and light of a suitable wavelength rapidly kills leukemia, lymphoma, and neuroblastoma cells but spares normal pluripotent hematopoietic stem cells. Tests in several preclinical models and early results of a phase I clinical trial suggest that MC 540-mediated photosensitization may be useful for the extracorporeal purging of autologous remission bone marrow grafts.

  2. Clonogenic assays and engraftment in allogeneic bone marrow transplantation.

    PubMed

    Gerhartz, H H; Kolb, H J; Clemm, C; Wilmanns, W

    1986-12-01

    The significance of clonogenic assays for determining the hematopoietic potential of bone marrow grafts is still a matter of controversy. We determined the number of myeloid (GM-CFU), early erythroid (BFUe) and mixed (CFU-GEM) clones in 23 consecutive allogeneic bone marrow grafts. The growth of GM-CFU was stimulated by placental-conditioned medium, whereas both phytohemagglutinin-stimulated leucocyte-conditioned medium (PHA-LCM) and 'pluripoietin' from the 5637 cell line served as equally efficient stimulators of BFUe and CFU-GEM growth. Plating efficiency (e.o.p.) of GM-CFU and numbers of myeloid and mixed progenitors transplanted per kg body weight were significantly lower in those patients who died in the aplastic phase 2-6 weeks postgrafting (n = 4). These data show that low numbers of clonogenic cells, in particular GM-CFU, indicate a higher risk of death from infection following bone marrow transplantation (BMT) and argue for a contribution of GM-CFU in the seeding of an aplastic bone marrow. PMID:2901871

  3. Late renal dysfunction in adult survivors of bone marrow transplantation

    SciTech Connect

    Lawton, C.A.; Cohen, E.P.; Barber-Derus, S.W.; Murray, K.J.; Ash, R.C.; Casper, J.T.; Moulder, J.E. )

    1991-06-01

    Until recently long-term renal toxicity has not been considered a major late complication of bone marrow transplantation (BMT). Late renal dysfunction has been described in a pediatric population status post-BMT which was attributable to the radiation in the preparatory regimen. A thorough review of adults with this type of late renal dysfunction has not previously been described. Fourteen of 103 evaluable adult patients undergoing allogeneic (96) or autologous (7) bone marrow transplantation, predominantly for leukemia and lymphomas, at the Medical College of Wisconsin (Milwaukee, WI) have had a syndrome of renal insufficiency characterized by increased serum creatinine, decreased glomerular filtration rate, anemia, and hypertension. This syndrome developed at a median of 9 months (range, 4.5 to 26 months) posttransplantation in the absence of specific identifiable causes. The cumulative probability of having this renal dysfunction is 20% at 1 year. Renal biopsies performed on seven of these cases showed the endothelium widely separated from the basement membrane, extreme thickening of the glomerular basement membrane, and microthrombi. Previous chemotherapy, antibiotics, and antifungals as well as cyclosporin may add to and possibly potentiate a primary chemoradiation marrow transplant renal injury, but this clinical syndrome is most analogous to clinical and experimental models of radiation nephritis. This late marrow transplant-associated nephritis should be recognized as a potentially limiting factor in the use of some intensive chemoradiation conditioning regimens used for BMT. Some selective attenuation of the radiation to the kidneys may decrease the incidence of this renal dysfunction.

  4. Neurokinin-1 Receptor Signalling Impacts Bone Marrow Repopulation Efficiency

    PubMed Central

    Berger, Alexandra; Frelin, Catherine; Shah, Divya K.; Benveniste, Patricia; Herrington, Robert; Gerard, Norma P.; Ziga-Pflcker, Juan-Carlos; Iscove, Norman N.; Paige, Christopher J.

    2013-01-01

    Tachykinins are a large group of neuropeptides with both central and peripheral activity. Despite the increasing number of studies reporting a growth supportive effect of tachykinin peptides in various in vitro stem cell systems, it remains unclear whether these findings are applicable in vivo. To determine how neurokinin-1 receptor (NK-1R) deficient hematopoietic stem cells would behave in a normal in vivo environment, we tested their reconstitution efficiency using competitive bone marrow repopulation assays. We show here that bone marrow taken from NK-1R deficient mice (Tacr1?/?) showed lineage specific B and T cell engraftment deficits compared to wild-type competitor bone marrow cells, providing evidence for an involvement of NK-1R signalling in adult hematopoiesis. Tachykinin knockout mice lacking the peptides SP and/or HK-1 (Tac1?/?, Tac4?/? and Tac1?/?/Tac4?/? mice) repopulated a lethally irradiated wild-type host with similar efficiency as competing wild-type bone marrow. The difference between peptide and receptor deficient mice indicates a paracrine and/or endocrine mechanism of action rather than autocrine signalling, as tachykinin peptides are supplied by the host environment. PMID:23516556

  5. Outcome following late marrow relapse in childhood acute lymphoblastic leukemia

    SciTech Connect

    Chessells, J.; Leiper, A.; Rogers, D.

    1984-10-01

    Thirty-four children with acute lymphoblastic leukemia, who developed bone marrow relapse after treatment was electively stopped, received reinduction, consolidation, continuing therapy, and intrathecal (IT) methotrexate (MTX). Sixteen children who relapsed within six months of stopping treatment had a median second-remission duration of 26 weeks; all next relapses occurred in the bone marrow. In 18 children who relapsed later, the median duration of second remission was in excess of two years, but after a minimum of four years follow-up, 16 patients have so far relapsed again (six in the CNS). CNS relapse occurred as a next event in four of 17 children who received five IT MTX injections only and in two of 14 children who received additional regular IT MTX. Although children with late marrow relapses may achieve long second remissions, their long-term out-look is poor, and regular IT MTX does not afford adequate CNS prophylaxis. It remains to be seen whether more intensive chemotherapy, including high-dose chemoradiotherapy and bone marrow transplantation, will improve the prognosis in this group of patients.

  6. Body/bone-marrow differential-temperature sensor

    NASA Technical Reports Server (NTRS)

    Anselmo, V. J.; Berdahl, C. M.

    1978-01-01

    Differential-temperature sensor developed to compare bone-marrow and body temperature in leukemia patients uses single stable amplifier to monitor temperature difference recorded by thermocouples. Errors are reduced by referencing temperatures to each other, not to separate calibration points.

  7. A Dosimetric Study of Radionuclide Therapy for Bone Marrow Ablation.

    NASA Astrophysics Data System (ADS)

    Bayouth, John Ellis

    In a phase I clinical trial, six multiple myeloma patients, who were non-responsive to conventional therapy and were scheduled for bone marrow transplantation, received Holmium-166 (166Ho) labeled to a bone seeking agent, DOTMP (1,4,7,10-tetraazacyclododecane -1,4,7,10-tetramethylene-phosphonic acid), for the purpose of bone marrow ablation. The specific aims of my research within this protocol were to evaluate the toxicity and efficacy of 166Ho DOTMP by quantifying the in vivo pharmacokinetics and radiation dosimetry, and by correlating these results to the biologic response observed. The reproducibility of pharmacokinetics from multiple injections of 166 Ho DOTMP administered to these myeloma patients was demonstrated from both blood and whole body retention. The skeletal concentration of 166 Ho DOTMP was heterogenous in all six patients: high in the ribs, pelvis, and lumbar vertebrae regions, and relatively low in the femurs, arms, and head. A novel technique was developed to calculate the radiation dose to the bone marrow in each skeletal ROI, and was applied to all six 166 Ho DOTMP patients. Radiation dose estimates for the bone marrow calculated using the standard MIRD "S" factors were compared with the average values derived from the heterogenous distribution of activity in the skeleton (i.e., the regional technique). The results from the two techniques were significantly different; the average of the dose estimates from the regional technique were typically 30% greater. Furthermore, the regional technique provided a range of radiation doses for the entire marrow volume, while the MIRD "S" factors only provided a single value. Dose volume histogram analysis of data from the regional technique indicated a range of dose estimates that varied by a factor of 10 between the high dose and low dose regions. Finally, the observed clinical response of cells and abnormal proteins measured in bone marrow aspirates and peripheral blood samples were compared with radiation dose estimates for the bone marrow calculated from the standard and regional technique. The results showed the regional technique values correlated more closely to several clinical response parameters. (Abstract shortened by UMI.).

  8. Bone marrow endothelium-targeted therapeutics for metastatic breast cancer.

    PubMed

    Mai, Junhua; Huang, Yi; Mu, Chaofeng; Zhang, Guodong; Xu, Rong; Guo, Xiaojing; Xia, Xiaojun; Volk, David E; Lokesh, Ganesh L; Thiviyanathan, Varatharasa; Gorenstein, David G; Liu, Xuewu; Ferrari, Mauro; Shen, Haifa

    2014-08-10

    Effective treatment of cancer metastasis to the bone relies on bone marrow drug accumulation. The surface proteins in the bone marrow vascular endothelium provide docking sites for targeted drug delivery. We have developed a thioaptamer that specifically binds to E-selectin that is overexpressed in the vasculature of tumor and inflammatory tissues. In this study, we tested targeted delivery of therapeutic siRNA loaded in the E-selectin thioaptamer-conjugated multistage vector (ESTA-MSV) drug carrier to bone marrow for the treatment of breast cancer bone metastasis. We evaluated tumor type- and tumor growth stage-dependent targeting in mice bearing metastatic breast cancer in the bone, and carried out studies to identify factors that determine targeting efficiency. In a subsequent study, we delivered siRNA to knock down expression of the human STAT3 gene in murine xenograft models of human MDA-MB-231 breast tumor, and assessed therapeutic efficacy. Our studies revealed that the CD31(+)E-selectin(+) population accounted for 20.8%, 26.4% and 29.9% of total endothelial cells respectively inside the femur of mice bearing early, middle and late stage metastatic MDA-MB-231 tumors. In comparison, the double positive cells remained at a basal level in mice with early stage MCF-7 tumors, and jumped to 23.9% and 28.2% when tumor growth progressed to middle and late stages. Accumulation of ESTA-MSV inside the bone marrow correlated with the E-selectin expression pattern. There was up to 5-fold enrichment of the targeted MSV in the bone marrow of mice bearing early or late stage MDA-MB-231 tumors and of mice with late stage, but not early stage, MCF-7 tumors. Targeted delivery of STAT3 siRNA in ESTA-MSV resulted in knockdown of STAT3 expression in 48.7% of cancer cells inside the bone marrow. Weekly systemic administration of ESTA-MSV/STAT3 siRNA significantly extended survival of mice with MDA-MB-231 bone metastasis. In conclusion, targeting the overexpressed E-selectin provides an effective approach for tissue-specific drug delivery to the bone marrow. Tumor growth in the bone can be effectively inhibited by blockage of the STAT3 signaling. PMID:24818768

  9. Red Ear Syndrome.

    PubMed

    Raieli, V; Compagno, A; D'Amelio, M

    2016-03-01

    The Red ear syndrome (RES) is an intriguing syndrome originally described for the first time nearly 20years ago. RES is characterized by unilateral/bilateral episodes of pain and burning sensation of the ear, associated with ipsilateral erythema. RES episodes are indeed isolated in some patients, but they can occur in association with primary headaches, including in particular migraine in the developmental age. Although the underlying pathophysiological mechanisms are still uncertain, in the recent years the described comorbidities have aroused increasing interest because of possible clinical implications. Moreover, RES seems to be more often associated with clinical features of migraine partially provoked by the involvement of the parasympathetic system. This clinical association has shed new light on the pathophysiology of RES, supporting the hypothesis of a shared pathophysiological background, for example, through the activation of the trigeminal autonomic reflex. Current therapies of RES will be also discussed. Finally, we will resume the more controversial aspects of this relatively new and probably underestimated neurological syndrome. PMID:26879877

  10. Mapping the Red Planet

    NASA Technical Reports Server (NTRS)

    Smith, David E.; Smith, David E.

    2001-01-01

    Since September 1997 the Mars Global Surveyor spacecraft has been orbiting the planet Mars and acquiring new data about the red planet that is changing our view of its present state and past history. Except for a few weeks in October 1997 and a few months in the Spring/Summer of 1998 when special science operations were conducted the spacecraft spent the first 18 months if its time at Mars getting to the right orbital geometry for the mapping mission. But on March 1, 1999 the MGS spacecraft trained its instruments onto the planet to begin a full Mars year (684 Earth days) of continuous systematic mapping and observation of the planet. The camera began wide angle and high resolution mapping, the thermal emission spectrometer began sensing the atmosphere and the material properties of the surface, the magnetometer searched out regions of abnormally high magnetism, the altimeter began determining the precise shape of the planet, and the radio science experiment began determining atmospheric pressures, temperatures and mapping the planet's gravity field. In a matter of a month more data was acquired about

  11. Chromosome aberrations in peripheral lymphocytes and radiation dose to active bone marrow in patients treated for cancer of the cervix

    SciTech Connect

    Kleinerman, R.A.; Littlefield, L.G.; Tarone, R.E.; Machado, S.G.; Blettner, M.; Peters, L.J.; Boice, J.D. Jr. )

    1989-07-01

    An international study of cervical cancer patients reported a doubling of the risk for leukemia following radiotherapy. To evaluate the extent of residual chromosome damage in circulating T-cell lymphocytes in this population, approximately 200 metaphases were examined from each of 96 irradiated and 26 nonirradiated cervical cancer patients treated more than 17 years ago (average 23 years). Radiation dose averaged over the total red bone marrow was estimated to be 8.1 Gy. The type and frequency of stable and unstable chromosome aberrations were quantified in 24,117 metaphases. Unstable aberrations did not differ significantly between irradiated and nonirradiated patients (P greater than 0.5). Stable aberrations (i.e., translocations, inversions, or chromosomes with deleted segments), however, were significantly higher among irradiated (2.8 per 100 cells) compared to nonirradiated (0.7 per 100 cells) women (P less than 10(4)). The frequency of these stable aberrations was found to increase significantly with increasing dose to the bone marrow. These data indicate that a direct relationship between radiation dose and extent of damage to somatic cells persists in populations and can be detected many years after partial-body radiation exposure. The stable aberration rate in irradiated cervical cancer patients was 50 to 75% lower than those observed 25 years or more after radiation exposure in atomic bomb survivors and in ankylosing spondylitis patients treated with radiotherapy. The average marrow dose was only 1 Gy in the examined atomic bomb survivors and 3.5 Gy in the ankylosing spondylitis patients. It appears, then, that a very high dose delivered to the pelvic cavity in fractionated doses resulted in far fewer persistent stable aberrations than lower doses delivered either in acute whole-body exposure or in fractionated doses to the spinal column and sacroiliac joints.

  12. Successful bone marrow transplantation in a patient with DNA ligase IV deficiency and bone marrow failure

    PubMed Central

    Gruhn, Bernd; Seidel, Joerg; Zintl, Felix; Varon, Raymonda; Tnnies, Holger; Neitzel, Heidemarie; Bechtold, Astrid; Hoehn, Holger; Schindler, Detlev

    2007-01-01

    Background DNA Ligase IV deficiency syndrome is a rare autosomal recessive disorder caused by hypomorphic mutations in the DNA ligase IV gene (LIG4). The clinical phenotype shows overlap with a number of other rare syndromes, including Seckel syndrome, Nijmegen breakage syndrome, and Fanconi anemia. Thus the clinical diagnosis is often delayed and established by exclusion. Methods We describe a patient with pre- and postnatal growth retardation and dysmorphic facial features in whom the diagnoses of Seckel-, Dubowitz-, and Nijmegen breakage syndrome were variably considered. Cellular radiosensitivity in the absence of clinical manifestations of Ataxia telangiectasia lead to the diagnosis of DNA ligase IV (LIG4) deficiency syndrome, confirmed by compound heterozygous mutations in the LIG4 gene. At age 11, after a six year history of progressive bone marrow failure and increasing transfusion dependency the patient was treated with matched sibling donor hematopoetic stem cell transplantation (HSCT) using a fludarabine-based conditioning regimen without irradiation. Results The post-transplantation course was uneventful with rapid engraftment leading to complete and stable chimerism. Now at age 16, the patient has gained weight and is in good clinical condition. Conclusion HSCT using mild conditioning without irradiation qualifies as treatment of choice in LIG4-deficient patients who have a matched sibling donor. PMID:17224058

  13. Stem cell plasticity in muscle and bone marrow.

    PubMed

    Goodell, M A; Jackson, K A; Majka, S M; Mi, T; Wang, H; Pocius, J; Hartley, C J; Majesky, M W; Entman, M L; Michael, L H; Hirschi, K K

    2001-06-01

    Recent discoveries have demonstrated the extraordinary plasticity of tissue-derived stem cells, raising fundamental questions about cell lineage relationships and suggesting the potential for novel cell-based therapies. We have examined this phenomenon in a potential reciprocal relationship between stem cells derived from the skeletal muscle and from the bone marrow. We have discovered that cells derived from the skeletal muscle of adult mice contain a remarkable capacity for hematopoietic differentiation. Cells prepared from muscle by enzymatic digestion and 5 day in vitro culture were harvested and introduced into each of six lethally irradiated recipients together with distinguishable whole bone marrow cells. Six and twelve weeks later, all recipients showed high-level engraftment of muscle-derived cells representing all major adult blood lineages. The mean total contribution of muscle cell progeny to peripheral blood was 56%, indicating that the cultured muscle cells generated approximately 10- to 14-fold more hematopoietic activity than whole bone marrow. Although the identity of the muscle-derived hematopoietic stem cells is still unknown, they may be identical to muscle satellite cells, some of which lack myogenic regulators and could respond to hematopoietic signals. We have also found that stem cells in the bone marrow can contribute to cardiac muscle repair and neovascularization after ischemic injury. We transplanted highly purified bone marrow stem cells into lethally irradiated mice that subsequently were rendered ischemic by coronary artery occlusion and reperfusion. The engrafted stem cells or their progeny differentiated into cardiomyocytes and endothelial cells and contributed to the formation of functional tissue. PMID:11458510

  14. Red blood cells, multiple sickle cells (image)

    MedlinePLUS

    Sickle cell anemia is an inherited disorder in which abnormal hemoglobin (the red pigment inside red blood cells) is produced. The abnormal hemoglobin causes red blood cells to assume a sickle shape, like the ones seen in this photomicrograph.

  15. Red ginseng and cancer treatment.

    PubMed

    Wang, Chong-Zhi; Anderson, Samantha; DU, Wei; He, Tong-Chuan; Yuan, Chun-Su

    2016-01-01

    The ginseng family, including Panax ginseng (Asian ginseng), Panax quinquefolius (American ginseng), and Panax notoginseng (notoginseng), is commonly used herbal medicine. White ginseng is prepared by air-drying after harvest, while red ginseng is prepared by a steaming or heating process. The anticancer activity of red ginseng is significantly increased, due to the production of active anticancer ginsenosides during the steaming treatment, compared with that of white ginseng. Thus far, anticancer studies have been mostly focused on Asian ginseng. In this article, we review the research progress made in the anticancer activities of red Asian ginseng, red American ginseng and red notoginseng. The major anticancer mechanisms of red ginseng compounds include cell cycle arrest, induction of apoptosis/paraptosis, and inhibition of angiogenesis. The structure-function relationship analysis has revealed that the protopanaxadiol group ginsenosides have more potent effects than the protopanaxatriol group. Sugar molecules in ginsenosides inversely impact the antiproliferative potential of these compounds. In addition, ginsenoside stereoselectivity and double bond position also influence the anticancer activity. Future studies should focus on characterizing active red ginseng derivatives as potential anticancer drugs. PMID:26850342

  16. The osteogenic differentiation stimulating activity of Sea cucumber methanolic crude extraction on rat bone marrow mesenchymal stem cells

    PubMed Central

    Baharara, Javad; Amini, Elaheh; Kerachian, Mohammad Amin; Soltani, Mozhgan

    2014-01-01

    Objective(s): Sea cucumber derived bioactive compound is considered efficient in treatment of bone disorders. This study was performed to evaluate the effect of this extract on differentiation of rat bone marrow mesenchymal stem cells (rBMMSc) into osteogenic lineage. Materials and Methods: Isolated rBMMSc were grown in DMEM supplemented with 10% FBS. The cells were exposed to different concentration of extract. After 21 days, Alizarin red staining, alkaline phosphatase assay and RT-PCR were performed. The results were analyzed by ANOVA software and P value <0.05 was considered significant. Results: Morphological methods revealed that appropriate concentrations of extract increased osteogenic differentiation in a dose-dependent manner. RT-PCR revealed that extract without or with osteogenic medium due to osteopontin expression had a potential role in osteogenesis. Conclusion: Based on our data it concluded that S. cucumber extract stimulated Bone marrow mesenchymal cells to differentiate into osteogenic lineage without existence of osteogenic medium. PMID:25422758

  17. Development of phenotypic screening assays for ?-globin induction using primary human bone marrow day 7 erythroid progenitor cells.

    PubMed

    Li, Hu; Xie, Wensheng; Gore, Elizabeth R; Montoute, Monica N; Bee, Weilin Tiger; Zappacosta, Francesca; Zeng, Xin; Wu, Zining; Kallal, Lorena; Ames, Robert S; Pope, Andrew J; Benowitz, Andrew; Erickson-Miller, Connie L

    2013-12-01

    Sickle cell anemia (SCA) is a genetic disorder of the ?-globin gene. SCA results in chronic ischemia with pain and tissue injury. The extent of SCA symptoms can be ameliorated by treatment with drugs, which result in increasing the levels of ?-globin in patient red blood cells. Hydroxyurea (HU) is a Food and Drug Administration-approved drug for SCA, but it has dose-limiting toxicity, and patients exhibit highly variable treatment responses. To identify compounds that may lead to the development of better and safer medicines, we have established a method using primary human bone marrow day 7 erythroid progenitor cells (EPCs) to screen for compounds that induce ?-globin production. First, human marrow CD34(+) cells were cultured and expanded for 7 days and characterized for the expression of erythroid differentiation markers (CD71, CD36, and CD235a). Second, fresh or cryopreserved EPCs were treated with compounds for 3 days in 384-well plates followed by ?-globin quantification by an enzyme-linked immunosorbent assay (ELISA), which was validated using HU and decitabine. From the 7408 compounds screened, we identified at least one new compound with confirmed ?-globin-inducing activity. Hits are undergoing analysis in secondary assays. In this article, we describe the method of generating fit-for-purpose EPCs; the development, optimization, and validation of the ELISA and secondary assays for ?-globin detection; and screening results. PMID:24163393

  18. Distribution and identity of the earliest proliferating progeny of colony-forming cells in regenerating murine spleen and bone marrow

    SciTech Connect

    Wolf, N.; Rosse, C.

    1982-02-01

    A study was made of the sites of development and the types of cells found in very early hemopoietic colonies in the mouse spleen. Two, 3, and 4 days after transplantation, the proliferating descendants of transplanted bone-marrow cells were identified on radioautographs of spleen sections and on spleen and bone-marrow smears of supralethally irradiated recipient mice which were injected with /sup 3/H-TdR at 12, 6, and 0.5 hours before sacrifice. Surprisingly the spleens of nontransplanted, irradiated mice contained proliferating medium and large lymphocytes in the white pulp which increased in numbers during the observation period. The early descendants of transplanted cells that lodged in the spleen could be clearly distinguished from the labeled indigenous cells because they formed discrete nodules or colonies beneath the splenic capsule or in the vicinity of venules and trabeculae of the red pulp. These cells were identifiable on day 2 as transitional cells or unknown hemopoietic blasts and on day 4 included early erythroid cells and small lymphocytes. There was evidence for the traffic of /sup 3/H-TdR-labeled cells through the splenic sinusoids.

  19. Fullerol antagonizes dexamethasone-induced oxidative stress and adipogenesis while enhancing osteogenesis in a cloned bone marrow mesenchymal stem cell.

    PubMed

    Liu, Hongjian; Yang, Xinlin; Zhang, Yi; Dighe, Abhijit; Li, Xudong; Cui, Quanjun

    2012-07-01

    Increased oxidative stress is currently considered as a crucial cause of corticosteroid-induced osteonecrosis. The aim of this study was to evaluate the effect of fullerol, a powerful antioxidant, on adipogenic and osteogenic differentiation of a mouse bone marrow derived multipotent cell line, D1. Upon treatment with dexamethasone, D1 cells containing lipid vesicles were distinguishable from the surrounding cells by Oil Red O staining at day 21. Simultaneous treatment of dexamethasone with antioxidant glutathione or fullerol decreased the number of cells containing lipid vesicles. Treatment with dexamethasone for 7 days resulted in a significant increase in adipogenic markers peroxisome proliferator-activated receptor gamma and adipocyte protein 2 gene expression and decrease in expression of osteogenic markers runt-related transcription factor 2 and osteocalcin and antioxidative enzymes superoxide dismutase and catalase as revealed by quantitative real-time PCR. While glutathione and fullerol both were able to antagonize the effects of dexamethasone, fullerol had a greater effect than glutathione. Staining with a fluorescent dye CM-H(2) DCFDA as indicator of cellular reactive oxygen species revealed that the percentage of positively stained cells increased after dexamethasone treatment, and addition of fullerol attenuated this activity. These results indicated that fullerol inhibited adipogenesis and simultaneously enhanced osteogenesis by marrow mesenchymal stem cells possibly through elimination of cellular reactive oxygen species. The results indicated that fullerol can potentially be used for prevention and treatment of corticosteroid-induced osteonecrosis. PMID:22570221

  20. Red Meat and Colorectal Cancer.

    PubMed

    Aykan, Nuri Faruk

    2015-02-10

    Colorectal cancer (CRC) is the third most common cancer in men and the second in women worldwide. More than half of cases occur in more developed countries. The consumption of red meat (beef, pork, lamb, veal, mutton) is high in developed countries and accumulated evidence until today demonstrated a convincing association between the intake of red meat and especially processed meat and CRC risk. In this review, meta-analyses of prospective epidemiological studies addressed to this association, observed link of some subtypes of red meat with CRC risk, potential carcinogenic compounds, their mechanisms and actual recommendations of international guidelines are presented. PMID:26779313

  1. Red Meat and Colorectal Cancer

    PubMed Central

    2015-01-01

    Colorectal cancer (CRC) is the third most common cancer in men and the second in women worldwide. More than half of cases occur in more developed countries. The consumption of red meat (beef, pork, lamb, veal, mutton) is high in developed countries and accumulated evidence until today demonstrated a convincing association between the intake of red meat and especially processed meat and CRC risk. In this review, meta-analyses of prospective epidemiological studies addressed to this association, observed link of some subtypes of red meat with CRC risk, potential carcinogenic compounds, their mechanisms and actual recommendations of international guidelines are presented. PMID:26779313

  2. The use of multiparameter flow cytometry and cell sorting to characterize native human bone marrow mesenchymal stem cells (MSC).

    PubMed

    Boxall, Sally; Jones, Elena

    2015-01-01

    This chapter describes a method for identification, phenotypic analysis, and cell sorting of rare mesenchymal stem cells (MSCs) from human bone marrow (BM) aspirates. The native BM MSC population is identified based on the CD45(-/low)CD271(+) phenotype. The method consists of three related procedures: Procedure 1 involves a microbead-based pre-enrichment step. Two other procedures describe direct flow cytometric analysis of MSCs following the isolation of the mononuclear cell (MNC) fraction (Procedure 2) or more rapidly, following a simple ammonium chloride-based red cell lysis (Procedure 3). Recently described multi-lineage transcript expression in the CD45(-/low)CD271(+) cells suggests that the native BM MSC fraction could be further subdivided into functionally distinct subpopulations. The present protocols are hoped to help MSC biologists to enter this exciting field of research and to take it forward towards a better understanding of MSC biology in vivo. PMID:25388391

  3. Multilineage differentiation of human bone marrow mesenchymal stem cells in vitro and in vivo.

    PubMed

    Zheng, You-Hua; Xiong, Wei; Su, Kai; Kuang, Shi-Jun; Zhang, Zhi-Guang

    2013-06-01

    The aim of the present study was to investigate the ability of human bone marrow-derived mesenchymal stem cells (BMSCs) to undergo multilineage differentiation. Human BMSCs were isolated from the ilia of donors by density gradient centrifugation, then purified by adherent separation and cultured in vitro. P3 or P4 BMSC populations were collected and induced for multilineage differentiation into osteoblasts, adipocytes and neuroblasts using an inductive medium in vitro. The BMSCs were cultured in either an osteoblast or chondroblast induction medium, seeded onto porous coral scaffolds and implanted into mice in vivo. The mice were sacrificed by anesthesia overdose at 6 or 9 weeks post-surgery. The scaffolds were then removed for analysis. Lipid vacuoles were observed subsequent to being cultured in an adipogenic medium. These accumulated lipid vacuoles were detected using Sudan Black B and Oil Red O (positive) staining. Deposited calcium was detected using von Kossa and Alizarin Red S (positive) staining subsequent to being cultured in an osteogenic medium. The BMSCs retracted to form neuron-like cells with axon- and dendrite-like processes following induction by ?-mercaptoethanol. The cells were positively stained by toluidine blue and glial fibrillary acidic protein (GFAP) immunohistochemistry. Newly formed bone tissues were observed and islands of cartilage tissue were also formed at 9 weeks post-implantation in vivo. The present study demonstrated that human BMSCs were homogeneous and differentiated with high fidelity to osteogenic, adipogenic, neurogenic or chondrogenic lineages. These cells also form bone and cartilage tissues when implanted in vivo and may therefore be used as seed cells in bone tissue engineering. PMID:23837034

  4. Red Yeast Rice: An Introduction

    MedlinePLUS

    ... as certain cholesterol-lowering drugs, and some may contain a potentially harmful contaminant. This fact sheet provides ... information. Key Facts Some red yeast rice products contain substantial amounts of monacolin K, which is chemically ...

  5. Red Blood Cell Antibody Identification

    MedlinePLUS

    ... but may react with a broad range of different red blood cell antigen types, including the person's own. These types of antibodies can occur in association with autoimmune disorders , lymphomas and chronic lymphocytic leukemia , ...

  6. CXCR2 modulates bone marrow vascular repair and haematopoietic recovery post-transplant

    PubMed Central

    Hale, Sarah J M; Hale, Ashley B H; Zhang, Youyi; Sweeney, Dominic; Fisher, Nita; van der Garde, Mark; Grabowska, Rita; Pepperell, Emma; Channon, Keith; Martin-Rendon, Enca; Watt, Suzanne M

    2015-01-01

    Murine models of bone marrow transplantation show that pre-conditioning regimens affect the integrity of the bone marrow endothelium and that the repair of this vascular niche is an essential pre-requisite for successful haematopoietic stem and progenitor cell engraftment. Little is known about the angiogenic pathways that play a role in the repair of the human bone marrow vascular niche. We therefore established an in vitro humanized model, composed of bone marrow stromal and endothelial cells and have identified several pro-angiogenic factors, VEGFA, ANGPT1, CXCL8 and CXCL16, produced by the stromal component of this niche. We demonstrate for the first time that addition of CXCL8 or inhibition of its receptor, CXCR2, modulates blood vessel formation in our bone marrow endothelial niche model. Compared to wild type, Cxcr2?/? mice displayed a reduction in bone marrow cellularity and delayed platelet and leucocyte recovery following myeloablation and bone marrow transplantation. The delay in bone marrow recovery correlated with impaired bone marrow vascular repair. Taken together, our data demonstrate that CXCR2 regulates bone marrow blood vessel repair/regeneration and haematopoietic recovery, and clinically may be a therapeutic target for improving bone marrow transplantation. PMID:25757087

  7. Consequences of irradiation on bone and marrow phenotypes, and its relation to disruption of hematopoietic precursors

    PubMed Central

    Green, Danielle E.; Rubin, Clinton T.

    2014-01-01

    The rising levels of radiation exposure, specifically for medical treatments and accidental exposures, have added great concern for the long term risks of bone fractures. Both the bone marrow and bone architecture are devastated following radiation exposure. Even sub-lethal doses cause a deficit to the bone marrow microenvironment, including a decline in hematopoietic cells, and this deficit occurs in a dose dependent fashion. Certain cell phenotypes though are more susceptible to radiation damage, with mesenchymal stem cells being more resilient than the hematopoietic stem cells. The decline in total bone marrow hematopoietic cells is accompanied with elevated adipocytes into the marrow cavity, thereby inhibiting hematopoiesis and recovery of the bone marrow microenvironment. Poor bone marrow is also associated with a decline in bone architectural quality. Therefore, the ability to maintain the bone marrow microenvironment would hinder much of the trabecular bone loss caused by radiation exposure, ultimately decreasing some comorbidities in patients exposed to radiation. PMID:24607941

  8. Intrathoracic extramedullary hematopoiesis: appearance on /sup 99m/Tc sulfur colloid marrow scan

    SciTech Connect

    Bronn, L.J.; Paquelet, J.R.; Tetalman, M.R.

    1980-06-01

    Imaging of the bone marrow by radionuclide scanning was performed using colloids, which are phagocytized by the reticuloendothelial cells of the marrow, or radioiron, which is incorporated into reticulocytes. The use of the former radiopharmaceutical is based on the assumption, generally valid except in aplastic states or after irradiation, that the distribution of hematopoietic and reticuloendothelial tissue in the marrow is similar. Regardless of the method used, active adult marrow is normally distributed only in the axial skeleton and proximal humeri and femurs. Marrow imaging has been used in the evaluation of myeloproliferative disorders, leukemia, lymphoma, aplastic states, malignancy metastatic to marrow, and hemolytic anemia. We report a case of thalassemia major in which the diagnosis of intrathoracic extramedullary hematopoiesis was confirmed with the /sup 99m/Tc sulfur colloid bone marrow scan.

  9. An assessment of bone marrow and bone endosteum dosimetry methods for photon sources

    NASA Astrophysics Data System (ADS)

    Lee, Choonik; Lee, Choonsik; Shah, Amish P.; Bolch, Wesley E.

    2006-11-01

    The rather complex and microscopic histological structure of the skeletal system generally limits one's ability to accurately model this tissue during dosimetric evaluations. Consequently, various assumptions must be made to evaluate the absorbed dose from external and internal photons to the radiosensitive tissues of the red (or haematopoietically active) bone marrow and the osteogenic tissues of the skeletal endosteum. These various methods for photon skeletal dosimetry have not been inter-compared, partly due to the lack of a realistic reference model that can provide a high-resolution three-dimensional geometry for secondary electron particle transport. In the present study, the paired-image radiation transport (PIRT) model developed by Shah et al (2005 J. Nucl. Med. 45 344) was utilized to evaluate the absorbed dose per incident photon fluence to these skeletal regions from idealized parallel beams of monoenergetic photons. The PIRT model results were then used as a local reference against which absorbed doses via other methods were compared. For red bone marrow dosimetry, four approximate techniques were considered: (1) the dose response function method (DRF method) presented in ORNL/TM-8381, (2) the mass-energy absorption coefficient ratio method (two-parameter MEAC method), (3) the MEAC method with the additional use of energy-dependent dose enhancement factors from King and Spiers (1985 Br. J. Radiol. 58 345) (three-parameter MEAC method), and (4) the three-parameter MEAC method applied at the voxel level through the use image-specific CT numbers (CTN method). For the bone endosteum (i.e., bone surfaces), two approximate techniques were compared: (1) the DRF method for bone surfaces and (2) the homogeneous bone approximation (HBA) method. In each case, the local reference standard was assumed to be that of the PIRT model. Four different ex vivo bone specimens with distinctively different internal structures were used in the study: the cranium, the lumbar vertebra, the os coxae and the left middle rib, each excised from a 66 year male cadaver (body mass index, 22.7 kg m-2). High-resolution CT images of these skeletal sites were used to construct computational voxel models for Monte Carlo radiation transport. Study results indicated that skeletal sites with thick cortical regions and thick trabeculae such as in the cranium provide considerable beam attenuation at low photon energies, which is not properly accounted for in methods based on a homogeneous skeletal tissue structure (DRF, MEAC, HBA). For bone marrow dose assessment, the CTN method showed the best agreement with PIRT model results over a broad range of photon energies, while the HBA method showed better agreement with the PIRT model in assessing bone endosteum dose at energies above 100 keV. Bone surface doses were better approximately by the DRF method at energies below 50 keV. Considerable secondary electron escape at photon energies over 1-3 MeV were accounted for in RBM dose assessment only in the PIRT model, as the other methods presume either an infinite expanse of spongiosa (DRF) or the existence of charge-particle equilibrium (MEAC, CTN).

  10. Red face and fungi infection.

    PubMed

    Welsh, Oliverio; Vera-Cabrera, Lucio

    2014-01-01

    Red face syndrome is characterized by an erythematous dermatitis that is produced by different entities. These include rosacea, seborrheic dermatitis, contact dermatitis, atopic dermatitis, psoriasis, cutaneous lupus, photodermatosis, post-topical steroid dermatosis, demodicosis, borderline borderline (BB) leprosy, mastocytosis, carcinoid, postneoplasia flushing, cutaneous lymphoma, tineas, ulerythema ophryogenes, and psychosomatic flushing. Red face is a relatively common dermatologic manifestation. Our goal is to review tinea corporis and other fungi that affect this region causing facial erythema and its therapeutic management. PMID:25441465

  11. Red Tide off Texas Coast

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Red tides (algae) bloomed late this summer along a 300-mile stretch of Texas' Gulf Coast, killing millions of fish and shellfish as well as making some people sick. State officials are calling this the worst red tide bloom in 14 years. The algae produces a poison that paralyzes fish and prevents them from breathing. There is concern that the deadly algae could impact or even wipe out this year's oyster harvest in Texas, which usually peaks during the Thanksgiving and Christmas holidays. The red tides were first observed off the Texas coast in mid-August and have been growing steadily in size ever since. Red tides tend to bloom and subside rapidly, depending upon changes in wind speed and direction, water temperature, salinity, and rainfall patterns (as the algae doesn't do as well in fresher water). This true-color image of the Texas Gulf Coast was acquired on September 29, 2000, by the Moderate-resolution Imaging Spectroradiometer (MODIS) flying aboard NASA's Terra spacecraft. The red tide can be seen as the dark reddish discoloration in the ocean running southwest to northeast along the coast. In this scene, the bloom appears to be concentrated north and east of Corpus Christi, just off Matagorda Island. The image was made at 500-meter resolution using a combination of MODIS' visible bands 1 (red), 4 (green), and 3 (blue). The city of Houston can be seen clearly as the large, greyish cluster of pixels to the north and west of Galveston Bay, which is about mid-way up the coastline in this image. Also visible in this image are plumes of smoke, perhaps wildfires, both to the north and northeast of Houston. For more information about red tides, refer to the Texas Red Tide Web site. Image courtesy Andrey Savtchenko, MODIS Data Support Team, and the MODIS Ocean Team, NASA's Goddard Space Flight Center

  12. Effects of a hybrid micro/nanorod topography-modified titanium implant on adhesion and osteogenic differentiation in rat bone marrow mesenchymal stem cells

    PubMed Central

    Zhang, Wenjie; Li, Zihui; Huang, Qingfeng; Xu, Ling; Li, Jinhua; Jin, Yuqin; Wang, Guifang; Liu, Xuanyong; Jiang, Xinquan

    2013-01-01

    Background and methods Various methods have been used to modify titanium implant surfaces with the aim of achieving better osseointegration. In this study, we fabricated a clustered nanorod structure on an acid-etched, microstructured titanium plate surface using hydrogen peroxide. We also evaluated biofunctionalization of the hybrid micro/nanorod topography on rat bone marrow mesenchymal stem cells. Scanning electron microscopy and x-ray diffraction were used to investigate the surface topography and phase composition of the modified titanium plate. Rat bone marrow mesenchymal stem cells were cultured and seeded on the plate. The adhesion ability of the cells was then assayed by cell counting at one, 4, and 24 hours after cell seeding, and expression of adhesion-related protein integrin ?1 was detected by immunofluorescence. In addition, a polymerase chain reaction assay, alkaline phosphatase and Alizarin Red S staining assays, and osteopontin and osteocalcin immunofluorescence analyses were used to evaluate the osteogenic differentiation behavior of the cells. Results The hybrid micro/nanoscale texture formed on the titanium surface enhanced the initial adhesion activity of the rat bone marrow mesenchymal stem cells. Importantly, the hierarchical structure promoted osteogenic differentiation of these cells. Conclusion This study suggests that a hybrid micro/nanorod topography on a titanium surface fabricated by treatment with hydrogen peroxide followed by acid etching might facilitate osseointegration of a titanium implant in vivo. PMID:23345973

  13. Multiparameter analysis of transplantable hemopoietic stem cells. I. The separation and enrichment of stem cells homing to marrow and spleen on the basis of rhodamine-123 fluorescence

    SciTech Connect

    Bertoncello, I.; Hodgson, G.S.; Bradley, T.R.

    1985-11-01

    A multiparameter cell separative procedure is described that enables normal transplantable hemopoietic stem cells that preferentially home to the marrow of lethally irradiated mice to be enriched and separated from the majority of spleen colony-forming cells that are assayed 13 days after transplantation (CFU-S13). First, bone marrow cells are centrifuged in a discontinuous bovine serum albumin gradient. Low-density cells are harvested and labeled with the supravital cationic fluorochrome rhodamine 123 (Rh123). Labeled cells are analyzed using a fluorescence-activated cell sorter, and cells are sorted on the basis of relative Rh123 fluorescence within a predetermined forward versus 90 degrees red light scatter window that has been optimized for the recovery and enrichment of cells with marrow repopulating ability (MRA). Cells with MRA were characterized by relatively low Rh123 fluorescence and could be separated from a fraction that fluoresced more intensely and contained the majority of CFU-S13 but low MRA. Cells with platelet repopulating ability cofractionate with MRA whereas cells with erythroid repopulating ability remain associated with CFU-S13.

  14. Herb-induced acute bone marrow intoxication and interstitial nephritis superimposing glomerular C1q deposition in a patient with paroxysmal nocturnal hemoglobinuria.

    PubMed

    Boqari, Deena T; Al Faraj, Shatha; Arafah, Maria; Aloudah, Nourah; Alkhairy, Khalid S; Alsuhaibani, Ahmed; Alsaad, Khaled O

    2015-01-01

    Paroxysmal nocturnal hemoglobinuria is a rare disease of the red blood cell membrane that renders it lyzable by the complement system, leading to chronic intravascular hemolysis. Renal hemosiderosis is a well-known complication of intravascular hemolytic anemia and can lead to acute kidney injury and renal failure. The use of herbal medicine is common worldwide. The nephrotoxicity of herbal remedies can take several forms, which include acute kidney injury and acute and chronic interstitial nephritis. In addition, the use of herbal remedies can result in bone marrow toxicity and suppression. C1q nephropathy is an uncommon form of glomerular disease characterized by dominant or co-dominant glomerular immunofluorescence positivity for C1q in the absence of clinical and serological evidence of systemic lupus erythematosus, and has various clinical presentations and outcome. Here, we report a patient of undiagnosed paroxysmal nocturnal hemoglobinuria who consumed herbal medicine of unknown constituents and clinically presented with anemia and acute kidney injury. The pathological findings of bone marrow and renal biopsies that include bone marrow intoxication, severe renal hemosiderosis and acute interstitial nephritis and kidney injury, as well as co-dominant glomerular deposition of C1q, are discussed. In addition, we discuss and hypothesize the possible pathogenesis of glomerular C1q deposition in the setting of paroxysmal nocturnal hemoglobulinuria. PMID:26022031

  15. Immune-mediated bone marrow failure in C57BL/6 mice.

    PubMed

    Chen, Jichun; Desierto, Marie J; Feng, Xingmin; Biancotto, Anglique; Young, Neal S

    2015-04-01

    We established a model of immune-mediated bone marrow (BM) failure in C57BL/6 (B6) mice with 6.5 G total-body irradiation followed by the infusion of 4-10 10(6) lymph node (LN) cells/recipient from Friend leukemia virus B/N (FVB) donors. Forty-three percent of animals succumbed, with surviving animals showing marked declines in blood neutrophils, red blood cells, platelets and total BM cells at 8 to 14 days following LN cell infusion. Lowering the total-body irradiation dose to 5 G or altering the LN source from FVB to BALB/cBy donors failed to produce BM destruction. Affected animals showed significant expansion and activation of CD8 T lymphocytes in both the blood and BM; cytotoxic T cells had elevated Fas ligand expression and were oligoclonal, mainly displaying V?7 and V?17 T cell receptors. There were significant increases in blood plasma interferon ? and tissue necrosis factor ? in affected animals. Chemokine ligands CCL3, CCL4, CCL5, CCL20, CXCL2, and CXCL5 and hematopoietic growth factors G-CSF, M-CSF, GM-CSF, VEGF were also elevated. In B6 mice carrying a Fas gene mutation, BM failure was attenuated when they were infused with FVB LN cells. Our model establishes a useful platform to define the roles of individual genes and their products in immune-mediated BM failure. PMID:25555453

  16. Effects of salinomycin on human bone marrow-derived mesenchymal stem cells in vitro.

    PubMed

    Scherzed, A; Hackenberg, S; Froelich, K; Rak, K; Technau, A; Radeloff, A; Nth, U; Koehler, C; Hagen, R; Kleinsasser, N

    2013-04-26

    Various hypotheses on the origin of cancer stem cells (CSCs) exist, including that CSCs develop from transformed human bone marrow mesenchymal stem cells (hBMSC). Since the polyether antibiotic salinomycin selectively kills CSCs, the present study aims to elucidate the effects of salinomycin on normal hBMSC. The immunophenotype of hBMSC after salinomycin exposure was observed by flow cytometry. The multi-differentiation capacity of hBMSC was evaluated by Oil Red O and van Kossa staining. Cytotoxic effects of salinomycin were monitored by the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] (MTT) assay. Furthermore, spheroid formation and migration capacity were assessed. There were no differences in the immunophenotype and multi-differentiation capacity of hBMSC induced by salinomycin treatment. Cytotoxic effects were observed at concentrations of 30 ?M and above. Neither the migration capability nor the ability to form spheroids was affected. Essential functional properties of hBMSC were unaffected by salinomycin. However, dose-dependent cytotoxicity effects could be observed. Overall, low dose salinomycin showed no negative effects on hBMSC. Since mesenchymal stem cells from various sources respond differently, further in vitro studies are needed to clarify the effect of salinomycin on tissue-specific stem cells. PMID:23410960

  17. CCR2 inhibition sequesters multiple subsets of leukocytes in the bone marrow

    PubMed Central

    Fujimura, Naoki; Xu, Baohui; Dalman, Jackson; Deng, Hongping; Aoyama, Kohji; Dalman, Ronald L

    2015-01-01

    Chemokine receptor CCR2 mediates monocyte mobilization from the bone marrow (BM) and subsequent migration into target tissues. The degree to which CCR2 is differentially expressed in leukocyte subsets, and the contribution of CCR2 to these leukocyte mobilization from the BM are poorly understood. Using red fluorescence protein CCR2 reporter mice, we found heterogeneity in CCR2 expression among leukocyte subsets in varying tissues. CCR2 was highly expressed by inflammatory monocytes, dendritic cells, plasmacytoid dendritic cells and NK cells in all tissues. Unexpectedly, more than 60% of neutrophils expressed CCR2, albeit at low levels. CCR2 expression in T cells, B cells and NK T cells was greatest in the BM compared to other tissues. Genetic CCR2 deficiency markedly sequestered all leukocyte subsets in the BM, with reciprocal reduction noted in the peripheral blood and spleen. CCR2 inhibition via treatment with CCR2 signaling inhibitor propagermanium produced similar effects. Propagermanium also mitigated lipopolysaccharide-induced BM leukocyte egress. Consistent with its functional significance, CCR2 antibody staining revealed surface CCR2 expression within a subset of BM neutrophils. These results demonstrate the central role CCR2 plays in mediating leukocyte mobilization from the BM, and suggest a role for CCR2 inhibition in managing monocytes/macrophages-mediated chronic inflammatory conditions. PMID:26206182

  18. Species variation in the spontaneous calcification of bone marrow-derived mesenchymal stem cells.

    PubMed

    Huang, Yi-Zhou; Cai, Jia-Qin; Lv, Feng-Juan; Xie, Hong-Lei; Yang, Zhi-Ming; Huang, Yong-Can; Deng, Li

    2013-03-01

    Bone marrow-derived mesenchymal stem cells (BM-MSCs) hold great promise for tissue regeneration. With increasing numbers of clinical trials, the safety of BM-MSCs attracts great interest. Previously, we determined that rat BM-MSCs possessed spontaneous calcification without osteogenic induction after continuous culture. However, it is unclear whether BM-MSCs from other species share this characteristic. In this study, spontaneous calcification of BM-MSCs from rat, goat, and human specimens was investigated in vitro. BM-MSCs were cultured in complete medium, and calcification was determined by morphologic observation and alizarin red staining. It was demonstrated that rat BM-MSCs possessed a typically spontaneous calcification, whereas goat and human BM-MSCs under the same system proliferated significantly but did not calcify spontaneously. The significant species variation in spontaneous calcification of BM-MSCs described in this study provides useful information regarding evaluation of numerous BM-MSC-based approaches for bone regeneration and the safety of BM-MSCs. PMID:23312450

  19. Icariside II promotes osteogenic differentiation of bone marrow stromal cells in beagle canine

    PubMed Central

    Luo, Guangming; Gu, Feifei; Zhang, Yingdi; Liu, Tianlin; Guo, Pengnv; Huang, Yuanliang

    2015-01-01

    Icariside II (ICS II) is a prenylated active flavonol from the roots of epimedium koreanum Nakai, and has many biological activities, including anti-osteoporosis, anti-hypoxia and anti-cancer activities. In this study, we aimed to study the effect of ICS II on osteogenic differentiation of bone marrow derived stromal cells (BMSCs). Cell surface markers of cultured BMSCs were analyzed by flow cytometry and identified by multi-lineage differentiation assays. BMSCs proliferation was determined by the cell counting kit-8 (CCK-8) assay for 2, 4, 6 and 8 days in a range of ICS II concentrations. The osteogenic response of BMSCs to ICS II in vitro was examined by alkaline phosphatase (ALP) activity assay and Alizarin red staining on calcium nodule formation. Results showed ICS II significantly improved ALP activity, and calcium deposition. The optimal concentration of ICS II for enhancing osteogenic differentiation of BMSCs was 10-5. Therefore, we concluded ICS II can enhance the osteogenic differentiation of BMSCs which may be useful in clinic. PMID:26191128

  20. Macrophage function in murine allogeneic bone marrow radiation chimeras in the early phase after transplantation

    SciTech Connect

    Roesler, J.; Baccarini, M.; Vogt, B.; Lohmann-Matthes, M.L. )

    1989-08-01

    We tested several of the functions of macrophages (M phi) in the early phase after allogeneic bone marrow transfer to get information about this important aspect of the nonspecific immune system in the T-cell-deficient recipient. On days 3-5 after transfer, the number of M phi was reduced in the spleen, liver, lungs, and peritoneal cavity (Pe). The phagocytosis of sheep red blood cells (SRBC) by these M phi was normal or even enhanced, as in the case of Pe-M phi. Already on days 8-12 after transfer, the number of M phi in spleen and liver exceeded that of controls, whereas the number was still reduced in lungs and Pe. We examined their ability to kill P815 tumor cells, to produce tumor necrosis factor-alpha (TNF alpha), to phagocytose SRBC, to produce reactive oxygen intermediates (ROI) in vitro and to kill Listeria monocytogenes in vivo. Most functions were normal and often even enhanced, depending on the organ origin, but the ability of Pe-M phi to produce ROI was reduced. Proliferative response to macrophage colony-stimulating factor (M-CSF) and killing of YAC-1 tumor cells revealed a high frequency of macrophage precursor cells in the spleen and liver and a high natural killer (NK) activity in the liver. Altogether, enhanced nonspecific immune function, especially preactivated M phi, may enable chimeras to survive attacks by opportunistic pathogens.

  1. Plasmodium falciparum transmission stages accumulate in the human bone marrow.

    PubMed

    Joice, Regina; Nilsson, Sandra K; Montgomery, Jacqui; Dankwa, Selasi; Egan, Elizabeth; Morahan, Belinda; Seydel, Karl B; Bertuccini, Lucia; Alano, Pietro; Williamson, Kim C; Duraisingh, Manoj T; Taylor, Terrie E; Milner, Danny A; Marti, Matthias

    2014-07-01

    Transmission of Plasmodium falciparum malaria parasites requires formation and development of gametocytes, yet all but the most mature of these sexual parasite forms are absent from the blood circulation. We performed a systematic organ survey in pediatric cases of fatal malaria to characterize the spatial dynamics of gametocyte development in the human host. Histological studies revealed a niche in the extravascular space of the human bone marrow where gametocytes formed in erythroid precursor cells and underwent development before reentering the circulation. Accumulation of gametocytes in the hematopoietic system of human bone marrow did not rely on cytoadherence to the vasculature as does sequestration of asexual-stage parasites. This suggests a different mechanism for the sequestration of gametocytes that could potentially be exploited to block malaria transmission. PMID:25009232

  2. [Femur head necrosis and bone marrow edema syndrome in pregnancy].

    PubMed

    Kramer, J; Hofmann, S; Engel, A; Leder, K; Neuhold, A; Imhof, H

    1993-08-01

    MR examinations were performed in 9 patients suffering from severe pain of the hip during the third trimenon without any relief after birth. Pathologic signal changes could be observed in 11 hips (oedema in the region of the femoral head and neck (n = 8); avascular necrosis of the femoral head surrounded by bone marrow oedema (n = 3)). In 7 hips a relatively rapid decrease of the oedema following core decompression was demonstrated. Focal necrosis, however, did not show any changes. In two patients, treated conservatively, markedly delayed healing was evident. MR imaging is the modality of choice for early diagnosis as well as follow-up of therapy of the bone marrow oedema syndrome or avascular necrosis and can be performed already during pregnancy. PMID:8353257

  3. Chemotherapy-induced bone marrow nerve injury impairs hematopoietic regeneration

    PubMed Central

    Lucas, Daniel; Scheiermann, Christoph; Chow, Andrew; Kunisaki, Yuya; Bruns, Ingmar; Barrick, Colleen; Tessarollo, Lino; Frenette, Paul S.

    2013-01-01

    Anti-cancer chemotherapy drugs challenge hematopoietic tissues to regenerate, but commonly produce long-term sequelae. Deficits in hematopoietic stem or stromal cell function have been described, but the mechanisms mediating chemotherapy-induced hematopoietic dysfunction remain unclear. Administration of multiple cycles of cisplatin chemotherapy causes significant sensory neuropathy. Here, we demonstrate that chemotherapy-induced nerve injury in the bone marrow is a critical lesion impairing hematopoietic regeneration. We show using various pharmacological and genetic models that the selective loss of adrenergic innervation in the BM alters its regeneration following genotoxic insult. Sympathetic nerves in the marrow promote the survival of stem cell niche constituents that initiate recovery. Neuroprotection by deletion of Trp53 in sympathetic neurons or neuro-regeneration using 4-methylcatechol or glial-derived neurotrophic factor (GDNF) administration can restore hematopoietic recovery. Thus, these results shed light on the potential benefit of adrenergic nerve protection to shield hematopoietic niches from injury. PMID:23644514

  4. Bone Marrow work-up: report of a pilot study.

    PubMed

    Anagnostopoulos, Ioannis; Lenze, Dido; Hummel, Michael; Dietel, Manfred; Jhrens, Korinna

    2015-01-01

    In this pilot study we changed several pre-analytical variables of bone marrow trephine biopsy processing with the task to achieve not only a preservation of morphology and antigens but also of nucleic acids. The changes involved employment of a newly established decalcification solution in conjunction with a short fixation time (2 h after receiving the specimens) and performance of decalcification at 37 C. The comparison of the obtained results from three specimens with those of our routinely established protocol unequivocally revealed that the novel decalcification solution results in a superior preservation of nucleic acids, with only slight differences in preservation of morphology and cellular antigens. These encouraging results imply that this novel decalcification solution will allow a widely accepted standardization of bone marrow trephine biopsy processing. PMID:25636433

  5. Total lymphatic irradiation and bone marrow in human heart transplantation

    SciTech Connect

    Kahn, D.R.; Hong, R.; Greenberg, A.J.; Gilbert, E.F.; Dacumos, G.C.; Dufek, J.H.

    1984-08-01

    Six patients, aged 36 to 59 years, had heart transplants for terminal myocardial disease using total lymphatic irradiation (TLI) and donor bone marrow in addition to conventional therapy. All patients were poor candidates for transplantation because of marked pulmonary hypertension, unacceptable tissue matching, or age. Two patients are living and well more than four years after the transplants. Two patients died of infection at six and seven weeks with normal hearts. One patient, whose preoperative pulmonary hypertension was too great for an orthotopic heart transplant, died at 10 days after such a procedure. The other patient died of chronic rejection seven months postoperatively. Donor-specific tolerance developed in 2 patients. TLI and donor bone marrow can produce specific tolerance to donor antigens and allow easy control of rejection, but infection is still a major problem. We describe a new technique of administering TLI with early reduction of prednisone that may help this problem.

  6. {delta}-ALAD activity variations in red blood cells in response to lead accumulation in rock doves (Columba livia)

    SciTech Connect

    Gonzalez, M.; Tejedor, M.C.

    1992-10-01

    The enzyme {delta}-aminolevulinic acid dehydratase ({delta}-ALAD, E.C. 4.2.1.24), catalyses the second step of the haeme biosynthetic pathway and is required to maintain the haemoglobin and cytochrome content in red cells. {delta}-ALAD is not only found in bone marrow cells, the major site of haeme synthesis, but also in circulating erythrocytes and other tissues. An inverse correlation was found between {delta}-ALAD activity in red blood cells and lead concentration in the blood. The degree of {delta}-ALAD inhibition in erythrocytes has been widely accepted as a standard bioassay to detect acute and chronic lead exposure in humans and in avians. The value of this parameter as an indicator for environmental lead has been often reported in doves and Scanlon. In lead-treated rats, an increase in {delta}-ALAD activity in bone marrow cells and in blood samples was shown by radioimmunoassay at 5 and 9 days after the treatment. Similarly, the amount of {delta}-ALAD seems to be more sensitive to lead in avian species than in mammals, the usefulness of blood {delta}-ALAD activity as an index of lead exposure has already been questioned by Hutton in the pigeon and by Jaffe et al. in humans. The present investigation studied the toxic effects of lead on rock dove red blood cell {delta}-ALAD activity in two situations: in doves treated with lead acetate in the laboratory and in doves exposed to the environment of Alcala de Henares. The final lead blood concentrations were lower in the environmental than in the laboratory doves. {delta}-ALAD activity in bone marrow cells and the relationships between lead accumulation and enzyme activity in red cells, are examined. 20 refs., 5 figs., 1 tab.

  7. Vitiligo as a post-bone marrow transplantation complication.

    PubMed

    Cathcart, Shelley; Morrell, Dean

    2007-07-01

    Vitiligo is an autoimmune condition in which T cells recognize and destroy melanocytes. We present a case of a 20-year-old male who developed generalized vitiligo 4 years after allogeneic bone marrow transplantation (BMT) for Fanconi anemia. Although other autoimmune conditions have been well characterized as post-BMT complications, vitiligo is very rare. We review the 9 previously reported cases of post-BMT vitiligo. PMID:17609627

  8. Stemness of B cell progenitors in multiple myeloma bone marrow

    PubMed Central

    Boucher, Kelly; Parquet, Nancy; Widen, Raymond; Shain, Kenneth; Baz, Rachid; Alsina, Melissa; Koomen, John; Anasetti, Claudio; Dalton, William; Perez, Lia E.

    2012-01-01

    Purpose In myeloma, B cells and plasma cells show a clonal relationship. Clonotypic B cells may represent a tumor-initiating compartment or cancer stem cell responsible for minimal residual disease in myeloma. Experimental Design We report a study of 58 patients with myeloma at time of diagnosis or relapse. B cells in bone marrow were evaluated by multicolor flow cytometry and sorting. Clonality was determined by light chain and/or immunoglobulin chain gene rearrangement PCR. We also determined aldehyde dehydrogenase activity and colony formation growth. Drug sensitivity was tested with conventional and novel agents. Results Marrow CD19+ cells express a light chain identical to plasma cells and are therefore termed light chain restricted (LCR). The LCR B cell mass is small in both newly diagnosed and relapsed patients (?1%). Few marrow LCR B cells (~10%) are CD19+/CD34+, with the rest being more differentiated CD19+/CD34? B cells. Marrow LCR CD19+ B cells exhibit enhanced aldehyde dehydrogenase activity versus healthy controls. Both CD19+/CD34+ and CD19+/CD34? cells showed colony formation activity, with colony growth efficiency optimized when stroma-conditioned medium was used. B cell progenitors showed resistance to melphalan, lenalidomide, and bortezomib. Panobinostat, a histone deacetylase inhibitor, induced apoptosis of LCR B cells and CD138+ cells. LCR B cells are CD117, survivin, and Notch positive. Conclusions We propose that antigen-independent B cell differentiation stages are involved in disease origination and progression in myeloma. Further investigations of myeloma putative stem cell progenitors may lead to novel treatments to eradicate the potential reservoir of minimal residual disease. PMID:22988056

  9. Shifts in bone marrow cell phenotypes caused by spaceflight.

    PubMed

    Ortega, M Teresa; Pecaut, Michael J; Gridley, Daila S; Stodieck, Louis S; Ferguson, Virginia; Chapes, Stephen K

    2009-02-01

    Bone marrow cells were isolated from the humeri of C57BL/6 mice after a 13-day flight on the space shuttle Space Transportation System (STS)-118 to determine how spaceflight affects differentiation of cells in the granulocytic lineage. We used flow cytometry to assess the expression of molecules that define the maturation/activation state of cells in the granulocytic lineage on three bone marrow cell subpopulations. These molecules included Ly6C, CD11b, CD31 (platelet endothelial cell adhesion molecule-1), Ly6G (Gr-1), F4/80, CD44, and c-Fos. The three subpopulations were small agranular cells [region (R)1], larger granular cells (R2), which were mostly neutrophils, and very large, very granular cells (R3), which had properties of macrophages. Although there were no composite phenotypic differences between total bone marrow cells isolated from spaceflight and ground-control mice, there were subpopulation differences in Ly6C (R1 and R3), CD11b (R2), CD31 (R1, R2, and R3), Ly6G (R3), F4/80 (R3), CD44(high) (R3), and c-Fos (R1, R2, and R3). In particular, the elevation of CD11b in the R2 subpopulation suggests neutrophil activation in response to landing. In addition, decreases in Ly6C, c-Fos, CD44(high), and Ly6G and an increase in F4/80 suggest that the cells in the bone marrow R3 subpopulation of spaceflight mice were more differentiated compared with ground-control mice. The presence of more differentiated cells may not pose an immediate risk to immune resistance. However, the reduction in less differentiated cells may forebode future consequences for macrophage production and host defenses. This is of particular importance to considerations of future long-term spaceflights. PMID:19056998

  10. Diagnosis of Fanconi anemia in patients with bone marrow failure

    PubMed Central

    Pinto, Fernando O.; Leblanc, Thierry; Chamousset, Delphine; Le Roux, Gwenaelle; Brethon, Benoit; Cassinat, Bruno; Larghero, Jrme; de Villartay, Jean-Pierre; Stoppa-Lyonnet, Dominique; Baruchel, Andr; Soci, Grard; Gluckman, Eliane; Soulier, Jean

    2009-01-01

    Background Patients with bone marrow failure and undiagnosed underlying Fanconi anemia may experience major toxicity if given standard-dose conditioning regimens for hematopoietic stem cell transplant. Due to clinical variability and/or potential emergence of genetic reversion with hematopoietic somatic mosaicism, a straightforward Fanconi anemia diagnosis can be difficult to make, and diagnostic strategies combining different assays in addition to classical breakage tests in blood may be needed. Design and Methods We evaluated Fanconi anemia diagnosis on blood lymphocytes and skin fibroblasts from a cohort of 87 bone marrow failure patients (55 children and 32 adults) with no obvious full clinical picture of Fanconi anemia, by performing a combination of chromosomal breakage tests, FANCD2-monoubiquitination assays, a new flow cytometry-based mitomycin C sensitivity test in fibroblasts, and, when Fanconi anemia was diagnosed, complementation group and mutation analyses. The mitomycin C sensitivity test in fibroblasts was validated on control Fanconi anemia and non-Fanconi anemia samples, including other chromosomal instability disorders. Results When this diagnosis strategy was applied to the cohort of bone marrow failure patients, 7 Fanconi anemia patients were found (3 children and 4 adults). Classical chromosomal breakage tests in blood detected 4, but analyses on fibroblasts were necessary to diagnose 3 more patients with hematopoietic somatic mosaicism. Importantly, Fanconi anemia was excluded in all the other patients who were fully evaluated. Conclusions In this large cohort of patients with bone marrow failure our results confirmed that when any clinical/biological suspicion of Fanconi anemia remains after chromosome breakage tests in blood, based on physical examination, history or inconclusive results, then further evaluation including fibroblast analysis should be made. For that purpose, the flow-based mitomycin C sensitivity test here described proved to be a reliable alternative method to evaluate Fanconi anemia phenotype in fibroblasts. This global strategy allowed early and accurate confirmation or rejection of Fanconi anemia diagnosis with immediate clinical impact for those who underwent hematopoietic stem cell transplant. PMID:19278965

  11. Bone Marrow Diseases - Multiple Languages: MedlinePlus

    MedlinePLUS

    ... features on this page, please enable JavaScript. French (français) Japanese (日本語) Korean (한국어) Russian (Русский) Somali (af Soomaali) Spanish (español) Ukrainian (Українська) French (français) Bone Marrow Biopsy Biopsie de moelle osseuse - français ( ...

  12. 39 CFR 259.2 - Red Cross.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Red Cross. 259.2 Section 259.2 Postal Service....2 Red Cross. (a) General. The Postal Service and the Red Cross cooperate to maintain communication... those caused by enemy action. (b) Role of Postal Service. The Postal Service and the Red Cross...

  13. 39 CFR 259.2 - Red Cross.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 39 Postal Service 1 2011-07-01 2011-07-01 false Red Cross. 259.2 Section 259.2 Postal Service....2 Red Cross. (a) General. The Postal Service and the Red Cross cooperate to maintain communication... those caused by enemy action. (b) Role of Postal Service. The Postal Service and the Red Cross...

  14. Esophageal squamous cell carcinoma with dural and bone marrow metastases

    PubMed Central

    Chen, Yen-Hao; Huang, Cheng-Hua

    2014-01-01

    Patients with esophageal squamous cell carcinoma generally present at an advanced stage at the time of diagnosis. The most common sites of visceral metastasis are the lung, liver and bone, but brain and bone marrow involvement is exceedingly rare. Herein, we report a 62-year-old man with a 4-wk history of progressive low back pain with radiation to bilateral lower legs, dysphagia and body weight loss. Esophageal squamous cell carcinoma with regional lymph node, liver and bone metastases was diagnosed. He underwent concurrent chemoradiotherapy and got a partial response. Four months later, he complained of headache, diplopia and severe hearing impairment in the left ear. There was no evidence for bacterial, fungal, tuberculous infection or neoplastic infiltration. Magnetic resonance imaging of the brain demonstrated thickening and enhancement of bilateral pachymeninges and multiple enhancing masses in bilateral skull. Dural metastasis was diagnosed and he received whole brain irradiation. In addition, laboratory examination revealed severe thrombocytopenia and leucopenia, and bone marrow study confirmed the diagnosis of metastatic squamous cell carcinoma. This is the first described case of esophageal squamous cell carcinoma with dural and bone marrow metastases. We also discuss the pathogenesis of unusual metastatic diseases and differential diagnosis of pachymeningeal thickening. PMID:25253978

  15. Bone Marrow Microenvironment Modulation of Acute Lymphoblastic Leukemia Phenotype

    PubMed Central

    Moses, Blake S; Slone, William L; Thomas, Patrick; Evans, Rebecca; Piktel, Debbie; Angel, Peggi M; Walsh, Callee M; Cantrell, Pamela S; Rellick, Stephanie L; Martin, Karen H; Simpkins, James W; Gibson, Laura F

    2015-01-01

    Acute lymphoblastic leukemia (ALL) treatment regimens have dramatically improved the survival of ALL patients. However, chemoresistant minimal residual disease (MRD) that persists following cessation of therapy contributes to aggressive relapse. The bone marrow microenvironment (BMM) is an established site of sanctuary for ALL as well as myeloid lineage hematopoietic disease, with signals in this unique anatomical location contributing to drug resistance. Several models have been developed to recapitulate the interactions between the BMM and ALL cells. However, many in vitro models fail to accurately reflect the level of protection afforded to the most resistant sub-set of leukemic cells during co-culture with BMM elements. Pre-clinical in vivo models have advantages, but can be costly, and are often not fully informed by optimal in vitro studies. In the current report we describe an innovative extension of 2D co-culture wherein ALL cells uniquely interact with bone marrow derived stromal cells. Tumor cells in this model bury beneath primary human bone marrow derived stromal cells or osteoblasts, termed phase dim (PD) ALL, and exhibit a unique phenotype characterized by altered metabolism, distinct protein expression profiles, increased quiescence, and pronounced chemotherapy resistance. Investigation focused on the PD subpopulation may more efficiently inform pre-clinical design and investigation of MRD and relapse that arises from BMM supported leukemic tumor cells. PMID:26407636

  16. Bone Marrow Stem Cell Contribution to Pulmonary Homeostasis and Disease

    PubMed Central

    McDonald, Lindsay T; LaRue, Amanda C

    2015-01-01

    The understanding of bone marrow stem cell plasticity and contribution of bone marrow stem cells to pathophysiology is evolving with the advent of innovative technologies. Recent data has led to new mechanistic insights in the field of mesenchymal stem cell (MSC) research, and an increased appreciation for the plasticity of the hematopoietic stem cell (HSC). In this review, we discuss current research examining the origin of pulmonary cell types from endogenous lung stem and progenitor cells as well as bone marrow-derived stem cells (MSCs and HSCs) and their contributions to lung homeostasis and pathology. We specifically highlight recent findings from our laboratory that demonstrate an HSC origin for pulmonary fibroblasts based on transplantation of a clonal population of cells derived from a single HSC. These findings demonstrate the importance of developing an understanding of the sources of effector cells in disease state. Finally, a perspective is given on the potential clinical implications of these studies and others addressing stem cell contributions to lung tissue homeostasis and pathology. PMID:26798846

  17. Bone marrow transplantation after the Chernobyl nuclear accident.

    PubMed

    Baranov, A; Gale, R P; Guskova, A; Piatkin, E; Selidovkin, G; Muravyova, L; Champlin, R E; Danilova, N; Yevseeva, L; Petrosyan, L

    1989-07-27

    On April 26, 1986, an accident at the Chernobyl nuclear power station in the Soviet Union exposed about 200 people to large doses of total-body radiation. Thirteen persons exposed to estimated total-body doses of 5.6 to 13.4 Gy received bone marrow transplants. Two transplant recipients, who received estimated doses of radiation of 5.6 and 8.7 Gy, are alive more than three years after the accident. The others died of various causes, including burns (the cause of death in five), interstitial pneumonitis (three), graft-versus-host disease (two), and acute renal failure and adult respiratory distress syndrome (one). There was hematopoietic (granulocytic) recovery in nine transplant recipients who could be evaluated, six of whom had transient partial engraftment before the recovery of their own marrow. Graft-versus-host disease was diagnosed clinically in four persons and suspected in two others. Although the recovery of endogenous hematopoiesis may occur after exposure to radiation doses of 5.6 to 13.4 Gy, we do not know whether it is more likely after the transient engraftment of transplanted stem cells. Because large doses of radiation affect multiple systems, bone marrow recovery does not necessarily ensure survival. Furthermore, the risk of graft-versus-host disease must be considered when the benefits of this treatment are being weighed. PMID:2664512

  18. Bone marrow microenvironment modulation of acute lymphoblastic leukemia phenotype.

    PubMed

    Moses, Blake S; Slone, William L; Thomas, Patrick; Evans, Rebecca; Piktel, Debbie; Angel, Peggi M; Walsh, Callee M; Cantrell, Pamela S; Rellick, Stephanie L; Martin, Karen H; Simpkins, James W; Gibson, Laura F

    2016-01-01

    Acute lymphoblastic leukemia (ALL) treatment regimens have dramatically improved the survival of ALL patients. However, chemoresistant minimal residual disease that persists following cessation of therapy contributes to aggressive relapse. The bone marrow microenvironment (BMM) is an established "site of sanctuary" for ALL, as well as myeloid-lineage hematopoieticdisease, with signals in this unique anatomic location contributing to drug resistance. Several models have been developed to recapitulate the interactions between the BMM and ALL cells. However, many invitro models fail to accurately reflect the level of protection afforded to the most resistant subset of leukemic cells during coculture with BMM elements. Preclinical invivo models have advantages, but can be costly, and are often not fully informed by optimal invitro studies. We describe an innovative extension of 2-D coculture wherein ALL cells uniquely interact with bone marrow-derived stromal cells. Tumor cells in this model bury beneath primary human bone marrow-derived stromal cells or osteoblasts, termed "phase dim" ALL, and exhibit a unique phenotype characterized by altered metabolism, distinct protein expression profiles, increased quiescence, and pronounced chemotherapy resistance. Investigation focused on the phase dim subpopulation may more efficiently inform preclinical design and investigation of the minimal residual disease and relapse that arise from BMM-supported leukemic tumor cells. PMID:26407636

  19. White pulp reconstitution after human bone marrow transplantation.

    PubMed Central

    Nakayama, A.; Hirabayashi, N.; Ito, M.; Kasai, K.; Fujino, M.; Ohbayashi, M.; Asai, J.

    1993-01-01

    To reveal the reconstitution process of the white pulp after bone marrow transplantation (BMT), spleens of 24 marrow recipients whose survival times ranged from 34 to 303 days after BMT, were analyzed at the histopathological and immunohistochemical level. Up to 3 months after BMT, the white pulp was atrophic and consisted mainly of T cells forming periarteriolar lymphatic sheaths (PALS). Approximately 100 days after BMT, B cells aggregated in some of the white pulp, forming primary follicles, whereas marginal zones could not be detected. Beyond 4 months after BMT, the PALS, the lymphoid follicle, and the marginal zone of the white pulp could be seen in most of the recipients' spleens. However, the recovery of the marginal zone was poor up to 10 months after BMT. Thus, the white pulp was reconstituted sequentially, beginning in the PALS, followed by reconstitution in lymphoid follicles, and finally in the marginal zone. The development of the PALS corresponded well with the appearance of interdigitating dendritic cell, as did the development of lymphoid follicles with the appearance of follicular dendritic cell. The sequential reconstitution of the white pulp demonstrated in this study provides the morphological basis for the functional immune recovery of marrow recipients. In particular, the delay of the marginal zone reconstitution seems to be responsible for the functional asplenia of long-term survivors. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:8214005

  20. Nitrergic Response TO Cyclophosphamide Treatment in Blood and Bone Marrow

    PubMed Central

    Kevorkian, G.A; Alchujyan, N.Kh; Movsesyan, N.H; Hayrapetyan, H.L; Guevorkian, A.G; Ohanyan, R.M; Dagbashyan, S.S

    2008-01-01

    Daily intraperitoneal injection of cyclophosphamide (CPA) (50 mg?kg-1 of body weight) for 5days resulted in reduced levels of marrow and blood cellularity, which was most pronounced in 18 days post-treatment (pt). On day 18 after CPA treatment the enhancedlevels of nitric oxide (NO) precursors and metabolites (L-arginine, L-citrulline, reactive nitrogen species (RNS)) of marrow and blood cells (platelet, neutrophil, lymphocyte and monocyte) resulted from up-regulation of Ca(II)/calmodulin(CaM)-independent inducible NO synthase (iNOS), with a lessercontribution of Ca(II)/CaM-dependent constitutive cNOS isoforms to systemic NO.Biphasic response to CPA of marrow nitrergic system, i.e. both iNOS and cNOS showed significantly depressed activities, as well as diminished levels of NO metabolites on day 9 pt, suggested that signals in addition to NO might be involved in CPA-induced inhibition of hematopoesis, while a gradual increase of neutrophil and platelet NOS activity appeared to be contributed to a CPA-induced development of granulopenia, thrombocytopenia and hemorrhage. PMID:18949079

  1. Effect of cyclophosphamide and electromagnetic fields on mouse bone marrow

    SciTech Connect

    Cadossi, R.; Zucchini, P.; Emilia, G.; Torelli, G. )

    1990-02-26

    The authors have previously shown that the exposure to low frequency pulsing electromagnetic fields (PEMF) of mice X-ray irradiated resulted in an increased damage to the bone marrow. The series of experiments here reported were designed to investigate the effect of PEMF exposure after intraperitoneum injection of 200mg/kg of cyclophosphamide (CY). Control mice were CY injected only; experimental mice were CY injected and then exposed to PEMF. Exposure to PEMF (24 hours/day) increased the rate of decline of white blood cells in peripheral blood. Spleen weight was statistically higher among control mice than among mice exposed to PEMF at day 6, 8 and 10 after CY injection. Spleen autoradiography proved to be higher among PEMF exposed mice than among controls at day 8 and 9 after CY injection. The grafting efficiency of the bone marrow obtained from control mice was higher than the grafting efficiency of the bone marrow recovered from mice exposed to PEMF. All these data indicate that the exposure to PEMF increases the cytotoxic effect of CY.

  2. [Treatment of hemophagocytic lymphohistiocytosis, HLH, with bone marrow transplantation].

    PubMed

    Drken, M; Schneider, E M; Bltters-Sawatzki, R; Stollmann-Gibbels, B; Nessler, G; Bretz, R; Krholz, D; Probst, E N; Holsten-Griffin, H; Harps, E; Zander, A R; Janka, G E

    1998-01-01

    Hemophagocytic lymphohistiocytosis (HLH) is a rare disease of infancy and young childhood. The clinical presentation includes recurrent unexplained fever with hepatosplenomegaly. Cytopenia, hypofibrinogenemia and/or hypertriglyceridemia and hemophagocytosis in bone marrow, spleen and lymphnode confirm the diagnosis. Hemophagocytosis may not be present at the beginning. In these cases, diagnosis is facilitated by a positive family history, a relapsing course of the disease, the frequent involvement of the central nervous system and positive findings on immunological work-up. Treatment by chemotherapy and immunosuppressants can achieve sustained remissions in most patients and reinduction of remission after relapse is possible. Most children however, eventually die from progressive disease. At present, allogeneic bone marrow transplantation is the only curative therapeutic option. Between August 1992 and May 1997 eleven consecutive patients with HLH received bone marrow from unrelated (n = 7) or matched sibling donors (n = 4). The conditioning regimen consisted of busulfan, VP-16 and cyclophosphamide. Patients engrafted after a median time of 16 days (13-43). Only one patient developed grade III acute GVHD, another patient, grade II acute GVHD. Although regimen-related toxicity was extensive, all patients have survived without signs of HLH after a median follow up of 20 months (8-63). One patient suffers from chronic GVHD, three patients reveal psychomotoric retardation and one patient has severe impairment with spastic tetraparesis, amaurosis and seizures. Our experience shows that HLH can be successfully treated by allogeneic BMT from unrelated donors. PMID:9743950

  3. Efficient generation of canine bone marrow-derived dendritic cells.

    PubMed

    Isotani, Mayu; Katsuma, Kensuke; Tamura, Kyoichi; Yamada, Misato; Yagihara, Hiroko; Azakami, Daigo; Ono, Kenichiro; Washizu, Tsukimi; Bonkobara, Makoto

    2006-08-01

    Because of their unsurpassed potency in presenting antigens to naive T cells, dendritic cells are considered to be an important candidate in the development of immunotherapeutic strategies. Despite the high potential of dendritic cell-based immunotherapy, as a so-called dendritic cell vaccination, few clinical approaches using dendritic cell vaccination have been performed in the dog because of very limited information regarding the generation of canine dendritic cells and their functional properties. We therefore established a protocol for the efficient generation of dendritic cells from canine bone marrow cells using recombinant feline granulocyte-macrophage colony-stimulating factor and canine interleukin-4. Dendritic cells were generated efficiently: a yield of 1-9 x 10(6) cells per approximately 0.5 ml of canine bone marrow aspiration was achieved. These dendritic cells showed features shared with mouse and human dendritic cells: dendrite morphology, expression of surface markers MHC class II and CD11c, and up-regulation of molecules related to antigen presentation (MHC class II, B7-1, and B7-2) by activation with lipopolysaccharide. Moreover, the dendritic cells demonstrated phagocytic activity, processing activity of pinocytosed proteins, and activation of allogeneic T cells far more potent than that by macrophages. Our findings suggest that the bone marrow-derived dendritic cells are functional for the capturing and processing of antigens and the initiation of T cell responses. PMID:16953080

  4. Bone marrow transplantation after the Chernobyl nuclear accident

    SciTech Connect

    Baranov, A.; Gale, R.P.; Guskova, A.; Piatkin, E.; Selidovkin, G.; Muravyova, L.; Champlin, R.E.; Danilova, N.; Yevseeva, L.; Petrosyan, L. )

    1989-07-27

    On April 26, 1986, an accident at the Chernobyl nuclear power station in the Soviet Union exposed about 200 people to large doses of total-body radiation. Thirteen persons exposed to estimated total-body doses of 5.6 to 13.4 Gy received bone marrow transplants. Two transplant recipients, who received estimated doses of radiation of 5.6 and 8.7 Gy, are alive more than three years after the accident. The others died of various causes, including burns (the cause of death in five), interstitial pneumonitis (three), graft-versus-host disease (two), and acute renal failure and adult respiratory distress syndrome (one). There was hematopoietic (granulocytic) recovery in nine transplant recipients who could be evaluated, six of whom had transient partial engraftment before the recovery of their own marrow. Graft-versus-host disease was diagnosed clinically in four persons and suspected in two others. Although the recovery of endogenous hematopoiesis may occur after exposure to radiation doses of 5.6 to 13.4 Gy, we do not know whether it is more likely after the transient engraftment of transplanted stem cells. Because large doses of radiation affect multiple systems, bone marrow recovery does not necessarily ensure survival. Furthermore, the risk of graft-versus-host disease must be considered when the benefits of this treatment are being weighed.

  5. Role of Bone Marrow-Derived Fibroblasts in Renal Fibrosis

    PubMed Central

    Yan, Jingyin; Zhang, Zhengmao; Jia, Li; Wang, Yanlin

    2016-01-01

    Renal fibrosis represents a common pathway leading to progression of chronic kidney disease. Renal interstitial fibrosis is characterized by extensive fibroblast activation and excessive production and deposition of extracellular matrix (ECM), which leads to progressive loss of kidney function. There is no effective therapy available clinically to halt or even reverse renal fibrosis. Although activated fibroblasts/myofibroblasts are responsible for the excessive production and deposition of ECM, their origin remains controversial. Recent evidence suggests that bone marrow-derived fibroblast precursors contribute significantly to the pathogenesis of renal fibrosis. Understanding the molecular signaling mechanisms underlying the recruitment and activation of the bone marrow-derived fibroblast precursors will lead to novel therapy for the treatment of chronic kidney disease. In this review, we summarize recent advances in our understanding of the recruitment and activation of bone marrow-derived fibroblast precursors in the kidney and the development of renal fibrosis and highlights new insights that may lead to novel therapies to prevent or reverse the development of renal fibrosis. PMID:26941655

  6. T2 vertebral bone marrow changes after space flight

    NASA Technical Reports Server (NTRS)

    LeBlanc, A.; Lin, C.; Evans, H.; Shackelford, L.; Martin, C.; Hedrick, T.

    1999-01-01

    Bone biopsies indicate that during immobilization bone marrow adipose tissue increases while the functional cellular fraction decreases. One objective of our Spacelab flight experiment was to determine, using in vivo volume-localized magnetic resonance spectroscopy (VLMRS), whether bone marrow composition was altered by space flight. Four crew members of a 17 day Spacelab mission participated in the experiment. The apparent cellular fraction and transverse relaxation time (T2) were determined twice before launch and at several times after flight. Immediately after flight, no significant change in the cellular fraction was found. However, the T2 of the cellular, but not the fat component increased following flight, although to a variable extent, in all crew members with a time course for return to baseline lasting several months. The T2 of seven control subjects showed no significant change. Although these observations may have several explanations, it is speculated that the observed T2 changes might reflect increased marrow osteoblastic activity during recovery from space flight.

  7. Photon and neutron fluence-to-kerma conversion factors for ICRP-1975 reference man using improved elemental compositions for bone and marrow of the skeleton

    SciTech Connect

    Kerr, G.D.

    1982-11-01

    A twelve-element approximation of the total-body, soft-tissue and skeletal components of ICRP-1975 Reference Man is used to investigate particle fluence-to-kerma conversion factors for photons with energies between 1 keV and 20 MeV and neutrons with energies between 0.0253 eV and 20 MeV. Several recent ICRP revisions to the elemental composition of Reference Man, which have not been included in other kerma-factor calculations, are taken into account. This work suggests some additional revisions to the major-element content (i.e., H, C, N, and O) and to the mineral and trace-element content (i.e., Na, Mg, P, S, Cl, K, Ca, and Fe) of various total-body, soft-tissue, and skeletal components of Reference Man. The revisions to the bone and red marrow of the skeleton offer significant new refinements in red-bone-marrow dosimetry.

  8. Enhanced accumulation of adipocytes in bone marrow stromal cells in the presence of increased extracellular and intracellular [Ca{sup 2+}

    SciTech Connect

    Hashimoto, Ryota; Katoh, Youichi; Nakamura, Kyoko; Itoh, Seigo; Iesaki, Takafumi; Daida, Hiroyuki; Nakazato, Yuji; Okada, Takao

    2012-07-13

    Highlights: Black-Right-Pointing-Pointer High [Ca{sup 2+}]{sub o} enhances adipocyte accumulation in the presence of adipogenic inducers. Black-Right-Pointing-Pointer High [Ca{sup 2+}]{sub o} enhances both proliferation and adipocyte differentiation in BMSCs. Black-Right-Pointing-Pointer High [Ca{sup 2+}]{sub o} induces an increase in [Ca{sup 2+}]{sub o} in BMSCs. Black-Right-Pointing-Pointer An intracellular Ca{sup 2+} chelator suppresses the enhancement in adipocyte accumulation. Black-Right-Pointing-Pointer Controlling [Ca{sup 2+}]{sub o} may govern the balance of adipocyte and osteoblast development. -- Abstract: The bone marrow stroma contains osteoblasts and adipocytes that have a common precursor: the pluripotent mesenchymal stem cell found in bone marrow stromal cells (BMSCs). Local bone marrow Ca{sup 2+} levels can reach high concentrations due to bone resorption, which is one of the notable features of the bone marrow stroma. Here, we describe the effects of high [Ca{sup 2+}]{sub o} on the accumulation of adipocytes in the bone marrow stroma. Using primary mouse BMSCs, we evaluated the level of adipocyte accumulation by measuring Oil Red O staining and glycerol-3-phosphate dehydrogenase (GPDH) activity. High [Ca{sup 2+}]{sub o} enhanced the accumulation of adipocytes following treatment with both insulin and dexamethasone together but not in the absence of this treatment. This enhanced accumulation was the result of both the accelerated proliferation of BMSCs and their differentiation into adipocytes. Using the fura-2 method, we also showed that high [Ca{sup 2+}]{sub o} induces an increase in [Ca{sup 2+}]{sub i}. An intracellular Ca{sup 2+} chelator suppressed the enhancement in adipocyte accumulation due to increased [Ca{sup 2+}]{sub o} in BMSCs. These data suggest a new role for extracellular Ca{sup 2+} in the bone marrow stroma: increased [Ca{sup 2+}]{sub o} induces an increase in [Ca{sup 2+}]{sub i} levels, which in turn enhances the accumulation of adipocytes under certain conditions.

  9. Irradiation alters the differentiation potential of bone marrow mesenchymal stem cells

    PubMed Central

    WANG, YU; ZHU, GUOYING; WANG, JIANPING; CHEN, JUNXIANG

    2016-01-01

    Bone injury following radiotherapy has been confirmed by epidemiological and animal studies. However, the underlying mechanism remains to be elucidated and no preventive or curative solution has been identified for this bone loss. The present study aimed to investigate the irradiation-altered osteogenesis and adipogenesis of bone marrow mesenchymal stem cells (BMSCs). BMSCs were derived and exposed to γ-irradiation at doses of 0, 0.25, 0.5, 1, 2, 5 and 10 Gy. Cell viability was assessed using a 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide assay, and clonal expansion in vitro was detected by colony forming unit assessment. The osteogenic differentiation ability was demonstrated by alkaline phosphatase (ALP) activity, ALP staining and mineralization alizarin red staining, and the adipogenic differentiation ability was determined using Oil O red staining. The osteogenesis-associated genes, RUNX2, ALP, osteocalcin (OCN) and adipogenesis-associated genes, PPAR-γ and C/EBPα, were detected using reverse transcription-quantitative polymerase chain reaction analyses. The protein expression levels of RUNX2, ALP and PPAR-γ were detected using western blotting. Compared with the control, significant decreases in the proliferation, ALP activity and mineralization ability of the BMSCs were observed in the γ-irradiation group, with a high level of correlation with the exposure dose. However, no significant changes were observed in the area of Oil red O positive staining. The mRNA levels of RUNX2, ALP and OCN were decreased (P<0.05), however, no significant changes were observed in the levels of C/EBPα and PPAR-γ. The protein expression levels of RUNX2 and ALP were decreased in the irradiated BMSCs, however, no significant difference was observed in the protein expression of PPAR-γ. Irradiation inhibited the osteogenic and adipogenic ability of the BMSCs, and the osteogenic differentiation was decreased. The results of the present study provided evidence to assist in further elucidating radiotherapy-associated side effects on the skeleton. PMID:26572960

  10. Leukemia prevention and long-term survival of AKR mice transplanted with MHC-matched or MHC-mismatched bone marrow

    SciTech Connect

    Longley, R.E.; Good, R.A.

    1986-09-01

    The current studies were designed to evaluate the effectiveness of marrow transplantation within and outside the major histocompatibility complex (MHC) on the long-term survival and occurrence of spontaneous leukemia in AKR mice. AKR mice, which were lethally irradiated and received MHC-matched marrow from CBA/J mice (CBA----AKR), never developed leukemia and were alive and remained healthy for up to 280 days post-transplant. These long-term surviving chimeras possessed substantial immune vigor when both cell-mediated and humoral responses were tested. Lethally irradiated AKR mice, which had received MHC-mismatched marrow (anti-Thy-1.2 treated or nontreated) from C57BL/6J mice (B6----AKR), never developed leukemia and survived up to 170 days post-transplant. However, both groups of these chimeras began dying 180 to 270 days post-transplant due to a disease process which could not be readily identified. Histological analysis of B6----AKR chimeras revealed severe lymphoid cell depletion in thymus and spleen; however, none of these chimeras exhibited classical features of acute graft versus host disease. Concanavalin A mitogenesis, primary antibody responses to sheep red blood cells and the production of interleukin 2 (IL-2) were suppressed in B6----AKR chimeras. IL-2 treatment of B6----AKR chimeras was shown to partially correct these deficiencies without stimulating mixed lymphocyte responsiveness to donor or host lymphocytes. These studies indicate that the use of MHC-mismatched marrow for the prevention of spontaneous AKR leukemia may rely on augmentative IL-2 therapy for complete immune reconstitution of leukemia-free chimeras.

  11. [Survey on examinations for diagnosis of bone marrow failure in Japan: a report from the Japanese National Research Group on Idiopathic Bone Marrow Failure Syndromes].

    PubMed

    Araseki, Kayano; Matsuda, Akira; Tohyama, Kaoru; Ishikawa, Takayuki; Kawabata, Hiroshi; Miyazaki, Yasushi; Nakao, Shinji; Tomonaga, Masao; Takaori-Kondo, Akifumi; Kurokawa, Mineo; Omine, Mitsuhiro; Ozawa, Keiya

    2012-07-01

    Using a registration sheet of a prospective registration system for aplastic anemia (AA)/myelodysplastic syndromes (MDS), by the National Research Group on Idiopathic Bone Marrow Failure Syndromes, Japan, we carried out a survey on examinations for diagnosis of bone marrow failure. Bone marrow trephine biopsy was performed in 66 of 105 cases (63%) [Original diagnosis: AA 51 cases (80%), MDS 12 (32%), undiagnosable 3 (75%)]. Bone marrow aspiration was performed in all cases, and aspiration was performed at least twice in 36 cases (34%). The first-line anatomic site for bone marrow aspiration was the posterior iliac crest (62%). Cytogenetic examination was performed in 93%. The concordance rate between the original and the central review diagnosis was 93% among the studied cases: AA, Idiopathic cytopenia of undetermined significance (ICUS) and MDS in total. Flow cytometry analysis to detect paroxysmal nocturnal hemoglobinuria (PNH)-type blood cells was performed in 32%. PMID:22975771

  12. Red cell metabolism studies on Skylab

    NASA Technical Reports Server (NTRS)

    Mengel, C. E.

    1977-01-01

    Blood samples from Spacelab crewmembers were studied for possible environment effects on red cell components. Analysis involved peroxidation of red cell lipids, enzymes of red cell metabolism, and levels of 2,3-diphosphoglyceric acid and adenosine triphosphate. Results show that there is no evidence of lipid peroxidation, that biochemical effect known to be associated with irreversible red cell damage. Changes observed in glycolytic intermediates and enzymes cannot be directly implicated as indicating evidence of red cell damage.

  13. Dipyridamole increases red cell deformability.

    PubMed Central

    Sowemimo-Coker, S O; Kovacs, I B; Pickles, H; Hedges, A; Turner, P

    1983-01-01

    The effects of dipyridamole on red cell filterability both in vitro and ex vivo were measured. In a balanced, randomised and double-blind trial, six healthy male and female volunteers (22-37 years) were given dipyridamole 400 mg/day or matching placebo in four divided doses for 3 days, and heparinised venous blood samples were taken 1 h after the ingestion of the last dose. Filterability of red cells was increased significantly (P less than 0.05 paired t-test) when the subjects were on dipyridamole compared with placebo. In separate experiments, 15 min incubation with 2 or 20 micrograms/ml dipyridamole in vitro was found to have no effect on the filterability of freshly prepared red cell suspensions. After 24 h storage at 4 degrees C, the filterability of red cells was significantly decreased (P less than 0.01) and this could be partially prevented by adding dipyridamole to the stored cells (P less than 0.05). These results suggest that dipyridamole has an effect on the behaviour of the red cell membrane to increase the deformability of the cells. This may contribute to its therapeutic effect. PMID:6626435

  14. [Suitability of autologous blood donation before bone marrow donation].

    PubMed

    Gouzec, H; Ferr, N; Herv, F; Lapart, C; Leberre, C; Bernard, M; Dauriac, C; Nimubona, S

    2015-06-01

    We assessed the benefit of predeposite autologous blood donation (PAD) before bone marrow (BM) donation on transfusion requirements, haemoglobin concentrations (Hb) and the occurrence of adverse events (AE). We collected data retrospectively from 50 donors of BM with PAD from 2010 to 2014. An autologous transfusion (AT) was given to 50% of the donors (group 1). In the group 2, the products from PAD were not used. The total volume median of marrow harvested was 17.7 mL/k (range 12.3-21.4) in the group 1 and 13.3 mL/k (8.6-22.6) in the group 2. The female ratio was higher in the group 1 (60%) than in the group 2 (16%). Bone marrow harvest led to a decline in Hb (from PAD to first day after BM donation) by 2.9 g/dL (1.5-5.5) in the group 1 and by 3.5 g/dL (1.2-5) in the group 2. The post-harvest Hb (D+1) median was identical in the two groups: 10.9 g/dL (7.6-13.5) in the group 1 versus 11.5 g/dL (9.3-13.4) in the group 2. Six AE were reported in each group. In the group with AE, the median weight was lower: 58 k (50-71) versus 75 k (52-110); and the median total volume of marrow harvested was higher: 20.1 mL/k (9.9-21.4) versus 14.3 mL/k (8.6-22.6). All post-harvest Hb were ? 7.6g/dL. This study shows the high loss of Hb after BM donation but not enough to prove a blood transfusion in BM donors with median age of 36 years (16-62) and without comorbidity. The occurrence of AE (25% of BM donors) justifies a careful surveillance after the BM donation. The PAD should not be routinely offered to bone marrow donors. PMID:25958026

  15. Adoptive transfer of activated marrow-infiltrating lymphocytes induces measurable antitumor immunity in the bone marrow in multiple myeloma

    PubMed Central

    Noonan, Kimberly A.; Huff, Carol A.; Davis, Janice; Lemas, M. Victor; Fiorino, Susan; Bitzan, Jeffrey; Ferguson, Anna; Emerling, Amy; Luznik, Leo; Matsui, William; Powell, Jonathan; Fuchs, Ephraim; Rosner, Gary L.; Epstein, Caroline; Rudraraju, Lakshmi; Ambinder, Richard F.; Jones, Richard J.; Pardoll, Drew; Borrello, Ivan

    2015-01-01

    Successful adoptive T cell therapy (ACT) requires the ability to activate tumor-specific T cells with the ability to traffic to the tumor site and effectively kill their target as well as persist over time. We hypothesized that ACT using marrow-infiltrating lymphocytes (MILs) in multiple myeloma (MM) could impart greater antitumor immunity in that they were obtained from the tumor microenvironment. We describe the results from the first clinical trial using MILs in MM. Twenty-five patients with either newly diagnosed or relapsed disease had their MILs harvested, activated and expanded, and subsequently infused on the third day after myeloablative therapy. Cells were obtained and adequately expanded in all patients with anti-CD3/CD28 beads plus interleukin-2, and a median of 9.5 × 108 MILs were infused. Factors indicative of response to MIL ACT included (i) the presence of measurable myeloma-specific activity of the ex vivo expanded product, (ii) low endogenous bone marrow T cell interferon-γ production at baseline, (iii) a CD8+ central memory phenotype at baseline, and (iv) the generation and persistence of myeloma-specific immunity in the bone marrow at 1 year after ACT. Achieving at least a 90% reduction in disease burden significantly increased the progression-free survival (25.1 months versus 11.8 months; P = 0.01). This study demonstrates the feasibility and efficacy of MILs as a form of ACT with applicability across many hematologic malignancies and possibly solid tumors infiltrating the bone marrow. PMID:25995224

  16. Collagenase digestion of bone marrow trephine biopsy specimens: an important adjunct to haematological diagnosis when marrow aspiration fails.

    PubMed Central

    Maung, Z T; Bown, N P; Hamilton, P J

    1993-01-01

    Failure to obtain sufficient material from marrow aspiration (dry tap) posed a diagnostic problem in two patients with pancytopenia. By using collagenase digestion of the trephine biopsy specimen, a precise diagnosis was reached. This technique is very useful because it permits flow cytometric and immunocytochemical analyses of cell suspensions obtained after collagenase digestion of the trephine biopsy specimen core. Acute leukaemia presenting with a dry tap can therefore be accurately immunophenotyped. The technique is easy to perform and merits wider use. PMID:8331187

  17. Clinical implementation of new region-specific S-values for marrow dosimetry: Dose distribution vs mean marrow dose in radioimmunotherapy of leukemia

    SciTech Connect

    Sgouros, G.; Stabin, M.G.; Jureidini, I.M.

    1994-05-01

    Radiolabeled antibodies that target hematologic disease often exhibit a highly variable as well as non-uniform spatial distribution within the marrow. Mean marrow absorbed dose estimates obtained using a single S-value to represent the absorbed dose per unit cumulated activity for the whole marrow may not adequately reflect potential normal marrow morbidity or tumor cytotoxicity in different marrow regions. New, region-specific, S-factors for marrow, developed at the Oak Ridge National Laboratory, were used to calculate the absorbed dose to three different marrow regions in 9 leukemia patients that were administered trace-labeled I-131-HuM195, the humanized version of (anti-CD33) M195 antibody. Time-activity curves for each marrow region were obtained by drawing contours around: the head and neck of both femurs, both humeral heads, and the third and fourth lumbar vertebra, in each of four daily conjugate-view images that were collected starting the day of the infusion. Based on data gathered in the regions over the spine and femur, we predict absorbed doses to the active marrow for various regions of the skeleton ranging from 0.16-0.63 mGy/MBq, with a region-weighted average of 0.46 mGy/MBq. This compares with estimates mGy/MBq, respectively. Analysis of marrow dosimetry by region and in a dose-volume histogram format will provide a more reliable dosimetry picture for the clinician than provided by the single dose estimates available previously.

  18. Study of maturation of membrane transport function in red blood cells by X-ray microanalysis

    SciTech Connect

    Lee, P.; Kirk, R.G.

    1982-01-01

    Red blood cells of certain species of animals, such as dogs and cats contain low potassium and high sodium, whereas the erythropoietic stem cells giving rise to these cells are of high potassium type. This paper examines the sequence of membrane transport changes during erythropoiesis by analyzing the K, Na and Fe in single bone marrow cells, reticulocytes and mature red blood cells with X-ray microanalysis. The relationship between K/Na ratios and Fe/(K + Na), which is analogous to hemoglobin concentration, gives an index of maturation stage. The relationships between K/Na and Fe/(K + Na) in the marrow cells of normal adult dog and those of a phenylhydrazine-injected dog with accelerated erythropoiesis show that the modification of cation composition occurs after the initiation of hemoglobin synthesis but before its completion. Similar relationships in the reticulocytes obtained from phenylhydrazine-injected dogs as well as from newborn dogs show a consistent decrease in K/Na with increased Hb, indicating a drastic change in cation composition during the maturation of the reticulocytes. Therefore the modification in membrane transport function must have occurred before or during the formation of reticulocytes.

  19. Growth declines in red spruce

    SciTech Connect

    McLaughlin, S.B. ); Adams, H.S. )

    1987-10-01

    In this letter, the authors take issue with Zedaker, Hyink, and Smith who have indicated that observed red spruce growth declines can be expected based on growth trends for even-aged stands of red spruce as documented in Meyer (1929). Recently, an examination was made of stand stocking levels at 750 sites where red spruce were cored and neither the rate of growth decline nor the extent of mortality were found to be related to stand stocking levels or previous disturbance history. The authors conclude that the Meyer data do not represent an appropriate model for stand dynamics of old-growth, high-elevation stands and no not adequately explain the growth declines observed at many of those sites.

  20. Effect of Increasing Doses of ?-Radiation on Bone Marrow Stromal Cells Grown on Smooth and Rough Titanium Surfaces

    PubMed Central

    Huang, Bo; Guang, Mengkai; Ye, Jun; Gong, Ping; Tang, Hua

    2015-01-01

    Radiation therapy for oral and maxillofacial tumors could damage bone marrow stromal cells (BMSCs) in jaw, which caused dental implant failure. However, how radiation affects BMSCs on SLA (sandblasted with large-grits, acid-etched) surfaces is still unknown. The aim of this study was to investigate effect of different dose of ?-radiation on BMSCs on SLA and PT (polished titanium) surfaces. Rat BMSCs were radiated with 2, 4, and 8?Gy ?-radiation and then seeded on both surfaces. Cell adhesion, spreading, and proliferation were tested. The osteogenesis and the adipogenesis ability were examined by Alizarin-Red and Oil-Red staining, respectively. Real-time PCR was performed to detect osteogenic (osteocalcin, OCN; runt-related transcription factor 2, Runx2) and adipogenic (peroxisome proliferator-activated receptor gamma, PPAR?) gene expression at days 7 and 14 postirradiation. Results showed that ?-radiation reduced cell proliferation, adhesion, spreading, and osteogenic differentiation. 2?Gy radiation promoted adipogenic differentiation, but it was significantly decreased when dosage reached 4?Gy. In conclusion, results suggest that ?-radiation influenced BMSCs behaviors in a dosage-dependent manner except adipogenic differentiation, low dose promoted it, and high dose inhibited it. This effect was influenced by surface characteristics, which may explain the different failure rate of various implants in patients after radiation. PMID:26257788

  1. Osteogenic Differentiation of Bone Marrow Stem Cell in Poly(Lactic-co-Glycolic Acid) Scaffold Loaded Various Ratio of Hydroxyapatite

    PubMed Central

    Kim, Hyeongseok; Kim, Hye Min; Jang, Ji Eun; Kim, Cho Min; Kim, Eun Young; Lee, Dongwon; Khang, Gilson

    2013-01-01

    Background and Objectives Hydroxyapatite has biocompatibility and bioactivity and similar to bone of in human body. The purpose of this study is to evaluate osteogenic differentiation of bone marrow stem cell (BMSC) in PLGA Scaffold added various ratio of hydroxyapatite (HAp). Methods and Results PLGA and PLGA/HAp scaffold were prepared using solvent casting/salt-leaching method. BMSC was seeded on the PLGA and PLGA/HAp scaffold and the samples were cultured in 37℃ incubator with 5% CO2 for 28 days. Alkaline phosphatase (ALP) was carried out to evaluate alkaline phosphatase activity at 1, 3, 7, 10 and 14 days. Alizarin Red S stating was performed to identify calcium in scaffold at 1, 7, 14, 21 and 28 days. Compressive strength was measured to evaluate mechanical property of scaffold. To confirm cell viability, MTT was carried out at 1, 3, 7, 14 and 28 days. RT-PCR was performed to verify specific marker expression of osteoblast and stem cell at 7, 14, 21 and 28 days. Conclusions Osteogenic differentiation of BMSC was confirmed through ALP, RT-PCR, and alizarin red S staining in this study. These results suggest that HAp helps osteogenic differentiation of BMSC. PMID:24298375

  2. Red Plague Control Plan (RPCP)

    NASA Technical Reports Server (NTRS)

    Cooke, Robert W.

    2010-01-01

    SCOPE: Prescribes the minimum requirements for the control of cuprous / cupric oxide corrosion (a.k.a. Red Plague) of silver-coated copper wire, cable, and harness assemblies. PURPOSE: Targeted for applications where exposure to assembly processes, environmental conditions, and contamination may promote the development of cuprous / cupric oxide corrosion (a.k.a. Red Plague) in silver-coated copper wire, cable, and harness assemblies. Does not exclude any alternate or contractor-proprietary documents or processes that meet or exceed the baseline of requirements established by this document. Use of alternate or contractor-proprietary documents or processes shall require review and prior approval of the procuring NASA activity.

  3. Red facts: Ethylene. Fact sheet

    SciTech Connect

    Not Available

    1992-09-01

    EPA is directed by the Federal Insecticide, Fungicide, and Rodenticide Act as amended in 1988 (FIFRA '88) to review all pesticide products containing active ingredients initially registered before November 1, 1984, and to reregister those products that have a substantially complete data base and do not pose unreasonable adverse effects to people or the environment. The pesticide reregistration program is to be completed by the late 1990's. The RED FACTS fact sheet summarizes EPA's conclusion, as set forth in the Reregistration Eligibility Document (or RED), that products containing a pesticide do not pose unreasonable risks when used as directed by Agency-approved labeling, and are eligible for reregistration.

  4. Bone Marrow Granuloma in Typhoid Fever: A Morphological Approach and Literature Review

    PubMed Central

    Muniraj, Kavitha; Padhi, Somanath; Phansalkar, Manjiri; Sivakumar, Periyasami; Varghese, Renu G'Boy; Kanungo, Reba

    2015-01-01

    Typhoid fever is one of the few bacterial infections in humans where bone marrow evaluation is routinely recommended. However, the morphological aspect of typhoid fever in bone marrow has been rarely described in the literature. We describe a 25-year-old male patient who presented with prolonged fever suspected to be of tubercular etiology. Bone marrow examination showed well-formed histiocytic and epithelioid granulomas and erythrophagocytosis; and the bone marrow aspirate culture grew Salmonella typhi A. In view of potential clinical implications, typhoid fever should be considered as a differential diagnosis to tuberculosis in the evaluation of prolonged fever; especially in high prevalent areas. We suggest that erythrophagocytosis may serve as a morphological marker in typhoid granulomas in the bone marrow; and bone marrow culture should be submitted in every suspected case for appropriate patient management. PMID:25789187

  5. Bone marrow granuloma in typhoid Fever: a morphological approach and literature review.

    PubMed

    Muniraj, Kavitha; Padhi, Somanath; Phansalkar, Manjiri; Sivakumar, Periyasami; Varghese, Renu G'Boy; Kanungo, Reba

    2015-01-01

    Typhoid fever is one of the few bacterial infections in humans where bone marrow evaluation is routinely recommended. However, the morphological aspect of typhoid fever in bone marrow has been rarely described in the literature. We describe a 25-year-old male patient who presented with prolonged fever suspected to be of tubercular etiology. Bone marrow examination showed well-formed histiocytic and epithelioid granulomas and erythrophagocytosis; and the bone marrow aspirate culture grew Salmonella typhi A. In view of potential clinical implications, typhoid fever should be considered as a differential diagnosis to tuberculosis in the evaluation of prolonged fever; especially in high prevalent areas. We suggest that erythrophagocytosis may serve as a morphological marker in typhoid granulomas in the bone marrow; and bone marrow culture should be submitted in every suspected case for appropriate patient management. PMID:25789187

  6. Use of spleen organ cultures to monitor hemopoietic progenitor cell regeneration following irradiation and marrow transplantation

    SciTech Connect

    von Melchner, H.; Metcalf, D.; Mandel, T.E.

    1980-11-01

    After lethal irradiation of C57BL mice followed by the injection of 10/sup 7/ marrow cells, total cellularity and progenitor cell levels exceeded pretreatment levels within 12 days in the spleen, but regeneration remained incomplete in the marrow. The exceptional regenerative capacity of progenitor populations in the spleen was observed in organ cultures of spleen slices prepared 24 h after irradiation and transplantation, excluding continuous repopulation from the marrow as a significant factor in splenic regeneration.

  7. PPAR? antagonist attenuates mouse immune-mediated bone marrow failure by inhibition of T cell function.

    PubMed

    Sato, Kazuya; Feng, Xingmin; Chen, Jichun; Li, Jungang; Muranski, Pawel; Desierto, Marie J; Keyvanfar, Keyvan; Malide, Daniela; Kajigaya, Sachiko; Young, Neal S

    2016-01-01

    Acquired aplastic anemia is an immune-mediated disease, in which T cells target hematopoietic cells; at presentation, the bone marrow is replaced by fat. It was reported that bone marrow adipocytes were negative regulators of hematopoietic microenvironment. To examine the role of adipocytes in bone marrow failure, we investigated peroxisomal proliferator-activated receptor gamma, a key transcription factor in adipogenesis, utilizing an antagonist of this factor called bisphenol-A-diglycidyl-ether. While bisphenol-A-diglycidyl-ether inhibited adipogenesis as expected, it also suppressed T cell infiltration of bone marrow, reduced plasma inflammatory cytokines, decreased expression of multiple inflammasome genes, and ameliorated marrow failure. In vitro, bisphenol-A-diglycidyl-ether suppressed activation and proliferation, and reduced phospholipase C gamma 1 and nuclear factor of activated T-cells 1 expression, as well as inhibiting calcium flux in T cells. The in vivo effect of bisphenol-A-diglycidyl-ether on T cells was confirmed in a second immune-mediated bone marrow failure model, using different strains and non-major histocompatibility antigen mismatched: bisphenol-A-diglycidyl-ether ameliorated marrow failure by inhibition of T cell infiltration of bone marrow. Our data indicate that peroxisomal proliferator-activated receptor gamma antagonists may attenuate murine immune-mediated bone marrow failure, at least in part, by suppression of T cell activation, which might hold implications in the application of peroxisomal proliferator-activated receptor gamma antagonists in immune-mediated pathophysiologies, both in the laboratory and in the clinic. Genetically "fatless" mice developed bone marrow failure with accumulation of marrow adipocytes in our model, even in the absence of body fat, suggesting different mechanisms of systematic and marrow adipogenesis and physiologic versus pathophysiologic fat accumulation. PMID:26589913

  8. PPARγ antagonist attenuates mouse immune-mediated bone marrow failure by inhibition of T cell function

    PubMed Central

    Sato, Kazuya; Feng, Xingmin; Chen, Jichun; Li, Jungang; Muranski, Pawel; Desierto, Marie J.; Keyvanfar, Keyvan; Malide, Daniela; Kajigaya, Sachiko; Young, Neal S.

    2016-01-01

    Acquired aplastic anemia is an immune-mediated disease, in which T cells target hematopoietic cells; at presentation, the bone marrow is replaced by fat. It was reported that bone marrow adipocytes were negative regulators of hematopoietic microenvironment. To examine the role of adipocytes in bone marrow failure, we investigated peroxisomal proliferator-activated receptor gamma, a key transcription factor in adipogenesis, utilizing an antagonist of this factor called bisphenol-A-diglycidyl-ether. While bisphenol-A-diglycidyl-ether inhibited adipogenesis as expected, it also suppressed T cell infiltration of bone marrow, reduced plasma inflammatory cytokines, decreased expression of multiple inflammasome genes, and ameliorated marrow failure. In vitro, bisphenol-A-diglycidyl-ether suppressed activation and proliferation, and reduced phospholipase C gamma 1 and nuclear factor of activated T-cells 1 expression, as well as inhibiting calcium flux in T cells. The in vivo effect of bisphenol-A-diglycidyl-ether on T cells was confirmed in a second immune-mediated bone marrow failure model, using different strains and non-major histocompatibility antigen mismatched: bisphenol-A-diglycidyl-ether ameliorated marrow failure by inhibition of T cell infiltration of bone marrow. Our data indicate that peroxisomal proliferator-activated receptor gamma antagonists may attenuate murine immune-mediated bone marrow failure, at least in part, by suppression of T cell activation, which might hold implications in the application of peroxisomal proliferator-activated receptor gamma antagonists in immune-mediated pathophysiologies, both in the laboratory and in the clinic. Genetically “fatless” mice developed bone marrow failure with accumulation of marrow adipocytes in our model, even in the absence of body fat, suggesting different mechanisms of systematic and marrow adipogenesis and physiologic versus pathophysiologic fat accumulation. PMID:26589913

  9. Role of immobilization of irradiated rats in the protective effect of bone marrow shielding

    NASA Technical Reports Server (NTRS)

    Gronskaya, N. F.; Strelin, G. S.

    1982-01-01

    Rats were exposed to X-radiation to study the influence of immobilization and shielding of part of bone marrow during exposure on survival. It is concluded that (1) the beneficial effect of the stress factor (created by the immobilization of rats during exposure) can aggregate with the effect of bone marrow shielding and, under certain conditions, imitate the latter; and (2) the probability of the protective effect of immobilization should be taken into account when assessing the influence of bone marrow shielding.

  10. Intravenous transplantation of bone marrow mesenchymal stem cells promotes neural regeneration after traumatic brain injury

    PubMed Central

    Anbari, Fatemeh; Khalili, Mohammad Ali; Bahrami, Ahmad Reza; Khoradmehr, Arezoo; Sadeghian, Fatemeh; Fesahat, Farzaneh; Nabi, Ali

    2014-01-01

    To investigate the supplement of lost nerve cells in rats with traumatic brain injury by intravenous administration of allogenic bone marrow mesenchymal stem cells, this study established a Wistar rat model of traumatic brain injury by weight drop impact acceleration method and administered 3 × 106 rat bone marrow mesenchymal stem cells via the lateral tail vein. At 14 days after cell transplantation, bone marrow mesenchymal stem cells differentiated into neurons and astrocytes in injured rat cerebral cortex and rat neurological function was improved significantly. These findings suggest that intravenously administered bone marrow mesenchymal stem cells can promote nerve cell regeneration in injured cerebral cortex, which supplement the lost nerve cells. PMID:25206912

  11. [Bone marrow plays an important role in joint destruction in patients with rheumatoid arthritis].

    PubMed

    Tomita, T; Kaneko, M; Takano, H; Takahi, K; Nakase, T; Tsuboi, H; Toritsuka, Y; Hashimoto, J; Yoshikawa, H; Ochi, T

    2001-05-01

    In iliac bone marrow the absolute number of mononuclear cells (MNCs) was increased in RA patients compared with the non-RA controls. In CD8 positive cell and myeloid cell fractions, significant differences were recognized between RA patients and non-RA controls. The presence of abnormal myeloid lineage cells in epiphyseal bone marrow adjacent to joints affected with severe RA was shown. Stroma cell lines from RA bone marrow with nursing activity were established and shown to play a pivotal role in the pathogenesis in RA bone marrow. Histologic study also shows that subchondral region expressing tissue-damaging proteinases plays an important role in joint destruction in RA. PMID:15775554

  12. The adipocyte component of bone marrow in heterotopic bone induced by demineralized incisor grafts.

    PubMed

    W?odarski, Krzysztof H; Galus, Ryszard; Brodzikowska, Aniela; W?odarski, Pawe? K

    2012-01-01

    The relative proportion of adipocytes to hematopoietic elements in the marrow of heterotopically induced bone evaluated 4-42 weeks post implantation of demineralized murine incisors was estimated by histological analysis of hematoxylin-eosin stained tissue sections. Using computerized image analysis of microphotographs,the proportion of nuclear cells vs. adipocytes was ascertained. The percentage of adipocytes in marrow increases over time. Such an effect, the replacement of myelopoietic marrow by adipogenic (yellow) marrow and the resorption of induced bone, is observed in human osteoporosis. A decline in the non-adipogenic cell compartments of bone marrow accompanying induced bone begins in the fourth week of induction, gradually progresses until the 26th week, and does not change after that. The luminosity, a parameter used in image analysis and proportional to the number of nuclear cells, was 124 3 in hematopoietic femoral bone marrow, and that of bone marrow of the induced bone was of a similar value (117 8) in the fourth week. An evident decline in luminosity of bone marrow filling the foci of heterotopic bone was observed in samples taken at nine weeks (82 20). This process progressed until the 26th week, reaching a luminosity of 70 21. At the 42nd week, the luminosity remained at the same level (71 27). This indicates that the replacement of hematopoietic bone marrow of heterotopically induced bone by unilocular adipocytes begins relatively early (the fourth week) and is persistent. PMID:23042277

  13. Contribution of Bone MarrowDerived Cells to Skin: Collagen Deposition and Wound Repair

    PubMed Central

    Fathke, Carrie; Wilson, Lynne; Hutter, Jonathan; Kapoor, Vishal; Smith, Andria; Hocking, Anne; Isik, Frank

    2005-01-01

    The bone marrow provides inflammatory cells and endothelial progenitor cells to healing cutaneous wounds. To further explore the bone marrow contribution to skin and healing wounds, we used a chimeric mouse model in which the bone marrow from enhanced green fluorescent protein (EGFP) transgenic mice is transplanted into normal C57BL mice. We found that normal skin is a target organ for bone marrowderived cells from both the hematopoietic and the mesenchymal stem cell pool. We present evidence that the bone marrow contribution to normal skin and the healing cutaneous wound is substantially greater than the previously recognized CD45+ sub-population, where 15%20% of the spindle-shaped dermal fibroblasts were bone marrowderived (EGFP+). Furthermore, the bone marrowderived cells were able to contract a collagen matrix and transcribe both collagen types I and III, whereas the skin-resident cells transcribed only collagen type I. Whereas endothelial progenitor cells were found early during the wound repair process, bone marrowderived endothelial cells were not seen after epithelialization was complete. Our data show that wound healing involves local cutaneous cells for reconstituting the epidermis but distant bone marrowderived cells and the adjacent uninjured dermal mesenchymal cells for reconstituting the dermal fibroblast population. PMID:15342945

  14. Effect of nephrotoxic drugs on the development of radiation nephropathy after bone marrow transplantation

    SciTech Connect

    Lawton, C.A.; Fish, B.L.; Moulder, J.E. )

    1994-03-01

    Chronic renal failure is a significant cause of late morbidity in bone marrow transplant patients whose conditioning regimen includes total body irradiation (TBI). Radiation is a major cause of this syndrome (bone marrow transplant nephropathy), but it may not be the only cause. These studies use a rat syngeneic bone marrow transplant model to determine whether nephrotoxic agents used in conjunction with bone marrow transplantation (BMT) could be enhancing or accelerating the development of radiation nephropathy. Rats received 11-17 Gy TBI in six fractions over 3 days followed by syngeneic bone marrow transplant. In conjunction with the bone marrow transplants, animals received either no drugs, cyclosporine, amphotericin, gentamicin, or busulfan. Drugs were given in schedules analogous to their use in clinical bone marrow transplantation. Drug doses were chosen so that the drug regimen alone caused detectable acute nephrotoxicity. Animals were followed for 6 months with periodic renal function tests. Gentamicin had no apparent interactions with TBI. Amphotericin increased the incidence of engraftment failure, but did not enhance radiation nephropathy. Cyclosporin with TBI caused late morbidity that appeared to be due to neurological problems, but did not enhance radiation nephropathy. Busulfan resulted in a significant enhancement of radiation nephropathy. Of the nephrotoxins used in conjunction with bone marrow transplantation only radiation and busulfan were found to be risk factors for bone marrow transplant nephropathy. 34 refs., 4 figs., 2 tabs.

  15. Use of impedance plethysmography to continually monitor bone marrow blood flow

    NASA Technical Reports Server (NTRS)

    Montgomery, L. D.; Mcewen, G. N., Jr.; Gerber, R. L.; Cann, C. E.; Morey, E. R.

    1984-01-01

    An impedance-plethysmographic technique is described which can be used to quantify temporal bone-marrow blood-flow changes. Results obtained with the impedance technique compare favorably with the data from simultaneously administered microspheres. Injection of sympathomimetic drugs produced measurable responses: isoproterenol caused a significant increase in bone-marrow blood flow within 1 min, and levarterenol decreased bone-marrow blood flow. Data obtained with impedance plethysmography suggest that the technique is feasible for multiple measurements on the same animal and that the technique can be used to study acute or chronic changes in bone-marrow blood flow following various experimental treatments.

  16. AMERICAN RED CROSS HEALTH CRUSADE

    PubMed Central

    Peters, William H.

    1919-01-01

    Dr. Peters draws attention to the fact that no big work has been generally done to relieve those debilitated by influenza. There is hardship and need and slow recovery. Cincinnati organized relief along these lines, the Red Cross and the Health Department working in coperation. Organization and results are given in some detail. PMID:18010213

  17. "Red Power" and Indian Education.

    ERIC Educational Resources Information Center

    Heath, G. Louis

    The document is the result of research conducted on 14 Indian reservations and one settlement in the Southwest, Midwest, West, and Pacific Northwest by Illinois State University in the summer of 1970. Some 124 Indians were interviewed, many of whom were leaders and participants in various Red Power organizations. As noted, the dominant impression

  18. Sunset over Red Rock Canyon

    USGS Multimedia Gallery

    Pine Creek Canyon is a remnant ecosystem of loblolly pines. A remnant ecosystem is the last vestige of an ecosystem type that used to be more widespred. Red Rock Canyon is a National Conservation Area managed by the Bureau of Land Management, located just outside of Las Vegas, Nevada. It is part of...

  19. Growth declines in red spruce

    SciTech Connect

    Zedaker, S.M.; Hyink, D.M.; Smith, D.W.

    1987-01-01

    Over the past two decades second-growth red spruce stands in the Northeast have demonstrated declines in radial increment. Some observers are implicating air pollution as a primary cause of the declines, based on recently acquired increment cores from dominant trees. Various forms of air pollution (O/sub 3/, NO/sub x/, SO/sub 2/, and trace metals) are known to reduce growth and development of tree species, but few studies have provided concrete evidence of regional pollution-caused declines in forest ecosystems. Recently published evidence of a synchronous, consistent, and unprecedented regional decline in red spruce should be weighed against the realization that radial increment in red spruce declines naturally as stands age. Separating anthropogenic stress-caused growth patterns from natural stand dynamics requires an in-depth knowledge of forest growth and yield, tree silvics, and forest ecosystem processes. Detailed analyses of growth by stand characteristics - site index, density, elevation, stand history - will be necessary to implicate air pollution as a primary cause of red spruce decline.

  20. Infra-red soft universality

    SciTech Connect

    Jack, I.

    1997-06-15

    In a special class of supersymmetric grand unified theories, the commonly assumed universal form of the soft supersymmetry-breaking terms is approached in the infra-red limit. The resulting universal scalar mass and trilinear coupling are predicted in terms of the gaugino mass.

  1. Pesa Large Red Dry Bean

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Released in 2006, Pesa was derived from the single cross Rojo x Kablanketi made in Dec-Jan 1992-93. The parent ‘Rojo’ is a large red-seeded cultivar released by SUA in 1997. It has I bc-12 resistance to BCMV and BCMNV, resistance to the prevalent races of ALS, and moderate resistance to CBB, and H...

  2. The Prognostic Role of Red Blood Cell Distribution Width in Coronary Artery Disease: A Review of the Pathophysiology

    PubMed Central

    Bujak, Kamil; Wasilewski, Jaros?aw; Osadnik, Tadeusz; Jonczyk, Sandra; Ko?odziejska, Aleksandra; Gierlotka, Marek; G?sior, Mariusz

    2015-01-01

    Red blood cell distribution width (RDW) is a measure of red blood cell volume variations (anisocytosis) and is reported as part of a standard complete blood count. In recent years, numerous studies have noted the importance of RDW as a predictor of poor clinical outcomes in the settings of various diseases, including coronary artery disease (CAD). In this paper, we discuss the prognostic value of RDW in CAD and describe the pathophysiological connection between RDW and acute coronary syndrome. In our opinion, the negative prognostic effects of elevated RDW levels may be attributed to the adverse effects of independent risk factors such as inflammation, oxidative stress, and vitamin D3 and iron deficiency on bone marrow function (erythropoiesis). Elevated RDW values may reflect the intensity of these phenomena and their unfavorable impacts on bone marrow erythropoiesis. Furthermore, decreased red blood cell deformability among patients with higher RDW values impairs blood flow through the microcirculation, resulting in the diminution of oxygen supply at the tissue level, particularly among patients suffering from myocardial infarction treated with urgent revascularization. PMID:26379362

  3. The co-existence of pure red cell aplasia and autoimmune haemolytic anaemia in a child with malignant lymphoma.

    PubMed

    Ahmed, Suhair Abbas; Hassan, Rosline

    2005-07-01

    The association between pure red cell aplasia (PRCA) and autoimmune haemolytic anaemia (AIHA) has rarely been reported. PRCA represents an isolated process, characterized by normochromic, normocytic anaemia, reticulocytopenia and erythroid hypoplasia in the bone marrow, and may be attributable to infection with Parvo virus B19. AIHA is a condition in which peripheral red blood cell destruction is induced by the presence of autoantibodies. However, the co-existence of these conditions is very rare, since only few cases of PRCA and AIHA associated with malignant lymphoma (ML) were reported. A case of PRCA and AIHA was detected and described, for the first time in Malaysia, in a 10-year-old child suffering from non-Hodgkin lymphoma from the Department of Haematology, Universiti Sains Malaysia. Following the induction course of chemotherapy, the patient turned anaemic, with tendency for red cell clumping, reticulocytopenia and anisocytosis. AIHA was suspected in spite of the weak Coomb reaction obtained. The bone marrow aspirate revealed the presence of giant pronormoblasts, suggesting PRCA. Serological tests for Parvo virus and other viruses were negative. PMID:22605959

  4. The congo red stain revisited.

    PubMed

    Elghetany, M T; Saleem, A; Barr, K

    1989-01-01

    The Congo red stain has undergone several modifications since it was first used by Bennhold in 1922 in order to increase the specificity for staining amyloid. Most of the laboratories in the United States use the method of Puchtler which uses alkaline Congo red solution. Some of the variables associated with the procedure were investigated by us. Our results showed the following: (1) amyloid showed green birefringence at all levels between 4 to 12 mu thick sections with better visualization of small deposits with increased thickness. Best results were obtained with 8 mu thick sections; (2) omission of the pretreatment with alkaline alcoholic solution of sodium chloride (NaCl) did not affect the sensitivity of the method; (3) the use of polar mounting media had no effect on amyloid and collagen birefringence; (4) 50 percent saturation of the Congo red staining solution with NaCl caused strong staining of collagen, elastic fibers and eosinophilic granules. In addition, collagen showed green birefringence and dichroism and its differentiation from amyloid became difficult; and (5) using the staining solution fully saturated with NaCl, no positive staining was seen with tissues other than amyloid. Collagen and elastic fibers showed red fluorescence which was of less intensity than amyloid. It is our conclusion that the method of Puchtler for detecting amyloid gives better results if the staining solution is fully saturated with NaCl. The pretreatment step may be deleted without compromising the quality of staining. Improved staining of amyloid enhances the specificity of green birefringence, dichroism, and red fluorescence. PMID:2471435

  5. BK virus associated pronounced hemorrhagic cystoureteritis after bone marrow transplantation.

    PubMed

    Haab, Alexander C; Keller, Isabelle S; Padevit, Christian; John, Hubert

    2015-10-01

    Ureteral stenosis due to reactivation of the BK virus (BKV) in a state of immunodeficiency is very rare. More common is the appearance of a hemorrhagic cystitis. This report not only shows bilateral ureteral stenosis after bone marrow transplantation, but also presents severe complications as chronic pelvic pain and impaired kidney function as well as irreparable damage to the whole urinary tract leading to nephroureterectomy, subtrigonal cystectomy and orthotopic ileal neobladder. Finally renal transplantation was required. To our knowledge this is the first case in the literature where such a severe course of BKV associated hemorrhagic cystoureteritis is described. PMID:26432975

  6. Multiorgan WU Polyomavirus Infection in Bone Marrow Transplant Recipient

    PubMed Central

    Siebrasse, Erica A.; Nguyen, Nang L.; Willby, Melisa J.; Erdman, Dean D.; Menegus, Marilyn A.

    2016-01-01

    WU polyomavirus (WUPyV) was detected in a bone marrow transplant recipient with severe acute respiratory distress syndrome who died in 2001. Crystalline lattices of polyomavirus-like particles were observed in the patient’s lung by electron microscopy. WUPyV was detected in the lung and other tissues by real-time quantitative PCR and identified in the lung and trachea by immunohistochemistry. A subset of WUPyV-positive cells in the lung had morphologic features of macrophages. Although the role of WUPyV as a human pathogen remains unclear, these results clearly demonstrate evidence for infection of respiratory tract tissues in this patient. PMID:26691850

  7. Cardiac involvement in mucopolysaccharidoses: effects of allogeneic bone marrow transplantation.

    PubMed Central

    Gatzoulis, M A; Vellodi, A; Redington, A N

    1995-01-01

    Echocardiography was performed in 16 children undergoing bone marrow transplantation (BMT) for mucopolysaccharidoses. Cardiac involvement before BMT was detected in seven (44%). One year after BMT (11 patients/five with cardiac involvement), left ventricular restriction resolved in 2/3 patients and hypertrophy in one. In the remainder, at mean follow up of 2.5 years, no progression of preexisting or development of new cardiac involvement was noted. It is concluded that in a significant proportion of patients with mucopolysaccharidoses, cardiac involvement improved after BMT. PMID:7492172

  8. Mouse models in bone marrow transplantation and adoptive cellular therapy.

    PubMed

    Arber, Caroline; Brenner, Malcolm K; Reddy, Pavan

    2013-04-01

    Mouse models of transplantation have been indispensable to the development of bone marrow transplantation (BMT). Their role in the generation of basic science knowledge is invaluable and is subject to discussion below. However, this article focuses on the direct role and relevance of mouse models towards the clinical development and advances in BMT and adoptive T-cell therapy for human diseases. The authors aim to present a thoughtful perspective on the pros and cons of mouse models while noting that despite imperfections these models are obligatory for the development of science-based medicine. PMID:24216170

  9. Gelatinous transformation of bone marrow in systemic lupus erythematosus.

    PubMed

    Ng, M H; Li, E K; Feng, C S

    1989-07-01

    Gelatinous transformation of marrow is a rare disease entity described in cachexia and various other disorders. Its association with systemic lupus erythematosus (SLE) has never been reported. We found gelatinous transformation in 3 of 30 patients with SLE with pancytopenia. Two of these patients were cachetic, one of whom also had active tuberculosis. We propose that gelatinous transformation can be associated with SLE, and its detection calls for an evaluation of nutritional status, and a search for chronic debilitating infections such as tuberculosis. PMID:2769671

  10. Effects of Mssbauer radiation on bone marrow cultures

    NASA Astrophysics Data System (ADS)

    Ortalli, I.; Pedrazzi, G.; Jiang, K.; Zhang, X.; Carlo-Stella, C.; Mangoni, L.; Rizzoli, V.

    1992-04-01

    A low radiation dose approach to cell eradication would be highly desirable in cancer treatments in order to reduce the side ellects of conventional radiotherapy. In the present work we present a preliminary study on coltures of bone marrow mononuclear cells collected from normal subjects and patients with chronic myelogenous leukaemia (CML). Hematin (104, 10-3, 10M) has been added to mattow culture cells which were then irradiated with a 3.7 GBq (100 mCi)57Co/Rh Mossbauer source for 4 hours. Significant inbibition has been observed on the cell growth due to hematin and irradiatron.

  11. Mouse Models in Bone Marrow Transplantation and Adoptive Cellular Therapy

    PubMed Central

    Arber, Caroline; Brenner, Malcolm K.; Reddy, Pavan

    2014-01-01

    Mouse models of transplantation have been indispensable to the development of bone marrow transplantation (BMT). Their role in the generation of basic science knowledge is invaluable and is subject to discussion below. However, this article focuses on the direct role and relevance of mouse models towards the clinical development and advances in BMT and adoptive T-cell therapy for human diseases. The authors aim to present a thoughtful perspective on the pros and cons of mouse models while noting that despite imperfections these models are obligatory for the development of science-based medicine. PMID:24216170

  12. Targeting the bone marrow microenvironment in multiple myeloma.

    PubMed

    Kawano, Yawara; Moschetta, Michele; Manier, Salomon; Glavey, Siobhan; Grgn, Gll T; Roccaro, Aldo M; Anderson, Kenneth C; Ghobrial, Irene M

    2015-01-01

    Multiple myeloma (MM) is characterized by clonal expansion of malignant plasma cells in the bone marrow (BM). Despite the significant advances in treatment, MM is still a fatal malignancy. This is mainly due to the supportive role of the BM microenvironment in differentiation, migration, proliferation, survival, and drug resistance of the malignant plasma cells. The BM microenvironment is composed of a cellular compartment (stromal cells, osteoblasts, osteoclasts, endothelial cells, and immune cells) and a non-cellular compartment. In this review, we discuss the interaction between the malignant plasma cell and the BM microenvironment and the strategy to target them. PMID:25510276

  13. The bone marrow niche for haematopoietic stem cells

    PubMed Central

    Morrison, Sean J.; Scadden, David T.

    2015-01-01

    Preface Niches are local tissue microenvironments that maintain and regulate stem cells. Haematopoiesis provides a paradigm for understanding mammalian stem cells and their niches, yet the haematopoietic stem cell (HSC) niche remains incompletely defined and beset by competing models. Here we review progress in elucidating the location and cellular components of the HSC niche in the bone marrow. The niche is perivascular, created partly by mesenchymal stromal cells and endothelial cells and often, but not always, located near trabecular bone. Outstanding questions concern the cellular complexity of the niche, the role of the endosteum, and functional heterogeneity among perivascular microenvironments. PMID:24429631

  14. Bone marrow mononuclears from murine tibia after spaceflight on biosatellite

    NASA Astrophysics Data System (ADS)

    Andreeva, Elena; Roe, Maria; Buravkova, Ludmila; Andrianova, Irina; Goncharova, Elena; Gornostaeva, Alexandra

    Elucidation of the space flight effects on the adult stem and progenitor cells is an important goal in space biology and medicine. A unique opportunity for this is provided by project "BION -M1". The purpose of this study was to evaluate the effects of a 30-day flight on biosatellite "BION - M1" and the subsequent 7-day recovery on the quantity, viability, immunophenotype of mononuclears from murine tibia bone marrow. Also the in vitro characterization of functional capacity of multipotent mesenchymal stromal cells (MSCs) was scheduled. Under the project, the S57black/6 mice were divided into groups: spaceflight/vivarium control, recovery after spaceflight/ vivarium control to recovery. Bone marrow mononuclears were isolated from the tibia and immunophenotyped using antibodies against CD45, CD34, CD90 on a flow cytometer Epics XL (Beckman Coulter). A part of the each pool was frozen for subsequent estimation of hematopoietic colony-forming units (CFU), the rest was used for the evaluation of fibroblast CFU (CFUf) number, MSC proliferative activity and osteogenic potency. The cell number in the flight group was significantly lower than in the vivarium control group. There were no differences in this parameter between flight and control groups after 7 days of recovery. The mononuclears viability was more than 95 percent in all examined groups. Flow cytometric analysis showed no differences in the bone marrow cell immunophenotype (CD45, CD34, CD90.1 (Thy1)), but the flight animals had more large-sized CD45+mononuclears, than the control groups of mice. There was no difference in the CFUf number between groups. After 7 days in vitro the MSC number in flight group was twice higher than in vivarium group, after 10 days - 4 times higher. These data may indicate a higher proliferative activity of MSCs after spaceflight. MSCs showed the same and high alkaline phosphatase activity, both in flight and in the control groups, suggesting no effect of spaceflight factors on early osteogenic potency of stromal cells. These results indicate that spaceflight factors had no significant damaging effects on the murine bone marrow mononuclears. These observations are consistent with previously made assumption of moderate and reversible stress reaction of mammals on spaceflight conditions. This work was supported by Program of Basic Research of IMBP RAS

  15. The use of recombinant cytokines for enhancing immunohematopoietic reconstitution following bone marrow transplantation. I. Effects of in vitro culturing with IL-3 and GM-CSF on human and mouse bone marrow cells purged with mafosfamide (ASTA-Z).

    PubMed

    Slavin, S; Mumcuoglu, M; Landesberg-Weisz, A; Kedar, E

    1989-09-01

    Enhanced colony formation (CFU-GM) in vitro was observed in murine and human bone marrow (BM) cells following pre-incubation for 2-3 days with recombinant murine GM-CSF or natural purified murine IL-3, and recombinant human GM-CSF or IL-3, respectively. Pre-incubation in the presence of both GM-CSF and IL-3 produced additive stimulatory effects. BM cells previously treated in vitro with mafosfamide (ASTA-Z) under conditions identical to those used in the purging of autologous BM grafts, also demonstrated an enhanced cumulative response to combinations of GM-CSF and IL-3, with up to 100-fold increase in CFU-GM as compared with controls (p less than 0.001). In mice, the number of CFU-S was also significantly increased (2-20 times) following incubation of unpurged and purged BM cells in murine IL-3 and/or GM-CSF. Interestingly, the frequency of both CFU-GM and CFU-S in BM cells first purged with ASTA-Z and then cultured with both cytokines was significantly higher (p less than 0.01) than that in fresh, intact BM cells. In addition, mice transplanted with unpurged or purged, cytokine cultured syngeneic BM cells exhibited a significantly (p less than 0.01) earlier reconstitution of peripheral white blood cells and of BM CFU-GM, and a significantly enhanced anti-sheep red blood cell plaque-forming cell response. Overall, the data suggest that it might be possible to enhance immunohematopoietic reconstitution in recipients of unmanipulated, as well as ASTA-Z purged autologous BM following short-term culture of BM cells with recombinant colony stimulating factors prior to bone marrow transplantation. PMID:2676042

  16. Improved expression of Sirt1 on thymic epithelial cells of SAMP10 after Intrabone marrow-bone marrow transplantation.

    PubMed

    Li, Ming; Shi, Ming; Abraham, Nader G; Ikehara, Susumu

    2014-01-01

    Aging is accompanied by various forms of immune dysfunction, leading to an increase in frequency of infections and the development of malignant tumors in mice and humans. Sirt1 has been implicated in processes as varied as metabolism, differentiation, cancer, and the stress response and aging. Senescence-accelerated mice prone 10 (SAMP10) show not only spontaneously occurring brain atrophy, with deficits in learning and memory, but also emotional disorders. We attempted in this study to clarify the deficits and found that the percentage of CD4/TNF-? T-cells in the spleen of 24-week-old (but not 6-week-old) SAMP10 to be significantly reduced. The thymus was significantly lighter, and the percentage of CD4?CD8? cells was significantly lower in the 24-week-old SAMP10 than 6-week-old SAMP10. Microarray analyses indicated that genes related to transcription coactivator activity, growth factor activity, hormone activity, cytokine activity, receptor activity, and regulation of the immune system were downregulated in the thymus of 24-week-old SAMP10. Real-time PCR analysis showed that the expression of KGF, Aire, and Sirt1 was decreased on the thymic epithelial cells (TECs) of 24-week-old SAMP10. However, these parameters improved after the mice were treated with intrabone marrow-bone marrow transplantation. This is the first report of age-related changes in immune system dysfunction in 24-week-old SAMP10 and the first to show that dysfunction on the TECs of 24-week-old SAMP10 was modulated by allogeneic bone marrow cells. PMID:23452762

  17. Red blood cells, sickle cell (image)

    MedlinePLUS

    Sickle cell anemia is an inherited blood disease in which the red blood cells produce abnormal pigment (hemoglobin). The abnormal hemoglobin causes deformity of the red blood cells into crescent or sickle-shapes, as seen in this photomicrograph.

  18. Pure red cell aplasia secondary to treatment with erythropoietin.

    PubMed

    Locatelli, Francesco; Del Vecchio, Lucia

    2003-01-01

    Pure red cell aplasia (PRCA) is a rare condition defined as severe anemia secondary to the virtual absence of red blood cell precursors in the bone marrow. In the setting of patients treated with rHuEPO, the disease is generated by epoetin-induced antibodies that neutralise all the exogenous rHuEPO and cross-react with endogenous erythropoietin. As a result, serum erythropoietin levels are undetectable and erythropoiesis becomes ineffective. Only 4 cases of PRCA associated with rh-EPO have been reported before 1998. Thereafter, a sharp increase in the incidence of this rare condition has been reported, mainly associated with epoetin alpha use outside the United States. A number of possible mechanisms leading to PRCA development have been identified. Among these, modification of drug formulation and down stream processing probably has had a major role. Indeed, in 1998 the formulation of epoetin alpha in Europe was modified because of the fear of the "mad cow" syndrome. However, differences in molecule structure and glycosylation among different epoetins can not be excluded. It should also be underlined that the rise in the incidence of PRCA cases has been coincident with a major shift from intravenous to subcutaneous administration of rHuEPO. The abrupt rise in the incidence of PRCA cases observed in the last few years, deserves particular attention; however, we have to balance its severity, but extreme rarity, with the high number of chronic kidney disease patients who die each year because of cardiovascular disease that could partially be reduced by anemia treatment. PMID:14696747

  19. Red cell age by flow cytometry.

    PubMed

    Nusbaum, N J

    1997-06-01

    A method is presented for the use of red cell markers to assess the age of red cells in clinical samples. The reticulocyte count and its variants are already in clinical use to measure the number of young circulating red cells, but tools have not been put into place for studying the overall distribution of red cell age. These data could be of significant value, not merely for hematologic investigations, but as a part of infectious disease, renal, and toxicologic studies. PMID:9247886

  20. Red cell distribution width and nonalcoholic steatohepatitis

    PubMed Central

    Gulcan Kurt, Yasemin; Cayci, Tuncer; Aydin, Fevzi Nuri; Agilli, Mehmet

    2014-01-01

    Red cell distribution width is a measure of deviation of the volume of red blood cells. It is a marker of anisocytosis and often used to evaluate the possible causes of anemia. Elevated red cell distribution width levels are also associated with acute and chronic inflammatory responses. In nonalcoholic steatohepatitis, inflammation is accompanied with steatosis. For assuming red cell distribution width as a marker of nonalcoholic steatohepatitis, intervening factors such as levels of inflammatory markers should also be evaluated. PMID:25473202

  1. The effect of Link N on differentiation of human bone marrow-derived mesenchymal stem cells

    PubMed Central

    2012-01-01

    Introduction We previously showed that Link N can stimulate extracellular matrix biosynthesis by intervertebral disc (IVD) cells, both in vitro and in vivo, and is therefore a potential stimulator of IVD repair. The purpose of the present study was to determine how Link N may influence human mesenchymal stem cell (MSC) differentiation, as a prelude to using Link N and MSC supplementation in unison for optimal repair of the degenerated disc. Methods MSCs isolated from the bone marrow of three osteoarthritis patients were cultured in chondrogenic or osteogenic differentiation medium without or with Link N for 21 days. Chondrogenic differentiation was monitored by proteoglycan staining and quantitation by using Alcian blue, and osteogenic differentiation was monitored by mineral staining and quantitation by using Alzarin red S. In addition, proteoglycan secretion was monitored with the sulfated glycosaminoglycan (GAG) content of the culture medium, and changes in gene expression were analyzed with real-time reverse transcription (RT) PCR. Results Link N alone did not promote MSC chondrogenesis. However, after MSCs were supplemented with Link N in chondrogenic differentiation medium, the quantity of GAG secreted into the culture medium, as well as aggrecan, COL2A1, and SOX9 gene expression, increased significantly. The gene expression of COL10A1 and osteocalcin (OC) were downregulated significantly. When MSCs were cultured in osteogenic differentiation medium, Link N supplementation led to a significant decrease in mineral deposition, and alkaline phosphatase (ALP), OC, and RUNX2 gene expression. Conclusions Link N can enhance chondrogenic differentiation and downregulate hypertrophic and osteogenic differentiation of human MSCs. Therefore, in principle, Link N could be used to optimize MSC-mediated repair of the degenerated disc. PMID:23227926

  2. Bone marrow-derived cell concentrates have limited effects on osteochondral reconstructions in the mini pig.

    PubMed

    Jagodzinski, Michael; Liu, Chaoxu; Guenther, Daniel; Burssens, Arne; Petri, Maximilian; Abedian, Reza; Willbold, Elmar; Krettek, Christian; Haasper, Carl; Witte, Frank

    2014-03-01

    This study investigates the effects of seeding a chondrogenic and osteogenic scaffold with a bone marrow-derived cell concentrate (BMCC) and reports the histological and mechanical properties 3 months after implantation in the miniature pig. Twenty defects (7×10 mm) were created in the femoral condyles of 10 miniature pigs. The defects were left empty (E), filled with the grafted cylinder upside down (U) or with a combined scaffold (S) containing a spongious bone cylinder (Tutobone®) covered with a collagen membrane (Chondrogide®). In a fourth group, the same scaffolds were implanted but seeded with a stem cell concentrate (S+ BMCC). The animals were stained with calcein green after 2 weeks and xylenol orange after 4 weeks. After 3 months, the animals were sacrificed, and a mechanical analysis (Young's modulus), macroscopic, and histologic (ICRS Score) examination of the specimens was conducted. Young's modulus in the periphery was significantly lower for group E (67.5±15.3 kPa) compared with untreated controls (171.7±21.6 kPa, p<0.04). Bone defects were smaller in group S (10%±8%) compared with E (27%±7%; p<0.05). There was a trend toward smaller bony defects on comparing groups E and S+ BMCC (11%±8%; p=0.07). More red fluorescence was detected in group S+ BMCC (2.3%±1.1%) compared with groups E (0.4%±0.2%) and U (0.5%±0.2%, p<0.03). ICRS scores were higher for groups S (25.3±3.8) and S+ BMCC (26.2±5.2, p<0.01). In this animal model of osteochondral defects, stem cell concentrates enhance new bone apposition but fail to improve mechanical properties or histological appearance of cartilage regenerates in critical-sized defects. PMID:23815398

  3. In vitro inhibitory effects of imatinib mesylate on stromal cells and hematopoietic progenitors from bone marrow

    PubMed Central

    Soares, P.B.; Jeremias, T.S.; Alvarez-Silva, M.; Licnio, M.A.; Santos-Silva, M.C.; Vituri, C.L.

    2012-01-01

    Imatinib mesylate (IM) is used to treat chronic myeloid leukemia (CML) because it selectively inhibits tyrosine kinase, which is a hallmark of CML oncogenesis. Recent studies have shown that IM inhibits the growth of several non-malignant hematopoietic and fibroblast cells from bone marrow (BM). The aim of the present study was to evaluate the effects of IM on stromal and hematopoietic progenitor cells, specifically in the colony-forming units of granulocyte/macrophage (CFU-GM), using BM cultures from 108 1.5- to 2-month-old healthy Swiss mice. The results showed that low concentrations of IM (1.25?M) reduced the growth of CFU-GM in clonogenic assays. In culture assays with stromal cells, fibroblast proliferation and ?-SMA expression by immunocytochemistry analysis were also reduced in a concentration-dependent manner, with a survival rate of approximately 50% with a dose of 2.5?M. Cell viability and morphology were analyzed using MTT and staining with acrydine orange/ethidium bromide. Most cells were found to be viable after treatment with 5?M IM, although there was gradual growth inhibition of fibroblastic cells while the number of round cells (macrophage-like cells) increased. At higher concentrations (15?M), the majority of cells were apoptotic and cell growth ceased completely. Oil red staining revealed the presence of adipocytes only in untreated cells (control). Cell cycle analysis of stromal cells by flow cytometry showed a blockade at the G0/G1 phases in groups treated with 5-15?M. These results suggest that IM differentially inhibits the survival of different types of BM cells since toxic effects were achieved. PMID:23011404

  4. Adipose lineage specification of bone marrow-derived myeloid cells

    PubMed Central

    Majka, Susan M.; Miller, Heidi L.; Sullivan, Timothy; Erickson, Paul F.; Kong, Raymond; Weiser-Evans, Mary; Nemenoff, Raphael; Moldovan, Radu; Morandi, Shelley A.; Davis, James A.; Klemm, Dwight J.

    2012-01-01

    We have reported the production of white adipocytes in adipose tissue from hematopoietic progenitors arising from bone marrow. However, technical challenges have hindered detection of this adipocyte population by certain other laboratories. These disparate results highlight the need for sensitive and definitive techniques to identify bone marrow progenitor (BMP)-derived adipocytes. In these studies we exploited new models and methods to enhance detection of this adipocyte population. Here we showed that confocal microscopy with spectrum acquisition could effectively identify green fluorescent protein (GFP) positive BMP-derived adipocytes by matching their fluorescence spectrum to that of native GFP. Likewise, imaging flow cytometry made it possible to visualize intact unilocular and multilocular GFP-positive BMP-derived adipocytes and distinguished them from non-fluorescent adipocytes and cell debris in the cytometer flow stream. We also devised a strategy to detect marker genes in flow-enriched adipocytes from which stromal cells were excluded. This technique also proved to be an efficient means for detecting genetically labeled adipocytes and should be applicable to models in which marker gene expression is low or absent. Finally, in vivo imaging of mice transplanted with BM from adipocyte-targeted luciferase donors showed a time-dependent increase in luciferase activity, with the bulk of luciferase activity confined to adipocytes rather than stromal cells. These results confirmed and extended our previous reports and provided proof-of-principle for sensitive techniques and models for detection and study of these unique cells. PMID:23700536

  5. Bone Marrow Stromal Cells As Immunomodulators. A Primer For Dermatologists

    PubMed Central

    Nemeth, Krisztian; Mezey, Eva

    2014-01-01

    Bone marrow stromal cells (BMSCs, also known as mesenchymal stem cells or MSCs) represent a unique cell population in the bone marrow with a long-known function to support hematopoiesis and replace skeletal tissues. The recent discovery that BMSCs also possess potent immunoregulatory features attracted a great deal of attention from stem cell biologists, immunologists and clinicians of different specialties worldwide. Initial clinical experience along with several animal models suggested that intravenously delivered BMSCs are able to regulate a wide variety of host immune cells and act in a way that is beneficial for the recipient in a variety of diseases. The role of the present review is to give a short introduction to the biology of BMSCs and to summarize our current understanding of how BMSCs modulate the immune system with special emphasis on available clinical data. Considering the audience of this journal we will also attempt to guide dermatologists in choosing the right skin conditions where BMSCs might be considered as a therapeutic alternative. PMID:25476233

  6. Venous drainage through bone marrow after replantation: an experimental study.

    PubMed

    Tanaka, K; Kobayashi, K; Murakami, R; Tasaki, Y; Fujii, T; Mukae, N

    1998-12-01

    Venous drainage is vital for successful replantation, but it is not always possible to reconstruct because of missing or damaged veins. We devised an experimental model to study venous drainage through bone marrow while the new subcutaneous venous system regenerated. Adult male Wistar rats were placed into three groups. Group A rats had their hindlimbs amputated at the lower leg, but the tibia and sural and saphenous artery connections were preserved. Group B rats were prepared the same as Group A, except that a step-cut osteotomy was performed in the tibia. The bone ends were then realigned and kept in place with stainless steel wire. Group C rats were prepared the same as Group B, except that the ends of the bone were not aligned. All unoperated limbs served as controls for evaluations of blood flow. Experimental limbs were evaluated for skin colour and viability, blood flow and dye injection. Skin colour was investigated daily. Blood flow was measured postoperatively during three phases: immediate (up to 1 h), early (from 1 h to 24 h), and late (from 1 day to 7 days after operation). Survival of limbs varied in Groups A and B, while all limbs in Group C necrosed by day 7. Blood flow was returning to near control (normal) levels by day 7 in Group A and B limbs. India ink was observed in the medullary cavity at day 7. After replantation, bone marrow plays a critical role in venous drainage until the subcutaneous venous drainage system regenerates. PMID:10209468

  7. The effects of simulated hypogravity on murine bone marrow cells

    NASA Technical Reports Server (NTRS)

    Lawless, Desales

    1989-01-01

    Mouse bone marrow cells grown in complete medium at unit gravity were compared with a similar population cultured in conditions that mimic some aspects of microgravity. After the cells adjusted to the conditions that simulated microgravity, they proliferated as fetal or oncogenic populations; their numbers doubled in twelve hour periods. Differentiated subpopulations were depleted from the heterogeneous mixture with time and the undifferentiated hematopoietic stem cells increased in numbers. The cells in the control groups in unit gravity and those in the bioreactors in conditions of microgravity were monitored under a number of parameters. Each were phenotyped as to cell surface antigens using a panel of monoclonal antibodies and flow cytometry. Other parameters compared included: pH, glucose uptake, oxygen consumption and carbon-dioxide production. Nuclear DNA was monitored by flow cytometry. Functional responses were studied by mitogenic stimulation by various lectins. The importance of these findings should have relevance to the space program. Cells should behave predictably in zero gravity; specific populations can be eliminated from diverse populations and other populations isolated. The availability of stem cell populations will enhance both bone marrow and gene transplant programs. Stem cells will permit developmental biologists study the paths of hematopoiesis.

  8. Current insights into inherited bone marrow failure syndromes.

    PubMed

    Chung, Nack-Gyun; Kim, Myungshin

    2014-08-01

    Inherited bone marrow failure syndrome (IBMFS) encompasses a heterogeneous and complex group of genetic disorders characterized by physical malformations, insufficient blood cell production, and increased risk of malignancies. They often have substantial phenotype overlap, and therefore, genotyping is often a critical means of establishing a diagnosis. Current advances in the field of IBMFSs have identified multiple genes associated with IBMFSs and their pathways: genes involved in ribosome biogenesis, such as those associated with Diamond-Blackfan anemia and Shwachman-Diamond syndrome; genes involved in telomere maintenance, such as dyskeratosis congenita genes; genes encoding neutrophil elastase or neutrophil adhesion and mobility associated with severe congenital neutropenia; and genes involved in DNA recombination repair, such as those associated with Fanconi anemia. Early and adequate genetic diagnosis is required for proper management and follow-up in clinical practice. Recent advances using new molecular technologies, including next generation sequencing (NGS), have helped identify new candidate genes associated with the development of bone marrow failure. Targeted NGS using panels of large numbers of genes is rapidly gaining potential for use as a cost-effective diagnostic tool for the identification of mutations in newly diagnosed patients. In this review, we have described recent insights into IBMFS and how they are advancing our understanding of the disease's pathophysiology; we have also discussed the possible implications they will have in clinical practice for Korean patients. PMID:25210520

  9. Sharpin Controls Osteogenic Differentiation of Mesenchymal Bone Marrow Cells.

    PubMed

    Jeschke, Anke; Catala-Lehnen, Philip; Sieber, Sabrina; Bickert, Thomas; Schweizer, Michaela; Koehne, Till; Wintges, Kristofer; Marshall, Robert P; Mautner, Andrea; Duchstein, Lara; Otto, Benjamin; Horst, Andrea K; Amling, Michael; Kreienkamp, Hans-Juergen; Schinke, Thorsten

    2015-10-15

    The cytosolic protein Sharpin is a component of the linear ubiquitin chain assembly complex, which regulates NF-?B signaling in response to specific ligands, such as TNF-?. Its inactivating mutation in chronic proliferative dermatitis mutation (Cpdm) mice causes multiorgan inflammation, yet this phenotype is not transferable into wild-type mice by hematopoietic stem cell transfer. Recent evidence demonstrated that Cpdm mice additionally display low bone mass, and that this osteopenia is corrected by Tnf deletion. Because the cellular mechanism underlying this pathology, however, was still undefined, we performed a thorough skeletal phenotyping of Cpdm mice on the basis of nondecalcified histology and cellular and dynamic histomorphometry. We show that the trabecular and cortical osteopenia in Cpdm mice is solely explained by impaired bone formation, whereas osteoclastogenesis is unaffected. Consistently, Cpdm primary calvarial cells display reduced osteogenic capacity ex vivo, and the same was observed with CD11b(-) bone marrow cells. Unexpectedly, short-term treatment of these cultures with TNF-? did not reveal an impaired molecular response in the absence of Sharpin. Instead, genome-wide and gene-specific expression analyses revealed that Cpdm mesenchymal cells display increased responsiveness toward TNF-?-induced expression of specific cytokines, such as CXCL5, IL-1?, and IL-6. Therefore, our data not only demonstrate that the skeletal defects of Cpdm mice are specifically caused by impaired differentiation of osteoprogenitor cells, they also suggest that increased cytokine expression in mesenchymal bone marrow cells contributes to the inflammatory phenotype of Cpdm mice. PMID:26363054

  10. Bone Marrow Gene Therapy for HIV/AIDS.

    PubMed

    Herrera-Carrillo, Elena; Berkhout, Ben

    2015-07-01

    Bone marrow gene therapy remains an attractive option for treating chronic immunological diseases, including acquired immunodeficiency syndrome (AIDS) caused by human immunodeficiency virus (HIV). This technology combines the differentiation and expansion capacity of hematopoietic stem cells (HSCs) with long-term expression of therapeutic transgenes using integrating vectors. In this review we summarize the potential of bone marrow gene therapy for the treatment of HIV/AIDS. A broad range of antiviral strategies are discussed, with a particular focus on RNA-based therapies. The idea is to develop a durable gene therapy that lasts the life span of the infected individual, thus contrasting with daily drug regimens to suppress the virus. Different approaches have been proposed to target either the virus or cellular genes encoding co-factors that support virus replication. Some of these therapies have been tested in clinical trials, providing proof of principle that gene therapy is a safe option for treating HIV/AIDS. In this review several topics are discussed, ranging from the selection of the antiviral molecule and the viral target to the optimal vector system for gene delivery and the setup of appropriate preclinical test systems. The molecular mechanisms used to formulate a cure for HIV infection are described, including the latest antiviral strategies and their therapeutic applications. Finally, a potent combination of anti-HIV genes based on our own research program is described. PMID:26193303

  11. A novel metric for bone marrow cells chromosome pairing.

    PubMed

    Khmelinskii, Artem; Ventura, Rodrigo; Sanches, Joo

    2010-06-01

    Karyotyping is a set of procedures, in the scope of the cytogenetics, that produces a visual representation of the 46 chromosomes observed during the metaphase step of the cellular division, called mitosis, paired and arranged in decreasing order of size. Automatic pairing of bone marrow cells is a difficult task because these chromosomes appear distorted, overlapped, and their images are usually blurred with undefined edges and low level of detail. In this paper, a new metric is proposed to compare this type of chromosome images toward the design of an automatic pairing algorithm for leukemia diagnostic purposes. Besides the features used in the traditional karyotyping procedures, a new feature, based on mutual information , is proposed to increase the discriminate power of the G-banding pattern dissimilarity between chromosomes and improve the performance of the classifier. The pairing algorithm is formulated as a combinatorial optimization problem where the distances between homologous chromosomes are minimized and the distances between nonhomologous ones are maximized. The optimization task is solved by using an integer programming approach. A new bone marrow chromosome dataset--Lisbon-K1 (LK1) chromosome dataset with 9200 chromosomes---was build for this study. These chromosomes have much lower quality than the classic Copenhagen, Edinburgh, and Philadelphia datasets, and its classification and pairing is therefore more difficult. Experiments using real images from the LK(1) and Grisan et al. datasets based on a leave-one-out cross-validation strategy are performed to test and validate the pairing algorithm. PMID:20172790

  12. Bone Marrow Gene Therapy for HIV/AIDS

    PubMed Central

    Herrera-Carrillo, Elena; Berkhout, Ben

    2015-01-01

    Bone marrow gene therapy remains an attractive option for treating chronic immunological diseases, including acquired immunodeficiency syndrome (AIDS) caused by human immunodeficiency virus (HIV). This technology combines the differentiation and expansion capacity of hematopoietic stem cells (HSCs) with long-term expression of therapeutic transgenes using integrating vectors. In this review we summarize the potential of bone marrow gene therapy for the treatment of HIV/AIDS. A broad range of antiviral strategies are discussed, with a particular focus on RNA-based therapies. The idea is to develop a durable gene therapy that lasts the life span of the infected individual, thus contrasting with daily drug regimens to suppress the virus. Different approaches have been proposed to target either the virus or cellular genes encoding co-factors that support virus replication. Some of these therapies have been tested in clinical trials, providing proof of principle that gene therapy is a safe option for treating HIV/AIDS. In this review several topics are discussed, ranging from the selection of the antiviral molecule and the viral target to the optimal vector system for gene delivery and the setup of appropriate preclinical test systems. The molecular mechanisms used to formulate a cure for HIV infection are described, including the latest antiviral strategies and their therapeutic applications. Finally, a potent combination of anti-HIV genes based on our own research program is described. PMID:26193303

  13. Multiple myeloma in the marrow: pathogenesis and treatments.

    PubMed

    Fairfield, Heather; Falank, Carolyne; Avery, Lindsey; Reagan, Michaela R

    2016-01-01

    Multiple myeloma (MM) is a B cell malignancy resulting in osteolytic lesions and fractures. In the disease state, bone healing is limited owing to increased osteoclastic and decreased osteoblastic activity, as well as an MM-induced forward-feedback cycle where bone-embedded growth factors further enhance tumor progression as bone is resorbed. Recent work on somatic mutation in MM tumors has provided insight into cytogenetic changes associated with this disease; the initiating driver mutations causing MM are diverse because of the complexity and multitude of mutations inherent in MM tumor cells. This manuscript provides an overview of MM pathogenesis by summarizing cytogenic changes related to oncogenes and tumor suppressors associated with MM, reviewing risk factors, and describing the disease progression from monoclonal gammopathy of undetermined significance to overt MM. It also highlights the importance of the bone marrow microenvironment (BMM) in the establishment and progression of MM, as well as associated MM-induced bone disease, and the relationship of the bone marrow to current and future therapeutics. This review highlights why understanding the basic biology of the healthy and diseased BMM is crucial in the quest for better treatments and work toward a cure for genetically diverse diseases such as MM. PMID:27002787

  14. Genetic expression and functional characterization of the RUNX2 gene in human adult bone marrow mesenchymal stem cells.

    PubMed

    Zhang, J Y; Li, L C

    2015-01-01

    Past studies have revealed the critical role of runt-related transcription factor 2 (RUNX2) in the proliferation and differentiation of mesenchymal stem cells (MSCs). This study therefore aimed to investigate the expression profile of the RUNX2 gene in human bone marrow MSCs and its biological characteristics. Bone marrow MSCs were separated from 12 patients who had received hip joint replacement surgery. After purification and culture, the MSCs were subjected to the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry, the alkaline phosphatase assay, reverse transcription polymerase chain reaction, and RUNX2 protein quantification. The cell growth curve, staining images, and information on the membrane antigens and the levels of RUNX2 mRNA and protein were obtained based on the results. The growth curve showed, after a 2-day lag period, cultured MSCs entered into the log phase between d3 (Day 3) and d6, when they reached a plateau. Flow cytometry data suggested 94.38% of MSCs were CD90-positive, while only 3.99 and 1.71% of total cells were positive for CD35 and CD45, respectively. With the elongated induction period, cultured MSCs were polygonal in shape. After a 14-day induction, cell fusion occurred in the center of the cell nodule accompanied by the disappearance of cellular structure to form the calcium nodule, which was stained red. There was also a statistically significant increase in the level of RUNX2 protein at d7 and d14. An osteogenic medium is required for the differentiation of adult MSCs, which is also under RUNX2 regulation. These findings are potentially valuable for clinical practice. PMID:26782468

  15. Histological Analyses Demonstrate the Temporary Contribution of Yolk Sac, Liver, and Bone Marrow to Hematopoiesis during Chicken Development

    PubMed Central

    Guedes, Priscila Tavares; de Oliveira, Barbara Cristina Euzbio Pereira Dias; Manso, Pedro Paulo de Abreu; Caputo, Luzia Ftima Gonalves; Pelajo-Machado, Marcelo

    2014-01-01

    The use of avian animal models has contributed to the understanding of many aspects of the ontogeny of the hematopoietic system in vertebrates. However, specific events that occur in the model itself are still unclear. There is a lack of consensus, among previous studies, about which is the intermediate site responsible for expansion and differentiation of hematopoietic cells, and the liver's contribution to the development of this system. Here we aimed to evaluate the presence of hematopoiesis in the yolk sac and liver in chickens, from the stages of intra-aortic clusters in the aorta-genital ridges-mesonephros (AGM) region until hatching, and how it relates to the establishment of the bone marrow. Gallus gallus domesticus L. embryos and their respective yolk sacs at embryonic day 3 (E3) and up to E21 were collected and processed according to standard histological techniques for paraffin embedding. The slides were stained with hematoxylin-eosin, Lennert's Giemsa, and Sirius Red at pH 10.2, and investigated by light microscopy. This study demonstrated that the yolk sac was a unique hematopoietic site between E4 and E12. Hematopoiesis occurred in the yolk sac and bone marrow between E13 and E20. The liver showed granulocytic differentiation in the connective tissue of portal spaces at E15 and onwards. The yolk sac showed expansion of erythrocytic and granulocytic lineages from E6 to E19, and E7 to E20, respectively. The results suggest that the yolk sac is the major intermediate erythropoietic and granulopoietic site where expansion and differentiation occur during chicken development. The hepatic hematopoiesis is restricted to the portal spaces and represented by the granulocytic lineage. PMID:24621665

  16. 27 CFR 9.167 - Red Mountain

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Red Mountain 9.167 Section... Mountain (a) Name. The name of the viticultural area described in this section is Red Mountain. (b) Approved maps. The appropriate map for determining the boundaries of the Red Mountain viticultural area...

  17. 27 CFR 9.167 - Red Mountain

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Red Mountain 9.167 Section... Mountain (a) Name. The name of the viticultural area described in this section is Red Mountain. (b) Approved maps. The appropriate map for determining the boundaries of the Red Mountain viticultural area...

  18. 27 CFR 9.167 - Red Mountain

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Red Mountain 9.167 Section... Mountain (a) Name. The name of the viticultural area described in this section is Red Mountain. (b) Approved maps. The appropriate map for determining the boundaries of the Red Mountain viticultural area...

  19. 21 CFR 184.1121 - Red algae.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Red algae. 184.1121 Section 184.1121 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN... Substances Affirmed as GRAS § 184.1121 Red algae. (a) Red algae are seaweeds of the species...

  20. 21 CFR 184.1121 - Red algae.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Red algae. 184.1121 Section 184.1121 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN... Substances Affirmed as GRAS § 184.1121 Red algae. (a) Red algae are seaweeds of the species...

  1. 21 CFR 184.1121 - Red algae.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Red algae. 184.1121 Section 184.1121 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN... Substances Affirmed as GRAS § 184.1121 Red algae. (a) Red algae are seaweeds of the species...

  2. 21 CFR 184.1121 - Red algae.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Red algae. 184.1121 Section 184.1121 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN... Substances Affirmed as GRAS § 184.1121 Red algae. (a) Red algae are seaweeds of the species...

  3. 21 CFR 184.1121 - Red algae.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Red algae. 184.1121 Section 184.1121 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DIRECT FOOD....1121 Red algae. (a) Red algae are seaweeds of the species Gloiopeltis furcata, Porphyra...

  4. 76 FR 23485 - Safety Zone; Red River

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-27

    ... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; Red River AGENCY: Coast Guard, DHS. ACTION... Red River in the State of North Dakota, including those portions of the river bordered by Richland... protect persons and vessels from safety hazards associated with flooding occurring on the Red River....

  5. 7 CFR 29.1053 - Red (R).

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 2 2011-01-01 2011-01-01 false Red (R). 29.1053 Section 29.1053 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Type 92) § 29.1053 Red (R). A brownish red....

  6. 27 CFR 9.167 - Red Mountain

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Red Mountain 9.167 Section... THE TREASURY LIQUORS AMERICAN VITICULTURAL AREAS Approved American Viticultural Areas § 9.167 Red Mountain (a) Name. The name of the viticultural area described in this section is “Red Mountain.”...

  7. 27 CFR 9.167 - Red Mountain

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Red Mountain 9.167 Section... THE TREASURY LIQUORS AMERICAN VITICULTURAL AREAS Approved American Viticultural Areas § 9.167 Red Mountain (a) Name. The name of the viticultural area described in this section is “Red Mountain.”...

  8. 7 CFR 29.1053 - Red (R).

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Red (R). 29.1053 Section 29.1053 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Type 92) § 29.1053 Red (R). A brownish red....

  9. Red Discoloration of Fully Cooked Poultry Meat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Red or bloody appearance of fully cooked poultry meat is a quality defect perceived as a food safety issue. Experiments were conducted to determine incidence rate, cause, and control methods for red discoloration. Breasts, thighs, and legs from four commercial products were evaluated for red disco...

  10. Registration of ‘Red Amber’ Wheat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Red Amber’ (Reg. No.__________ PI _______) soft red winter wheat (Triticum aestivum L.) was developed by the Michigan Agricultural Experiment Station and released March 28, 2008 in a licensing agreement through Michigan State University (MSU) Technologies. Red Amber was selected from the cross ‘255...

  11. Red-Cockaded Woodpecker Classroom Activities.

    ERIC Educational Resources Information Center

    Texas State Dept. of Parks and Wildlife, Austin.

    This packet provides information on the balance between the endangered red-cockaded woodpecker and modern forestry in Texas. A set of classroom activities about the Red-cockaded Woodpecker and its habitat for grades 3-6, and a booklet, a pamphlet, and a poster are featured. Sections of the booklet include: (1) "The Red-cockaded Woodpecker"; (2)…

  12. Of macrophages and red blood cells; a complex love story

    PubMed Central

    de Back, Djuna Z.; Kostova, Elena B.; van Kraaij, Marian; van den Berg, Timo K.; van Bruggen, Robin

    2013-01-01

    Macrophages tightly control the production and clearance of red blood cells (RBC). During steady state hematopoiesis, approximately 1010 RBC are produced per hour within erythroblastic islands in humans. In these erythroblastic islands, resident bone marrow macrophages provide erythroblasts with interactions that are essential for erythroid development. New evidence suggests that not only under homeostasis but also under stress conditions, macrophages play an important role in promoting erythropoiesis. Once RBC have matured, these cells remain in circulation for about 120 days. At the end of their life span, RBC are cleared by macrophages residing in the spleen and the liver. Current theories about the removal of senescent RBC and the essential role of macrophages will be discussed as well as the role of macrophages in facilitating the removal of damaged cellular content from the RBC. In this review we will provide an overview on the role of macrophages in the regulation of RBC production, maintenance and clearance. In addition, we will discuss the interactions between these two cell types during transfer of immune complexes and pathogens from RBC to macrophages. PMID:24523696

  13. 76 FR 22033 - Safety Zone; Red River Safety Zone, Red River, MN

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-20

    ... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AAOO Safety Zone; Red River Safety Zone, Red River, MN AGENCY... Safety Unit Duluth, MN is establishing a temporary safety zone on the Red River, MN. This safety zone is... entering all navigable waters of the Red River in the State of Minnesota north of a line drawn...

  14. 33 CFR 165.T09-0263 - Safety zone; Red River Safety Zone, Red River, MN.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Safety zone; Red River Safety Zone, Red River, MN. 165.T09-0263 Section 165.T09-0263 Navigation and Navigable Waters COAST GUARD... § 165.T09-0263 Safety zone; Red River Safety Zone, Red River, MN. (a) Location. The following area is...

  15. AmaRosa, a red skinned, red fleshed fingerling with high phytonutrient value

    Technology Transfer Automated Retrieval System (TEKTRAN)

    AmaRosa is a mid season specialty potato with red skin and red flesh. This selection is unique among commercially available potato varieties in that plants set a large number of smooth, small, fingerling-shaped tubers with red skin and red flesh. AmaRosa tubers have higher total anthocyanin and hyd...

  16. t10c12-CLA maintains higher bone mineral density during aging by modulating osteoclastogenesis and bone marrow adiposity

    PubMed Central

    Rahman, M; Halade, Ganesh V; Williams, Paul J; Fernandes, Gabriel

    2011-01-01

    Conjugated linoleic acid (CLA) has been shown to positively influence calcium and bone metabolism. Earlier, we showed that CLA (equal mixture of c9t11-CLA and t10c12-CLA) could protect age-associated bone loss by modulating inflammatory markers and osteoclastogenesis. Since, c9t11-CLA and t10c12-CLA isomers differentially regulate functional parameters and gene expression in different cell types, we examined the efficacy of individual CLA isomers against age-associated bone loss using 12 months old C57BL/6 female mice fed for 6 months with 10% corn oil (CO), 9.5% CO + 0.5% c9t11-CLA, 9.5% CO + 0.5% t10c12-CLA or 9.5% CO + 0.25% c9t11-CLA + 0.25% t10c12-CLA. Mice fed a t10c12-CLA diet maintained a significantly higher bone mineral density (BMD) in femoral, tibial and lumbar regions than those fed CO and c9t11-CLA diets as measured by dual-energy-x-ray absorptiometry (DXA). The increased BMD was accompanied by a decreased production of osteoclastogenic factors i.e. RANKL, TRAP5b, TNF-alpha and IL-6 in serum. Moreover, a significant reduction of high fat diet-induced bone marrow adiposity was observed in t10c12-CLA fed mice as compared to that of CO and c9t11-CLA fed mice, as measured by Oil-Red-O staining of bone marrow sections. In addition, a significant reduction of osteoclast differentiation and bone resorbing pit formation was observed in t10c12-CLA treated RAW 264.7 cell culture stimulated with RANKL as compared to that of c9t11-CLA and linoleic acid treated cultures. In conclusion, these findings suggest that t10c12-CLA is the most potent CLA isomer and it exerts its anti-osteoporotic effect by modulating osteoclastogenesis and bone marrow adiposity. PMID:21660964

  17. Genomic analysis of bone marrow failure and myelodysplastic syndromes reveals phenotypic and diagnostic complexity

    PubMed Central

    Zhang, Michael Y.; Keel, Siobn B.; Walsh, Tom; Lee, Ming K.; Gulsuner, Suleyman; Watts, Amanda C.; Pritchard, Colin C.; Salipante, Stephen J.; Jeng, Michael R.; Hofmann, Inga; Williams, David A.; Fleming, Mark D.; Abkowitz, Janis L.; King, Mary-Claire; Shimamura, Akiko

    2015-01-01

    Accurate and timely diagnosis of inherited bone marrow failure and inherited myelodysplastic syndromes is essential to guide clinical management. Distinguishing inherited from acquired bone marrow failure/myelodysplastic syndrome poses a significant clinical challenge. At present, diagnostic genetic testing for inherited bone marrow failure/myelodysplastic syndrome is performed gene-by-gene, guided by clinical and laboratory evaluation. We hypothesized that standard clinically-directed genetic testing misses patients with cryptic or atypical presentations of inherited bone marrow failure/myelodysplastic syndrome. In order to screen simultaneously for mutations of all classes in bone marrow failure/myelodysplastic syndrome genes, we developed and validated a panel of 85 genes for targeted capture and multiplexed massively parallel sequencing. In patients with clinical diagnoses of Fanconi anemia, genomic analysis resolved subtype assignment, including those of patients with inconclusive complementation test results. Eight out of 71 patients with idiopathic bone marrow failure or myelodysplastic syndrome were found to harbor damaging germline mutations in GATA2, RUNX1, DKC1, or LIG4. All 8 of these patients lacked classical clinical stigmata or laboratory findings of these syndromes and only 4 had a family history suggestive of inherited disease. These results reflect the extensive genetic heterogeneity and phenotypic complexity of bone marrow failure/myelodysplastic syndrome phenotypes. This study supports the integration of broad unbiased genetic screening into the diagnostic workup of children and young adults with bone marrow failure and myelodysplastic syndromes. PMID:25239263

  18. Multiple Myeloma Impairs Bone Marrow Localization of Effector Natural Killer Cells by Altering the Chemokine Microenvironment.

    PubMed

    Ponzetta, Andrea; Benigni, Giorgia; Antonangeli, Fabrizio; Sciumè, Giuseppe; Sanseviero, Emilio; Zingoni, Alessandra; Ricciardi, Maria Rosaria; Petrucci, Maria Teresa; Santoni, Angela; Bernardini, Giovanni

    2015-11-15

    Natural killer (NK) cells are key innate immune effectors against multiple myeloma, their activity declining in multiple myeloma patients with disease progression. To identify the mechanisms underlying NK cell functional impairment, we characterized the distribution of functionally distinct NK cell subsets in the bone marrow of multiple myeloma-bearing mice. Herein we report that the number of KLRG1(-) NK cells endowed with potent effector function rapidly and selectively decreases in bone marrow during multiple myeloma growth, this correlating with decreased bone marrow NK cell degranulation in vivo. Altered NK cell subset distribution was dependent on skewed chemokine/chemokine receptor axes in the multiple myeloma microenvironment, with rapid downmodulation of the chemokine receptor CXCR3 on NK cells, increased CXCL9 and CXCL10, and decreased CXCL12 expression in bone marrow. Similar alterations in chemokine receptor/chemokine axes were observed in patients with multiple myeloma. Adoptive transfer experiments demonstrated that KLRG1(-) NK cell migration to the bone marrow was more efficient in healthy than multiple myeloma-bearing mice. Furthermore, bone marrow localization of transferred CXCR3-deficient NK cells with respect to wild type was enhanced in healthy and multiple myeloma-bearing mice, suggesting that CXCR3 restrains bone marrow NK cell trafficking. Our results indicate that multiple myeloma-promoted CXCR3 ligand upregulation together with CXCL12 downmodulation act as exit signals driving effector NK cells outside the bone marrow, thus weakening the antitumor immune response at the primary site of tumor growth. PMID:26438594

  19. Marrow adipocyte-derived CXCL1 and CXCL2 contribute to osteolysis in metastatic prostate cancer.

    PubMed

    Hardaway, Aimalie L; Herroon, Mackenzie K; Rajagurubandara, Erandi; Podgorski, Izabela

    2015-04-01

    Increased bone marrow adiposity is a common feature of advanced age, obesity and associated metabolic pathologies. Augmented numbers of marrow adipocytes positively correlate with dysregulated bone remodeling, also a well-established complication of metastatic disease. We have shown previously that marrow adiposity accelerates prostate tumor progression in the skeleton and promotes extensive destruction of the bone; however, the factors behind adipocyte-driven osteolysis in the skeletal tumor microenvironment are not currently known. In this study, utilizing in vivo diet-induced models of bone marrow adiposity, we reveal evidence for positive correlation between increased marrow fat content, bone degradation by ARCaP(M) and PC3 prostate tumors, and augmented levels of host-derived CXCL1 and CXCL2, ligands of CXCR2 receptor. We show by in vitro osteoclastogenesis assays that media conditioned by bone marrow adipocytes is a significant source of CXCL1 and CXCL2 proteins. We also demonstrate that both the adipocyte-conditioned media and the recombinant CXCL1 and CXCL2 ligands efficiently accelerate osteoclast maturation, a process that can be blocked by neutralizing antibodies to each of the chemokines. We further confirm the contribution of CXCR2 signaling axis to adiposity-driven osteoclastogenesis by blocking fat cell-induced osteoclast differentiation with CXCR2 antagonist or neutralizing antibodies. Together, our results link CXCL1 and CXCL2 chemokines with bone marrow adiposity and implicate CXCR2 signaling in promoting effects of marrow fat on progression of skeletal tumors in bone. PMID:25802102

  20. Bone marrow cell recruitment to the brain in the absence of irradiation or parabiosis bias.

    PubMed

    Kierdorf, Katrin; Katzmarski, Natalie; Haas, Carola A; Prinz, Marco

    2013-01-01

    The engraftment of bone marrow-derived cells has been described not only during diseases of the central nervous system (CNS) but also under healthy conditions. However, previous studies pointing to an ample bone marrow cell engraftment used irradiation-induced bone marrow chimeras that evoked severe alterations of the CNS micromilieu including disturbances of the blood brain barrier (BBB), damage of endothelial cells and local induction of proinflammatory cytokines. On the other hand, parabiosis experiments using temporarily joined circulatory systems generally yielded low levels of myeloid cell chimerism thereby potentially underestimating bone marrow cell turnover with the CNS. To avoid these drawbacks we established a protocol using the alkylating agent busulfan prior to allogenic bone marrow transplantation from CX3CR1(GFP/+) donors. This regimen resulted in a stable and high peripheral myeloid chimerism, significantly reduced cytokine induction and preserved BBB integrity. Importantly, bone marrow cell recruitment to the CNS was strongly diminished under these conditions and only weakly enhanced during local neurodegeneration induced by facial nerve axotomy. These results underscore the requirement of local CNS conditioning for efficient recruitment of bone marrow cells, establish busulfan as an alternative treatment for studying bone marrow chimeras and suggest a critical re-evaluation of earlier chimeric studies involving irradiation or parabiosis regimens. PMID:23526995

  1. The Role of Bone Marrow Cells in the Phenotypic Changes Associated with Diabetic Nephropathy

    PubMed Central

    Yang, Guang; Cheng, Qingli; Liu, Sheng; Zhao, Jiahui

    2015-01-01

    The aim of our study was to investigate the role of bone marrow cells in the phenotypic changes that occur in diabetic nephropathy. Bone marrow cells were obtained from either streptozotocin-induced diabetic or untreated control C3H/He mice and transplanted into control C3H/He mice. Eight weeks after bone marrow cell transplantation, renal morphologic changes and clinical parameters of diabetic nephropathy, including the urine albumin/creatinine ratio and glucose tolerance, were measured in vivo. Expression levels of the genes encoding ?1 type IV collagen and transforming growth factor-?1 in the kidney were assayed. Our results demonstrated that glucose tolerance was normal in the recipients of bone marrow transplants from both diabetic and control donors. However, compared with recipients of the control bone marrow transplant, the urinary albumin/creatinine ratio, glomerular size, and the mesangial/glomerular area ratio increased 3.3-fold (p < 0.01), 1.23-fold (p < 0.01), and 2.13-fold (p < 0.001), respectively, in the recipients of the diabetic bone marrow transplant. Expression levels of the genes encoding glomerular ?1 type IV collagen and transforming growth factor-?1 were also significantly increased (p < 0.01) in the recipients of the diabetic bone marrow transplant. Our data suggest that bone marrow cells from the STZ-induced diabetic mice can confer a diabetic phenotype to recipient control mice without the presence of hyperglycemia. PMID:26340671

  2. Differential adhesiveness between blood and marrow leukemic cells having similar pattern of VLA adhesion molecule expression.

    PubMed

    Thomas, X; Anglaret, B; Bailly, M; Maritaz, O; Magaud, J P; Archimbaud, E

    1998-10-01

    Functional adhesion of blood and marrow leukemic cells from 14 acute myeloid leukemia patients presenting with hyperleukocytosis was evaluated by performing cytoadhesion assays on purified (extracellular matrix proteins) and non-purified supports (MRC5 fibroblastic cell line). Results, in 30-min chromium release assay, show a mean +/- S.D. adhesion to fibronectin, collagen, and laminin respectively of 30 +/- 17%, 20 +/- 13%, 25 +/- 17% for blood leukemic cells and 18 +/- 11%, 11 +/- 10%, 11 +/- 8% for marrow leukemic cells. These differences between blood and marrow cells were statistically significant (respectively P = 0.005, P = 0.01 and P = 0.002), while no difference was noted regarding adhesion to non-purified supports. The higher adhesion of blood blast cells to purified supports was observed regardless of CD34 expression. No significant difference was observed in the expression of cell surface VLA-molecules (CD29, CD49b, CD49d, CD49e, CD49f) between blood and marrow blast cells. The addition of GM-CSF or G-CSF induced increased adhesion of marrow blasts and decreased adhesion of blood blasts leading to a loss of the difference between blood and marrow cells. In a 60-min chromium release assay, marrow blasts adhered even more than blood leukemic cells to fibronectin. In contrast, marrow blasts from 'aleukemic' acute myeloid leukemia patients did not show any modification regarding their adhesion to extracellular matrix proteins when co-cultured with growth factors. PMID:9766756

  3. Chronic granulomatous disease. Expression of the metabolic defect by in vitro culture of bone marrow progenitors.

    PubMed Central

    Newburger, P E; Kruskall, M S; Rappeport, J M; Robinson, S H; Chovaniec, M E; Cohen, H J

    1980-01-01

    Chronic granulomatous disease (CGD), an often fatal syndrome of recurrent infections results from the inability of patients' peripheral blood phagocytic leukocytes to generate superoxide despite otherwise normal phagocytic functions such as ingestion and degranulation. Circulating granulocytes and monocytes are the progeny of bone marrow progenitor cells, colony-forming units in culture. We compared the function of cells grown in two different in vitro cuture systems from the bone marrow of a CGD patient with those from normal subjects. The cells of normal colony-forming unit in culture colonies grown in semisolid medium reduced nitroblue tetrazolium dye when stimulated by phorbol myristate acetate; none of the cells from colonies derived from CGD marrow did so. Cells grown in liquid suspension culture from normal marrow generated superoxide nearly as well as normal peripheral blood granulocytes; those from CGD marrow produced no superoxide, similarly cultured cells from both normal and CGD marrow ingested opsonized bacteria at rates equal to peripheral blood granulocytes. CGD marrow-derived cells showed increased exocytic degranulation relative to both normal marrow-derived cells and normal peripheral blood granulocytes. These studies demonstrate that the basic functional characteristics of CGD are embedded in the genetic program of granulocyte progenitors. Images PMID:6249853

  4. Effects of age and shear rate on the rheological properties of human yellow bone marrow.

    PubMed

    Zhong, Ziwei; Akkus, Ozan

    2011-01-01

    Bone marrow is the niche for stem cells and is within close proximity to bone lining cells. Forces experienced by these cells guide their differentiation and proliferation. As these forces are dependent on the viscosity of the medium, the knowledge about the viscosity of marrow is essential to modeling the mechanical environment of bone. This study sought to examine the effects of age on the rheological properties of human yellow bone marrow. Samples were harvested from the femurs of male donors ranging from 22 to 82 years of age (N=19) and subjected to stress and frequency sweeps to determine viscosity and dynamic moduli, respectively. The viscosity of bone marrow at physiologically plausible shear rates ranged from 44 to 142 mPas. The coefficients of variation ranged up to 0.40 within subjects and 0.14 between subjects. Regressions of viscosity values against age did not generate a strong level of significance; therefore, earlier reported changes in the composition of marrow with age did not translate into variation in viscosity of marrow. Since age does not seem to offer a governing effect, the observed variation within and between donors may stem from other factors (genetic, nutrition, etc.). The wide range of variation in the viscosity of marrow within subject, between subjects and with age implies that the fluid shear experienced by cells resident in marrow may also vary substantially. PMID:21811014

  5. Canine bone marrow cytological examination, classification and reference values: A retrospective study of 295 cases.

    PubMed

    Turinelli, Vanessa; Gavazza, Alessandra; Stock, Graham; Fournel-Fleury, Corinne

    2015-12-01

    Cytologic assessment of bone marrow with knowledge of the hemogram represents an effective method to investigate hemic tissue and its function. To determine the spectrum and prevalence of canine bone marrow disorders over a 2year period in a diagnostic laboratory setting achieved through a standard approach to cytologic bone marrow assessment. A retrospective study of bone marrow fine needle aspirates sample preparations, blood smears, hemogram data and case records. Of the 295 bone marrow samples evaluated, 90 (30.5%) were nondiagnostic samples. Of the remaining samples, 25.1% were classified as hyperplasia of which most were granulocytic hyperplasia (58.1% of the total hyperplasia), 19.3% had no cytological abnormalities, 12.9% had malignant hemopathy and 7.8% had hypo-aplastic conditions. Only a small proportion of cases involved dysplasia (1.7%) and metastatic disease was detected in only one case (0.3%). Reference values of nucleated cells and the M/E ratio were calculated for normal and erythroid and granulocytic hyperplastic bone marrow. This study provides the spectrum and the prevalence of canine bone marrow disorders as well as a differential bone marrow cell counting and determination of reference intervals for diseases. PMID:26679822

  6. Knowledge and attitude of Lublin universities students' toward the opportunity of becoming unrelated bone marrow donor.

    PubMed

    Sikora, Agnieszka; Wiorkowski, Krzysztof; Szara, Paulina; Drabko, Katarzyna

    2014-01-01

    Hematopoietic Stem Cell Transplantation (HSCT) is a very important life-saving procedure to treat many disorders. In August 2014, there were more than 24.5 million donor registered in the Worldwide Bone Marrow Donor Register. In the Polish Register of Unrelated Bone Marrow and Umbilical Cord Blood Donors at the end of 2013 there were almost 540 thousand registered bone marrow donors. Despite increasing numbers of registered donors, the amount of requests also increased. It shows that the number of donors is still insufficient. The analysis of knowledge and attitude of Lublin universities students' toward the opportunity to become an unrelated bone marrow donor was the aim of our study. 1609 Lublin students from non-medical universities from different years and specializations of study, of both sexes, aged 19-35 took part in the survey. It consisted of 16 questions. There were knowledge-testing questions, and also personal ones. Among interviewees, 16% were registered as potential bone marrow donors. The reason for not being registered registration chosen most often was that the surveyed did not take this into consideration. Correct answers to all of the questions were given by 21% of students. The biggest number of incorrect answers was given to the question about a place from bone marrow is harvested - nearly 49%. Registered students showed a better level of knowledge than the unregistered. We noted a low level of knowledge about bone marrow donation and possibility of becoming potential bone marrow donor among Lublin universities students. PMID:25648307

  7. Transplanted Bone Marrow Cells Repair Heart Tissue and Reduce Myocarditis in Chronic Chagasic Mice

    PubMed Central

    Soares, Milena B. P.; Lima, Ricardo S.; Rocha, Leonardo L.; Takyia, Christina M.; Pontes-de-Carvalho, Lain; Campos de Carvalho, Antonio C.; Ribeiro-dos-Santos, Ricardo

    2004-01-01

    A progressive destruction of the myocardium occurs in ?30% of Trypanosoma cruzi-infected individuals, causing chronic chagasic cardiomyopathy, a disease so far without effective treatment. Syngeneic bone marrow cell transplantation has been shown to cause repair and improvement of heart function in a number of studies in patients and animal models of ischemic cardiopathy. The effects of bone marrow transplant in a mouse model of chronic chagasic cardiomyopathy, in the presence of the disease causal agent, ie, the T. cruzi, are described herein. Bone marrow cells injected intravenously into chronic chagasic mice migrated to the heart and caused a significant reduction in the inflammatory infiltrates and in the interstitial fibrosis characteristics of chronic chagasic cardiomyopathy. The beneficial effects were observed up to 6 months after bone marrow cell transplantation. A massive apoptosis of myocardial inflammatory cells was observed after the therapy with bone marrow cells. Transplanted bone marrow cells obtained from chagasic mice and from normal mice had similar effects in terms of mediating chagasic heart repair. These results show that bone marrow cell transplantation is effective for treatment of chronic chagasic myocarditis and indicate that autologous bone marrow transplant may be used as an efficient therapy for patients with chronic chagasic cardiomyopathy. PMID:14742250

  8. 40 CFR 798.5385 - In vivo mammalian bone marrow cytogenetics tests: Chromosomal analysis.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... report. In addition to the reporting recommendations as specified under 40 CFR part 792, subpart J the... 40 Protection of Environment 32 2011-07-01 2011-07-01 false In vivo mammalian bone marrow... Genetic Toxicity § 798.5385 In vivo mammalian bone marrow cytogenetics tests: Chromosomal analysis....

  9. 40 CFR 798.5395 - In vivo mammalian bone marrow cytogenetics tests: Micronucleus assay.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... recommendations as specified under 40 CFR part 792, subpart J, the following specific information shall be... 40 Protection of Environment 32 2011-07-01 2011-07-01 false In vivo mammalian bone marrow... Genetic Toxicity § 798.5395 In vivo mammalian bone marrow cytogenetics tests: Micronucleus assay....

  10. 40 CFR 798.5395 - In vivo mammalian bone marrow cytogenetics tests: Micronucleus assay.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... recommendations as specified under 40 CFR part 792, subpart J, the following specific information shall be... 40 Protection of Environment 32 2014-07-01 2014-07-01 false In vivo mammalian bone marrow... Genetic Toxicity § 798.5395 In vivo mammalian bone marrow cytogenetics tests: Micronucleus assay....

  11. 40 CFR 798.5395 - In vivo mammalian bone marrow cytogenetics tests: Micronucleus assay.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... recommendations as specified under 40 CFR part 792, subpart J, the following specific information shall be... 40 Protection of Environment 33 2013-07-01 2013-07-01 false In vivo mammalian bone marrow... Genetic Toxicity § 798.5395 In vivo mammalian bone marrow cytogenetics tests: Micronucleus assay....

  12. 40 CFR 798.5395 - In vivo mammalian bone marrow cytogenetics tests: Micronucleus assay.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... recommendations as specified under 40 CFR part 792, subpart J, the following specific information shall be... 40 Protection of Environment 33 2012-07-01 2012-07-01 false In vivo mammalian bone marrow... Genetic Toxicity § 798.5395 In vivo mammalian bone marrow cytogenetics tests: Micronucleus assay....

  13. 40 CFR 798.5385 - In vivo mammalian bone marrow cytogenetics tests: Chromosomal analysis.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... report. In addition to the reporting recommendations as specified under 40 CFR part 792, subpart J the... 40 Protection of Environment 32 2014-07-01 2014-07-01 false In vivo mammalian bone marrow... Genetic Toxicity § 798.5385 In vivo mammalian bone marrow cytogenetics tests: Chromosomal analysis....

  14. 40 CFR 798.5385 - In vivo mammalian bone marrow cytogenetics tests: Chromosomal analysis.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... report. In addition to the reporting recommendations as specified under 40 CFR part 792, subpart J the... 40 Protection of Environment 33 2013-07-01 2013-07-01 false In vivo mammalian bone marrow... Genetic Toxicity § 798.5385 In vivo mammalian bone marrow cytogenetics tests: Chromosomal analysis....

  15. 40 CFR 798.5385 - In vivo mammalian bone marrow cytogenetics tests: Chromosomal analysis.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... report. In addition to the reporting recommendations as specified under 40 CFR part 792, subpart J the... 40 Protection of Environment 33 2012-07-01 2012-07-01 false In vivo mammalian bone marrow... Genetic Toxicity § 798.5385 In vivo mammalian bone marrow cytogenetics tests: Chromosomal analysis....

  16. Combination therapies prevent the neuropathic, proinflammatory characteristics of bone marrow in streptozotocin-induced diabetic rats.

    PubMed

    Dominguez, James M; Yorek, Mark A; Grant, Maria B

    2015-02-01

    We previously showed that peripheral neuropathy of the bone marrow was associated with loss of circadian rhythmicity of stem/progenitor cell release into the circulation. Bone marrow neuropathy results in dramatic changes in hematopoiesis that lead to microvascular complications, inflammation, and reduced endothelial repair. This series of events represents early pathogenesis before development of diabetic retinopathy. In this study we characterized early alterations within the bone marrow of streptozotocin (STZ)-induced diabetic rats following treatments that prevent experimental peripheral neuropathy. We asked whether bone marrow neuropathy and the associated bone marrow pathology were reversed with treatments that prevent peripheral neuropathy. Three strategies were tested: inhibition of neutral endopeptidase, inhibition of aldose reductase plus lipoic acid supplementation, and insulin therapy with antioxidants. All strategies prevented loss of nerve conduction velocity resulting from STZ-induced diabetes and corrected the STZ-induced diabetes-associated increase of immunoreactivity of neuropeptide Y, tyrosine hydroxylase, and somatostatin. The treatments also reduced concentrations of interleukin-1?, granulocyte colony-stimulating factor, and matrix metalloproteinase 2 in STZ-induced diabetic bone marrow supernatant and decreased the expression of NADPH oxidase 2, nitric oxide synthase 2, and nuclear factor-?B1 mRNA in bone marrow progenitor cells. These therapies represent novel approaches to attenuate the diabetic phenotype within the bone marrow and may constitute an important therapeutic strategy for diabetic microvascular complications. PMID:25204979

  17. Recovery of hair coat color in Gray Collie (cyclic neutropenia)-normal bone marrow transplant chimeras.

    PubMed Central

    Yang, T. J.

    1978-01-01

    Gray Collie-normal bone marrow transplantation chimeras showed normal coloration of the hair coat on tails and several other areas 2 years after successful transplantation of bone marrow to correct cyclic neutropenia of the Gray Collie syndrome. Images Figures 1-2 PMID:347941

  18. Short-Term Effect of Estrogen on Human Bone Marrow Fat.

    PubMed

    Limonard, Eelkje J; Veldhuis-Vlug, Annegreet G; van Dussen, Laura; Runge, Jurgen H; Tanck, Michael W; Endert, Erik; Heijboer, Annemieke C; Fliers, Eric; Hollak, Carla E; Akkerman, Erik M; Bisschop, Peter H

    2015-11-01

    Bone marrow fat, an unique component of the bone marrow cavity increases with aging and menopause and is inversely related to bone mass. Sex steroids may be involved in the regulation of bone marrow fat, because men have higher bone marrow fat than women and clinical observations have suggested that the variation in bone marrow fat fraction is greater in premenopausal compared to postmenopausal women and men. We hypothesized that the menstrual cycle and/or estrogen affects the bone marrow fat fraction. First, we measured vertebral bone marrow fat fraction with Dixon Quantitative Chemical Shift MRI (QCSI) twice a week during 1 month in 10 regularly ovulating women. The vertebral bone marrow fat fraction increased 0.02 (95% CI, 0.00 to 0.03) during the follicular phase (p = 0.033), and showed a nonsignificant decrease of 0.02 (95% CI, -0.01 to 0.04) during the luteal phase (p = 0.091). To determine the effect of estrogen on bone marrow fat, we measured vertebral bone marrow fat fraction every week for 6 consecutive weeks in 6 postmenopausal women before, during, and after 2 weeks of oral 17-? estradiol treatment (2 mg/day). Bone marrow fat fraction decreased by 0.05 (95% CI, 0.01 to 0.09) from 0.48 (95% CI, 0.42 to 0.53) to 0.43 (95% CI, 0.34 to 0.51) during 17-? estradiol administration (p < 0.001) and increased again after cessation. During 17-? estradiol administration the bone formation marker procollagen type I N propeptide (P1NP) increased (p = 0.034) and the bone resorption marker C-terminal crosslinking telopeptides of collagen type I (CTx) decreased (p < 0.001). In conclusion, we described the variation in vertebral bone marrow fat fraction among ovulating premenopausal women. And among postmenopausal women, we demonstrated that 17-? estradiol rapidly reduces the marrow fat fraction, suggesting that 17-? estradiol regulates bone marrow fat independent of bone mass. PMID:25982922

  19. Changes in vertebral bone marrow fat and bone mass after gastric bypass surgery: A pilot study.

    PubMed

    Schafer, A L; Li, X; Schwartz, A V; Tufts, L S; Wheeler, A L; Grunfeld, C; Stewart, L; Rogers, S J; Carter, J T; Posselt, A M; Black, D M; Shoback, D M

    2015-05-01

    Bone marrow fat may serve a metabolic role distinct from other fat depots, and it may be altered by metabolic conditions including diabetes. Caloric restriction paradoxically increases marrow fat in mice, and women with anorexia nervosa have high marrow fat. The longitudinal effect of weight loss on marrow fat in humans is unknown. We hypothesized that marrow fat increases after Roux-en-Y gastric bypass (RYGB) surgery, as total body fat decreases. In a pilot study of 11 morbidly obese women (6 diabetic, 5 nondiabetic), we measured vertebral marrow fat content (percentage fat fraction) before and 6 months after RYGB using magnetic resonance spectroscopy. Total body fat mass declined in all participants (mean SD decline 19.1 6.1 kg or 36.5% 10.9%, p<0.001). Areal bone mineral density (BMD) decreased by 5.2% 3.5% and 4.1% 2.6% at the femoral neck and total hip, respectively, and volumetric BMD decreased at the spine by 7.4% 2.8% (p<0.001 for all). Effects of RYGB on marrow fat differed by diabetes status (adjusted p=0.04). There was little mean change in marrow fat in nondiabetic women (mean +0.9%, 95% CI -10.0 to +11.7%, p=0.84). In contrast, marrow fat decreased in diabetic women (-7.5%, 95% CI -15.2 to +0.1%, p=0.05). Changes in total body fat mass and marrow fat were inversely correlated among nondiabetic (r=-0.96, p=0.01) but not diabetic (r=0.52, p=0.29) participants. In conclusion, among those without diabetes, marrow fat is maintained on average after RYGB, despite dramatic declines in overall fat mass. Among those with diabetes, RYGB may reduce marrow fat. Thus, future studies of marrow fat should take diabetes status into account. Marrow fat may have unique metabolic behavior compared with other fat depots. PMID:25603463

  20. [Method for concentrating marrow stem cells using the IBM 2991 washer. Necessary preparation before in vitro treatment of bone marrow by pharmacologic or immunologic means].

    PubMed

    Hervé, P; Coffe, C; Peters, A

    1983-04-01

    The technique using the IBM 2991 blood cell processor is an effective technique for the concentration of mononuclear cells from large volumes of bone marrow. The marrow cells are layered on to Ficoll Metrizoate using the IBM processing set. The mononuclear cells and CFU-GM recoveries are in close relationship with the hematocrit of the cell suspension processed. Twenty two bone marrows have been collected and purified according to this protocol. The mononuclear cell recovery is an average of 78,3% (range: 44-92%) and the CFU-GM recovery is in average of 67,5% (range: 40-89%). At the end of the procedure the cell viability is satisfying (97,1% +/- 1,7 are trypan blue negatives). When it is necessary to remove from the bone marrow collected either malignant cells prior autologous bone marrow graft or T lymphocytes in an attempt to prevent GVHD in allogeneic BMT, the purity of marrow cell suspension become a fundamental parameter. PMID:6348924

  1. Direct comparison of steady-state marrow, primed marrow, and mobilized peripheral blood for transduction of hematopoietic stem cells in dogs.

    PubMed

    Thomasson, Bobbie; Peterson, Laura; Thompson, Jesse; Goerner, Martin; Kiem, Hans-Peter

    2003-11-20

    The optimal stem cell source for stem cell gene therapy has not been defined. Most gene transfer studies have used peripheral blood or marrow repopulating cells collected after administration of granulocyte colony-stimulating factor and stem cell factor (G-CSF/SCF). For clinical applications, however, growth factor administration may not be feasible. Thus, in the current study we used a competitive repopulation assay in the dog to directly compare transduction efficiency of steady-state marrow, G-CSF/SCF-primed marrow, and G-CSF/SCF-mobilized peripheral blood. Cells from all three sources were transduced, cryopreserved, and thawed together before infusion into myeloablated dogs. Gene marking in hematopoietic repopulating cells was assessed by polymerase chain reaction. While primed marrow resulted in the highest long-term marking levels, steady-state marrow was transduced at least as efficiently as mobilized peripheral blood in all three dogs. These results suggest that steady-state marrow may be an appropriate source for genetic modification of hematopoietic stem cells. PMID:14633410

  2. Role of marrow architecture and stromal cells in the recovery process of aplastic marrow of lethally irradiated rats parabiosed with healthy litter mates

    SciTech Connect

    Hayashi, K.; Kagawa, K.; Awai, M.; Irino, S.

    1986-01-01

    Bone marrow aplasia was induced in rats by whole body lethal irradiation (1,000 rads by x-ray), and rats died of irradiation injury within 7 days. Correlative studies at light (LM), transmission (TEM) and scanning electron microscopy (SEM) demonstrated swelling of endothelial and reticular cells and hemorrhage due to detachment of sinus endothelial cells on days 1 and 2. With time, structural recovery occurred without hemopoietic recovery. Reticular cells developed small intracytoplasmic lipid droplets on days 3 and 4. This resulted in fatty aplastic marrow within 7 days. On the other hand, in the marrow of irradiated rats parabiosed with healthy mates by aortic anastomosis, hemopoiesis was initiated by adhesion of nucleated blood cells to fine cytoplasmic pseudopods of fat-stored cells on days 1 and 2 after parabiosis. On days 3 to 5, reticular cells with large lipid droplets and fine pseudopods increased, then hemopoietic foci became clear and extensive. On day 8 after parabiosis, the aplastic bone marrow recovered completely both its structure and hemopoietic activity. Thus, hemopoietic recovery in lethally irradiated marrow begins with recovery of vascular endothelial cells, re-establishment of sinusoidal structure, and morphological and functional recoveries of reticular cells from fat-storage cells by releasing intracytoplasmic lipid droplets. Marrow stromal cells, namely reticular, fat-storage and fibroblastoid cells, share a common cellular origin, and regain their structure and function when fat-storage cells and fibroid cells are placed in contact with hemopoietic precursor cells.

  3. Burkitt leukemia limited to the bone marrow has a better prognosis than Burkitt lymphoma with bone marrow involvement in adults.

    PubMed

    Song, Joo Y; Venkataraman, Girish; Fedoriw, Yuri; Herrera, Alex F; Siddiqi, Tanya; Alikhan, Mir B; Kim, Young S; Murata-Collins, Joyce; Weisenburger, Dennis D; Liu, Xueli; Duffield, Amy S

    2016-04-01

    Burkitt lymphoma patients with bulky disease often have bone marrow involvement. However, leukemic presentation of Burkitt lymphoma in the absence of a mass (pure Burkitt leukemia; PBL) is uncommon. Both PBL and Burkitt lymphoma/leukemia, presenting with a tumor mass and marrow involvement (BLL), are considered stage IV disease, which is associated with a poor prognosis. However, there is limited information on the prognosis in adults with PBL because they have typically been included in cohorts of patients with BLL. This study identified 23 patients, which included 10 PBL and 13 BLL cases. Complex karyotypes (100%) were seen in all BLL cases compared to the PBL group (40%; p = 0.061). Patients with PBL had a significantly better 5-year overall survival of 87.5% vs only 24.3% in the BLL group (p = 0.005). The 5-year overall survival of patients with PBL treated with intensive chemotherapy is superior to those with BLL who are similarly treated. PMID:26450341

  4. Chitosan-collagen porous scaffold and bone marrow mesenchymal stem cell transplantation for ischemic stroke

    PubMed Central

    Yan, Feng; Yue, Wei; Zhang, Yue-lin; Mao, Guo-chao; Gao, Ke; Zuo, Zhen-xing; Zhang, Ya-jing; Lu, Hui

    2015-01-01

    In this study, we successfully constructed a composite of bone marrow mesenchymal stem cells and a chitosan-collagen scaffold in vitro, transplanted either the composite or bone marrow mesenchymal stem cells alone into the ischemic area in animal models, and compared their effects. At 14 days after co-transplantation of bone marrow mesenchymal stem cells and the hitosan-collagen scaffold, neurological function recovered noticeably. Vascular endothelial growth factor expression and nestin-labeled neural precursor cells were detected in the ischemic area, surrounding tissue, hippocampal dentate gyrus and subventricular zone. Simultaneously, a high level of expression of glial fibrillary acidic protein and a low level of expression of neuron-specific enolase were visible in BrdU-labeled bone marrow mesenchymal stem cells. These findings suggest that transplantation of a composite of bone marrow mesenchymal stem cells and a chitosan-collagen scaffold has a neuroprotective effect following ischemic stroke. PMID:26604902

  5. Bone Marrow-Derived Stem Cells: a Mixed Blessing in the Multifaceted World of Diabetic Complications.

    PubMed

    Mangialardi, Giuseppe; Madeddu, Paolo

    2016-05-01

    Diabetes is one of the main economic burdens in health care, which threatens to worsen dramatically if prevalence forecasts are correct. What makes diabetes harmful is the multi-organ distribution of its microvascular and macrovascular complications. Regenerative medicine with cellular therapy could be the dam against life-threatening or life-altering complications. Bone marrow-derived stem cells are putative candidates to achieve this goal. Unfortunately, the bone marrow itself is affected by diabetes, as it can develop a microangiopathy and neuropathy similar to other body tissues. Neuropathy leads to impaired stem cell mobilization from marrow, the so-called mobilopathy. Here, we review the role of bone marrow-derived stem cells in diabetes: how they are affected by compromised bone marrow integrity, how they contribute to other diabetic complications, and how they can be used as a treatment for these. Eventually, we suggest new tactics to optimize stem cell therapy. PMID:27025211

  6. Bone and bone-marrow blood flow in chronic granulocytic leukemia and primary myelofibrosis

    SciTech Connect

    Lahtinen, R.; Lahtinen, T.; Romppanen, T.

    1982-03-01

    Blood flow in hematopoietic bone marrow and in nonhematopoietic bone has been measured with a Xe-133 washout method in 20 patients with chronic granulocytic leukemia (CGL) and in seven with primary myelofibrosis. Age-matched healthy persons served as controls. Bone-marrow blood flow in CGL was dependent upon the phase of the disease. In the metamorphosis phase, bone-marrow blood flow was high compared with that in the well-controlled phase. Apart from the initial phase, the mean values for bone blood flow in CGL were increased compared with the values of the healthy controls. In myelofibrosis the bone blood flow was also increased. Bone-marrow blood flow in these diseases was dependent upon the cellularity of bone marrow as measured morphometrically.

  7. ASTA Z 7557 (INN mafosfamide) for the in vitro treatment of human leukemic bone marrows.

    PubMed

    Douay, L; Gorin, N C; Laporte, J P; Lopez, M; Najman, A; Duhamel, G

    1984-01-01

    The in vitro treatment of leukemic bone marrows, collected during complete remission, aims at eliminating residual blast cells prior to freezing and preservation, while sparing normal hematopoietic stem cells. We report our experience on the activity of ASTA Z 7557 on human leukemic (CFU-L) and normal hematopoietic stem cells. The sensitivity of human leukemic and normal progenitor cells (CFU-c), detected in semi-solid media cultures, is similar. However, pre-CFUc progenitors detected in long term marrow cultures are much less sensitive to ASTA Z 7557. Therefore autologous bone marrow transplantation can successfully be done with pretreated marrows containing 5 +/- 5% residual CFUc. The wide range of stem cells sensitivity to ASTA Z 7557 justify the predetermination of the optimal dose of drug for incubation prior to marrow collection for each individual patient. Our preliminary clinical experience is exposed. PMID:6381382

  8. Effects of OK-432 on murine bone marrow and the production of natural killer cells

    SciTech Connect

    Pollack, S.B.; Rosse, C.

    1985-01-01

    The streptococcal preparation, OK-432, which augments anti-tumor responses in humans and mice, has been shown to be a potent immunomodulator. Among its effects is a pronounced augmentation of natural killer (NK) activity. The hypothesis that OK-432 alters the rates of production and maturation of NK cells in the bone marrow was tested. Studies to determine the kinetic parameters of NK cell production in normal C57BL/6J mice using tritiated thymidine, /sup 3/H-TdR, as a DNA marker are described. We are now extending those studies to determine the effect of OK-432 on the bone marrow and on the production of NK cells in the marrow. Initial observations are reported which indicate that OK-432 has profound effects on the cellularity and mitotic activity of the bone marrow, and in particular, on cells with the characteristics of natural killer cells within the marrow. 17 refs., 3 figs., 4 tabs.

  9. Alveolar macrophage kinetics and function after interruption of canine marrow function

    SciTech Connect

    Springmeyer, S.C.; Altman, L.C.; Kopecky, K.J.; Deeg, H.J.; Storb, R.

    1982-03-01

    To study the kinetics and function of alveolar macrophages after interruption of marrow function, we performed serial bronchoalveolar lavages in dogs. The studies were performed before and after 9.0 to 9.5 Grey total body irradiation and marrow infusion. Monocytes had disappeared from the bloodstream by Day 7 after the irradiation. Alveolar macrophages were significantly decreased at Day 21. At Days 14 and 21 myeloperoxidase-positive alveolar macrophages were also significantly decreased. Beyond Day 30 the number of circulating monocytes, myeloperoxidase-positive and total alveolar macrophages had returned. Sex chromatin stains of alveolar macrophages obtained from a male dog that received female marrow indicated that the repopulating macrophages were of marrow origin. In vitro studies of alveolar macrophage migration and phagocytosis demonstrated increased activities beyond Day 30. These studies suggest that in this model the alveolar macrophage is dependent on the bone marrow for support and that the alveolar macrophage depletion may impair lung defense mechanisms.

  10. Bilateral diffuse pulmonary ectopic ossification after marrow allograft in a dog. Evidence for allotransplantation of hemopoietic and mesenchymal stem cells

    SciTech Connect

    Sale, G.E.; Storb, R.

    1983-11-01

    In light of recent studies showing successful transplantation of both bony and stromal elements by marrow transplantation, we report an unexpected phenomenon occurring in a canine radiation chimera. Nine hundred fifty-six days after a successful and uneventful DLA-matched marrow allograft, a dog suddenly died of respiratory failure. Autopsy revealed extensive ossification of the lungs with multiple sites of trilineage marrow engraftment. The entire complement of bony elements can apparently be allografted using marrow grafting techniques.

  11. Failure to Generate Bone Marrow Adipocytes Does Not Protect Mice from Ovariectomy-Induced Osteopenia

    PubMed Central

    Iwaniec, Urszula T.; Turner, Russell T.

    2012-01-01

    A reciprocal association between bone marrow fat and bone mass has been reported in ovariectomized rodents, suggesting that bone marrow adipogenesis has a negative effect on bone growth and turnover balance. Mice with loss of function mutations in kit receptor (kitW/W-v) have no bone marrow adipocytes in tibia or lumbar vertebra. We therefore tested the hypothesis that marrow fat contributes to development of osteopenia by comparing the skeletal response to ovariectomy (ovx) in growing wild type (WT) and bone marrow adipocyte-deficient kitW/W-v mice. Mice were ovx at 4 weeks of age and sacrificed 4 or 10 weeks post-surgery. Body composition was measured at necropsy by dual-energy X-ray absorptiometry. Cortical (tibia) and cancellous (tibia and lumbar vertebra) bone architecture were evaluated by microcomputed tomography. Bone marrow adipocyte size and density, osteoblast- and osteoclast-lined bone perimeters, and bone formation were determined by histomorphometry. Ovx resulted in an increase in total body fat mass at 10 weeks post-ovx in both genotypes, but the response was attenuated in the in kitW/W-v mice. Adipocytes were present in bone marrow of tibia and lumbar vertebra in WT mice and bone marrow adiposity increased following ovx. In contrast, marrow adipocytes were not detected in either intact or ovx kitW/W-v mice. However, ovx in WT and kitW/W-v mice resulted in statistically indistinguishable changes in cortical and cancellous bone mass, cortical and cancellous bone formation rate, and cancellous osteoblast and osteoclast-lined bone perimeters. In conclusion, our findings do not support a causal role for increased bone marrow fat as a mediator of ovx-induced osteopenia in mice. PMID:23246792

  12. [Indications, technique and risks in bone marrow transplantation in adulthood].

    PubMed

    Heyll, A; Shngen, D; Minning, H; Meckenstock, G; Aul, C; Schneider, W

    1996-03-19

    The option of bone marrow transplantation (BMT) significantly improved prognosis of adult patients with hematologic malignancies aged less than 50 years. Allogeneic BMT using the marrow of an HLA-identical family member still provides the most effective method of BMT. Conventional indications for this form of BMT are chronic myeloid leukemia (CML), acute leukemias presenting with adverse risk factors, myelodysplastic syndromes and severe aplastic anemia. If performed early in the disease course (e.g. during the chronic phase of CML or first remission of acute leukemia and MDS) allogeneic BMT cures 50 to 60% of patients. About 20% die of therapy related complications, e.g. graft versus host disease (GvHD), fatal infections or venoocclusive disease of the liver (VOD) and about 20% of patients succumb to relapse of their hematologic disorder. 80% presenting with severe aplastic anemia can be cured, if allogeneic BMT is performed soon after diagnosis without previous immunosuppressive therapy and blood transfusions. BMT with the marrow of a matched unrelated donor or autologous BMT are increasingly used as alternative procedures. A rate of lethal complications as high as 50% hinders rapid extension of BMT with unrelated donors. Therefore, this form of BMT should be restricted to young patients with leukemias, who cannot achieve long-term remission with conventional chemotherapy (in case of acute leukemias) or alpha-interferon (in case of CML). Reconstitution of hematopoiesis is more rapid after peripheral blood stem cell transplantation (PBSCT) compared with autologous BMT. Therefore, PBSCT will replace autologous BMT in most cases. Most favourable results of PBSCT have been reported in patients with malignant lymphomas after relapse or inferior response to primary induction therapy. Due to the higher relapse rate autologous BMT is inferior to allogeneic BMT in leukemia patients. Trials are required to clarify the potential role of myeloablative therapy with stem cell support in the treatment of patients with solid tumors. Many of the preliminary results already published are unsatisfactory and data of larger trials are still lacking. Therefore, BMT or PBSCT cannot be recommended generally for the therapy of patients with solid tumors. PMID:8643901

  13. Synthesis and assembly of membrane skeletal proteins in mammalian red cell precursors

    SciTech Connect

    Hanspal, M.; Palek, J.

    1987-09-01

    The synthesis of membrane skeletal proteins in avian nucleated red cells has been the subject of extensive investigation, whereas little is known about skeletal protein synthesis in bone marrow erythroblasts and peripheral blood reticulocytes in mammals. To address this question, we have isolated nucleated red cell precursors and reticulocytes from spleens and from the peripheral blood, respectively, of rats with phenylhydrazine-induced hemolytic anemia and pulse-labeled them with (/sup 35/S)methionine. Pulse-labeling of nucleated red cell precursors shows that the newly synthesized alpha- and beta-spectrins are present in the cytosol, with a severalfold excess of alpha-spectrin over beta-spectrin. However, in the membrane-skeletal fraction, newly synthesized alpha- and beta-spectrins are assembled in stoichiometric amounts, suggesting that the association of alpha-spectrin with the membrane skeleton may- be rate-limited by the amount of beta-spectrin synthesized, as has been shown recently in avian erythroid cells. Pulse-chase experiments in the rat nucleated red cell precursors show that the newly synthesized alpha- and beta-spectrin of the cytosol turn over coordinately and extremely rapidly. In contrast, in the membrane-skeletal fraction, the newly synthesized polypeptides of spectrin are stable. In contrast to nucleated erythroid cells, in reticulocytes the synthesis of alpha- and beta-spectrins is markedly diminished compared with the synthesis and assembly of proteins comigrating with bands 2.1 and 4.1 on SDS gels. Thus, in nucleated red cell precursors, the newly synthesized spectrin may be attached to the plasma membrane before proteins 2.1 and 4.1 are completely synthesized and incorporated in the membrane.

  14. Transplanted Bone Marrow-Derived Cells Contribute to Human Adipogenesis.

    PubMed

    Rydn, Mikael; Uzunel, Mehmet; Hrd, Joanna L; Borgstrm, Erik; Mold, Jeff E; Arner, Erik; Mejhert, Niklas; Andersson, Daniel P; Widlund, Yvonne; Hassan, Moustapha; Jones, Christina V; Spalding, Kirsty L; Svahn, Britt-Marie; Ahmadian, Afshin; Frisn, Jonas; Bernard, Samuel; Mattsson, Jonas; Arner, Peter

    2015-09-01

    Because human white adipocytes display a high turnover throughout adulthood, a continuous supply of precursor cells is required to maintain adipogenesis. Bone marrow (BM)-derived progenitor cells maycontribute to mammalian adipogenesis; however, results in animal models are conflicting. Here we demonstrate in 65 subjects who underwent allogeneic BM or peripheral blood stem cell (PBSC) transplantation that, over the entire lifespan, BM/PBSC-derived progenitor cells contribute ?10% to the subcutaneous adipocyte population. While this is independent of gender, age, and different transplantation-related parameters, body fat mass exerts a strong influence, with up to 2.5-fold increased donor cell contribution in obese individuals. Exome and whole-genome sequencing of single adipocytes suggests that BM/PBSC-derived progenitors contribute to adipose tissue via both differentiation and cell fusion. Thus, at least in the setting of transplantation, BM serves as a reservoir for adipocyte progenitors, particularly in obese subjects. PMID:26190649

  15. CNS Inflammation and Bone Marrow Neuropathy in Type 1 Diabetes

    PubMed Central

    Hu, Ping; Thinschmidt, Jeffrey S.; Yan, Yuanqing; Hazra, Sugata; Bhatwadekar, Ashay; Caballero, Sergio; Salazar, Tatiana; Miyan, Jaleel A.; Li, Wencheng; Derbenev, Andrei; Zsombok, Andrea; Tikhonenko, Maria; Dominguez, James M.; McGorray, Susan P.; Saban, Daniel R.; Boulton, Michael E.; Busik, Julia V.; Raizada, Mohan K.; Chan-Ling, Tailoi; Grant, Maria B.

    2014-01-01

    By using pseudorabies virus expressing green fluorescence protein, we found that efferent bone marrow–neural connections trace to sympathetic centers of the central nervous system in normal mice. However, this was markedly reduced in type 1 diabetes, suggesting a significant loss of bone marrow innervation. This loss of innervation was associated with a change in hematopoiesis toward generation of more monocytes and an altered diurnal release of monocytes in rodents and patients with type 1 diabetes. In the hypothalamus and granular insular cortex of mice with type 1 diabetes, bone marrow–derived microglia/macrophages were activated and found at a greater density than in controls. Infiltration of CD45+/CCR2+/GR-1+/Iba-1+ bone marrow–derived monocytes into the hypothalamus could be mitigated by treatment with minocycline, an anti-inflammatory agent capable of crossing the blood-brain barrier. Our studies suggest that targeting central inflammation may facilitate management of microvascular complications. PMID:24160325

  16. Local Bone Marrow Renin-Angiotensin System and Atherosclerosis

    PubMed Central

    Beyazit, Yavuz; Purnak, Tugrul; Guven, Gulay Sain; Haznedaroglu, Ibrahim C.

    2011-01-01

    Local hematopoietic bone marrow (BM) renin-angiotensin system (RAS) affects the growth, production, proliferation differentiation, and function of hematopoietic cells. Angiotensin II (Ang II), the dominant effector peptide of the RAS, regulates cellular growth in a wide variety of tissues in pathobiological states. RAS, especially Ang II and Ang II type 1 receptor (AT1R), has considerable proinflammatory and proatherogenic effects on the vessel wall, causing progression of atherosclerosis. Recent investigations, by analyzing several BM chimeric mice whose BM cells were positive or negative for AT1R, disclosed that AT1R in BM cells participates in the pathogenesis of atherosclerosis. Therefore, AT1R blocking not only in vascular cells but also in the BM could be an important therapeutic approach to prevent atherosclerosis. The aim of this paper is to review the function of local BM RAS in the pathogenesis of atherosclerosis. PMID:21234405

  17. Evaluation of Toxicity in Mouse Bone Marrow Progenitor Cells.

    PubMed

    Ezeh, Peace C; Xu, Huan; Wang, Shu Chun; Medina, Sebastian; Burchiel, Scott W

    2016-01-01

    Development of blood cells through hematopoiesis occurs in the bone marrow (BM), and can be adversely impacted by various substances and/or conditions ranging from known therapeutic, intentionally administered xenobiotics to unintentional food additives and exposure to environmental chemicals. The principles underlying the techniques for evaluating toxicity to BM progenitors (erythroid, myeloid, and lymphoid) exploit changes in the normal hematopoietic process, biochemical cell surface and intracellular markers, as well as components of the BM microenvironment. Toxicological investigations following in vivo exposures of mice or in vitro exposures of mouse primary BM cell cultures allow the assessment of the developmental and functional integrity of BM cells, cell population shifts, and adverse biochemical effects due to toxicity. Colony forming unit (CFU) assays and flow cytometry are indispensable techniques in these toxicity studies. 2016 by John Wiley & Sons, Inc. PMID:26828331

  18. Protecting the interests of the child bone marrow donor.

    PubMed

    Terry, Louise M; Campbell, Anne

    2004-01-01

    At a time when designer babies have been created to act as cord blood donors to sick siblings, ethical debate has focused predominantly on the extent to which it is acceptable to create one human being to assist another. However, children are frequently used this way, by their families and doctors who extract their bone marrow, to try to save the life of another, usually a sibling. With any life-threatening illness, there is the possibility that the urgency of the sick sibling's need means that the short-term welfare of the donor child receives less attention than it should by parents and doctors. This article suggests ways to protect the interests of such children and empower them within the decision-making process and concludes that the drive to save life must be tempered by recognition of the intrinsic worth of donor children and their rights not to be exploited. PMID:15685919

  19. Autologous Bone Marrow Aspirate Therapy in Wound Healing

    PubMed Central

    Chittoria, Ravi Kumar; Nandhagopal, Vijayaraghavan; Mohapatra, Devi Prasad; Thiruvoth, Friji Meethale; Sivakumar, Dinesh Kumar; Asokan, Arjun

    2016-01-01

    Objective: To study the role of autologous bone marrow aspirate therapy (ABMAT) in wound healing. Approach: This is a retrospective analysis of 9 patients (11 chronic nonhealing wounds) in whom ABMAT was used. Patients (wounds) were grouped into two groups. Group 1 included 4 patients (5 wounds) refusing/unfit for reconstruction and managed only with ABMAT. Group 2 included 5 patients (6 wounds) who agreed/fit for reconstruction after wound bed preparation with ABMAT. End point of the study was complete wound healing. Results: ABMAT helped in complete healing of chronic nonhealing wounds by secondary intention in group 1 patients and enhanced process of wound bed preparation for reconstruction in group 2 patients. Innovation: This study highlights the importance of ABMAT in the management of chronic nonhealing wounds. Conclusion: ABMAT helps in wound bed preparation to allow the wound to heal completely or cover by skin graft/flap. PMID:26989576

  20. Dysplastic bone marrow changes during maintenance therapy for acute leukemia.

    PubMed

    Chinello, Matteo; Naviglio, Samuele; Shardlow, Alison; Severino, Alessandro; Ventura, Alessandro; Locasciulli, Anna

    2015-03-01

    We describe the case of an 8-year-old girl with common precursor B-cell acute lymphoblastic leukemia who presented with severe pancytopenia during maintenance therapy with methotrexate and 6-mercaptopurine. The bone marrow smear showed moderate hypocellularity and trilinear dysplastic changes consistent with a diagnosis of drug toxicity, with no evidence of lymphoblasts. Flow cytometric immunophenotyping was negative for leukemic cells. Blood cell counts normalized after treatment with folinic acid. Maintenance therapy was gradually restarted and she remained well at follow-up visits. Myelotoxicity from methotrexate and 6-mercaptopurine may represent an unpredictable incident during an otherwise uneventful maintenance therapy, and may occur independently of other organ toxicities. PMID:25493456

  1. Neonatal manifestations of inherited bone marrow failure syndromes.

    PubMed

    Khincha, Payal P; Savage, Sharon A

    2016-02-01

    The inherited bone marrow failure syndromes (IBMFS) are a rare yet clinically important cause of neonatal hematological and non-hematological manifestations. Many of these syndromes, such as Fanconi anemia, dyskeratosis congenita and Diamond-Blackfan anemia, confer risks of multiple medical complications later in life, including an increased risk of cancer. Some IBMFS may present with cytopenias in the neonatal period whereas others may present only with congenital physical abnormalities and progress to pancytopenia later in life. A thorough family history and detailed physical examination are integral to the work-up of any neonate in whom there is a high index of suspicion for an IBMFS. Correct detection and diagnosis of these disorders is important for appropriate long-term medical surveillance and counseling not only for the patient but also for appropriate genetic counselling of their families regarding recurrence risks in future children and generations. PMID:26724991

  2. Chronic bacteraemia due to Staphylococcus epidermidis after bone marrow transplantation.

    PubMed

    Lina, B; Forey, F; Tigaud, J D; Fleurette, J

    1995-03-01

    A chronic bacteraemia due to Staphylococcus epidermidis occurred in a patient undergoing allogeneic bone marrow transplantation. Forty-two S. epidermidis isolates were obtained from blood cultures over a period of 5 months. Isolates were separated into three groups by SmaI macrorestriction characterisation with pulsed-field gel electrophoresis (PFE-1, one isolate; PFE-2, 32 isolates; PFE-3, nine isolates). Differences were detected in antimicrobial susceptibility patterns among isolates belonging to group PFE-2. The two strains, PFE-2 and PFE-3, were both responsible for the chronic bacteraemia and were isolated during different admissions to the hospital. A central venous catheter was the portal of entry for PFE-2. DNA macro-restriction analysis with pulsed-field gel electrophoresis was helpful in the epidemiological investigation of this S. epidermidis chronic bacteraemia. PMID:7884795

  3. Multiple autoimmune events after autologous bone marrow transplantation.

    PubMed

    Lambertenghi-Deliliers, G L; Annaloro, C; Della Volpe, A; Oriani, A; Pozzoli, E; Soligo, D

    1997-04-01

    A 36-year-old woman with RAEB-t and severe bone marrow fibrosis undergoing autologous BMT, developed a histologically documented GVHD-like skin rash. Thereafter, autoimmune thyroiditis, autoimmune thrombocytopenic purpura and autoimmune hemolytic anemia and a lupus anti-coagulant (LAC) were diagnosed. The patient is still alive, symptom-free and in first complete remission (CR); however, all of the autoantibodies are still detectable, with the exception being the anti-erythrocyte antibody. The most outstanding feature of the present case is the polymorphism of the autoimmune events, in the absence of a coexisting systemic autoimmune disease. This patient has achieved long-term disease-free survival (DFS) in first CR despite high-risk MDS and the repeated immunosuppressant therapy required because of the complications described above; a GVL reaction somewhat similar to the autoimmune events may have contributed towards maintaining disease control. PMID:9156254

  4. Bone marrow mononuclear cells and acute myocardial infarction

    PubMed Central

    2012-01-01

    Stem cell transplantation is emerging as a potential therapy to treat heart diseases. Promising results from early animal studies led to an explosion of small, non-controlled clinical trials that created even further excitement by showing that stem cell transplantation improved left ventricular systolic function and enhanced remodelling. However, the specific mechanisms by which these cells improve heart function remain largely unknown. A large variety of cell types have been considered to possess the regenerative ability needed to repair the damaged heart. One of the most studied cell types is the bone marrow-derived mononuclear cells and these form the focus of this review. This review article aims to provide an overview of their use in the setting of acute myocardial infarction, the challenges it faces and the future of stem cell therapy in heart disease. PMID:22264393

  5. Bone marrow-derived cell regulation of skeletal muscle regeneration

    PubMed Central

    Sun, Dongxu; Martinez, Carlo O.; Ochoa, Oscar; Ruiz-Willhite, Lourdes; Bonilla, Jose R.; Centonze, Victoria E.; Waite, Lindsay L.; Michalek, Joel E.; McManus, Linda M.; Shireman, Paula K.

    2009-01-01

    Limb regeneration requires the coordination of multiple stem cell populations to recapitulate the process of tissue formation. Therefore, bone marrow (BM) -derived cell regulation of skeletal muscle regeneration was examined in mice lacking the CC chemokine receptor 2 (CCR2). Myofiber size, numbers of myogenic progenitor cells (MPCs), and recruitment of BM-derived cells and macrophages were assessed after cardiotoxin-induced injury of chimeric mice produced by transplanting BM from wild-type (WT) or CCR2?/? mice into irradiated WT or CCR2?/? host mice. Regardless of the host genotype, muscle regeneration and recruitment of BM-derived cells and macrophages were similar in mice replenished with WT BM, whereas BM-derived cells and macrophage accumulation were decreased and muscle regeneration was impaired in all animals receiving CCR2?/? BM. Furthermore, numbers of MPCs (CD34+/Sca-1?/CD45? cells) were significantly increased in mice receiving CCR2?/? BM despite the decreased size of regenerated myofibers. Thus, the expression of CCR2 on BM-derived cells regulated macrophage recruitment into injured muscle, numbers of MPC, and the extent of regenerated myofiber size, all of which were independent of CCR2 expression on host-derived cells. Future studies in regenerative medicine must include consideration of the role of BM-derived cells, possibly macrophages, in CCR2-dependent events that regulate effective skeletal muscle regeneration.Sun, D., Martinez, C. O., Ochoa, O., Ruiz-Willhite, L., Bonilla, J. R., Centonze, V. E., Waite, L. L., Michalek, J. E., McManus, L. M., Shireman, P. K. Bone marrow-derived cell regulation of skeletal muscle regeneration. PMID:18827026

  6. Bone Marrow Transplantation for Recessive Dystrophic Epidermolysis Bullosa

    PubMed Central

    Wagner, John E.; Ishida-Yamamoto, Akemi; McGrath, John A.; Hordinsky, Maria; Keene, Douglas R.; Riddle, Megan J.; Osborn, Mark J.; Lund, Troy; Dolan, Michelle; Blazar, Bruce R.; Tolar, Jakub

    2010-01-01

    Background Recessive dystrophic epidermolysis bullosa is an incurable, often fatal mucocutaneous blistering disease caused by mutations in COL7A1, the gene encoding type VII collagen (C7). On the basis of preclinical data showing biochemical correction and prolonged survival in col7?/? mice, we hypothesized that allogeneic marrow contains stem cells capable of ameliorating the manifestations of recessive dystrophic epidermolysis bullosa in humans. Methods Between October 2007 and August 2009, we treated seven children who had recessive dystrophic epidermolysis bullosa with immunomyeloablative chemotherapy and allogeneic stem-cell transplantation. We assessed C7 expression by means of immunofluorescence staining and used transmission electron microscopy to visualize anchoring fibrils. We measured chimerism by means of competitive polymerase-chain-reaction assay, and documented blister formation and wound healing with the use of digital photography. Results One patient died of cardiomyopathy before transplantation. Of the remaining six patients, one had severe regimen-related cutaneous toxicity, with all having improved wound healing and a reduction in blister formation between 30 and 130 days after transplantation. We observed increased C7 deposition at the dermalepidermal junction in five of the six recipients, albeit without normalization of anchoring fibrils. Five recipients were alive 130 to 799 days after transplantation; one died at 183 days as a consequence of graft rejection and infection. The six recipients had substantial proportions of donor cells in the skin, and none had detectable anti-C7 antibodies. Conclusions Increased C7 deposition and a sustained presence of donor cells were found in the skin of children with recessive dystrophic epidermolysis bullosa after allogeneic bone marrow transplantation. Further studies are needed to assess the long-term risks and benefits of such therapy in patients with this disorder. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00478244.) PMID:20818854

  7. Leukemia cells induce changes in human bone marrow stromal cells

    PubMed Central

    2013-01-01

    Background Bone marrow stromal cells (BMSCs) are multipotent cells that support angiogenesis, wound healing, and immunomodulation. In the hematopoietic niche, they nurture hematopoietic cells, leukemia, tumors and metastasis. BMSCs secrete of a wide range of cytokines, growth factors and matrix proteins which contribute to the pro-tumorigenic marrow microenvironment. The inflammatory cytokines IFN-? and TNF-? change the BMSC secretome and we hypothesized that factors produced by tumors or leukemia would also affect the BMSC secretome and investigated the interaction of leukemia cells with BMSCs. Methods BMSCs from healthy subjects were co-cultured with three myeloid leukemia cell lines (TF-1, TF-1? and K562) using a trans-well system. Following co-culture, the BMSCs and leukemia cells were analyzed by global gene expression analysis and culture supernatants were analyzed for protein expression. As a control, CD34+ cells were also cocultured with BMSCs. Results Co-culture induced leukemia cell gene expression changes in stem cell pluripotency, TGF-? signaling and carcinoma signaling pathways. BMSCs co-cultured with leukemia cells up-regulated a number of proinflammatory genes including IL-17 signaling-related genes and IL-8 and CCL2 levels were increased in co-culture supernatants. In contrast, purine metabolism, mTOR signaling and EIF2 signaling pathways genes were up-regulated in BMSCs co-cultured with CD34+ cells. Conclusions BMSCs react to the presence of leukemia cells undergoing changes in the cytokine and chemokine secretion profiles. Thus, BMSCs and leukemia cells both contribute to the creation of a competitive niche more favorable for leukemia stem cells. PMID:24304929

  8. Micrometastatic bone marrow involvement: detection and prognostic significance.

    PubMed

    Braun, S; Pantel, K

    1999-09-01

    The present review focuses on the methodology and clinical significance of new diagnostic approaches to identify individual cancer cells present in bone marrow, both as a frequent site of metastasis formation and an indicator organ for hematogenous tumor cell dissemination. The steadily increasing number of studies on this issue is characterized by considerable methodological variations of important variables, such as the size of the study population, and the reliability of monoclonal antibodies used for tumor cell detection. Emerging data indicate that this disturbing heterogeneity might be overcome by the use of reliable and specific anti-cytokeratin antibodies (for example, A45-B/B3) as, for the time, standard markers for the detection of micrometastatic tumor cells in bone marrow. Prospective clinical studies have shown that immunoassays based on anti-CK antibodies identify patients' subgroups with a poor clinical prognosis with regard to early metastasis manifestation and reduced overall survival in various epithelial tumor entities, including breast, colon, rectum, stomach, esophagus, prostate, renal, bladder, and non-small cell lung cancer. The immunocytochemical assays may be therefore used to improve tumor staging with potential consequences for adjuvant therapy, because disseminated cells appeared to be dormant, non-cycling (for example Ki-67 antigen-negative) cells, suggesting a resistance to cell-cycle dependent therapy, such as chemotherapy. Therefore, cell-cycle independent antibody-based immunotherapy might be an interesting option to complement chemotherapy. Another promising clinical application is monitoring the response of micrometastatic cells to adjuvant therapies, which, at present, can only be assessed retrospectively after an extended period of clinical follow-up. The outlined current strategies for detection and characterization of cancer micrometastasis might help to design and control new therapeutic strategies for secondary prevention of metastatic relapse in patients with operable primary carcinomas. PMID:10523795

  9. MSC Therapy Attenuates Obliterative Bronchiolitis after Murine Bone Marrow Transplant

    PubMed Central

    Raza, Kashif; Price, Andrew P.; Meyer, Carolyn; Matson, Amy; Ehrhardt, Michael J.; Fogas, Samuel; Tolar, Jakub; Hertz, Marshall I.; Panoskaltsis-Mortari, Angela

    2014-01-01

    Rationale Obliterative bronchiolitis (OB) is a significant cause of morbidity and mortality after lung transplant and hematopoietic cell transplant. Mesenchymal stromal cells (MSCs) have been shown to possess immunomodulatory properties in chronic inflammatory disease. Objective Administration of MSCs was evaluated for the ability to ameliorate OB in mice using our established allogeneic bone marrow transplant (BMT) model. Methods Mice were lethally conditioned and received allogeneic bone marrow without (BM) or with spleen cells (BMS), as a source of OB-causing T-cells. Cell therapy was started at 2 weeks post-transplant, or delayed to 4 weeks when mice developed airway injury, defined as increased airway resistance measured by pulmonary function test (PFT). BM-derived MSC or control cells [mouse pulmonary vein endothelial cells (PVECs) or lung fibroblasts (LFs)] were administered. Route of administration [intratracheally (IT) and IV] and frequency (every 1, 2 or 3 weeks) were compared. Mice were evaluated at 3 months post-BMT. Measurements and Main Results No ectopic tissue formation was identified in any mice. When compared to BMS mice receiving control cells or no cells, those receiving MSCs showed improved resistance, compliance and inspiratory capacity. Interim PFT analysis showed no difference in route of administration. Improvements in PFTs were found regardless of dose frequency; but once per week worked best even when administration began late. Mice given MSC also had decreased peribronchiolar inflammation, lower levels of hydroxyproline (collagen) and higher frequencies of macrophages staining for the alternatively activated macrophage (AAM) marker CD206. Conclusions These results warrant study of MSCs as a potential management option for OB in lung transplant and BMT recipients. PMID:25272285

  10. Kinetics of amino acid transport across bone marrow cell membranes

    PubMed Central

    Lin, Max S.; Winchell, H. Saul

    1970-01-01

    Dog bone marrow nucleated cells were incubated in media containing labeled L-amino acids, and the cellular accumulation of radioactivity as a function of time was measured and analyzed according to a three-compartment model. (a) The turnover half-time of intracellular histidine arising from extracellular sources was 6.0 0.7 (SEM) min. Similar turnover half-time for serine was 10 2 (SEM) min; for tryptophan, 6.5 1.2 (SEM) min; and for methionine, 4.4 0.6 (SEM) min. Loss of the intracellular amino acids to the extracellular space accounted for the major portion of their turnover. (b) Each of the four amino acids noted above appeared to be actively transported into the cell. (c) At physiologic extracellular histidine concentrations, histidine entered the cell predominantly by a facilitated process with an apparent Michaelis constant of 0.28 mmole/liter and a limiting flux of 14 10-8 m?mole/min per cell. Loss of histidine from the cell appeared to be substantially facilitated with an apparent Michaelis constant greater than that for histidine entry. (d) Insulin and glucagon had no measurable effect on histidine transport across the bone marrow cell membrane. (e) Methionine depressed the influx and the fractional turnover rate of the intracellular pool of both histidine and serine. (f) The extent of cellular accumulation of ?-N-formiminoglutamate and ?-N-formylglutamate was about 1/100 that of histidine. ?-N-formiminoglutamate added to the culture was about as effective as histidine in providing monocarbon fragments for DNA thymine synthesis. PMID:5443176

  11. Qualitative assessment of red blood cell parameters for signs of anemia in patients with chronic periodontitis

    PubMed Central

    Khan, Nubesh S.; Luke, Roji; Soman, Rino Roopak; Krishna, Praveen M.; Safar, Iqbal P.; Swaminathan, Senthil Kumar

    2015-01-01

    Aim: Anemia of chronic disease is defined as anemia occurring in chronic infections and inflammatory conditions that is not caused by marrow deficiencies or other diseases and in the presence of adequate iron stores and vitamins. The present case control study was aimed to assess the red blood cell parameters for signs of anemia in patients with mild, moderate, and severe chronic periodontitis. Materials and Methods: A simple random sampling method was used to select 80 healthy male patients, who were divided into four groups based on full mouth periodontal examination as follows: group I patients comprised the control group (n = 20), which included patients with a clinically healthy periodontium, group II patients (n = 20) were diagnosed with mild chronic periodontitis, group III (n = 20) included moderate chronic periodontitis patients, and patients with severe chronic periodontitis formed group IV (n = 20). Laboratory blood investigations included total number of erythrocytes, hemoglobin concentration, packed cell volume, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. Results: Data analysis showed a statistically significant decrease in red blood cell parameters with increase in different grades of periodontitis. Conclusion: Results of the present study show a substantial decrease in red blood cell parameters with increase in the severity of periodontal destruction. PMID:26759801

  12. Malignant transformation of host stromal ?broblasts derived from the bone marrow traced in a dual-color fluorescence xenograft tumor model.

    PubMed

    Dai, Xingliang; Chen, Hua; Chen, Yanming; Wu, Jinding; Wang, Haiyang; Shi, Jia; Fei, Xifeng; Wang, Zhimin; Wang, Aidong; Dong, Jun; Lan, Qing; Huang, Qiang

    2015-12-01

    Solid tumors are abnormal tissues containing tumor and non-tumor cells, also known as tumor stromal cells. However, the malignant potential of tumor stromal cells remains largely unknown. The aim of the present study was to investigate the malignant potential of host bone marrow?derived stroma cells in transplanted subcutaneous tumors of the glioma stem/progenitor cells (GSPCs) labeled using the dual-color fluorescent tracer technique. The previously established human glioma stem/progenitor cell line SU3 was transfected with red fluorescence protein (SU3-RFP) and transplanted subcutaneously into green fluorescent protein (GFP) transgenic nude mice and chimeric mice in which GFP was only expressed by bone marrow-derived cells (BMDCs). The xenograft tumors were subcultured in vitro and two immortalized GFP-expressing stromal cell lines were cloned from the transplanted tumors. The two cloned cell lines showed an accelerated growth rate, loss of cell contact inhibition, high cloning efficiency, and high DNA content and telocentric (murine) chromosomes with heteroploid characteristics. The tumorigenesis rate (10/10, 1x10(6)) of these host stromal cells was further evidence of malignant transformation. Immunofluorescence assay of the two host cell lines showed that they expressed fibroblast markers such as FAP, S100A4 and ?-SMA, as well as mesenchymal cell markers such as CD44 and CD105. In conclusion, bone marrow-derived stromal ?broblasts recruited to tumors have the potential for malignant transformation induced by the tumor microenvironment, which provides new evidence for the role of the stroma in malignant transformation. PMID:26397840

  13. Red giants: then and now

    NASA Astrophysics Data System (ADS)

    Faulkner, John

    Fred Hoyle's work on the structure and evolution of red giants, particularly his pathbreaking contribution with Martin Schwarzschild (Hoyle and Schwarzschild 1955), is both lauded and critically assessed. In his later lectures and work with students in the early 1960s, Hoyle presented more physical ways of understanding some of the approximations used, and results obtained, in that seminal paper. Although later ideas by other investigators will be touched upon, Hoyle's viewpoint - that low-mass red giants are essentially white dwarfs with a serious mass-storage problem - is still extremely fruitful. Over the years, I have further developed his method of attack. Relatively recently, I have been able to deepen and broaden the approach, finally extending the theory to provide a unifying treatment of the structure of low-mass stars from the main sequence though both the red-giant and horizontal-branch phases of evolution. Many aspects of these stars that had remained puzzling, even mysterious, for decades have now fallen into place, and some questions have been answered that were not even posed before. With low-mass red giants as the simplest example, this recent work emphasizes that stars, in general, may have at least two distinct but very important centres: (I) a geometrical centre, and (II) a separate nuclear centre, residing in a shell outside a zero-luminosity dense core for example. This two-centre perspective leads to an explicit, analytical, asymptotic theory of low-mass red-giant structure. It enables one to appreciate that the problem of understanding why such stars become red giants is one of anticipating a remarkable yet natural structural bifurcation that occurs in them. This bifurcation occurs because of a combination of known and understandable facts just summarized namely that, following central hydrogen exhaustion, a thin nuclear-burning shell does develop outside a more-or-less dense core. In the resulting theory, both ?sh/?olinec and ?sh?olinec prove to be important self-consistently derived quantities. I present some striking, explicit, asymptotic analytical theorems and results involving these quantities. Perhaps the most astonishingly unexpected and gratifying single result is this: for the very value Nature gives us for the relevant temperature exponent (?=15; CNO cycle) for nuclear-energy generation, ?sh and ?olinec behave in a well defined, precisely inverse manner for a given value of core-mass, Mc. This emphasizes that the internal behaviour of such stars is definitely anti-homologous rather than homologous: dense cores physically promote diffuse surrounding envelopes. I also extend the ideas yet further in a way which (I) links the structural and evolutionary behaviour of stars from the main sequence through horizontal-branch phases of evolution, and (II) also has implications for post-main-sequence developments in more massive stars. The end results is that the post-main-sequence developments of all stars - low-mass, intermediate-mass, and high-mass - as they expand to become giants, are finally seen to be examples of one underpinning fact: that dense cores with this surrounding shells naturally follow hydrogen exhaustion. While "this has been know all along" from oft-repeated computer calculations, we now know why analytically. That matters to true theorists. What follows is a requested, much expanded version of my Cambridge talk.

  14. Effect of low benzene exposure on neurobehavioral function, AChE in blood and brain and bone marrow picture in mice

    SciTech Connect

    Sun, W.; Gong, Z.; Li, X. )

    1992-12-01

    The purpose of this study was to examine the effect of low level benzene exposure on neurobehavioral functions, AChE in blood and brain, bone marrow picture in Kunming mice. Forty adult Kunming male mice were divided into 4 groups. They were exposed to 12.52, 3.13, 0.78 and 0 ppm benzene for 2 h.d-1 for 30 d. Central nervous system (CNS) function was inhibited by 12.52 ppm and excited by 0.78 ppm benzene exposure, but irregularly affected by 3.13 ppm. AChE in blood and brain was decreased in 12.52, 3.13 ppm group. The weight of liver to body weight ratios in 12.52 ppm group was higher than those of control group significantly. Bone marrow picture revealed inhibited proliferation of white and red cell systems, especially in 12.52 ppm group, consisting of decrease of percentage of myeloblast, premyelocytes, myelocytes, erythroblasts and megakaryocytes, especially in 12.52 ppm group.

  15. Autologous bone marrow transplantation for acute leukemia using transplant chemopurified with metabolite of oxazaphosphorines (ASTA Z 7557, INN mafosfamide). First clinical results.

    PubMed

    Herv, P; Cahn, J Y; Plouvier, E; Flesch, M; Tamayo, E; Leconte des Floris, R; Peters, A

    1984-01-01

    The contamination of autologous marrow with clonogenic tumor cells has been the main argument against ABMT in acute leukemia. In a preclinical study we evaluated an active cyclophosphamide derivative named "ASTA Z 7557". We observed that the toxic effect of this drug on CFU-GM growth was dependent on nucleated cell concentration as well as on red blood cell contamination. The potency of the drug was in close relationship with the incubation temperature. The growth of leukemic CFU was inhibited with an ASTA Z dose higher than 30 micrograms/ml. In our system, beyond 40 micrograms/ml more than 95% of committed stem cells are destroyed. Fifteen patients had autotransplant because of AML for 10 patients and because of ALL for 5 patients (4 patients were grafted in relapse and 11 patients in remission). We demonstrated that the marrow take was possible although the inoculum is CFU-GM depleted. Five of the 10 AML patients are alive and remain disease-free at 45+, 65+, 190+, 345+ and 570+ days from ABMT without any maintenance treatment. Four of the 5 ALL patients are alive, three of them in complete remission (40+, 110+, 250+ days). The number of patients reported in this clinical study was relatively small and more cases should be evaluated to be conclusive. Nevertheless the feasibility of chemopurified ABMT was demonstrated. PMID:6381384

  16. Staphylococcal enterotoxin C injection in combination with ascorbic acid promotes the differentiation of bone marrow-derived mesenchymal stem cells into osteoblasts in vitro.

    PubMed

    Wan, Xiao-Chen; Liu, Cui-Ping; Li, Meng; Hong, Dun; Li, Dong-Mei; Chen, Hai-Xiao; Li, Ji-Cheng

    2008-09-01

    Staphylococcal enterotoxin C injection is established as a clinical therapy for delayed healing or disunion of bone fractures. In the present study, the effects of staphylococcal enterotoxin C injection in combination with ascorbic acid (SEC-AA) on the differentiation of bone marrow-derived mesenchymal stem cells (MSCs) and their influences on the mineralization of osteoblasts were investigated. SEC-AA treatment induced increased levels of alkaline phosphatase activity in MSCs and increased numbers of alizarin red-stained calcified nodules, indicating enhanced differentiation of MSCs into osteoblasts. The findings demonstrated that SEC-AA promoted the differentiation of MSCs into osteoblasts and accelerated the cytopoiesis of osteoblasts. Our data provide a cytological model for bone fracture therapy aimed at shortening the time required for healing and improving the clinical outcome, and also provide a theoretical basis for inducible differentiation of MSCs, mineralization of osteoblasts and reconstruction of bone tissues. PMID:18572015

  17. Molecular evidence for the localization of Plasmodium falciparum immature gametocytes in bone marrow

    PubMed Central

    Aguilar, Ruth; Magallon-Tejada, Ariel; Achtman, Ariel H.; Moraleda, Cinta; Joice, Regina; Cister, Pau; Li Wai Suen, Connie S. N.; Nhabomba, Augusto; Macete, Eusebio; Mueller, Ivo; Marti, Matthias; Alonso, Pedro L.; Menndez, Clara; Schofield, Louis

    2014-01-01

    Plasmodium falciparum immature gametocytes are not observed in peripheral blood. However, gametocyte stages in organs such as bone marrow have never been assessed by molecular techniques, which are more sensitive than optical microscopy. We quantified P falciparum sexual stages in bone marrow (n = 174) and peripheral blood (n = 70) of Mozambican anemic children by quantitative polymerase chain reaction targeting transcripts specific for early (PF14_0748; PHISTa), intermediate (PF13_0247; Pfs48/45), and mature (PF10_0303; Pfs25) gametocytes. Among children positive for the P falciparum housekeeping gene (PF08_0085; ubiquitin-conjugating enzyme gene) in bone marrow (n = 136) and peripheral blood (n = 25), prevalence of immature gametocytes was higher in bone marrow than peripheral blood (early: 95% vs 20%, P < .001; intermediate: 80% vs 16%; P < .001), as were transcript levels (P < .001 for both stages). In contrast, mature gametocytes were more prevalent (100% vs 51%, P < .001) and abundant (P < .001) in peripheral blood than in the bone marrow. Severe anemia (3.57, 95% confidence interval 1.49-8.53) and dyserythropoiesis (6.21, 95% confidence interval 2.24-17.25) were independently associated with a higher prevalence of mature gametocytes in bone marrow. Our results highlight the high prevalence and abundance of early sexual stages in bone marrow, as well as the relationship between hematological disturbances and gametocyte development in this tissue. PMID:24335496

  18. Quantitative observations on iliac bone marrow mast cells in chronic renal failure.

    PubMed Central

    Peart, K M; Ellis, H A

    1975-01-01

    Mast cells have been counted in sections of iliac bone from 61 control subjects at necropsy. Mast cells were found in all but three, and the range was 0-33-7, median 1-95 per mm2 marrow. The majority (82%) had less than 4-99 mast cells per mm2 marrow; in 37-7% there was less than 1 mast cell per mm2 marrow. In a group of 45 patients with chronic renal failure there was a significant increase in the numbers of mast cells (P less than 0-001) with a range of 0-96-55-63, median 9-55 per mm2 marrow. Mast cells were common in the areas of marrow fibrosis associated with osteitis fibrosa but this was not the sole cause of the increase since there was also an excess of mast cells in the non-fibrous parts of the marrow. There was a tendency towards greater numbers of mast cells in those cases with most marked osteitis fibrosa in association with the prominent marrow fibrosis, but there was no significant relationship between mast cell numbers and other features of oesteitis fibrosa such as the number of osteoclasts and the amount of woven bone formation. There was no relationship between the numbers of mast cells and the amounts of total bone, ostoid, percentage mineralization of cancellous bone, or the presence of osteomalacia. PMID:1206118

  19. Effects of ionizing radiation on differentiation of murine bone marrow cells into mast cells.

    PubMed

    Murakami, Sho; Yoshino, Hironori; Ishikawa, Junya; Yamaguchi, Masaru; Tsujiguchi, Takakiyo; Nishiyama, Ayaka; Yokoyama, Kouki; Kashiwakura, Ikuo

    2015-11-01

    Mast cells, immune effector cells produced from bone marrow cells, play a major role in immunoglobulin E-mediated allergic responses. Ionizing radiation affects the functions of mast cells, which are involved in radiation-induced tissue damage. However, whether ionizing radiation affects the differential induction of mast cells is unknown. Here we investigated whether bone marrow cells of X-irradiated mice differentiated into mast cells. To induce mast cells, bone marrow cells from X-irradiated and unirradiated mice were cultured in the presence of cytokines required for mast cell induction. Although irradiation at 0.5 Gy and 2 Gy decreased the number of bone marrow cells 1 day post-irradiation, the cultured bone marrow cells of X-irradiated and unirradiated mice both expressed mast cell-related cell-surface antigens. However, the percentage of mast cells in the irradiated group was lower than in the unirradiated group. Similar decreases in the percentage of mast cells induced in the presence of X-irradiation were observed 10 days post irradiation, although the number of bone marrow cells in irradiated mice had recovered by this time. Analysis of mast cell function showed that degranulation of mast cells after immunoglobulin E-mediated allergen recognition was significantly higher in the X-irradiated group compared with in the unirradiated group. In conclusion, bone marrow cells of X-irradiated mice differentiated into mast cells, but ionizing radiation affected the differentiation efficiency and function of mast cells. PMID:26453633

  20. Role of T cells in sex differences in syngeneic bone marrow transfers

    SciTech Connect

    Raveche, E.S.; Santoro, T.; Brecher, G.; Tjio, J.H.

    1985-11-01

    Transferred marrow cells will proliferate in normal mice not exposed to irradiation or any other type of stem cell depletion when five consecutive transfers of 40 million cells are given. Approximately 25% of the mitotic cells are of male donor origin observed cytogenetically in all of the female recipient spleens and marrow analyzed from two weeks to one and one-half years after transfusions. Male donor stem cells are accepted and form a stable component of the self-renewing stem cell pool. In contrast, only 5% female cells are found in male recipients. This sex difference in engraftment is not hormonal since castration of recipients does not alter the percentage of donor cells. Rigorous T depletion of female donor bone marrow, however, increases the percentage of donor engraftment to the level observed when male marrow, either whole or T depleted, is transferred to female recipients. The success of T-depleted female stem cells to seed male recipients is observed in both C57BL/6 and CBA/J. In addition, recipient nude BALB/c males, which lack a thymus, fail to accept whole bone marrow from BALB/c females. However, male bone marrow cells seed BALB/c nude females. These studies demonstrate that the poor engraftment of female cells in transfused male recipients is abrogated by the removal of T cells from the donor female marrow.

  1. Bone Marrow Recovery by Morphometry during Induction Chemotherapy for Acute Lymphoblastic Leukemia in Children

    PubMed Central

    Nguyen, Tuong-Vi; Melville, Anna; Nath, Shriram; Story, Colin; Howell, Stuart; Sutton, Rosemary; Zannettino, Andrew; Revesz, Tamas

    2015-01-01

    Bone marrow architecture is grossly distorted at the diagnosis of ALL and details of the morphological changes that accompany response to Induction chemotherapy have not been reported before. While marrow aspirates are widely used to assess initial response to ALL therapy and provide some indications, we have enumerated marrow components using morphometric analysis of trephine samples with the aim of achieving a greater understanding of changes in bone marrow niches. Morphometric analyses were carried out in the bone marrow trephine samples of 44 children with ALL, using a NanoZoomer HT digital scanner. Diagnostic samples were compared to those of 32 control patients with solid tumors but without marrow involvement. Samples from patients with ALL had significantly increased fibrosis and the area occupied by bony trabeculae was lower than in controls. Cellularity was higher in ALL samples due to leukemic infiltration while the percentage of normal elements such as megakaryocytes, adipocytes, osteoblasts and osteoclasts were all significantly lower. During the course of Induction therapy, there was a decrease in the cellularity of ALL samples at day 15 of therapy with a further decrease at the end of Induction and an increase in the area occupied by adipocytes and the width of sinusoids. Reticulin fibrosis decreased throughout Induction. Megakaryocytes increased, osteoblasts and osteoclasts remained unchanged. No correlation was found between clinical presentation, early response to treatment and morphological changes. Our results provide a morphological background to further studies of bone marrow stroma in ALL. PMID:25962143

  2. Cytokeratin-positive cells in the bone marrow of breast cancer patients and noncancer donors.

    PubMed

    Krag, David N; Kusminsky, Roberto; Manna, Edward; Weaver, Donald; Harlow, Seth P; Covelli, Michael; Stanley, Mary A; McCahill, Laurence; Ittleman, Frank; Leavitt, Bruce; Krag, Martin; Amarante, Patricia

    2009-10-01

    Detection of disseminated tumor cells in the bone marrow may provide important prognostic information in breast cancer patients. With few exceptions the number of stained cells scored as cancer is very low; there may be only 1 cell per slide. This makes definitive interpretation of cancer in marrow challenging. False-positive staining of marrow cells with cytokeratin (CK) antibody is relatively common and makes interpretation more difficult. In this report we focus on false-positive staining of marrow specimens from breast cancer patients and noncancer controls and demonstrate that the frequency of false-positive events is common. Bone marrow was collected from 23 cancer-free donors and 60 breast cancer patients. Samples were processed by Ficoll density gradient centrifugation and slides were prepared for immunocytochemical staining with CK and irrelevant (IR) antibody. Slides were evaluated manually and positive cells were categorized as tumor cells, hematopoetic cells, or questionable cells. False-positive staining events were commonly observed in noncancer cases stained with CK or IR antibodies and in breast cancer cases stained with IR antibody. There was little difference in the number of breast cancer marrow specimens scored as tumor cells regardless of whether the antibody used was CK or IR. It is important to devise improved criteria and methods for accurate detection and interpretation of disseminated tumor cells in the marrow of breast cancer patients. PMID:19417625

  3. In vivo cell kinetics of the bone marrow transplantation using dual colored transgenic rat system

    NASA Astrophysics Data System (ADS)

    Kai, Kotaro; Teraoka, Satoshi; Adachi, Yasushi; Ikehara, Susumu; Murakami, Takashi; Kobayashi, Eiji

    2008-02-01

    Because bone marrow is an adequate site for bone marrow stem cells, intra-bone marrow - bone marrow transplantation (IBM-BMT) is an efficient strategy for bone marrow transplantation (BMT). However, the fate of the transplanted cells remains unclear. Herein, we established a dual-colored transgenic rat system utilizing green fluorescent protein (GFP) and a luciferase (luc) marker. We then utilized this system to investigate the in vivo kinetics of transplanted bone marrow cells (BMCs) after authentic intravenous (IV)-BMT or IBM-BMT. The in vivo fate of the transplanted cells was tracked using an in vivo luminescent imaging technique; alterations in peripheral blood chimerism were also followed using flow cytometry. IBM-BMT and IV-BMT were performed using syngeneic and allogeneic rat combinations. While no difference in the proliferation pattern was observed between the two treatment groups at 7 days after BMT, different distribution patterns were clearly observed during the early phase. In the IBM-BMT-treated rats, the transplanted BMCs were engrafted immediately at the site of the injected bone marrow and expanded more rapidly than in the IV-BMT-treated rats during this phase. Graft-versus-host disease was also visualized. Our bio-imaging system using dual-colored transgenic rats is a powerful tool for performing quantitative and morphological assessments in vivo.

  4. The cultivation of bone marrow mesenchymal stem cells derived from patients with high altitude polycythemia.

    PubMed

    Zheng, J; Guo, N; Xi, Y; Li, H-Q; Zhang, H; Ji, L-H; Cui, S; Li, Z-Q

    2015-01-01

    The aim of this study was to isolate and culture bone marrow mesenchymal stem cells (MSCs) from patients with high altitude polycythemia (HAPC) in order to provide a foundation for further exploration of their biological characteristics. MSCs were isolated and cultured from 10 HAPC patients and 10 healthy controls by using a density gradient centrifugation and an adherent screening method. The morphous of MSCs were observed under an inverted microscope, and its surface antigens were determined using flow cytometry. The growth of the MSCs was also detected to evaluate its proliferation. Bone marrow mononuclear cells were isolated from the bone marrow using a density gradient centrifugation, and they were cultured in vitro. The bone marrow MSCs were successfully isolated and cultured, which presented as fusiform and adherent cells. The MSCs in both groups expressed CD90,CD44,CD29,CD105, CD106, CD146, CD166,Stro1 and CD13, but they did not express CD45, CD4,CD8,CD19,CD20,CD80,CD14,CD3,CD34 or HLADR (P>0.05). The bone marrow MSCs from HAPC patients had a higher proliferation than the bone marrow MSCs from the healthy controls (P<0.01). The bone marrow MSCs from HAPC patients can be effectively cultured in vitro. PMID:25817341

  5. [Evaluation of bone marrow by opposed phase T1-weighted images and enhanced MR imaging].

    PubMed

    Amano, Y; Tanabe, Y; Miyashita, T; Hayashi, H; Horiuchi, J; Nomura, T; Kumazaki, T

    1994-09-25

    We investigated bone marrow in a control group, cases of aplastic anemia and post-irradiation patients by examining T1-weighted (T1WI), short TI inversion recovery (STIR), opposed phase T1WI (op-T1WI) and Gd-DTPA enhanced op-T1WI images obtained by 0.5T MRI. Bone marrow was classified into four types based on MR findings. Normal marrow showed low intensity on op-T1WI and STIR images without enhancement (I). Fatty marrow, which showed high intensity on T1WI and op-T1WI images was observed in aplastic anemia and post-irradiation patients (II). Hematopoietic marrow (III) showed low intensity on op-T1WI and enhanced, while active hematopoietic marrow (IV) revealed high intensity on both STIR and op-T1WI images and was enhanced following Gd-DTPA infusion. Aplastic anemia of moderate grade included types II, III and IV. Enhanced MR was needed to differentiate between types I and III since both types showed low intensity on op-T1WI images. Furthermore, type IV was considered as hyperplastic compared with type III. Enhanced MR and op-T1WI images were useful in evaluating hematopoiesis of bone marrow. PMID:7971187

  6. Effects of ionizing radiation on differentiation of murine bone marrow cells into mast cells

    PubMed Central

    Murakami, Sho; Yoshino, Hironori; Ishikawa, Junya; Yamaguchi, Masaru; Tsujiguchi, Takakiyo; Nishiyama, Ayaka; Yokoyama, Kouki; Kashiwakura, Ikuo

    2015-01-01

    Mast cells, immune effector cells produced from bone marrow cells, play a major role in immunoglobulin Emediated allergic responses. Ionizing radiation affects the functions of mast cells, which are involved in radiation-induced tissue damage. However, whether ionizing radiation affects the differential induction of mast cells is unknown. Here we investigated whether bone marrow cells of X-irradiated mice differentiated into mast cells. To induce mast cells, bone marrow cells from X-irradiated and unirradiated mice were cultured in the presence of cytokines required for mast cell induction. Although irradiation at 0.5 Gy and 2 Gy decreased the number of bone marrow cells 1 day post-irradiation, the cultured bone marrow cells of X-irradiated and unirradiated mice both expressed mast cellrelated cell-surface antigens. However, the percentage of mast cells in the irradiated group was lower than in the unirradiated group. Similar decreases in the percentage of mast cells induced in the presence of X-irradiation were observed 10 days post irradiation, although the number of bone marrow cells in irradiated mice had recovered by this time. Analysis of mast cell function showed that degranulation of mast cells after immunoglobulin Emediated allergen recognition was significantly higher in the X-irradiated group compared with in the unirradiated group. In conclusion, bone marrow cells of X-irradiated mice differentiated into mast cells, but ionizing radiation affected the differentiation efficiency and function of mast cells. PMID:26453633

  7. Age-related Marrow Adipogenesis Is Linked to Increased Expression of RANKL*

    PubMed Central

    Takeshita, Sunao; Fumoto, Toshio; Naoe, Yoshinori; Ikeda, Kyoji

    2014-01-01

    With advancing age bone marrow is progressively replaced with adipose tissue, accompanied by a concomitant decline in bone mass and strength. The mechanism underlying the increase in marrow fat and bone destruction remains elusive. We found that on the way of adipogenic differentiation of marrow stromal cells, receptor activator for NF-κB ligand (Rankl) expression was induced, concomitantly with a down-regulation of osteoprotegerin, which prompted us to hypothesize that cells at a preadipocyte stage express RANKL. This concept was supported by the findings that the early adipogenic transcription factors C/EBPβ and C/EBPδ, but not the late factor peroxisome proliferator-activated receptor γ, bind to the Rankl promoter and stimulate Rankl gene transcription. In fact, when cells isolated from the bone marrow of aging mice were analyzed by flow cytometry, we found that cells expressing the pre-adipocyte marker Pref-1 were RANKL-positive, and the number of these cells was increased with aging, with concomitant down-regulation of osteoprotegerin, and most importantly, that these RANKL+/Pref-1+ marrow cells were capable of generating osteoclasts from bone marrow macrophages. Thus, the capacity of cells at a pre-adipocyte stage to express RANKL via C/EBPβ and C/EBPδ and to support osteoclastogenesis may account partly for the co-progression of fatty marrow and bone destruction with aging. PMID:24753250

  8. An Autologous Bone Marrow Mesenchymal Stem CellDerived Extracellular Matrix Scaffold Applied with Bone Marrow Stimulation for Cartilage Repair

    PubMed Central

    Tang, Cheng; Jin, Chengzhe; Du, Xiaotao; Yan, Chao; Min, Byoung-Hyun; Xu, Yan

    2014-01-01

    Purpose: It is well known that implanting a bioactive scaffold into a cartilage defect site can enhance cartilage repair after bone marrow stimulation (BMS). However, most of the current scaffolds are derived from xenogenous tissue and/or artificial polymers. The implantation of these scaffolds adds risks of pathogen transmission, undesirable inflammation, and other immunological reactions, as well as ethical issues in clinical practice. The current study was undertaken to evaluate the effectiveness of implanting autologous bone marrow mesenchymal stem cellderived extracellular matrix (aBMSC-dECM) scaffolds after BMS for cartilage repair. Methods: Full osteochondral defects were performed on the trochlear groove of both knees in 24 rabbits. One group underwent BMS only in the right knee (the BMS group), and the other group was treated by implantation of the aBMSC-dECM scaffold after BMS in the left knee (the aBMSC-dECM scaffold group). Results: Better repair of cartilage defects was observed in the aBMSC-dECM scaffold group than in the BMS group according to gross observation, histological assessments, immunohistochemistry, and chemical assay. The glycosaminoglycan and DNA content, the distribution of proteoglycan, and the distribution and arrangement of type II and I collagen fibers in the repaired tissue in the aBMSC-dECM scaffold group at 12 weeks after surgery were similar to that surrounding normal hyaline cartilage. Conclusions: Implanting aBMSC-dECM scaffolds can enhance the therapeutic effect of BMS on articular cartilage repair, and this combination treatment is a potential method for successful articular cartilage repair. PMID:24666429

  9. Effects of T cell depletion in radiation bone marrow chimeras. III. Characterization of allogeneic bone marrow cell populations that increase allogeneic chimerism independently of graft-vs-host disease in mixed marrow recipients

    SciTech Connect

    Sykes, M.; Chester, C.H.; Sundt, T.M.; Romick, M.L.; Hoyles, K.A.; Sachs, D.H. )

    1989-12-01

    The opposing problems of graft-vs-host disease vs failure of alloengraftment severely limit the success of allogeneic bone marrow transplantation as a therapeutic modality. We have recently used a murine bone marrow transplantation model involving reconstitution of lethally irradiated mice with mixtures of allogeneic and syngeneic marrow to demonstrate that an allogeneic bone marrow subpopulation, removed by T cell depletion with rabbit anti-mouse brain serum and complement (RAMB/C), is capable of increasing levels of allogeneic chimerism. This effect was observed in an F1 into parent genetic combination lacking the potential for graft-vs-host disease, and radiation protection studies suggested that it was not due to depletion of stem cells by RAMB/C. We have now attempted to characterize the cell population responsible for increasing allogeneic chimerism in this model. The results indicate that neither mature T cells nor NK cells are responsible for this activity. However, an assay involving mixed marrow reconstitution in an Ly-5 congenic strain combination was found to be more sensitive to small degrees of stem cell depletion than radiation protection assays using three-fold titrations of bone marrow cells. Using this assay, we were able to detect some degree of stem cell depletion by treatment with RAMB/C, but not with anti-T cell mAb. Nevertheless, if the effects of alloresistance observed in this model are considered, the degree of stem cell depletion detected by such mixing studies in insufficient to account for the effects of RAMB/C depletion on levels of allogeneic chimerism, suggesting that another cell population with this property remains to be identified.

  10. The possible role of anemia in bone marrow uptake of radiocolloid

    SciTech Connect

    Skarzynski, J.J.; Spencer, R.P.; Karlmeddini, M.K.

    1984-01-01

    Entry of Tc-99m-sulfur colloid into bone marrow is a frequent observation and possible causes have been discussed in the literature. Using a present formulation of the radiocolloid (Medi+Physics), the authors sought to define the distribution patterns of bone marrow uptake, and relate these back to the primary diagnosis. Three hundred consecutive cases (with spleen present) were analyzed. Only 18% of the patients were under age 29 years and 62% were age 50 or older. Posterior images were evaluated so that liver, spleen and bone marrow could be compared visually. Twelve % of the studies were within normal limits. In 33% of the patients, the liver or spleen showed a defect without a radiocolloid shift. In 41% of the cases, there was a shift of radioactivity to the spleen (spleen/liver greater than 1), but not to the bone marrow. In 12% of the patients, there was both a radiocolloid shift to the spleen and visible uptake in the bone marrow. Least common was uptake of radiocolloid in the vertebral bone marrow without a splenic radiocolloid shift: this occurred in only 5 cases (under 2% of the total). Looked at another way the authors can normalize the cases with radiocolloid shift to the spleen (but not elsewhere) to 100%. Then radiocolloid shift to both spleen and bone marrow occurred only 29% as frequently. Radicolloid in the bone marrow, but not shifted to the spleen, was unusual (5% as frequent). These 5 patients were analyzed; all had anemia. The Hb ranged from 7.9 - 10.6 gm/dl, and hematocrits from 23 - 30. Several etiologies were involved. Anemia may be a stimulus to bone marrow uptake of radiocolloid without major splenic accumulation.

  11. CCR2 Regulates the Uptake of Bone Marrow-Derived Fibroblasts in Renal Fibrosis

    PubMed Central

    Xia, Yunfeng; Entman, Mark L.; Wang, Yanlin

    2013-01-01

    Recent studies have shown that bone marrow-derived fibroblasts contribute significantly to the pathogenesis of renal fibrosis. However, the molecular mechanisms underlying the recruitment of bone marrow-derived fibroblasts into the kidney are incompletely understood. Bone marrow-derived fibroblasts express the chemokine receptor - CCR2. In this study, we tested the hypothesis that CCR2 participates in the recruitment of fibroblasts into the kidney during the development of renal fibrosis. Bone marrow-derived collagen-expressing GFP+ fibroblasts were detected in the obstructed kidneys of chimeric mice transplanted with donor bone marrow from collagen ?1(I)-GFP reporter mice. These bone marrow-derived fibroblasts expressed PDGFR-? and CCR2. CCR2 knockout mice accumulated significantly fewer bone marrow-derived fibroblast precursors expressing the hematopoietic marker-CD45 and the mesenchymal markers-PDGFR-? or procollagen I in the obstructed kidneys compared with wild-type mice. Furthermore, CCR2 knockout mice displayed fewer bone marrow-derived myofibroblasts and expressed less ?-SMA or FSP-1 in the obstructed kidneys compared with wild-type mice. Consistent with these findings, genetic deletion of CCR2 inhibited total collagen deposition and suppressed expression of collagen I and fibronectin. Moreover, genetic deletion of CCR2 inhibits MCP-1 and CXCL16 gene expression associated with a reduction of inflammatory cytokine expression and macrophage infiltration, suggesting a linear interaction between two chemokines/ligand receptors in tubular epithelial cells. Taken together, our results demonstrate that CCR2 signaling plays an important role in the pathogenesis of renal fibrosis through regulation of bone marrow-derived fibroblasts. These data suggest that inhibition of CCR2 signaling could constitute a novel therapeutic approach for fibrotic kidney disease. PMID:24130892

  12. Bone marrow infiltration by multiple myeloma causes anemia by reversible disruption of erythropoiesis.

    PubMed

    Bouchnita, Anass; Eymard, Nathalie; Moyo, Tamara K; Koury, Mark J; Volpert, Vitaly

    2016-06-01

    Multiple myeloma (MM) infiltrates bone marrow and causes anemia by disrupting erythropoiesis, but the effects of marrow infiltration on anemia are difficult to quantify. Marrow biopsies of newly diagnosed MM patients were analyzed before and after four 28-day cycles of nonerythrotoxic remission induction chemotherapy. Complete blood cell counts and serum paraprotein concentrations were measured at diagnosis and before each chemotherapy cycle. At diagnosis, marrow area infiltrated by myeloma correlated negatively with hemoglobin, erythrocytes, and marrow erythroid cells. After successful chemotherapy, patients with less than 30% myeloma infiltration at diagnosis had no change in these parameters, whereas patients with more than 30% myeloma infiltration at diagnosis increased all three parameters. Clinical data were used to develop mathematical models of the effects of myeloma infiltration on the marrow niches of terminal erythropoiesis, the erythroblastic islands (EBIs). A hybrid discrete-continuous model of erythropoiesis based on EBI structure/function was extended to sections of marrow containing multiple EBIs. In the model, myeloma cells can kill erythroid cells by physically destroying EBIs and by producing proapoptotic cytokines. Following chemotherapy, changes in serum paraproteins as measures of myeloma cells and changes in erythrocyte numbers as measures of marrow erythroid cells allowed modeling of myeloma cell death and erythroid cell recovery, respectively. Simulations of marrow infiltration by myeloma and treatment with nonerythrotoxic chemotherapy demonstrate that myeloma-mediated destruction and subsequent reestablishment of EBIs and expansion of erythroid cell populations in EBIs following chemotherapy provide explanations for anemia development and its therapy-mediated recovery in MM patients. Am. J. Hematol. 91:371-378, 2016. © 2016 Wiley Periodicals, Inc. PMID:26749142

  13. Anticonvulsant activity of bone marrow cells in electroconvulsive seizures in mice

    PubMed Central

    2013-01-01

    Background Bone marrow is an accessible source of progenitor cells, which have been investigated as treatment for neurological diseases in a number of clinical trials. Here we evaluated the potential benefit of bone marrow cells in protecting against convulsive seizures induced by maximum electroconvulsive shock (MES), a widely used model for screening of anti-epileptic drugs. Behavioral and inflammatory responses were measured after MES induction in order to verify the effects promoted by transplantation of bone marrow cells. To assess the anticonvulsant effects of bone marrow cell transplantation, we measured the frequency and duration of tonic seizure, the mortality rate, the microglial expression and the blood levels of cytokine IL-1, IL-6, IL-10 and TNF-α after MES induction. We hypothesized that these behavioral and inflammatory responses to a strong stimulus such as a convulsive seizure could be modified by the transplantation of bone marrow cells. Results Bone marrow transplanted cells altered the convulsive threshold and showed anticonvulsant effect by protecting from tonic seizures. Bone marrow cells modified the microglial expression in the analyzed brain areas, increased the IL-10 and attenuate IL-6 levels. Conclusions Bone marrow cells exert protective effects by blocking the course of electroconvulsive seizures. Additionally, electroconvulsive seizures induced acute inflammatory responses by altering the pattern of microglia expression, as well as in IL-6 and IL-10 levels. Our findings also indicated that the anticonvulsant effects of these cells can be tested with the MES model following the same paradigm used for drug testing in pharmacological screening. Studies on the inflammatory reaction in response to acute seizures in the presence of transplanted bone marrow cells might open a wide range of discussions on the mechanisms relevant to the pathophysiology of epilepsies. PMID:24011127

  14. JAK3/STAT6 Stimulates Bone Marrow-Derived Fibroblast Activation in Renal Fibrosis.

    PubMed

    Yan, Jingyin; Zhang, Zhengmao; Yang, Jun; Mitch, William E; Wang, Yanlin

    2015-12-01

    Renal fibrosis is a final common manifestation of CKD resulting in progressive loss of kidney function. Bone marrow-derived fibroblast precursors contribute significantly to the pathogenesis of renal fibrosis. However, the signaling mechanisms underlying the activation of bone marrow-derived fibroblast precursors in the kidney are not fully understood. In this study, we investigated the role of the Janus kinase 3 (JAK3)/signal transducer and activator of transcription (STAT6) signaling pathway in the activation of bone marrow-derived fibroblasts. In cultured mouse monocytes, IL-4 or IL-13 activated STAT6 and induced expression of ?-smooth muscle actin and extracellular matrix proteins (fibronectin and collagen I), which was abolished by a JAK3 inhibitor (CP690,550) in a dose-dependent manner or blocked in the absence of STAT6. In vivo, STAT6 was activated in interstitial cells of the obstructed kidney, an effect that was abolished by CP690,550. Mice treated with CP690,550 accumulated fewer bone marrow-derived fibroblasts in the obstructed kidneys compared with vehicle-treated mice. Treatment with CP690,550 also significantly reduced myofibroblast transformation, matrix protein expression, fibrosis development, and apoptosis in obstructed kidneys. Furthermore, STAT6-deficient mice accumulated fewer bone marrow-derived fibroblasts in the obstructed kidneys, produced less extracellular matrix protein, and developed much less fibrosis. Finally, wild-type mice engrafted with STAT6(-/-) bone marrow cells displayed fewer bone marrow-derived fibroblasts in the obstructed kidneys and showed less severe renal fibrosis compared with wild-type mice engrafted with STAT6(+/+) bone marrow cells. Our results demonstrate that JAK3/STAT6 has an important role in bone marrow-derived fibroblast activation, extracellular matrix production, and interstitial fibrosis development. PMID:26032813

  15. Red is romantic, but only for feminine females: sexual dimorphism moderates red effect on sexual attraction.

    PubMed

    Wen, Fangfang; Zuo, Bin; Wu, Yang; Sun, Shan; Liu, Ke

    2014-01-01

    Previous researchers have documented that the color red enhances one's sexual attraction to the opposite sex. The current study further examined the moderating role of sexual dimorphism in red effects. The results indicated that red enhanced men's sexual attraction to women with more feminine facial characteristics but had no effect on ratings of perceived general attractiveness. Red clothing also had a marginally significant effect on men's sexual attractiveness. In addition, regardless of sexual dimorphism cues, male participants rated women with red as warmer and more competent. The underlying mechanisms of the red effect, the limitations of the current study, and suggestions for future directions are discussed. PMID:25300050

  16. Still from Red Spot Movie

    NASA Technical Reports Server (NTRS)

    2000-01-01

    This image is one of seven from the narrow-angle camera on NASA's Cassini spacecraft assembled as a brief movie of cloud movements on Jupiter. It was taken with a blue filter. The smallest features visible are about 500 kilometers (about 300 miles) across.

    Small bright clouds appear suddenly to the west of the Great Red Spot. Based on data from NASA's Galileo spacecraft, scientists suspect that these small white features are lightning storms, where falling raindrops create an electrical charge. The lightning storms eventually merge with the Red Spot and surrounding jets, and may be the main energy source for these large-scale features. Imaging observations of the darkside of the planet in the weeks following Cassini's closest approach to Jupiter on Dec. 30, 2000 will search for lightning storms like these.

    This image was re-projected by cylindrical-map projection of an image taken in the first week of October 2000. It shows an area from 50 degrees north of Jupiter's equator to 50 degrees south, extending 100 degrees east west, about one quarter of Jupiter's circumference.

    Cassini is a cooperative project of NASA, the European Space Agency and the Italian Space Agency. The Jet Propulsion Laboratory, a division of the California Institute of Technology in Pasadena, manages the Cassini mission for NASA's Office of Space Science, Washington, D.C.

  17. Bone marrow-derived mesenchymal stem cells effectively regenerate fibrotic liver in bile duct ligation rat model.

    PubMed

    Mohamed, Hoda E; Elswefy, Sahar E; Rashed, Laila A; Younis, Nahla N; Shaheen, Mohamed A; Ghanim, Amal Mh

    2016-03-01

    Mesenchymal stem cells (MSCs) have attracted lots of attention for the treatment of acute liver failure and end-stage liver diseases. This study aimed at investigating the fundamental mechanism by which bone marrow-derived MSCs (BM-MSCs) induce liver regeneration of fibrotic liver in rats. Rats underwent bile duct ligation (BDL) surgery and four weeks later they were treated with either BM-MSCs (3 × 10(6) cells /rat, once, tail vein injection) or silymarin (100 mg/kg, daily, orally) for four weeks. Liver function tests and hepatic oxidative stress were determined. Hepatic injury and fibrosis were assessed by H and E, Sirus red staining and immunohistochemical expression of α-smooth muscle actin (α-SMA). Hepatocyte growth factor (HGF) and the gene expression of cytokeratin-19 (CK-19) and matrix metalloproteinase-2 (MMP-2) in liver tissue were determined. BDL induced cholestatic liver injury characterized by elevated ALT and AST activities, bilirubin and decreased albumin. The architecture damage was staged as Metavir score: F3, A3. Fibrosis increased around proliferating bile duct as indicated by sirus red staining and α-SMA immunostaining. Fibrogenesis was favored over fibrolysis and confirmed by decreased HGF with increased expression of CK-19, but decreased MMP-2 expression. BM-MSCs treatment restored deteriorated liver functions and restored the histological changes, resolved fibrosis by improving liver regenerative capabilities (P < 0.001), increases in HGF and MMP-2 mRNA and downregulating CK-19 mRNA. Sliymarin, however, induced similar but less prominent effects compared to BM-MSCs. In conclusion, liver regenerative capabilities can be stimulated by BM-MSCs via augmentation of HGF that subsequently up-regulate MMP-2 mRNA while downregulating CK-19 mRNA. PMID:26811102

  18. Isolation of adipose and bone marrow mesenchymal stem cells using CD29 and CD90 modifies their capacity for osteogenic and adipogenic differentiation

    PubMed Central

    Cooper, Paul R; Shelton, Richard M; Smith, Anthony J; Scheven, Ben A

    2015-01-01

    Mesenchymal stem cells isolated from rats are frequently used for tissue engineering research. However, considerable differences have been identified between rat mesenchymal stem cells and those derived from humans, and no defined panel of markers currently exists for the isolation of these cells. The aim of this study was to examine the effects of cell sorting for CD29+/CD90+ cells from rat adipose and bone marrow tissues on their differentiation and expression of stem cell–associated genes. Flow cytometry showed 66% and 78% CD29+/CD90+ positivity within passage 1 of adipose and bone marrow cultures, respectively. CD29+/CD90+ cells showed a reduction in both osteogenic and adipogenic differentiation when compared with unsorted cells, as determined by alizarin red and Oil Red-O staining, respectively. These findings could not entirely be explained by fluorescence-activated cell sorting–induced cell injury as sort recovery was only modestly affected in adipose-derived cells. Maintaining cells in fluorescence-activated cell sorting buffer did not affect adipose-derived cell viability, but a significant (p < 0.05) reduction was found in bone marrow–derived cell viability. Additionally, CD29+/CD90+ selection was associated with a significant decrease in the expression of Lin28, Sox2, Nanog and CD73 in adipose-derived cell cultures, whereas differences in stem cell–associated gene expression were not observed in sorted bone marrow–derived cell cultures. In summary, this study demonstrated that fluorescence-activated cell sorting had differential effects on adipose-derived cells and bone marrow–derived cells, and both CD29+/CD90+ cells displayed a significantly reduced capacity for osteogenic/adipogenic differentiation. In conclusion, we identify that maintaining heterogeneity within the mesenchymal stem cell population may be important for optimal differentiation. PMID:26380065

  19. Methyl-substitution of benzene and toluene in preparations of human bone marrow

    SciTech Connect

    Flesher, J.W.; Myers, S.R. )

    1991-01-01

    The metabolism of benzene and toluene was investigated in preparations of human bone marrow incubated with S-adenosyl-L-methionine. Benzene undergoes a methyl-substitution reaction to yield toluene as a metabolite. Furthermore, toluene undergoes methyl-substitution in preparations of human bone marrow incubated with S-adenosyl-L-methionine to yield o-xylene, m-xylene, and p-xylene. Metabolites were detected by gas chromatography and mass spectroscopy. No metabolism of either benzene or toluene was detected when a boiled bone marrow preparation was used in the incubation, demonstrating the enzymatic nature of the S-adenosyl-L-methionine dependent methylation of both benzene and toluene.

  20. Selective resistance of bone marrow-derived hemopoietic progenitor cells to gliotoxin

    SciTech Connect

    Muellbacher, A.; Hume, D.; Braithwaite, A.W.; Waring, P.; Eichner, R.D.

    1987-06-01

    The fungal metabolite gliotoxin at low concentrations prevents mitogen stimulation of mature lymphocytes as a result of gliotoxin-induced genomic DNA degradation. Bone marrow, on the other hand, contains a subpopulation of cells resistant to gliotoxin at similar concentrations. This population includes the hemopoietic progenitor cells that grow in vitro in response to appropriate colony-stimulating factors and cells that form colonies in the spleens of lethally irradiated recipients. Gliotoxin treatment of lymph node cell-enriched bone marrow significantly delayed the onset of graft-versus-host disease in fully allogeneic bone marrow chimeras.