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Sample records for red marrow 131ina

  1. Mesenchymal progenitor cells in red and yellow bone marrow.

    PubMed

    Gurevitch, O; Slavin, S; Resnick, I; Khitrin, S; Feldman, A

    2009-01-01

    Marrow cavities in all bones of newborn mammals contain haematopoietic tissue and stromal microenvironment that support haematopoiesis (haematopoietic microenvironment), known as red bone marrow (BM). From the early postnatal period onwards, the haematopoietic microenvironment, mainly in tubular bones of the extremities, is replaced by mesenchymal cells that accumulate lipid drops, known as yellow BM, whereas haematopoietic tissue gradually disappears. We analysed the ability of mesenchymal cell progenitors in red and yellow BM to produce bone and haematopoietic microenvironment in vivo after transplantation into normal or haematopoietically deficient (irradiated and old) recipients. We found that (1) normal substitution of red with yellow BM results from a gradual loss of mesenchymal stem cells (MSCs) capable of developing bone and haematopoietic microenvironment; (2) the mesenchymal cell population in tubular bones still containing active haematopoietic tissue gradually becomes depleted of MSCs, starting from a young age; (3) haematopoietic microenvironment is incapable of self-maintenance and its renewal depends on the presence of precursor cells; (4) the mesenchymal cell population remaining in areas with yellow BM contains cells able to develop functionally active haematopoietic microenvironment in conditions of haematopoietic insufficiency. Our data also indicate the possible existence of bi-potential stromal precursor cells producing either bone in normal, or bone together with active haematopoietic microenvironment in irradiated or old recipients. This study opens a spectrum of opportunities for the extension of haematopoietic territories by substituting the fat contents of BM cavities with haematopoietic tissue, thereby improving haematopoiesis compromised by cytotoxic treatments, irradiation, ageing, etc.

  2. THE FACTOR DETERMINING THE SPREAD OF RED MARROW DURING ANEMIA

    PubMed Central

    McMaster, Philip D.; Haessler, Herbert

    1921-01-01

    Rabbits in which a chronic anemia of moderate grade is induced by repeated bleedings repair the hemoglobin loss much more rapidly when given subcutaneous injections of hemoglobin than when this is not the case. But the effect of the injections is not manifest for several weeks, during which many pale corpuscles are put out by the marrow; whence it follows that the introduced pigment does not find its way in quantity direct to the new-formed cells but must follow a more or less roundabout metabolic route, perhaps the same one as that of ordinary iron compounds destined for the blood. The rapid replacement of the circulating hemoglobin in the injected animals occurs chiefly through an increased production of corpuscular substance having the same color index as that found in uninjected, anemic controls. By color index in this connection is meant the relation of hemoglobin to the volume of the massed corpuscles. Late in the period of bleedings and hemoglobin injections the demand for stroma for the new-formed blood is far greater than in control animals that have been merely bled, yet the circulating corpuscles show no lessening in resistance to salt solution, such as might perhaps be expected were there a stroma lack. The hematopoietic tissue of the injected animals undergoes an extensive increase—a fact which speaks strongly for the view that the elements out of which stroma is formed are still abundant. The factor which determines the spread of red marrow during anemia is shown by our experiments to be the presence in the body of hemoglobin, or perhaps of its precursors, in excess of the amount which can be utilized by the marrow already existing. Numerous illustrations in support of the point can be adduced from human pathology. Two will suffice. The widespread "currant jelly" marrow of pernicious anemia is found in an organism rendered anemic but supplied with hemoglobin in excess; while the pale, restricted marrow of cases suffering from chronic anemia due to

  3. 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.

  4. 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.

  5. Bone marrow transplantation for CVID-like humoral immune deficiency associated with red cell aplasia.

    PubMed

    Sayour, Elias J; Mousallem, Talal; Van Mater, David; Wang, Endi; Martin, Paul; Buckley, Rebecca H; Barfield, Raymond C

    2016-10-01

    Patients with common variable immunodeficiency (CVID) have a higher incidence of autoimmune disease, which may mark the disease onset; however, anemia secondary to pure red cell aplasia is an uncommon presenting feature. Here, we describe a case of CVID-like humoral immune deficiency in a child who initially presented with red cell aplasia and ultimately developed progressive bone marrow failure. Although bone marrow transplantation (BMT) has been associated with high mortality in CVID, our patient was successfully treated with a matched sibling BMT and engrafted with >98% donor chimerism and the development of normal antibody titers to diphtheria and tetanus toxoids. PMID:27273469

  6. Rh antibodies against the pretransplant red cells following Rh-incompatible bone marrow transplantation.

    PubMed

    Heim, M U; Schleuning, M; Eckstein, R; Huhn, D; Siegert, W; Clemm, C; Ledderose, G; Kolb, H J; Wilmanns, W; Mempel, W

    1988-01-01

    A 22-year-old, blood group O, Rh-positive (R2r) man received bone marrow from his blood group A, Rh-negative (rr), HLA-identical sister for treatment of acute lymphocytic leukemia. The patient's pretransplantation serum contained anti-A in a low concentration; therefore, plasmapheresis was not done prior to transfusion of bone marrow. To prevent graft-versus-host disease, bone marrow was incubated with absorbed rabbit antithymocyte globulin prior to infusion, and the patient was treated with methotrexate in the posttransplantation period. After transplantation, the patient received 6 units of group O, Rh-negative (rr) packed red cells from random donors and 6 units of platelets from the marrow donor. Three months after transplantation, 0.5 percent of his red cells were still of the host's type (group O, Rh-positive), as detected by immunofluorescence technique in blood smears. Four months after transplantation, three different Rh antibodies--anti-D, -E, and -G--were detected. Since the patient received only Rh-negative red cell transfusions, it is concluded that he was immunized to his original red cells.

  7. Rh antibodies against the pretransplant red cells following Rh-incompatible bone marrow transplantation.

    PubMed

    Heim, M U; Schleuning, M; Eckstein, R; Huhn, D; Siegert, W; Clemm, C; Ledderose, G; Kolb, H J; Wilmanns, W; Mempel, W

    1988-01-01

    A 22-year-old, blood group O, Rh-positive (R2r) man received bone marrow from his blood group A, Rh-negative (rr), HLA-identical sister for treatment of acute lymphocytic leukemia. The patient's pretransplantation serum contained anti-A in a low concentration; therefore, plasmapheresis was not done prior to transfusion of bone marrow. To prevent graft-versus-host disease, bone marrow was incubated with absorbed rabbit antithymocyte globulin prior to infusion, and the patient was treated with methotrexate in the posttransplantation period. After transplantation, the patient received 6 units of group O, Rh-negative (rr) packed red cells from random donors and 6 units of platelets from the marrow donor. Three months after transplantation, 0.5 percent of his red cells were still of the host's type (group O, Rh-positive), as detected by immunofluorescence technique in blood smears. Four months after transplantation, three different Rh antibodies--anti-D, -E, and -G--were detected. Since the patient received only Rh-negative red cell transfusions, it is concluded that he was immunized to his original red cells. PMID:3130695

  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. Normalization of red cell enolase level following allogeneic bone marrow transplantation in a child with Diamond-Blackfan anemia.

    PubMed

    Park, Jeong A; Lim, Yeon Jung; Park, Hyeon Jin; Kong, Sun Young; Park, Byung Kiu; Ghim, Thad T

    2010-04-01

    We describe a girl with Diamond-Blackfan anemia with accompanying red cell enolase deficiency. At the age of 9 yr old, the patient received allogeneic bone marrow transplantation from her HLA-identical sister who had normal red cell enolase activity. While the post transplant DNA analysis with short tandem repeat has continuously demonstrated a stable mixed chimerism on follow-up, the patient remains transfusion independent and continues to show a steady increase in red cell enolase activity for over two and a half years following bone marrow transplantation.

  10. 660 nm red light-enhanced bone marrow mesenchymal stem cell transplantation for hypoxic-ischemic brain damage treatment.

    PubMed

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

    2014-02-01

    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 600-1,000 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/cm(2), 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 × 10(6) bone marrow mesenchymal stem cells, followed by irradiation under red light-emitting diodes at 660 nm and 60 mW/cm(2) 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.

  11. 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 600–1,000 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

  12. 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.

  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. 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.

  15. Bone marrow pathology in dogs and cats with non-regenerative immune-mediated haemolytic anaemia and pure red cell aplasia.

    PubMed

    Weiss, D J

    2008-01-01

    Many dogs and cats with immune-mediated haemolytic anaemia (IMHA) lack a bone marrow erythroid regenerative response. To better understand the failure of the bone marrow to respond to the anaemia, bone marrow pathology associated with non-regenerative IMHA and pure red cell aplasia (PRCA) was reviewed. Eighty-two affected dogs and 57 affected cats were identified from a population presenting to a referral hospital over a 10-year period. Fifty-five dogs had non-regenerative IMHA (38 had bone marrow erythroid hyperplasia and 17 had erythroid maturation arrest) and 27 had pure red cell aplasia (PRCA). Twenty-eight cats had non-regenerative IMHA (24 had erythroid hyperplasia and 4 had erythroid maturation arrest) and 29 had PRCA. A variety of pathological changes were observed in bone marrow aspirates and core biopsy specimens taken from these animals. These changes included dysmyelopoiesis, myelonecrosis, myelofibrosis, interstitial oedema, haemorrhage, acute inflammation, haemophagocytic syndrome, lymphocyte aggregation, and lymphocyte or plasma cell hyperplasia. In both dogs and cats, dysmyelopoiesis, myelonecrosis, myelofibrosis, interstitial oedema, haemorrhage, acute inflammation and haemophagocytic syndrome were primarily noted in bone marrow specimens where there was evidence of erythroid hyperplasia. These animals were also more often neutropenic and thrombocytopenic, and had decreased 60 day survival when compared with dogs or cats with non-regenerative anaemia associated with erythroid maturation arrest or PRCA. Therefore, the pathogenesis of the non-regenerative anaemia in non-regenerative IMHA may involve both antibody-mediated destruction of bone marrow precursor cells and pathological events within the bone marrow that result in ineffective erythropoiesis.

  16. 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

  17. 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.

  18. Red marrow and blood dosimetry in 131I treatment of metastatic thyroid carcinoma: pre-treatment versus in-therapy results

    NASA Astrophysics Data System (ADS)

    Giostra, A.; Richetta, E.; Pasquino, M.; Miranti, A.; Cutaia, C.; Brusasco, G.; Pellerito, R. E.; Stasi, M.

    2016-06-01

    Treatment with radioiodine is a standard procedure for patients with well-differentiated thyroid cancer, but the main approach to the therapy is still empiric, consisting of the administration of fixed activities. A predictive individualized dosimetric study may represent an important tool for physicians to determine the best activity to prescribe. The aim of this work is to compare red marrow and blood absorbed dose values obtained in the pre-treatment (PT) dosimetry phase with those obtained in the in-treatment (IT) dosimetry phase in order to estimate the predictive power of PT trial doses and to determine if they can be used as a decision-making tool to safely administer higher 131I activity to potentially increase the efficacy of treatment. The PT and IT dosimetry for 50 patients has been evaluated using three different dosimetric approaches. In all three approaches blood and red marrow doses, are calculated as the sum of two components, the dose from 131I activity in the blood and the dose from 131I activity located in the remainder of the body (i.e. the blood and whole-body contributions to the total dose). PT and IT dose values to blood and red marrow appear to be well correlated irrespective of the dosimetric approach used. Linear regression analyses of PT and IT total doses, for blood and red marrow, and the whole-body contribution to these doses, showed consistent best fit slope and correlation coefficient values of approximately 0.9 and 0.6, respectively: analyses of the blood dose contribution to the total doses also yielded similar values for the best fit slope but with correlation coefficient values of approximately 0.4 reflecting the greater variance in these dose estimates. These findings suggest that pre-treatment red marrow dose assessments may represent an important tool to personalize metastatic thyroid cancer treatment, removing the constraints of a fixed activity approach and permitting potentially more effective higher 131I activities to be

  19. Bone Marrow Aspiration and Biopsy

    MedlinePlus

    ... the bone marrow and capability for blood cell production, including red blood cells (RBCs), white blood cells ( ... can affect the bone marrow and blood cell production. A specialist who has expertise in the diagnosis ...

  20. Estimating 131I biokinetics and radiation doses to the red marrow and whole body in thyroid cancer patients: probe detection versus image quantification*

    PubMed Central

    Willegaignon, José; Pelissoni, Rogério Alexandre; Lima, Beatriz Christine de Godoy Diniz; Sapienza, Marcelo Tatit; Coura-Filho, George Barberio; Queiroz, Marcelo Araújo; Buchpiguel, Carlos Alberto

    2016-01-01

    Objective To compare the probe detection method with the image quantification method when estimating 131I biokinetics and radiation doses to the red marrow and whole body in the treatment of thyroid cancer patients. Materials and Methods Fourteen patients with metastatic thyroid cancer, without metastatic bone involvement, were submitted to therapy planning in order to tailor the therapeutic amount of 131I to each individual. Whole-body scans and probe measurements were performed at 4, 24, 48, 72, and 96 h after 131I administration in order to estimate the effective half-life (Teff) and residence time of 131I in the body. Results The mean values for Teff and residence time, respectively, were 19 ± 9 h and 28 ± 12 h for probe detection, compared with 20 ± 13 h and 29 ± 18 h for image quantification. The average dose to the red marrow and whole body, respectively, was 0.061 ± 0.041 mGy/MBq and 0.073 ± 0.040 mGy/MBq for probe detection, compared with 0.066 ± 0.055 mGy/MBq and 0.078 ± 0.056 mGy/MBq for image quantification. Statistical analysis proved that there were no significant differences between the two methods for estimating the Teff (p = 0.801), residence time (p = 0.801), dose to the red marrow (p = 0.708), and dose to the whole body (p = 0.811), even when we considered an optimized approach for calculating doses only at 4 h and 96 h after 131I administration (p > 0.914). Conclusion There is full agreement as to the feasibility of using probe detection and image quantification when estimating 131I biokinetics and red-marrow/whole-body doses. However, because the probe detection method is inefficacious in identifying tumor sites and critical organs during radionuclide therapy and therefore liable to skew adjustment of the amount of 131I to be administered to patients under such therapy, it should be used with caution. PMID:27403014

  1. 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

  2. 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.

  3. Red blood cell production

    MedlinePlus

    ... cells are an important element of blood. Their job is to transport oxygen to the body’s tissues in exchange for carbon dioxide, which is carried to and eliminated by the lungs. Red blood cells are formed in the red bone marrow of bones. Stem cells in the red bone marrow called hemocytoblasts ...

  4. Establishment of a γ-H2AX foci-based assay to determine biological dose of radon to red bone marrow in rats.

    PubMed

    Wang, Jing; He, Linfeng; Fan, Dunhuang; Ding, Defang; Wang, Xufei; Gao, Yun; Zhang, Xuxia; Li, Qiang; Chen, Honghong

    2016-01-01

    The biodosimetric information is critical for assessment of cancer risk in populations exposed to high radon. However, no tools are available for biological dose estimation following radon exposure. Here, we established a γ-H2AX foci-based assay to determine biological dose to red bone marrow (RBM) in radon-inhaled rats. After 1-3 h of in vitro radon exposure, a specific pattern of γ-H2AX foci, linear tracks with individual p-ATM and p-DNA-PKcs foci, was observed, and the yield of γ-H2AX foci and its linear tracks displayed a linear dose-response manner in both rat peripheral blood lymphocytes (PBLs) and bone-marrow lymphocytes (BMLs). When the cumulative doses of radon inhaled by rats reached 14, 30 and 60 working level months (WLM), the yields of three types of foci markedly increased in both PBLs and BMLs, and γ-H2AX foci-based dose estimates to RBM were 0.97, 2.06 and 3.94 mGy, respectively. Notably, BMLs displayed a more profound increase of three types of foci than PBLs, and the absorbed dose ratio between BMLs and PBLs was similar between rats exposed to 30 and 60 WLM of radon. Taken together, γ-H2AX foci quantitation in PBLs is able to estimate RBM-absorbed doses with the dose-response curve of γ-H2AX foci after in vitro radon exposure and the ratio of RBM- to PBL-absorbed doses in rats following radon exposure. PMID:27445126

  5. Bone marrow histopathology in the diagnostic evaluation of splenic marginal-zone and splenic diffuse red pulp small B-cell lymphoma: a reliable substitute for spleen histopathology?

    PubMed

    Ponzoni, Maurilio; Kanellis, George; Pouliou, Evi; Baliakas, Panagiotis; Scarfò, Lydia; Ferreri, Andrés J M; Doglioni, Claudio; Bikos, Vasilis; Dagklis, Antonis; Anagnostopoulos, Achilles; Ghia, Paolo; Stamatopoulos, Kostas; Papadaki, Theodora

    2012-11-01

    Primary splenic small B-cell lymphomas mostly comprise the distinct entity of splenic marginal-zone lymphoma (SMZL) and the provisional category of splenic lymphoma/leukemia unclassifiable, mainly represented by the hairy cell leukemia variant and splenic diffuse red pulp small B-cell lymphoma (SDRL). Until recently, histopathologic examination of splenectomy specimens was considered mandatory for the diagnosis of SMZL. However, nowadays, mainly because of advances in chemoimmunotherapy, splenectomy is performed much less frequently. We evaluated the diagnostic efficacy of bone marrow biopsy (BMB) histopathology in the diagnostic approach toward SMZL and SDRL and tested whether it may serve as a substitute for spleen histopathology in the differential diagnosis between these 2 entities. To this end, we conducted a paired assessment of BMB and spleen diagnostic samples from 46 cases with a diagnosis of SMZL (n=32) or SDRL (n=14) based on spleen histopathology. We demonstrate that detailed immunohistopathologic BMB evaluation offers adequate evidence for the confirmation of these entities and their differential diagnosis from other small B-cell lymphoma histotypes. Notably, the immunophenotypical profile of SMZL and SDRL was identical in both BMB and spleen specimens for 21 evaluated markers. Paired assessment of BMB and spleen specimens did not identify discriminating patterns of BMB infiltration, cytology, and/or immunohistology between SMZL and SDRL. Accordingly, bone marrow histopathology contributes significantly in confirming the diagnosis of SMZL and SDRL. However, presently it is not possible to distinguish SMZL from SDRL on the basis of BMB evaluation alone; hence, histopathologic examination of the spleen remains the "gold standard" approach.

  6. Establishment of a γ-H2AX foci-based assay to determine biological dose of radon to red bone marrow in rats

    PubMed Central

    Wang, Jing; He, Linfeng; Fan, Dunhuang; Ding, Defang; Wang, Xufei; Gao, Yun; Zhang, Xuxia; Li, Qiang; Chen, Honghong

    2016-01-01

    The biodosimetric information is critical for assessment of cancer risk in populations exposed to high radon. However, no tools are available for biological dose estimation following radon exposure. Here, we established a γ-H2AX foci-based assay to determine biological dose to red bone marrow (RBM) in radon-inhaled rats. After 1–3 h of in vitro radon exposure, a specific pattern of γ-H2AX foci, linear tracks with individual p-ATM and p-DNA-PKcs foci, was observed, and the yield of γ-H2AX foci and its linear tracks displayed a linear dose-response manner in both rat peripheral blood lymphocytes (PBLs) and bone-marrow lymphocytes (BMLs). When the cumulative doses of radon inhaled by rats reached 14, 30 and 60 working level months (WLM), the yields of three types of foci markedly increased in both PBLs and BMLs, and γ-H2AX foci-based dose estimates to RBM were 0.97, 2.06 and 3.94 mGy, respectively. Notably, BMLs displayed a more profound increase of three types of foci than PBLs, and the absorbed dose ratio between BMLs and PBLs was similar between rats exposed to 30 and 60 WLM of radon. Taken together, γ-H2AX foci quantitation in PBLs is able to estimate RBM-absorbed doses with the dose-response curve of γ-H2AX foci after in vitro radon exposure and the ratio of RBM- to PBL-absorbed doses in rats following radon exposure. PMID:27445126

  7. Establishment of a γ-H2AX foci-based assay to determine biological dose of radon to red bone marrow in rats

    NASA Astrophysics Data System (ADS)

    Wang, Jing; He, Linfeng; Fan, Dunhuang; Ding, Defang; Wang, Xufei; Gao, Yun; Zhang, Xuxia; Li, Qiang; Chen, Honghong

    2016-07-01

    The biodosimetric information is critical for assessment of cancer risk in populations exposed to high radon. However, no tools are available for biological dose estimation following radon exposure. Here, we established a γ-H2AX foci-based assay to determine biological dose to red bone marrow (RBM) in radon-inhaled rats. After 1–3 h of in vitro radon exposure, a specific pattern of γ-H2AX foci, linear tracks with individual p-ATM and p-DNA-PKcs foci, was observed, and the yield of γ-H2AX foci and its linear tracks displayed a linear dose-response manner in both rat peripheral blood lymphocytes (PBLs) and bone-marrow lymphocytes (BMLs). When the cumulative doses of radon inhaled by rats reached 14, 30 and 60 working level months (WLM), the yields of three types of foci markedly increased in both PBLs and BMLs, and γ-H2AX foci-based dose estimates to RBM were 0.97, 2.06 and 3.94 mGy, respectively. Notably, BMLs displayed a more profound increase of three types of foci than PBLs, and the absorbed dose ratio between BMLs and PBLs was similar between rats exposed to 30 and 60 WLM of radon. Taken together, γ-H2AX foci quantitation in PBLs is able to estimate RBM-absorbed doses with the dose-response curve of γ-H2AX foci after in vitro radon exposure and the ratio of RBM- to PBL-absorbed doses in rats following radon exposure.

  8. Regeneration of red bone marrow in rat lower jaw after transplantation of mesenchymal stem cells into the site of injury.

    PubMed

    Maiborodin, I V; Matveeva, V A; Kolesnikov, I S; Drovosekov, M N; Toder, M S; Shevela, A I

    2012-02-01

    Regeneration processes in rat mandibular bone after transplantation of a suspension of autologous BM MSC in culture medium were studied by methods of light microscopy and X-ray densitometry. It was found that the structures of red BM in the callus after transplantation of autologous BM MSC formed earlier than in natural reparation. The formation of cavities containing BM determines lower tissue density at the site of injury after transplantation of autologous BM MSC on weeks 4 and 5 of observation than during spontaneous healing. These changes progressed throughout the observation period and attested to accelerated bone tissue reparation.

  9. 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; Umbilical ...

  10. 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.

  11. 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 - ...

  12. 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

  13. Bone Marrow Transplantation

    MedlinePlus

    Bone marrow is the spongy tissue inside some of your bones, such as your hip and thigh bones. ... platelets, which help the blood to clot. A bone marrow transplant is a procedure that replaces a person's ...

  14. Bone Marrow Diseases

    MedlinePlus

    ... that help with blood clotting. With bone marrow disease, there are problems with the stem cells or ... marrow makes too many white blood cells Other diseases, such as lymphoma, can spread into the bone ...

  15. Bone marrow aspiration

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/003658.htm Bone marrow aspiration To use the sharing features on this page, please enable JavaScript. Bone marrow is the soft tissue inside bones that helps ...

  16. 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 ... This captures a tiny sample, or core, of bone marrow within the needle. The sample and needle are ...

  17. [Pharmacokinetic substantiation of the use of 111In-citrate in bone marrow studies].

    PubMed

    Korsunskiĭ, V N; Tarasenko, Iu I; Koval'chuk, N D; Kosheleva, I Iu; Popov, V I

    1986-07-01

    Soviet radiopharmaceutical 111In-citrin has been studied to define its possible application for marrow visualization. 111In-citrin has been shown to accumulate in the red marrow, parenchymal organs and to be excreted from animal organism by urinary system predominately. 111In-citrin has advantages in defining the nuclide concentrations in marrow blood and serum as compared with colloid preparations and 111In-chloride. 111In-citrin is supposed to be an adequate radiopharmaceutical preparation for visualization of the red marrow. PMID:3736386

  18. Microdosimetry of astatine-211 using histological images: application to bone marrow.

    PubMed

    Akabani, G; Zalutsky, M R

    1997-12-01

    A method is presented for calculating the small-scale dosimetry of 211At in red bone marrow using chord-length distributions obtained from digitized histological images. This study used histological samples of bone marrow from beagle dogs to convey morphological information about cell conglomerations within bone marrow. Two 211At activity distributions were considered within the extracellular fluid and the surface of red bone marrow cells. Results confirmed the influence of cell conglomeration and activity distribution in determining the microdosimetry of red bone marrow. Average S* values of 1.6 x 10(-9) and 1.90 x 10(-9) Gy g Bq(-1) s(-1) were calculated for activity distributions located within the extracellular fluid and the surface of red bone marrow cells, respectively. The cumulated activity required to reduce survival probability to 0.37 also was calculated as a function of cell sensitivity for both activity distributions. The activity distribution on the cell surface resulted in a higher cell-killing efficiency, requiring a lower activity concentration of approximately 25% when compared with activity located in the extracellular fluid. Of relevance to potential clinical studies with 211At, the probability for zero hits for red bone marrow cells was > 10% for cumulated activities of less than 5.5 x 10(8) Bq s g(-1) in bone marrow.

  19. What Is a Blood and Marrow Stem Cell Transplant?

    MedlinePlus

    ... procedure allows the recipient to get new stem cells that work properly. Stem cells are found in bone marrow, ... the body doesn't make enough red blood cells or they don't work properly. Certain immune-deficiency diseases that prevent the ...

  20. Bone-marrow transplant - slideshow

    MedlinePlus

    ... this page: //medlineplus.gov/ency/presentations/100112.htm Bone-marrow transplant - series—Normal anatomy To use the sharing ... Go to slide 4 out of 4 Overview Bone-marrow is a soft, fatty tissue found inside of ...

  1. 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 ...

  2. Bone marrow transplantation in sickle cell anaemia.

    PubMed Central

    Vermylen, C; Cornu, G; Philippe, M; Ninane, J; Borja, A; Latinne, D; Ferrant, A; Michaux, J L; Sokal, G

    1991-01-01

    Sickle cell anaemia is still responsible for severe crippling and death in young patients living in developing countries. Apart from prophylaxis and treatment of infections, no active treatment can be safely proposed in such areas of the world. Therefore a bone marrow transplantation was performed in 12 patients staying in Belgium and planning to return to Africa. Twelve patients, aged between 11 months and 23 years (median 4 years), underwent a HLA identical bone marrow transplantation. The conditioning regimen included oral busulphan for four consecutive days (4 mg/kg) followed by four days of intravenous cyclophosphamide (50 mg/kg). In 10 patients the engraftment was rapid and sustained. A further patient suffered transient red cell hypoplasia and another underwent a second bone marrow transplantation from the same donor at day 62 because of graft rejection. All patients are alive and well with a follow up ranging from 9-51 months (median 27 months). In all cases a complete cessation of vaso-occlusive episodes and haemolysis was observed as was a change in the haemoglobin pattern in accordance with the donor's electrophoretic pattern. PMID:1953001

  3. 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.

  4. Bone marrow invasion in multiple myeloma and metastatic disease.

    PubMed

    Vilanova, J C; Luna, A

    2016-04-01

    Magnetic resonance imaging (MRI) of the spine is the imaging study of choice for the management of bone marrow disease. MRI sequences enable us to integrate structural and functional information for detecting, staging, and monitoring the response the treatment of multiple myeloma and bone metastases in the spine. Whole-body MRI has been incorporated into different guidelines as the technique of choice for managing multiple myeloma and metastatic bone disease. Normal physiological changes in the yellow and red bone marrow represent a challenge in analyses to differentiate clinically significant findings from those that are not clinically significant. This article describes the findings for normal bone marrow, variants, and invasive processes in multiple myeloma and bone metastases. PMID:26767542

  5. Effects of Spaceflight on Cells of Bone Marrow Origin

    PubMed Central

    Özçivici, Engin

    2013-01-01

    Once only a subject for science fiction novels, plans for establishing habitation on space stations, the Moon, and distant planets now appear among the short-term goals of space agencies. This article reviews studies that present biomedical issues that appear to challenge humankind for long-term spaceflights. With particularly focus on cells of bone marrow origin, studies involving changes in bone, immune, and red blood cell populations and their functions due to extended weightlessness were reviewed. Furthermore, effects of mechanical disuse on primitive stem cells that reside in the bone marrow were also included in this review. Novel biomedical solutions using space biotechnology will be required in order to achieve the goal of space exploration without compromising the functions of bone marrow, as spaceflight appears to disrupt homeostasis for all given cell types. Conflict of interest:None declared. PMID:24385745

  6. Bone marrow invasion in multiple myeloma and metastatic disease.

    PubMed

    Vilanova, J C; Luna, A

    2016-04-01

    Magnetic resonance imaging (MRI) of the spine is the imaging study of choice for the management of bone marrow disease. MRI sequences enable us to integrate structural and functional information for detecting, staging, and monitoring the response the treatment of multiple myeloma and bone metastases in the spine. Whole-body MRI has been incorporated into different guidelines as the technique of choice for managing multiple myeloma and metastatic bone disease. Normal physiological changes in the yellow and red bone marrow represent a challenge in analyses to differentiate clinically significant findings from those that are not clinically significant. This article describes the findings for normal bone marrow, variants, and invasive processes in multiple myeloma and bone metastases.

  7. Bone marrow edema pattern around the knee on magnetic resonance imaging excluding acute traumatic lesions.

    PubMed

    Steinbach, Lynne S; Suh, Kyung Jin

    2011-07-01

    Magnetic resonance imaging (MRI) is very sensitive for the detection of marrow abnormalities. Bone marrow edema on MRI has been defined as an area of low signal intensity on T1-weighted images, associated with intermediate or high signal intensity findings on T2-weighted images. The bone marrow edema pattern is a nonspecific finding with multiple etiologies. The knee is a common place for bone marrow signal abnormalities to appear on MRI. Besides contusions and fractures from acute trauma, there are a variety of other causes of the bone marrow edema pattern. It is important for the interpreter of the study to be aware of the different etiologies responsible for producing these changes and to be able to narrow the differential diagnosis without mistaking such a pattern for acute trauma or infiltrative tumor. This article concentrates on those entities that produce a bone marrow edema pattern not related to acute trauma including red marrow proliferation, stress, osteochondral lesions, osteonecrosis, bone marrow edema syndrome, arthropathy, infection, Paget's disease, and marrow replacement disorders. PMID:21644195

  8. 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.; Alcalá, Luis; Anadón, Pere; Peñalver-Mollá, 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.

  9. Starvation marrow – gelatinous transformation of bone marrow

    PubMed Central

    Osgood, Eric; Muddassir, Salman; Jaju, Minal; Moser, Robert; Farid, Farwa; Mewada, Nishith

    2014-01-01

    Gelatinous bone marrow transformation (GMT), also known as starvation marrow, represents a rare pathological entity of unclear etiology, in which bone marrow histopathology demonstrates hypoplasia, fat atrophy, and gelatinous infiltration. The finding of gelatinous marrow transformation lacks disease specificity; rather, it is an indicator of severe illness and a marker of poor nutritional status, found in patients with eating disorders, acute febrile illnesses, acquired immunodeficiency syndrome, alcoholism, malignancies, and congestive heart failure. We present a middle-aged woman with a history of alcoholism, depression, and anorexia nervosa who presented with failure to thrive and macrocytic anemia, with bone marrow examination demonstrative of gelatinous transformation, all of which resolved with appropriate treatment. To our knowledge, there are very few cases of GMT which have been successfully treated; thus, our case highlights the importance of proper supportive management. PMID:25317270

  10. Red Sea

    Atmospheric Science Data Center

    2013-04-16

    article title:  The Red Sea     View Larger Image ... Imaging SpectroRadiometer (MISR) image of the Red Sea was acquired on August 13, 2000. Located between the East African coast and the Saudi Arabian peninsula, the Red Sea got its name because the blooms of a type of algae,  Trichodesmium ...

  11. 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.

  12. 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.

  13. Bone marrow-targeted liposomal carriers

    PubMed Central

    Sou, Keitaro; Goins, Beth; Oyajobi, Babatunde O.; Travi, Bruno L.; Phillips, William T.

    2011-01-01

    Introduction Bone marrow targeted drug delivery systems appear to offer a promising strategy for advancing diagnostic, protective, and/or therapeutic medicine for the hematopoietic system. Liposome technology can provide a drug delivery system with high bone marrow targeting that is mediated by specific phagocytosis in bone marrow. Area covered This review focuses on a bone marrow specific liposome formulation labeled with technetium-99m (99mTc). Interspecies differences in bone marrow distribution of the bone marrow targeted formulation are emphasized. This review provides a liposome technology to target bone marrow. In addition, the selection of proper species for the investigation of bone marrow targeting is suggested. Expert opinion It can be speculated that the bone marrow macrophages have a role in the delivery of lipids to the bone marrow as a source of energy and for membrane biosynthesis or in the delivery of fat soluble vitamins for hematopoiesis. This homeostatic system offers a potent pathway to deliver drugs selectively into bone marrow tissues from blood. High selectivity of the present BMT-liposome formulation for bone marrow suggests the presence of an active and specific mechanism, but specific factors affecting the uptake of the bone marrow MPS are still unknown. Further investigation of this mechanism will increase our understanding of factors required for effective transport of agents to the bone marrow, and may provide an efficient system for bone marrow delivery for therapeutic purposes. PMID:21275831

  14. Evaluation of the in vivo 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.

  15. Evaluation of the in vivo 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

  16. Telomeres and marrow failure.

    PubMed

    Calado, Rodrigo T

    2009-01-01

    Telomeres, repeat sequences at the ends of chromosomes, are protective chromosomal structures highly conserved from primitive organisms to humans. Telomeres inevitably shorten with every cell cycle, and telomere attrition has been hypothesized to be fundamental to normal senescence of cells, tissues, and organisms. Molecular mechanisms have evolved to maintain their length and protective function; telomerase (TERT) is a reverse transcriptase enzyme that uses an RNA molecule (TERC) as the template to elongate the 3' ends of telomeres. Shelterin is a collection of DNA-binding proteins that cover and protect telomeres. The recent discovery of inherited mutations in genes that function to repair telomeres as etiologic in a range of human diseases, which have clinical manifestations in diverse tissues, including the hematopoietic tissue, suggests that defects in telomere repair and protection can cause organ failure. Dyskeratosis congenita is the prototype of telomere diseases; it is characterized by bone marrow failure, mucocutaneous abnormalities, pulmonary fibrosis, liver cirrhosis, and increased susceptibility to cancer, including acute myeloid leukemia. Aplastic anemia, acute myeloid leukemia, and idiopathic pulmonary fibrosis also are associated with inherited mutations in telomere repair or protection genes. Additionally, telomere defects associate with predisposition to hematologic malignancy and epithelial tumors. Telomere erosion is abnormally rapid in patients with mutations in telomerase genes but also after hematopoietic stem cell transplant, and telomeres are naturally shorter in older individuals-all conditions associated with higher rates of malignant diseases. In human tissue culture, short telomeres produce end-to-end chromosome fusion, nonreciprocal translocations, and aneuploidy.

  17. 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

  18. Characteristics of marrow production and reticulocyte maturation in normal man in response to anemia

    PubMed Central

    Hillman, Robert S.

    1969-01-01

    Erythropoiesis in normal man was studied during periods of phlebotomy-induced anemia of varying severity. This study permitted a comparison of marrow production measurements over a wide range of marrow production levels. As long as the serum iron remained above 50 μg/100 ml, measurements of plasma iron turnover provided an excellent index of marrow production at all levels of red cell production. In contrast, the absolute reticulocyte count demonstrated a poor correlation with the other measurements. This was shown to be the result of a prolongation of the time required for circulating reticulocytes to lose their reticulum, which correlated with the severity of the anemia. For the clinical application of the reticulocyte count as a measurement of marrow production, an adjustment must be made for this alteration in the circulating reticulocyte maturation time. PMID:5773082

  19. Red Sky with Red Mesa

    ScienceCinema

    None

    2016-07-12

    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.

  20. 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.

  1. Red Capes, Red Herrings, and Red Flags.

    ERIC Educational Resources Information Center

    Fiske, Donald W.

    The argument that the personality structures obtained from retrospective ratings reflect semantic similarity structures has been as provocative as a red cape in the bull ring. High congruence between those two kinds of structures seems well established. What is less clear is how and why those structures differ from that for immediate judgments of…

  2. 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.

  3. 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.

  4. Birthmarks - red

    MedlinePlus

    Strawberry mark; Vascular skin changes; Angioma cavernosum; Capillary hemangioma; Hemangioma simplex ... There are two main categories of birthmarks: Red birthmarks are ... are called vascular birthmarks. Pigmented birthmarks are areas ...

  5. 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

  6. [Inherited bone marrow failure syndromes].

    PubMed

    Okuno, Yusuke

    2016-02-01

    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

  7. Planning for a Bone Marrow Transplant (BMT)

    MedlinePlus

    ... us Digg Facebook Google Bookmarks Planning for a Bone Marrow Transplant (BMT) If you're going to have ... to a friend or family member undergoing a bone marrow or cord blood transplant. Help Your Loved One ...

  8. 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 ...

  9. 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 α-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

  10. 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 α-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

  11. 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.

  12. 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 500 billion 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.

  13. 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.

  14. Red blood cell morphology.

    PubMed

    Ford, J

    2013-06-01

    The foundation of laboratory hematologic diagnosis is the complete blood count and review of the peripheral smear. In patients with anemia, the peripheral smear permits interpretation of diagnostically significant red blood cell (RBC) findings. These include assessment of RBC shape, size, color, inclusions, and arrangement. Abnormalities of RBC shape and other RBC features can provide key information in establishing a differential diagnosis. In patients with microcytic anemia, RBC morphology can increase or decrease the diagnostic likelihood of thalassemia. In normocytic anemias, morphology can assist in differentiating among blood loss, marrow failure, and hemolysis-and in hemolysis, RBC findings can suggest specific etiologies. In macrocytic anemias, RBC morphology can help guide the diagnostic considerations to either megaloblastic or nonmegaloblastic causes. Like all laboratory tests, RBC morphologies must be interpreted with caution, particularly in infants and children. When used properly, RBC morphology can be a key tool for laboratory hematology professionals to recommend appropriate clinical and laboratory follow-up and to select the best tests for definitive diagnosis. PMID:23480230

  15. Red blood cell morphology.

    PubMed

    Ford, J

    2013-06-01

    The foundation of laboratory hematologic diagnosis is the complete blood count and review of the peripheral smear. In patients with anemia, the peripheral smear permits interpretation of diagnostically significant red blood cell (RBC) findings. These include assessment of RBC shape, size, color, inclusions, and arrangement. Abnormalities of RBC shape and other RBC features can provide key information in establishing a differential diagnosis. In patients with microcytic anemia, RBC morphology can increase or decrease the diagnostic likelihood of thalassemia. In normocytic anemias, morphology can assist in differentiating among blood loss, marrow failure, and hemolysis-and in hemolysis, RBC findings can suggest specific etiologies. In macrocytic anemias, RBC morphology can help guide the diagnostic considerations to either megaloblastic or nonmegaloblastic causes. Like all laboratory tests, RBC morphologies must be interpreted with caution, particularly in infants and children. When used properly, RBC morphology can be a key tool for laboratory hematology professionals to recommend appropriate clinical and laboratory follow-up and to select the best tests for definitive diagnosis.

  16. Primary bone marrow oedema syndromes.

    PubMed

    Patel, Sanjeev

    2014-05-01

    MRI scanning in patients with rheumatological conditions often shows bone marrow oedema, which can be secondary to inflammatory, degenerative, infective or malignant conditions but can also be primary. The latter condition is of uncertain aetiology and it is also uncertain whether it represents a stage in the progression to osteonecrosis in some patients. Patients with primary bone marrow oedema usually have lower limb pain, commonly the hip, knee, ankle or feet. The diagnosis is one of exclusion with the presence of typical MRI findings. Treatment is usually conservative and includes analgesics and staying off the affected limb. The natural history is that of gradual resolution of symptoms over a number of months. Evidence for medical treatment is limited, but open-label studies suggest bisphosphonates may help in the resolution of pain and improve radiological findings. Surgical decompression is usually used as a last resort.

  17. Effects of glucan on bone marrow

    PubMed Central

    Vannucci, Luca; Vetvicka, Vaclav

    2014-01-01

    Bone marrow damage represents a significant problem in cancer treatment. Therefore, it is clear that the pharmacologic protection against bone marrow damage is of considerable interest, since the development of novel and effective medical approaches to combat radiation or cytotoxic damage are of major importance not only to the medical field but also to several industries and the military. This review represents a summary of our knowledge of the effects of various glucans on bone marrow protection. PMID:25332994

  18. Use of Marrow Scintigraphy to Confirm Compensatory Marrow Rather than Active Myeloma.

    PubMed

    Bartel, Twyla B; Yarbrough, Tracy L; De Blanche, Lorraine E

    2016-09-01

    We present the case of a 40-year-old male with multiple myeloma for whom bone marrow scintigraphy was utilized to help differentiate between active bony myelomatous disease versus treated lesions with compensatory marrow uptake. This case demonstrates technetium (Tc-99m) sulfur colloid imaging as an inexpensive technique to quickly distinguish between active focal bone disease and reactive marrow. PMID:27651743

  19. Use of Marrow Scintigraphy to Confirm Compensatory Marrow Rather than Active Myeloma

    PubMed Central

    Bartel, Twyla B.; Yarbrough, Tracy L.; De Blanche, Lorraine E.

    2016-01-01

    We present the case of a 40-year-old male with multiple myeloma for whom bone marrow scintigraphy was utilized to help differentiate between active bony myelomatous disease versus treated lesions with compensatory marrow uptake. This case demonstrates technetium (Tc-99m) sulfur colloid imaging as an inexpensive technique to quickly distinguish between active focal bone disease and reactive marrow. PMID:27651743

  20. Use of Marrow Scintigraphy to Confirm Compensatory Marrow Rather than Active Myeloma

    PubMed Central

    Bartel, Twyla B.; Yarbrough, Tracy L.; De Blanche, Lorraine E.

    2016-01-01

    We present the case of a 40-year-old male with multiple myeloma for whom bone marrow scintigraphy was utilized to help differentiate between active bony myelomatous disease versus treated lesions with compensatory marrow uptake. This case demonstrates technetium (Tc-99m) sulfur colloid imaging as an inexpensive technique to quickly distinguish between active focal bone disease and reactive marrow.

  1. 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.

  2. Monoclonal gammopathy-associated pure red cell aplasia.

    PubMed

    Korde, Neha; Zhang, Yong; Loeliger, Kelsey; Poon, Andrea; Simakova, Olga; Zingone, Adriana; Costello, Rene; Childs, Richard; Noel, Pierre; Silver, Samuel; Kwok, Mary; Mo, Clifton; Young, Neal; Landgren, Ola; Sloand, Elaine; Maric, Irina

    2016-06-01

    Pure red cell aplasia (PRCA) is a rare disorder characterized by inhibition of erythroid precursors in the bone marrow and normochromic, normocytic anaemia with reticulocytopenia. Among 51 PRCA patients, we identified 12 (24%) patients having monoclonal gammopathy, monoclonal gammopathy of undetermined significance or smouldering multiple myeloma, with presence of monoclonal protein or abnormal serum free light chains and atypical bone marrow features of clonal plasmacytosis, hypercellularity and fibrosis. Thus far, three patients treated with anti-myeloma based therapeutics have responded with reticulocyte recovery and clinical transfusion independence, suggesting plasma cells play a key role in the pathogenesis of this specific monoclonal gammopathy-associated PRCA. PMID:26999424

  3. Fat Embolism Syndrome Secondary to Bone Marrow Necrosis in Patients with Hemoglobinopathies.

    PubMed

    Gangaraju, Radhika; Reddy, Vishnu V B; Marques, Marisa B

    2016-09-01

    Bone marrow necrosis with subsequent embolization of the fat and necrotic tissues into the systemic circulation causing fat embolism syndrome and multiorgan failure is a rare complication of patients with hemoglobinopathies. The exact etiology of this condition is not known. Because it occurs more often in patients with compound heterozygous conditions than in sickle cell disease, some patients are unaware of their predisposition. The initial symptoms are nonspecific, such as back and/or abdominal pain, fever, and fatigue, which may rapidly progress to respiratory failure and severe neurologic compromise. Common laboratory tests reveal anemia without reticulocytosis, thrombocytopenia, leukoerythroblastic picture with immature white cells and nucleated red blood cells, increased lactate dehydrogenase, high ferritin, and, sometimes increased creatinine. The diagnosis can be delayed because of an apparent lack of awareness about bone marrow necrosis with fat embolism syndrome, its rarity, and its similarities with other conditions such as thrombotic thrombocytopenic purpura. Although a bone marrow biopsy is diagnostic, waiting for it delays definitive treatment, which appears to be essential for the recovery of end-organ damage, such as neurologic and pulmonary damage. In our experience, either multiple units of red blood cell transfusion or, preferably, red cell exchange initiated promptly, is lifesaving. PMID:27598359

  4. 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.

  5. 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

  6. Bone marrow examination in pancytopenia.

    PubMed

    Rangaswamy, M; Prabhu; Nandini, N M; Manjunath, G V

    2012-08-01

    Pancytopenia is defined by reduction of all the three formed elements of blood below the normal reference. It may be a manifestation of a wide variety of disorders, which primarily or secondarily affect the bone marrow. Haematological investigation forms the bedrock in the management of patients with pancytopenia and therefore needs detailed study. The total number of cases studied were 100 over a period of two years in the department of pathology, JSS Hospital, Mysore. Megaloblastic anaemia (33%) was the commonest cause of pancytopenia. Other causes were nutritional anaemia (16%), aplastic anaemia (14%), hypersplenism (10%), sepsis (9%) and leukaemia (5%). Less common causes were alcoholic liver disease, haemolytic anaemia, HIV, dengue, systemic lupus erythematosus, viral hepatitis, disseminated TB and multiple myeloma. Most of the patients were in the age group of 11-30 years with a male:female ratio of 1.6:1.Generalised weakness and fatigue (88%) were the commonest presenting complaints. Haemoglobin level varied from 1-10 g/dl with majorIty (70%) of them in the range of 5.1-10 g/dI. TLC was in the range of 500-4000 cells/cmm. Most (34%) of them had 3100-4000 cells/cmm. Platelet count was in the range of 4000-1,40,000 cells/cmm. Reticulocyte count varied from 0.1%-15% with majority (82%) of them ranging from 0.1%-2%. The bone marrow cellularity was hypocellular in 14%, hypercellular in 75%, and normocellular in 11% of the patients. Pancytopenia is a relatively common entity with inadequate attention in Indian subcontinent. A comprehensive clinical and haematological study of patients with pancytopenia will usually help in the identification of the underlying cause. However in view of wide array of aetiologies, pancytopenia continues to be a diagnostic challenge for haematologists. PMID:23741821

  7. Bone marrow examination in pancytopenia.

    PubMed

    Rangaswamy, M; Prabhu; Nandini, N M; Manjunath, G V

    2012-08-01

    Pancytopenia is defined by reduction of all the three formed elements of blood below the normal reference. It may be a manifestation of a wide variety of disorders, which primarily or secondarily affect the bone marrow. Haematological investigation forms the bedrock in the management of patients with pancytopenia and therefore needs detailed study. The total number of cases studied were 100 over a period of two years in the department of pathology, JSS Hospital, Mysore. Megaloblastic anaemia (33%) was the commonest cause of pancytopenia. Other causes were nutritional anaemia (16%), aplastic anaemia (14%), hypersplenism (10%), sepsis (9%) and leukaemia (5%). Less common causes were alcoholic liver disease, haemolytic anaemia, HIV, dengue, systemic lupus erythematosus, viral hepatitis, disseminated TB and multiple myeloma. Most of the patients were in the age group of 11-30 years with a male:female ratio of 1.6:1.Generalised weakness and fatigue (88%) were the commonest presenting complaints. Haemoglobin level varied from 1-10 g/dl with majorIty (70%) of them in the range of 5.1-10 g/dI. TLC was in the range of 500-4000 cells/cmm. Most (34%) of them had 3100-4000 cells/cmm. Platelet count was in the range of 4000-1,40,000 cells/cmm. Reticulocyte count varied from 0.1%-15% with majority (82%) of them ranging from 0.1%-2%. The bone marrow cellularity was hypocellular in 14%, hypercellular in 75%, and normocellular in 11% of the patients. Pancytopenia is a relatively common entity with inadequate attention in Indian subcontinent. A comprehensive clinical and haematological study of patients with pancytopenia will usually help in the identification of the underlying cause. However in view of wide array of aetiologies, pancytopenia continues to be a diagnostic challenge for haematologists.

  8. Therapy Effect: Impact on Bone Marrow Morphology.

    PubMed

    Li, K David; Salama, Mohamed E

    2016-03-01

    This article highlights the most common morphologic features identified in the bone marrow after chemotherapy for hematologic malignancies, growth-stimulating agents, and specific targeted therapies. The key is to be aware of these changes while reviewing post-therapeutic bone marrow biopsies and to not mistake reactive patterns for neoplastic processes. In addition, given the development and prevalent use of targeted therapy, such as tyrosine kinase inhibitors and immune modulators, knowledge of drug-specific morphologic changes is required for proper bone marrow interpretation and diagnosis.

  9. 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.

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

    PubMed Central

    Ozkalemkas, Fahir; Ali, Rıdvan; 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

  11. Bone marrow transplant – children - discharge

    MedlinePlus

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

  12. Bone marrow lesions: A systematic diagnostic approach

    PubMed Central

    Grande, Filippo Del; Farahani, Sahar J; Carrino, John A; Chhabra, Avneesh

    2014-01-01

    Bone marrow lesions on magnetic resonance (MR) imaging are common and may be seen with various pathologies. The authors outline a systematic diagnostic approach with proposed categorization of various etiologies of bone marrow lesions. Utilization of typical imaging features on conventional MR imaging techniques and other problem-solving techniques, such as chemical shift imaging and diffusion-weighted imaging (DWI), to achieve accurate final diagnosis has been highlighted. PMID:25114392

  13. 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.

  14. Feasibility of marrow harvesting from pediatric sibling donors without hematopoietic growth factors and allotransfusion.

    PubMed

    Yabe, M; Morimoto, T; Shimizu, T; Koike, T; Takakura, H; Ohtsubo, K; Fukumura, A; Kato, S; Yabe, H

    2014-07-01

    We retrospectively studied 108 marrow harvests from 105 pediatric sibling donors. The median age of donors was 8 years (range: 1-15) and the median body weight was 27 kg (range: 10-100). The volumes of aspirated marrow were 5.0-23.8 mL/kg donor body weight, and harvested bone marrow volume exceeded 15 mL/kg in 42% of the donors. A total of 100 autologous blood donations were performed, and eight donors had red cells salvaged from their harvests reinfused. The median Hb levels before and after harvests were 12.3 g/dL (range: 10.0-14.7) and 11.0 g/dL (range: 8.9-13.8), respectively. None of the donors received allogeneic blood transfusions or hematopoietic growth factors such as EPO and G-CSF before or after collection. Transplanted dose was 1.4-10.8 × 10(8) cells/kg recipient body weight without differences due to donor age. Higher concentrations of nucleated and CD34(+) cells were obtained from younger donors. All donors tolerated the procedures well, with no serious complications. Thus, children may safely donate marrow for allogeneic transplantation, and the yields of nucleated cells for engraftment are substantial. PMID:24777192

  15. Erythropoietin stimulation decreases hepcidin expression through hematopoietic activity on bone marrow cells in mice.

    PubMed

    Sasaki, Yusuke; Noguchi-Sasaki, Mariko; Yasuno, Hideyuki; Yorozu, Keigo; Shimonaka, Yasushi

    2012-12-01

    Erythropoiesis-stimulating agents (ESA) are now central to the treatment of renal anemia and are associated with improved clinical outcomes. It is well known that erythropoietin (EPO) is a key regulator of erythropoiesis through its promotion of red blood cell production. In order to investigate the role of ESA on iron metabolism, we analyzed the regulation of the iron regulatory hormone hepcidin by ESA treatment in a bone marrow transplant model in mouse. After treating C57BL/6 mice with continuous erythropoietin receptor activator (C.E.R.A.), recombinant human epoetin-β (rhEPO), or recombinant human carbamylated epoetin-β (rhCEPO), we investigated serum hepcidin concentrations and parameters of erythropoiesis. Serum hepcidin concentrations after rhEPO treatment were analyzed in mice subjected to total body irradiation followed by bone marrow transplantation. C.E.R.A. administration caused long-term downregulation of serum hepcidin levels. Serum hepcidin levels in rhEPO-treated mice decreased significantly, whereas there was no change in rhCEPO-treated mice. The reduction in circulating hepcidin levels after rhEPO administration was not observed in irradiated mice. Finally, bone marrow transplantation recovered the response to rhEPO administration that downregulates hepcidin concentration in irradiated mice. These results indicate that ESA treatment downregulates serum hepcidin concentrations, mainly by indirect mechanisms affecting hematopoietic activity in bone marrow cells. PMID:23160767

  16. Chimaerism of immunocompetent cells in allogeneic bone marrow-reconstituted lethally irradiated chickens.

    PubMed

    Lydyard, P M; Ivanvi, J

    1975-08-01

    Injection of parental bone marrow cells into 12-day-old lethally irradiated F1 hybrid chickens resulted in chimaerism of donor-type graft-versus-host (GVH)-reactive cells and suppression of antisheep red blood cell antibody response. These manifestations of a chronic graft-versus-host reaction were prevented by pretreatment of the donor marrow with specific anti-T cell globulin. In some chimaeras donor-type GVH-reactive cells developed gradually from T cells precursors of donor origin. Transplantation of spleen and marrow cells from sheep red blood cell-primed F1 hybrid donors into lethally irradiated parental recipients resulted in the loss of memory potential within 1-2 weeks of transfer, whereas donor-type IgG allotype synthesis was preserved. Injection of goat antichicken thymocyte serum to recipients 1 day before reconstitution enabled the antibody response of memory cells at 1-2 weeks, although it failed to prevent their rejection by 8-9 weeeks after transplantation. Split chimaerism of donor-type GVH-reactive cells was demonstrated in chickens which had previously rejected the B cells derived from the same graft. PMID:241144

  17. Fabrication of biofunctionalized, cell-laden macroporous 3D PEG hydrogels as bone marrow analogs for the cultivation of human hematopoietic stem and progenitor cells.

    PubMed

    Rödling, Lisa; Raic, Annamarija; Lee-Thedieck, Cornelia

    2014-01-01

    In vitro proliferation of hematopoietic stem cells (HSCs) is yet an unresolved challenge. Found in the bone marrow, HSCs can undergo self-renewing cell division and thereby multiply. Recapitulation of the bone marrow environment in order to provide the required signals for their expansion is a promising approach.Here, we describe a technique to produce biofunctionalized, macroporous poly(ethylene glycol) diacrylate (PEGDA) hydrogels that mimic the spongy 3D architecture of trabecular bones, which host the red, blood-forming bone marrow. After seeding these scaffolds with cells, they can be used as simplified bone marrow analogs for the cultivation of HSCs. This method can easily be conducted with standard laboratory chemicals and equipment. The 3D hydrogels are produced via salt leaching and biofunctionalization of the material is achieved by co-polymerizing the PEGDA with an RGD peptide. Finally, cell seeding and retrieval are described.

  18. Pure red cell aplasia caused by parvovirus B19 in a heart transplant recipient.

    PubMed

    Invernizzi, Rosangela; Bastia, Raffaella; Quaglia, Federica

    2016-09-01

    A case of parvovirus B19-induced pure red cell aplasia occurring in a heart transplant recipient is reported. The diagnosis of this rare but clinically important complication can be suspected on the basis of the pathognomonic morphological features of the bone marrow. PMID:27648265

  19. Tracking mouse bone marrow monocytes in vivo.

    PubMed

    Hamon, Pauline; Rodero, Mathieu Paul; Combadière, 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

  20. Leptin-receptor-expressing mesenchymal stromal cells represent the main source of bone formed by adult bone marrow.

    PubMed

    Zhou, Bo O; Yue, Rui; Murphy, Malea M; Peyer, James G; Morrison, Sean J

    2014-08-01

    Studies of the identity and physiological function of mesenchymal stromal cells (MSCs) have been hampered by a lack of markers that permit both prospective identification and fate mapping in vivo. We found that Leptin Receptor (LepR) is a marker that highly enriches bone marrow MSCs. Approximately 0.3% of bone marrow cells were LepR(+), 10% of which were CFU-Fs, accounting for 94% of bone marrow CFU-Fs. LepR(+) cells formed bone, cartilage, and adipocytes in culture and upon transplantation in vivo. LepR(+) cells were Scf-GFP(+), Cxcl12-DsRed(high), and Nestin-GFP(low), markers which also highly enriched CFU-Fs, but negative for Nestin-CreER and NG2-CreER, markers which were unlikely to be found in CFU-Fs. Fate-mapping showed that LepR(+) cells arose postnatally and gave rise to most bone and adipocytes formed in adult bone marrow, including bone regenerated after irradiation or fracture. LepR(+) cells were quiescent, but they proliferated after injury. Therefore, LepR(+) cells are the major source of bone and adipocytes in adult bone marrow.

  1. [In-vitro studies on the kinetics of bone-marrow erythropoesis during the first trimester of life (Trimenonreduction)].

    PubMed

    Kurz, R

    1975-01-01

    This study tries to give further insight into the mechanism and location of the physiological reduction of the bone marrow erythropoiesis during the first trimester (Trimenonreduction). Methods utilized included red blood values, bone marrow morphology, 3H-Thymidine Autoradiography, Feulgen-cytophotometry and 3H-, 14C-Thymidine double labelling techniques of bone marrow erythroblasts of healthy children of different age groups. Besides already known techniques we used especially a modification of the double labelling techniques, developed in our laboratories. We draw the following conclusions from our results: 1. Newborns have a higher rate of bone marrow erythropoiesis in comparison with normal controls of other ages. The reduction of the bone marrow erythropoiesis starts already in the first 2 days of life. 2. The reduction of the bone marrow erythropoiesis in the investigated infants in the second week of life was about to one fifth of values which proved to be normal for healthy older children. 3. This reduction is caused partially by prolongation of proliferation and maturation phases of erythroblasts, partially by a decrease of new erythroblast-formation from the stem cell pool. Medium values of DNA-synthesistime of infants with the highest reduction is double compared with values of healthy controls in vitro. 4. The decrease of cell proliferation and maturation during the reduction of the bone-marrow erythropoiesis includes all precursors and all phases of the cell cycle equally. In the first few days of life however it seems that the decrease of DNA synthesizing erythroblasts surpasses the reduction of maturing cells. 5. An ineffectiveness of erythropoiesis could not be found responsible for the reduction. 6. The reduction in erythropoiesis is seen in those steps in which other autors found stimulations by erythropoietin. Therefore this study supports the thesis, that the trimenonreduction is caused by a lack of erythropoietin stimulation. 7. The sequence

  2. Bone marrow blood vessel ossification and "microvascular dead space" in rat and human long bone.

    PubMed

    Prisby, Rhonda D

    2014-07-01

    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 (4-6 month; n=8) and old (22-24 month; 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 (Goldner's Trichrome) and calcified (Alizarin Red) vessels. Adipocyte content was also determined. Additional femora (n=5/age group) were scanned via μCT to quantify microvascular ossification. Bone marrow blood vessels from the 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 the 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 the old vs. young rats. Ossified and patent vessel number was higher (171%) and lower (40%), respectively, in the 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 regard to loss of patency and vasomotor function as opposed to necrosis. 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

  3. Bone Marrow Immunity and Myelodysplasia.

    PubMed

    Lambert, Claude; Wu, Yuenv; Aanei, Carmen

    2016-01-01

    Myelodysplastic syndrome (MDS) is characterized by an ineffective hematopoiesis with production of aberrant clones and a high cell apoptosis rate in bone marrow (BM). Macrophages are in charge of phagocytosis. Innate Immune cells and specific T cells are in charge of immunosurveillance. Little is known on BM cell recruitment and activity as BM aspirate is frequently contaminated with peripheral blood. But evidences suggest an active role of immune cells in protection against MDS and secondary leukemia. BM CD8(+) CD28(-) CD57(+) T cells are directly cytotoxic and have a distinct cytokine signature in MDS, producing TNF-α, IL-6, CCL3, CCL4, IL-1RA, TNFα, FAS-L, TRAIL, and so on. These tools promote apoptosis of aberrant cells. On the other hand, they also increase MDS-related cytopenia and myelofibrosis together with TGFβ. IL-32 produced by stromal cells amplifies NK cytotoxicity but also the vicious circle of TNFα production. Myeloid-derived suppressing cells (MDSC) are increased in MDS and have ambiguous role in protection/progression of the diseases. CD33 is expressed on hematopoietic stem cells on MDS and might be a potential target for biotherapy. MDS also has impact on immunity and can favor chronic inflammation and emergence of autoimmune disorders. BM is the site of hematopoiesis and thus contains a complex population of cells at different stages of differentiation from stem cells and early engaged precursors up to almost mature cells of each lineage including erythrocytes, megakaryocytes, myelo-monocytic cells (monocyte/macrophage and granulocytes), NK cells, and B cells. Monocytes and B cell finalize their maturation in peripheral tissues or lymph nodes after migration through the blood. On the other hand, T cells develop in thymus and are present in BM only as mature cells, just like other well vascularized tissues. BM precursors have a strong proliferative capacity, which is usually associated with a high risk for genetic errors, cell dysfunction, and

  4. Bone Marrow Immunity and Myelodysplasia

    PubMed Central

    Lambert, Claude; Wu, Yuenv; Aanei, Carmen

    2016-01-01

    Myelodysplastic syndrome (MDS) is characterized by an ineffective hematopoiesis with production of aberrant clones and a high cell apoptosis rate in bone marrow (BM). Macrophages are in charge of phagocytosis. Innate Immune cells and specific T cells are in charge of immunosurveillance. Little is known on BM cell recruitment and activity as BM aspirate is frequently contaminated with peripheral blood. But evidences suggest an active role of immune cells in protection against MDS and secondary leukemia. BM CD8+ CD28− CD57+ T cells are directly cytotoxic and have a distinct cytokine signature in MDS, producing TNF-α, IL-6, CCL3, CCL4, IL-1RA, TNFα, FAS-L, TRAIL, and so on. These tools promote apoptosis of aberrant cells. On the other hand, they also increase MDS-related cytopenia and myelofibrosis together with TGFβ. IL-32 produced by stromal cells amplifies NK cytotoxicity but also the vicious circle of TNFα production. Myeloid-derived suppressing cells (MDSC) are increased in MDS and have ambiguous role in protection/progression of the diseases. CD33 is expressed on hematopoietic stem cells on MDS and might be a potential target for biotherapy. MDS also has impact on immunity and can favor chronic inflammation and emergence of autoimmune disorders. BM is the site of hematopoiesis and thus contains a complex population of cells at different stages of differentiation from stem cells and early engaged precursors up to almost mature cells of each lineage including erythrocytes, megakaryocytes, myelo-monocytic cells (monocyte/macrophage and granulocytes), NK cells, and B cells. Monocytes and B cell finalize their maturation in peripheral tissues or lymph nodes after migration through the blood. On the other hand, T cells develop in thymus and are present in BM only as mature cells, just like other well vascularized tissues. BM precursors have a strong proliferative capacity, which is usually associated with a high risk for genetic errors, cell dysfunction, and

  5. 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 ...

  6. 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 Col2.3Δtk (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.

  7. 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 Col2.3Δtk (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

  8. [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; Lémann, 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.

  9. Blood and Bone Marrow Evaluation for Eosinophilia.

    PubMed

    Boyer, Daniel F

    2016-10-01

    Evaluation of peripheral blood and bone marrow for an indication of persistent eosinophilia can be a challenging task because there are many causes of eosinophilia and the morphologic differences between reactive and neoplastic causes are often subtle or lack specificity. The purpose of this review is to provide an overview of the differential diagnosis for eosinophilia, to recommend specific steps for the pathologist evaluating blood and bone marrow, and to emphasize 2 important causes of eosinophilia that require specific ancillary tests for diagnosis: myeloproliferative neoplasm with PDGFRA rearrangement and lymphocyte-variant hypereosinophilic syndrome. PMID:27684977

  10. The effect of Arbas Cashmere goat bone marrow stromal cells on production of transgenic cloned embryos.

    PubMed

    Ren, Yu; Wu, Haiqing; Wang, Hefei; Wang, Xiao; Liang, Hao; Liu, Dongjun

    2014-06-01

    The aim of this study was to develop a method for the in vitro separation and culture of Arbas Cashmere goat bone marrow stromal cells (gBMSCs). Arbas Cashmere gBMSCs were isolated and cultured in vitro, and cell surface markers were identified immunohistochemically. The gBMSCs were differentiated into neurocytes and osteoblasts, and the expression of neuron-specific enolase and osteocalcin was identified by immunohistochemistry. The gBMSCs and goat fetal fibroblast cells (gFFCs) were compared for transient transfection efficiency and fluorescent colony-forming efficiency with Arbas Cashmere gFFCs as a control. pDsRed2-1 encodes DsRed2, a variant of the Discosoma sp. red fluorescent protein (DsRed). In addition, the coding sequence for DsRed2 contains a series of silent base-pair changes for higher expression in mammalian cells. Of the gBMSCs-pDsRed2-1, one fraction was tested for pluripotency, whereas the other fraction was manipulated using somatic cell nuclear transfer, and the in vitro growth status of transgenic embryos derived from gBMSCs-pDsRed2-1 and gFFCs-pDsRed2-1 was compared. The findings showed that gBMSCs were isolated and amplified to express CD29, CD44, and CD90 through adherent culture, with no marked signs of aging after multiple passages. Expression of neuron-specific enolase and osteocalcin by gBMSCs and gBMSCs-pDsRed2-1 was strongly induced by neuronal and osteogenic differentiation, whereas the integrated exogenous genes did not influence pluripotency (P > 0.05). The transient transfection efficiencies of gBMSCs and gFFCs after 48 hours were not significantly different; however, the fluorescent colony-forming efficiency of gBMSCs-pDsRed2-1 after G418 screening was approximately 13% higher than that of gFFCs-pDsRed2-1. The convergence and cleavage rates of cloned embryos derived from gBMSCs-pDsRed2-1 were higher than those derived from gFFCs-pDsRed2-1, whereas their eight-cell and blastocyst rates were similar. The red fluorescent protein

  11. Adult hemolytic-uremic syndrome and bone marrow necrosis

    SciTech Connect

    Hicks, C.B.; Redmond, J. III

    1984-11-01

    A case is reported of adult hemolytic-uremic syndrome in which massive bone marrow necrosis developed, a previously undescribed complication. Technetium-99m minicolloid scanning and indium-111 bone marrow scans were used to demonstrate lack of bone marrow activity in the patient. 11 references, 2 figures.

  12. Intracranial extramedullary hematopoiesis. CT and bone marrow scan findings

    SciTech Connect

    Urman, M.; O'Sullivan, R.A.; Nugent, R.A.; Lentle, B.C. )

    1991-06-01

    This case concerns a patient with intracranial extramedullary hematopoiesis (EH) suspected on a CT scan and subsequently confirmed with In-111 chloride and Tc-99m SC bone marrow scans. The bone marrow scans also provided additional information by demonstrating other sites of EH in the paravertebral tissues and bone marrow expansion into the distal extremities.

  13. Bone Marrow Transplantation for Feline Mucopolysaccharidosis I

    PubMed Central

    Ellinwood, N. Matthew; Colle, Marie-Anne; Weil, Margaret A.; Casal, Margret L.; Vite, Charles H.; Wiemelt, Staci; Hasson, Christopher W.; O’Malley, Thomas M.; He, Xingxuan; Prociuk, Ulana; Verot, Lucie; Melniczek, John R.; Lannon, Anne; Aguirre, Gustavo D.; Knox, Van W.; Evans, Sydney M.; Vanier, Marie T.; Schuchman, Edward H.; Walkley, Steven U.; Haskins, Mark E.

    2009-01-01

    Severe mucopolysaccharidosis type I (MPS I) is a fatal neuropathic lysosomal storage disorder with significant skeletal involvement. Treatment involves bone marrow transplantation (BMT), and although effective, is suboptimal, due to treatment sequelae and residual disease. Improved approaches will need to be tested in animal models and compared to BMT. Herein we report on bone marrow transplantation to treat feline mucopolysaccharidosis I (MPS I). Five MPS I stably engrafted kittens, transplanted with unfractionated bone marrow (6.3 × 107 to 1.1 × 109 nucleated bone marrow cells per kilogram) were monitored for 13–37 months post-engraftment. The tissue total glycosaminoglycan (GAG) content was reduced to normal levels in liver, spleen, kidney, heart muscle, lung, and thyroid. Aorta GAG content was between normal and affected levels. Treated cats had a significant decrease in the brain GAG levels relative to untreated MPS I cats and a paradoxical decrease relative to normal cats. The α-L-iduronidase (IDUA) activity in the livers and spleens of transplanted MPS I cats approached heterozygote levels. In kidney cortex, aorta, heart muscle, and cerebrum, there were decreases in GAG without significant increases in detectable IDUA activity. Treated animals had improved mobility and decreased radiographic signs of disease. However, significant pathology remained, especially in the cervical spine. Corneal clouding appeared improved in some animals. Immunohistochemical and biochemical analysis documented decreased central nervous system ganglioside storage. This large animal MPS I study will serve as a benchmark of future therapies designed to improve on BMT. PMID:17482862

  14. Allogeneic and Autologous Bone-Marrow Transplantation

    PubMed Central

    Deeg, H. Joachim

    1988-01-01

    The author of this paper presents an overview of the current status of bone marrow transplantation, including indications, pre-transplant considerations, the transplant procedure, acute and delayed transplant-related problems, results currently attainable, and a short discussion of possible future developments. PMID:21253121

  15. Comparison of bone marrow aspiration and bone marrow biopsy in neoplastic diseases.

    PubMed

    Hamid, G A; Hanbala, N

    2009-07-01

    Naturally trephine biopsies have definitive advantages over aspirates in case of dry tap bone marrow aspirates as a result of fibrosis or densely packed bone marrow by tumour cells and may be informative independent of cytology especially in bone marrow involvement by lymphomas and carcinomas. In this prospective descriptive study we aimed to compare between the bone marrow trephine biopsy (BMTB) and bone marrow aspirates (BMAs) regarding the detection rate of solid tumours, lymphoma and myeloma involvement of the bone marrow. The study was carried out in the department of pathology and Haematology-Oncology of Al-Gamhouria Teaching Hospital/Aden during the period between Jan 2005 to Dec 2005. A total of 32 patients with suspected or confirmed malignancy undergone both BMTB and BMA from the posterior superior iliac crest and both results were compared. We divided them into three groups: those with solid tumours (21) patients, lymphoma (7) patients and with MM (4) patients. Our results showed that BMA had a 47.6% sensitivity, 100.0% specificity, with positive predictive value (100%), and negative predictive value (50.0%). In solid tumours alone it had a sensitivity of (40.0%), 100% specificity, with positive predictive value (100%), and negative predictive value (64.7%). This gives the BMA a lower sensitivity in detecting solid tumour metastasis and lymphoma involvement in comparison to BMTB. In conclusion, any patient with suspected or confirmed cancer should undergo BMTB because of its high sensitivity compared to BMA. PMID:20194084

  16. Bone marrow: its contribution to heme catabolism.

    PubMed

    Mähönen, Y; Anttinen, M; Vuopio, P; Tenhunen, R

    1976-01-01

    Heme oxygenase (HO) and biliverdin reductase (BR), the two NADPH-dependent enzymes involved in the degradation of hemoglobin and its derivatives, were measured in bone marrow aspirates from 5 hematologically normal persons, 4 patients with chronic leucemia (CL), 11 patients with acute leucemia (AL), 8 patients with refractory sideroblastic anemia (RA), 7 patients with iron-deficiency anemia (IA), 5 patients with hemolytic anemia (HA), and 7 patients with secondary anemia (SA) to determine the enzymatic capacity of the bone marrow in different hematologic disorders for heme catabolism. HO activity in the bone marrow of normal persons was 0.42 +/- 0.28 (SD) nmoles bilirubin/10 mg protein/min; in CL, 2.15 +/- 1.34; in AL, 0.39 +/- 0.25; in RA, 0.58 +/- 0.37; in IA, 0.41 +/- 0.28; in HA, 2.56 +/- 1.40; and in SA, 1.72 +/- 1.06. BR activity, respectively, was in normal persons 8.7 +/- 2.4 (SD) nmoles bilirubin/10 mg protein/min; in CL, 13.6 +/- 9.1; in AL, 3.8 +/- 3.1 in RA, 5.1 +/- 2.7; in IA, 5.5 +/- 3.7; in HA, 17.0 +/- 7.2; and in SA, 10.5 +/- 4.2. On the basis of these findings it seems evident that both oxygenase and biliverdin reductase activities of the bone marrow are capable of adaptive regulation. The physiologic role of bone marrow in heme catabolism seems to be of significant importance.

  17. Bone marrow processing for transplantation using Cobe Spectra cell separator.

    PubMed

    Veljković, Dobrila; Nonković, Olivera Šerbić; Radonjić, Zorica; Kuzmanović, Miloš; Zečević, Zeljko

    2013-06-01

    Concentration of bone marrow aspirates is an important prerequisite prior to infusion of ABO incompatible allogeneic marrow and prior to cryopreservation and storage of autologous marrow. In this paper we present our experience in processing 15 harvested bone marrow for ABO incompatible allogeneic and autologous bone marrow (BM) transplantation using Cobe Spectra® cell separator. BM processing resulted in the median recovery of 91.5% CD34+ cells, erythrocyte depletion of 91% and volume reduction of 81%. BM processing using cell separator is safe and effective technique providing high rate of erythrocyte depletion and volume reduction, and acceptable recovery of the CD34+ cells.

  18. Pure red cell aplasia following autoimmune hemolytic anemia: an enigma.

    PubMed

    Saha, M; Ray, S; Kundu, S; Chakrabarti, P

    2013-01-01

    A 26-year-old previously healthy female presented with a 6-month history of anemia. The laboratory findings revealed hemolytic anemia and direct antiglobulin test was positive. With a diagnosis of autoimmune hemolytic anemia (AIHA), prednisolone was started but was ineffective after 1 month of therapy. A bone marrow trephine biopsy revealed pure red cell aplasia (PRCA) showing severe erythroid hypoplasia. The case was considered PRCA following AIHA. This combination without clear underlying disease is rare. Human parvovirus B19 infection was not detected in the marrow aspirate during reticulocytopenia. The patient received azathioprine, and PRCA improved but significant hemolysis was once again documented with a high reticulocyte count. The short time interval between AIHA and PRCA phase suggested an increased possibility of the evolution of a single disease.

  19. Peripheral Red Blood Cell Split Chimerism as a Consequence of Intramedullary Selective Apoptosis of Recipient Red Blood Cells in a Case of Sickle Cell Disease

    PubMed Central

    Marziali, Marco; Isgrò, Antonella; Sodani, Pietro; Gaziev, Javid; Fraboni, Daniela; Paciaroni, Katia; Gallucci, Cristiano; Alfieri, Cecilia; Roveda, Andrea; De Angelis, Gioia; Cardarelli, Luisa; Ribersani, Michela; Andreani, Marco; Lucarelli, Guido

    2014-01-01

    Allogeneic cellular gene therapy through hematopoietic stem cell transplantation is the only radical cure for congenital hemoglobinopathies like thalassemia and sickle cell anemia. Persistent mixed hematopoietic chimerism (PMC) has been described in thalassemia and sickle cell anemia. Here, we describe the clinical course of a 6-year-old girl who had received bone marrow transplant for sickle cell anemia. After the transplant, the patient showed 36% donor hematopoietic stem cells in the bone marrow, whereas in the peripheral blood there was evidence of 80% circulating donor red blood cells (RBC). The analysis of apoptosis at the Bone Marrow level suggests that Fas might contribute to the cell death of host erythroid precursors. The increase in NK cells and the regulatory T cell population observed in this patient suggests that these cells might contribute to the condition of mixed chimerism. PMID:25408852

  20. [Pulmonary arterial hypertension, bone marrow, endothelial cell precursors and serotonin].

    PubMed

    Ayme-Dietrich, Estelle; Banas, Sophie M; Monassier, Laurent; Maroteaux, Luc

    2016-01-01

    Serotonin and bone-marrow-derived stem cells participate together in triggering pulmonary hypertension. Our work has shown that the absence of 5-HT2B receptors generates permanent changes in the composition of the blood and bone-marrow in the myeloid lineages, particularly in endothelial cell progenitors. The initial functions of 5-HT2B receptors in pulmonary arterial hypertension (PAH) are restricted to bone-marrow cells. They contribute to the differentiation/proliferation/mobilization of endothelial progenitor cells from the bone-marrow. Those bone-marrow-derived cells have a critical role in the development of pulmonary hypertension and pulmonary vascular remodeling. These data indicate that bone-marrow derived endothelial progenitors play a key role in the pathogenesis of PAH and suggest that interactions involving serotonin and bone morphogenic protein type 2 receptor (BMPR2) could take place at the level of the bone-marrow. PMID:27687599

  1. MR imaging of therapy-induced changes of bone marrow

    PubMed Central

    Henning, Tobias; Link, Thomas M.

    2006-01-01

    MR imaging of bone marrow infiltration by hematologic malignancies provides non-invasive assays of bone marrow cellularity and vascularity to supplement the information provided by bone marrow biopsies. This article will review the MR imaging findings of bone marrow infiltration by hematologic malignancies with special focus on treatment effects. MR imaging findings of the bone marrow after radiation therapy and chemotherapy will be described. In addition, changes in bone marrow microcirculation and metabolism after anti-angiogenesis treatment will be reviewed. Finally, new specific imaging techniques for the depiction of regulatory events that control blood vessel growth and cell proliferation will be discussed. Future developments are directed to yield comprehensive information about bone marrow structure, function and microenvironment. PMID:17021706

  2. Fibrillin-1 microfibrils influence adult bone marrow hematopoiesis.

    PubMed

    Smaldone, Silvia; Bigarella, Carolina L; Del Solar, Maria; Ghaffari, Saghi; Ramirez, Francesco

    2016-01-01

    We have recently demonstrated that fibrillin-1 assemblies regulate the fate of skeletal stem cells (aka, mesenchymal stem cells [MSCs]) by modulating TGFβ activity within the microenvironment of adult bone marrow niches. Since MSCs can also influence hematopoietic stem cell (HSC) activities, here we investigated adult hematopoiesis in mice with Cre-mediated inactivation of the fibrillin-1 (Fbn1) gene in the mesenchyme of the forming limbs (Fbn1(Prx1-/-) mice). Analyses of 3-month-old Fbn1(Prx1-/-) mice revealed a statistically significant increase of circulating red blood cells, which a differentiation assay correlated with augmented erythropoiesis. This finding, together with evidence of fibrillin-1 deposition in erythroblastic niches, supported the notion that this extracellular matrix protein normally restricts differentiation of erythroid progenitors. Whereas flow cytometry measurements identified a decreased HSC frequency in mutant relative to wild type mice, no appreciable differences were noted with regard to the relative abundance and differentiation potential of myeloid progenitor cells. Together these findings implied that fibrillin-1 normally promotes HSC expansion but does not influence cell lineage commitment. Since local TGFβ hyperactivity has been associated with abnormal osteogenesis in Fbn1(Prx1-/-) mice, 1-month-old mutant and wild type animals were systemically treated for 8weeks with either a pan-TGF-β-neutralizing antibody or an antibody of the same IgG1 isotype. The distinct outcomes of these pharmacological interventions strongly suggest that fibrillin-1 differentially modulates TGFβ activity in HSC vs. erythroid niches.

  3. 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

  4. 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

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

    PubMed

    Özdal-Kurt, F; Tuğlu, I; Vatansever, H S; Tong, S; Deliloğlu-Gürhan, S I

    2015-01-01

    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

  6. [Bone marrow autograft and cancer in children].

    PubMed

    Gentet, J C; Plouvier, E; Coze, C

    1993-11-01

    Since about 15 years intensive chemotherapy followed by autologous bone marrow transplantation has been used on the basis of "dose-response" principle to treat certain children with tumours of sombre prognosis. At present, the main indications for this method are metastatif neuroblastoma in less than one-year old children, non-Hodgkin's malignant lymphomas in partial remission or relapse, refractory or recurrent Hodgkin's disease and some peculiar forms of Wilms' tumour. In other tumours, such as rhabdomyosarcoma, Ewing's sarcoma or brain tumours, the indications have not yet been clearly determined. The treatment must be administered as part of multicentre French or European trials conducted in specialized centres. The practice and application of autologous bone marrow transplantation are being revolutionized by the availability of haematopoietic growth factors and the development of the peripheral blood stem cells reinjection technique. Genic therapy will soon have major repercussions in this field.

  7. [Bone marrow involvement and eosinophilia in paracoccidioidomycosis].

    PubMed

    Shikanai-Yasuda, M A; Higaki, Y; Uip, D E; Mori, N S; Del Negro, G; Melo, N T; Hutzler, R U; Amato Neto, V

    1992-01-01

    The authors described three acute paracoccidioidomycosis patients with bone marrow involvement. P. brasiliensis yeast forms were observed in bone marrow smears of all them, and in one case, culture also revealed fungus growth. The mononuclear phagocytic system involvement, the blood eosinophilia and the negative skin hypersensibility responses were emphasized in all of them, as well as the severity of the disease in one case, with disseminated bone lesions and 20.260 eosinophils/mm3 in peripheral blood. The authors discuss the possible role of eosinophil in the host-parasite interaction in paracoccidioidomycosis, suggesting that TH 2 subpopulation activation and increased IL 5 and GM-CSF secretions may be responsible by eosinophilia in the most severe case. PMID:1340036

  8. 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)

  9. 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

  10. Concentration of bone marrow mononuclear cells for in vitro treatment and AB0-incompatible transplantation: a rapid and reproducible procedure using the haemonetics V50 cell separator.

    PubMed

    Wiesneth, M; Hertenstein, B; Koerner, K; Heimpel, H; Heit, W

    1988-01-01

    Forty-nine allogeneic and 14 autologous bone marrow grafts were processed with the Haemonetics V50 cell separator (Haemonetics Corp., Braintree, USA) for in vitro treatment with antibodies and cryopreservation respectively. The concentration of hemopoietic progenitor cells was performed without any sedimentation or density gradient agents. The recovery is given in percent (mean +/- sd) of the original marrow values: mononuclear cells (MNC) 74 +/- 10%, polymorphonuclear cells (PMC) 48 +/- 17%, red blood cells (RBC) 12 +/- 5%, granulocyte/monocyte progenitors (CFU-GM) 83 +/- 36%, and erythroid progenitors (BFU-E) 78 +/- 38%. The recovery of nucleated cells (NC) was 90 +/- 13% and the viability 82 +/- 11% after cryopreservation. The technique described provides a simple, rapid and efficient preparation of large bone marrow volumes for in vitro treatment and AB0-incompatible transplantation.

  11. 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

  12. Mechanisms of dengue virus-induced bone marrow suppression.

    PubMed

    La Russa, V F; Innis, B L

    1995-03-01

    Infection with many flaviviruses is associated with transient suppression of haematopoiesis. Of the flaviviruses of man, none are more accessible to clinical and laboratory study than dengue. Consequently, the clinical syndrome of dengue-associated bone marrow suppression has been well documented. A review of experimental dengue infections of volunteers and histopathological studies of bone marrow from patients with severe dengue virus infection suggests that marrow suppression evolves rapidly through several phases: (1) onset of marrow suppression within 3-4 days of infection; (2) onset of host inflammatory responses in the marrow and of fever shortly thereafter; (3) occurrence of a neutrophil nadir on the fourth to fifth day after onset of fever; (4) almost simultaneously, immune activation sufficient to neutralize viraemia and accelerate elimination of infected cells; (5) remission of symptoms; and (6) resolution of cytopenias. Clinical observations and experimental data bear on possible mechanisms of dengue virus-mediated marrow suppression. Work from the authors' laboratory in which long-term bone marrow cultures were used to investigate interactions between dengue virus and bone marrow cells (stromal elements and haematopoietic progenitors) is also reviewed. Long-term marrow culture (LTMC) was a useful experimental system. In vitro, early blast cells as well as the more differentiated haematopoietic elements were abortively infected, killed and eliminated by phagocytosis by specialized marrow macrophages called dendritic cells. Moreover, the ARC from stroma rather than haematopoietic precursors were productively infected. When ARC were infected, stroma failed to support haematopoiesis. Cytokine production by virus-infected stromal cells was altered. A hypothesis is proposed to account for dengue virus-induced marrow suppression. Down-regulation of haematopoiesis is probably a protective mechanism of the microenvironment that limits injury to the marrow stem

  13. Bone marrow fibrosis in myelofibrosis: pathogenesis, prognosis and targeted strategies

    PubMed Central

    Zahr, Abdallah Abou; Salama, Mohamed E.; Carreau, Nicole; Tremblay, Douglas; Verstovsek, Srdan; Mesa, Ruben; Hoffman, Ronald; Mascarenhas, John

    2016-01-01

    Bone marrow fibrosis is a central pathological feature and World Health Organization major diagnostic criterion of myelofibrosis. Although bone marrow fibrosis is seen in a variety of malignant and non-malignant disease states, the deposition of reticulin and collagen fibrosis in the bone marrow of patients with myelofibrosis is believed to be mediated by the myelofibrosis hematopoietic stem/progenitor cell, contributing to an impaired microenvironment favoring malignant over normal hematopoiesis. Increased expression of inflammatory cytokines, lysyl oxidase, transforming growth factor-β, impaired megakaryocyte function, and aberrant JAK-STAT signaling have all been implicated in the pathogenesis of bone marrow fibrosis. A number of studies indicate that bone marrow fibrosis is an adverse prognostic variable in myeloproliferative neoplasms. However, modern myelofibrosis prognostication systems utilized in risk-adapted treatment approaches do not include bone marrow fibrosis as a prognostic variable. The specific effect on bone marrow fibrosis of JAK2 inhibition, and other rationally based therapies currently being evaluated in myelofibrosis, has yet to be fully elucidated. Hematopoietic stem cell transplantation remains the only curative therapeutic approach that reliably results in resolution of bone marrow fibrosis in patients with myelofibrosis. Here we review the pathogenesis, biological consequences, and prognostic impact of bone marrow fibrosis. We discuss the rationale of various anti-fibrogenic treatment strategies targeting the clonal hematopoietic stem/progenitor cell, aberrant signaling pathways, fibrogenic cytokines, and the tumor microenvironment. PMID:27252511

  14. 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

  15. Bone marrow fibrosis in myelofibrosis: pathogenesis, prognosis and targeted strategies.

    PubMed

    Zahr, Abdallah Abou; Salama, Mohamed E; Carreau, Nicole; Tremblay, Douglas; Verstovsek, Srdan; Mesa, Ruben; Hoffman, Ronald; Mascarenhas, John

    2016-06-01

    Bone marrow fibrosis is a central pathological feature and World Health Organization major diagnostic criterion of myelofibrosis. Although bone marrow fibrosis is seen in a variety of malignant and non-malignant disease states, the deposition of reticulin and collagen fibrosis in the bone marrow of patients with myelofibrosis is believed to be mediated by the myelofibrosis hematopoietic stem/progenitor cell, contributing to an impaired microenvironment favoring malignant over normal hematopoiesis. Increased expression of inflammatory cytokines, lysyl oxidase, transforming growth factor-β, impaired megakaryocyte function, and aberrant JAK-STAT signaling have all been implicated in the pathogenesis of bone marrow fibrosis. A number of studies indicate that bone marrow fibrosis is an adverse prognostic variable in myeloproliferative neoplasms. However, modern myelofibrosis prognostication systems utilized in risk-adapted treatment approaches do not include bone marrow fibrosis as a prognostic variable. The specific effect on bone marrow fibrosis of JAK2 inhibition, and other rationally based therapies currently being evaluated in myelofibrosis, has yet to be fully elucidated. Hematopoietic stem cell transplantation remains the only curative therapeutic approach that reliably results in resolution of bone marrow fibrosis in patients with myelofibrosis. Here we review the pathogenesis, biological consequences, and prognostic impact of bone marrow fibrosis. We discuss the rationale of various anti-fibrogenic treatment strategies targeting the clonal hematopoietic stem/progenitor cell, aberrant signaling pathways, fibrogenic cytokines, and the tumor microenvironment. PMID:27252511

  16. Red Bull Stratos Presentation

    NASA Video Gallery

    Red Bull Stratos High Performance Director Andy Walshe & Technical Project Director Art Thompson share the Stratos story with JSC. Supported by a team of experts, Felix Baumgartner reached 128,100 ...

  17. Whence the red panda?

    PubMed

    Flynn, J J; Nedbal, M A; Dragoo, J W; Honeycutt, R L

    2000-11-01

    The evolutionary history of the red panda (Ailurus fulgens) plays a pivotal role in the higher-level phylogeny of the "bear-like" arctoid carnivoran mammals. Characters from morphology and molecules have provided inconsistent evidence for placement of the red panda. Whereas it certainly is an arctoid, there has been major controversy about whether it should be placed with the bears (ursids), ursids plus pinnipeds (seals, sea lions, walrus), raccoons (procyonids), musteloids (raccoons plus weasels, skunks, otters, and badgers [mustelids]), or as a monotypic lineage of uncertain phylogenetic affinities. Nucleotide sequence data from three mitochondrial genes and one nuclear intron were analyzed, with more complete taxonomic sampling of relevant taxa (arctoids) than previously available in analyses of primary molecular data, to clarify the phylogenetic relationships of the red panda to other arctoid carnivorans. This study provides detailed phylogenetic analyses (both parsimony and maximum-likelihood) of primary character data for arctoid carnivorans, including bootstrap and decay indices for all arctoid nodes, and three statistical tests of alternative phylogenetic hypotheses for the placement of the red panda. Combined phylogenetic analyses reject the hypotheses that the red panda is most closely related to the bears (ursids) or to the raccoons (procyonids). Rather, evidence from nucleotide sequences strongly support placement of the red panda within a broad Musteloidea (sensu lato) clade, including three major lineages (the red panda, the skunks [mephitids], and a clearly monophyletic clade of procyonids plus mustelids [sensu stricto, excluding skunks]). Within the Musteloidea, interrelationships of the three major lineages are unclear and probably are best considered an unresolved trichotomy. These data provide compelling evidence for the relationships of the red panda and demonstrate that small taxonomic sample sizes can result in misleading or possibly erroneous

  18. Whence the red panda?

    PubMed

    Flynn, J J; Nedbal, M A; Dragoo, J W; Honeycutt, R L

    2000-11-01

    The evolutionary history of the red panda (Ailurus fulgens) plays a pivotal role in the higher-level phylogeny of the "bear-like" arctoid carnivoran mammals. Characters from morphology and molecules have provided inconsistent evidence for placement of the red panda. Whereas it certainly is an arctoid, there has been major controversy about whether it should be placed with the bears (ursids), ursids plus pinnipeds (seals, sea lions, walrus), raccoons (procyonids), musteloids (raccoons plus weasels, skunks, otters, and badgers [mustelids]), or as a monotypic lineage of uncertain phylogenetic affinities. Nucleotide sequence data from three mitochondrial genes and one nuclear intron were analyzed, with more complete taxonomic sampling of relevant taxa (arctoids) than previously available in analyses of primary molecular data, to clarify the phylogenetic relationships of the red panda to other arctoid carnivorans. This study provides detailed phylogenetic analyses (both parsimony and maximum-likelihood) of primary character data for arctoid carnivorans, including bootstrap and decay indices for all arctoid nodes, and three statistical tests of alternative phylogenetic hypotheses for the placement of the red panda. Combined phylogenetic analyses reject the hypotheses that the red panda is most closely related to the bears (ursids) or to the raccoons (procyonids). Rather, evidence from nucleotide sequences strongly support placement of the red panda within a broad Musteloidea (sensu lato) clade, including three major lineages (the red panda, the skunks [mephitids], and a clearly monophyletic clade of procyonids plus mustelids [sensu stricto, excluding skunks]). Within the Musteloidea, interrelationships of the three major lineages are unclear and probably are best considered an unresolved trichotomy. These data provide compelling evidence for the relationships of the red panda and demonstrate that small taxonomic sample sizes can result in misleading or possibly erroneous

  19. 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.

  20. Red cell metabolism in red and grey kangaroos.

    PubMed

    Agar, N S

    1977-12-15

    Glucose utilization, lactate production and glutathione regeneration were measured in the red blood cells of 2 species of Australian Marsupials, Eastern grey Kangaroo (Macropus gigantus) and red kangaroo (Macropus rufus), and were found to be significantly lower in the red blood cells from grey than that of red kangaroos.

  1. Autologous bone marrow transplantation by photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Gulliya, Kirpal S.

    1992-06-01

    Simultaneous exposure of Merocyanine 540 dye containing cultured tumor cells to 514-nm laser light (93.6 J/cm2) results in virtually complete cell destruction. Under identical conditions, 40% of the normal progenitor (CFU-GM) cells survive the treatment. Laser- photoradiation treated, cultured breast cancer cells also were killed, and living tumor cells could not be detected by clonogenic assays or by anti-cytokeratin monoclonal antibody method. Thus, laser photoradiation therapy could be useful for purging of contaminating tumor cells from autologous bone marrow.

  2. Ocular complications of bone marrow transplantation.

    PubMed

    Livesey, S J; Holmes, J A; Whittaker, J A

    1989-01-01

    Thirty-four patients who had undergone bone marrow transplantation (BMT) were examined; 83.3% of those who received single shot and none of those who received fractionated total body irradiation (TBI) developed cataracts. The use of steroids to treat chronic Graft Versus Host Disease (GVHD) produced more severe cataracts in those who had allogeneic transplants after single shot TBI, but follow-up has not been long enough to assess their effect following fractionated TBI. Keratoconjunctivitis sicca (KCS) was seen in 81.8% of patients with chronic GVHD and in 33.3% of patients after autologous BMT. PMID:2693135

  3. 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

  4. Clinical utility of bone marrow culture.

    PubMed

    Moore, M A

    1976-01-01

    Standardized culture of bone marrow in soft agar permits the detection of a population of granulocyte-macrophage progenitor cells (CFU-c). A spectrum of qualitative abnormalities serves to distinguish myeloid leukemic CFU-c from normal and remission populations. These abnormalities in maturation and proliferation are diagnostic of a myeloid leukemic state and serve to functionally reclassify acute myeloid leukemia at diagnosis into a number of categories based on in vitro growth pattern. The virtue of this classification is that it permits detection of a substantial number of patients who are refractory to conventional remission induction protocols. The clear distinction between normal and leukemic growth in vitro permits early detection of emerging remission CFU-c during induction therapy and of early onset of relapse in patients who are otherwise in complete remission. In patients with leukemia undergoing allogeneic bone marrow engraftment, marrow culture has proved of value in documenting the reconstitution of the patient and in detecting re-emergence of the original leukemic stem line prior to its detection by cytogenetic and hematological techniques. Serial studies on patients with chronic myeloid leukemia have allowed early diagnosis of blastic transformation and classification of blastic phase disease on the basis of in vitro growth pattern has revealed a similar spectrum of in vitro abnormalities as seen in AML. The cloning of normal or leukemic human myeloid progenitor cells (CFU-c) in agar or methylcellulose has permitted analysis of both quantitative and qualitative changes in this cell compartment in leukemia and other myelodysplastic states (1-7). Among these changes are abnormalities in maturation of leukemic cells in vitro (4, 5, 6), defective proliferation as measured by colony size or cluster to colony ratio (5, 6), abnormalities in biophysical characteristics of leukemic CFU-c (4, 5), regulatory defects in responsiveness to positive and negative

  5. The National Marrow Donor Program and Be The Match Registry | NIH MedlinePlus the Magazine

    MedlinePlus

    ... Marrow Transplants The National Marrow Donor Program and Be The Match Registry Past Issues / Summer 2011 Table ... the National Marrow Donor Program (NMDP) and its Be The Match Registry are nonprofit organizations dedicated to ...

  6. 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.

  7. Splenocytes seed bone marrow of myeloablated mice: implication for atherosclerosis.

    PubMed

    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.

  8. 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.

  9. 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 α4β1-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

  10. Effects of the bone marrow microenvironment on hematopoietic malignancy.

    PubMed

    Askmyr, Maria; Quach, Julie; Purton, Louise E

    2011-01-01

    The bone marrow (BM) is contained within the bone cavity and is the main site of hematopoiesis, the continuous development of blood cells from immature hematopoietic stem and progenitor cells. The bone marrow consists of developing hematopoietic cells and non-hematopoietic cells, the latter collectively termed the bone marrow microenvironment. These non-hematopoietic cells include cells of the osteoblast lineage, adipocytes and endothelial cells. For many years these bone marrow microenvironment cells were predicted to play active roles in regulating hematopoiesis, and recent studies have confirmed such roles. Importantly, more recent data has indicated that cells of the BM microenvironment may also contribute to hematopoietic diseases. In this review we provide an overview of the roles of the data suggesting that the cells of the bone marrow microenvironment may play an active role in the initiation and progression of hematopoietic malignancy.

  11. [Bone marrow stromal damage mediated by immune response activity].

    PubMed

    Vojinović, J; Kamenov, B; Najman, S; Branković, Lj; Dimitrijević, H

    1994-01-01

    The aim of this work was to estimate influence of activated immune response on hematopoiesis in vitro, using the experimental model of BCG immunized BALB/c mice and in patients with chronic immunoactivation: long-lasting infections, autoimmunity or malignancy. We correlated changes in long term bone marrow cultures (Dexter) and NBT reduction with appearance of anemia in patients and experimental model of immunization by BCG. Increased spontaneous NBT reduction pointed out role of macrophage activation in bone marrow stroma damage. Long-term bone marrow cultures showed reduced number of hematopoietic cells, with predomination of fibroblasts and loss of fat cells. This results correlated with anemia and leucocytosis with stimulated myelopoiesis in peripheral blood. Activation of immune response, or acting of any agent that directly changes extracellular matrix and cellularity of bone marrow, may result in microenviroment bone marrow damage that modify hematopoiesis.

  12. Red cell enzymes.

    PubMed

    Paniker, N V

    1975-03-01

    As compared to other cells of the body, the mammalian red cell has one of the simplest structural organizations. As a result, this cell has been extensively used in studies involving the structure, function, and integrity of cell membranes as well as cytoplasmic events. Additionally, the metabolic activities of the red blood cell are also relatively simple. During the past quarter century or so, an ocean of knowledge has been gathered on various aspects of red cell metabolism and function. The fields of enzymes, hemoglobin, membrane, and metabolic products comprise the major portion of this knowledge. These advances have made valuable contributions to biochemistry and medicine. Despite these favorable aspects of this simple, anucleated cell, it must be conceded that our knowledge about the red cell is far from complete. We are still in the dark concerning the mechanism involved in several aspects of its membrane, hemoglobin, enzymes, and a large number of other constituents. For example, a large number of enzymes with known catalytic activity but with unknown function have eluded investigators despite active pursuit. This review will be a consolidation of our present knowledge of human red cell enzymes, with particular reference to their usefulness in the diagnosis and therapy of disease. Owing to the multitude of publications by prominent investigators on each of the approximately 50 enzymes discussed in this review, it was impossible to cite a majority of them.

  13. 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.

  14. Red-based cumulus.

    PubMed

    Gedzelman, Stanley David

    2015-02-01

    Observations and model simulations of cumulus clouds whose bases are tinted red when the Sun is well above the horizon are presented. Conditions for seeing red bases include (1) a red underlying surface (which may consist of dust clouds, as from haboobs) with high albedo, (2) small fractional cloud cover when the Sun is far enough below the zenith for direct sunlight to illuminate much of the surface directly below and around cloud base, (3) optically thick clouds so that the bases are dark, and (4) clouds with bases that are near enough to the observer to appear high in the sky so that the admixture of scattered light from the intervening atmosphere is minimized.

  15. Comparative Study of Bone Marrow and Blood B Cells in Infantile and Acquired Agammaglobulinemia

    PubMed Central

    Abdou, Nabih I.; Casella, Salvatore R.; Abdou, Nancy L.; Abrahamsohn, Ises A.

    1973-01-01

    The status of immunoglobulin (Ig) receptors of the bone marrow dependent (B) cells present in either the bone marrow (BM) or peripheral blood (PB) of three patients with infantile agammaglobulinemia (I-AGG), or seven patients with acquired agammaglobulinemia (A-AGG) is compared with those of 12 controls. Quantitative and qualitative changes of the different classes of Ig receptors on B cells were evaluated by their capacity to bind [125I]anti-Ig, to be stained with fluorescinated anti-Ig and their in vitro proliferative capacity upon incubation with the anti-Ig. Patients with I-AGG lacked B cells in both the BM and PB. Whereas BM cells of patients with A-AGG carried receptors similar to control cells, their blood B cells had fewer IgM, IgG, and IgA cells which failed to proliferate in vitro in the presence of the anti-Ig. An anti-IgM of the IgG class was detected in the sera of patients with A-AGG but not in sera of I-AGG. The isolated anti-IgM agglutinated human red cells coated with IgM. The anti-IgM partially blocked the binding of fluorescinated or radiolabeled anti-IgM to IgM peripheral blood lymphocytes of normal controls. The eluted anti-IgM in presence of complement was partially cytotoxic to normal cells. It is concluded that I-AGG-B cell defect is due to failure of B cell development in the bone marrow compartment whereas the peripheral exclusion of IgM cells by an anti-IgM with the subsequent failure of differentiation of both IgG and IgA cells could be an important mechanism in A-AGG-B cell defect. PMID:4580388

  16. Exercise Regulation of Marrow Adipose Tissue

    PubMed Central

    Pagnotti, Gabriel M.; Styner, Maya

    2016-01-01

    Despite association with low bone density and skeletal fractures, marrow adipose tissue (MAT) remains poorly understood. The marrow adipocyte originates from the mesenchymal stem cell (MSC) pool that also gives rise to osteoblasts, chondrocytes, and myocytes, among other cell types. To date, the presence of MAT has been attributed to preferential biasing of MSC into the adipocyte rather than osteoblast lineage, thus negatively impacting bone formation. Here, we focus on understanding the physiology of MAT in the setting of exercise, dietary interventions, and pharmacologic agents that alter fat metabolism. The beneficial effect of exercise on musculoskeletal strength is known: exercise induces bone formation, encourages growth of skeletally supportive tissues, inhibits bone resorption, and alters skeletal architecture through direct and indirect effects on a multiplicity of cells involved in skeletal adaptation. MAT is less well studied due to the lack of reproducible quantification techniques. In recent work, osmium-based 3D quantification shows a robust response of MAT to both dietary and exercise intervention in that MAT is elevated in response to high-fat diet and can be suppressed following daily exercise. Exercise-induced bone formation correlates with suppression of MAT, such that exercise effects might be due to either calorie expenditure from this depot or from mechanical biasing of MSC lineage away from fat and toward bone, or a combination thereof. Following treatment with the anti-diabetes drug rosiglitazone – a PPARγ-agonist known to increase MAT and fracture risk – mice demonstrate a fivefold higher femur MAT volume compared to the controls. In addition to preventing MAT accumulation in control mice, exercise intervention significantly lowers MAT accumulation in rosiglitazone-treated mice. Importantly, exercise induction of trabecular bone volume is unhindered by rosiglitazone. Thus, despite rosiglitazone augmentation of MAT, exercise

  17. Exercise Regulation of Marrow Adipose Tissue.

    PubMed

    Pagnotti, Gabriel M; Styner, Maya

    2016-01-01

    Despite association with low bone density and skeletal fractures, marrow adipose tissue (MAT) remains poorly understood. The marrow adipocyte originates from the mesenchymal stem cell (MSC) pool that also gives rise to osteoblasts, chondrocytes, and myocytes, among other cell types. To date, the presence of MAT has been attributed to preferential biasing of MSC into the adipocyte rather than osteoblast lineage, thus negatively impacting bone formation. Here, we focus on understanding the physiology of MAT in the setting of exercise, dietary interventions, and pharmacologic agents that alter fat metabolism. The beneficial effect of exercise on musculoskeletal strength is known: exercise induces bone formation, encourages growth of skeletally supportive tissues, inhibits bone resorption, and alters skeletal architecture through direct and indirect effects on a multiplicity of cells involved in skeletal adaptation. MAT is less well studied due to the lack of reproducible quantification techniques. In recent work, osmium-based 3D quantification shows a robust response of MAT to both dietary and exercise intervention in that MAT is elevated in response to high-fat diet and can be suppressed following daily exercise. Exercise-induced bone formation correlates with suppression of MAT, such that exercise effects might be due to either calorie expenditure from this depot or from mechanical biasing of MSC lineage away from fat and toward bone, or a combination thereof. Following treatment with the anti-diabetes drug rosiglitazone - a PPARγ-agonist known to increase MAT and fracture risk - mice demonstrate a fivefold higher femur MAT volume compared to the controls. In addition to preventing MAT accumulation in control mice, exercise intervention significantly lowers MAT accumulation in rosiglitazone-treated mice. Importantly, exercise induction of trabecular bone volume is unhindered by rosiglitazone. Thus, despite rosiglitazone augmentation of MAT, exercise significantly

  18. Multiparameter Analysis of Human Bone Marrow Stromal Cells Identifies Distinct Immunomodulatory and Differentiation-Competent Subtypes

    PubMed Central

    James, Sally; Fox, James; Afsari, Farinaz; Lee, Jennifer; Clough, Sally; Knight, Charlotte; Ashmore, James; Ashton, Peter; Preham, Olivier; Hoogduijn, Martin; Ponzoni, Raquel De Almeida Rocha; Hancock, Y.; Coles, Mark; Genever, Paul

    2015-01-01

    Summary Bone marrow stromal cells (BMSCs, also called bone-marrow-derived mesenchymal stromal cells) provide hematopoietic support and immunoregulation and contain a stem cell fraction capable of skeletogenic differentiation. We used immortalized human BMSC clonal lines for multi-level analysis of functional markers for BMSC subsets. All clones expressed typical BMSC cell-surface antigens; however, clones with trilineage differentiation capacity exhibited enhanced vascular interaction gene sets, whereas non-differentiating clones were uniquely CD317 positive with significantly enriched immunomodulatory transcriptional networks and high IL-7 production. IL-7 lineage tracing and CD317 immunolocalization confirmed the existence of a rare non-differentiating BMSC subtype, distinct from Cxcl12-DsRed+ perivascular stromal cells in vivo. Colony-forming CD317+ IL-7hi cells, identified at ∼1%–3% frequency in heterogeneous human BMSC fractions, were found to have the same biomolecular profile as non-differentiating BMSC clones using Raman spectroscopy. Distinct functional identities can be assigned to BMSC subpopulations, which are likely to have specific roles in immune control, lymphopoiesis, and bone homeostasis. PMID:26070611

  19. 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.

  20. Correction of bone marrow failure in dyskeratosis congenita by bone marrow transplantation.

    PubMed

    Ghavamzadeh, A; Alimoghadam, K; Nasseri, P; Jahani, M; Khodabandeh, A; Ghahremani, G

    1999-02-01

    Dyskeratosis congenita is recognized by its dermal lesions and constitutional aplastic anemia in some cases. We report successful allogeneic bone marrow transplantation in two siblings with this disease from their sister, and their long term follow-up. We used reduced doses of cyclophosphamide and busulfan for conditioning instead of total body irradiation. Also, we report late adverse effects of transplantation which are not distinguishable from the natural course of disease.

  1. Induction of tolerance to a soluble antigen following irradiation and bone marrow reconstitution.

    PubMed

    Schleimer, R P; Scibienski, R J; Vollger, H F; Benjamini, E

    1982-01-01

    Antigen-specific tolerance was induced in mice by lethal irradiation followed by reconstitution with syngeneic, anti-T-cell-treated bone marrow and injection of the protein antigen lysozyme. Animals tolerized with lysozyme responded normally to a second antigen, sheep red blood cells, and animals treated with the same tolerizing regimen using a different protein antigen, bovine serum albumin, responded normally to lysozyme. Challenge of the tolerant mice with lysozyme covalently coupled to LPS induced an antilysozyme response indicating that if tolerance was expressed on the B-cell level that antigen-specific B-cells were still present. These results eliminate clonal abortion and clonal selection as the mechanism of tolerance generation. The tolerance generated by this procedure is either expressed on the T-cell level or is produced by a state of B-cell clonal anergy which can be overcome by the use of antigen coupled to lipopolysaccharide.

  2. The Inherited Bone Marrow Failure Syndromes

    PubMed Central

    Chirnomas, S. Deborah; Kupfer, Gary M

    2013-01-01

    In spite of the rarity of inherited bone marrow failure syndromes (IBMFS), they represent diseases for which the molecular pathogenesis may be elucidated. Their study and presentation of the details of their molecular biology and biochemistry is warranted not only for appropriate diagnosis and management of afflicted patients but also because they lend clues to the normal physiology of the normal hematopoiesis and, in many cases, mechanisms of carcinogenesis. Several themes have emerged within each subsection of IBMFS, including the ribosomopathies that entail both ribosome assembly as well as ribosomal RNA processing. The Fanconi anemia (FA) pathway itself has become interdigitated with the familial breast cancer syndromes. The sections that follow present a more detailed analysis of the diseases that account for the majority of IBMFS diagnoses. PMID:24237972

  3. 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.

  4. Psychosocial effects of unrelated bone marrow donation: experiences of the National Marrow Donor Program.

    PubMed

    Butterworth, V A; Simmons, R G; Bartsch, G; Randall, B; Schimmel, M; Stroncek, D F

    1993-04-01

    In this study, we investigated the psychosocial effects of unrelated marrow donation. Survey questionnaires were administered pre-donation, shortly post-donation, and 1 year post-donation to all donors through the National Marrow Donor Program over a 3-year period. Univariate, bivariate, and multivariate analyses were then performed. Donors were generally quite positive about the donation 1 year post-donation: 87% felt it was "very worthwhile" and 91% would be willing to donate again in the future. Marrow donors were more likely than kidney donors to feel better about themselves as a result of the donation (P < .001). Donors with longer collection times, in general, had less positive psychosocial outcomes from the donation. Donors who experienced lower back pain or difficulty walking as a result of the donation were more likely to experience the donation as more stressful and painful than expected, but no more likely to experience it as less positive emotionally than donors who did not experience these side effects.

  5. '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...

  6. 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 ...

  7. Red mud product development

    SciTech Connect

    Kirkpatrick, D.B.

    1996-10-01

    Kaiser Alumina and Chemical Co. impounds red mud, the byproduct of alumina production, behind levees. Kaiser recognizes that this action cannot be maintained indefinitely. Therefore, a project is in progress to produce useful products from red mud that increase the profitability of the Gramercy facility. Before products could be developed, an obstacle had to be overcome. The annual rainfall in South Louisiana prevents evaporative drying of the mud lakes. Innovative methods were applied to dry the lake mud. Two products have been developed. A daily landfill cover and an absorbant, which are marketed under the Cajunite{trademark} banner. Both products are currently being tested by potential customers at their sites. Environmental concerns were addressed during development. Extensive TCLP results show no metal leachate problems. All pilot tests and plant trials received LADEQ approval. Products that are under development include levee core, road base, fertilizer fillers and synthetic soils. State and Federal agencies are interested in using red mud to remediate coastal erosion. Kaiser is also pursuing the recovery of metals from red mud.

  8. 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)

  9. 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

  10. 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.

  11. Detection of Bone Marrow Derived Lung Epithelial Cells

    PubMed Central

    Kassmer, Susannah H.; Krause, Diane S.

    2010-01-01

    Studies on the ability of bone marrow derived cells to adopt the morphology and protein expression of epithelial cells in vivo have expanded rapidly over the last decade, and hundreds of publications report that bone marrow derived cells can become epithelial cells of multiple organs including lung, liver, GI tract, skin, pancreas and others. In this review, we critically evaluate the literature related to engraftment of bone marrow derived cells as epithelial cells in the lung. Over 40 manuscripts focused on whether bone marrow cells can differentiate into lung epithelial cells have been published, nearly all of which claim to identify marrow derived epithelial cells. A few investigations have concluded that no such cells are present and that the phenomenon of marrow derived epithelial cells is based on detection artifacts. Here we discuss the problems that exist in published papers identifying marrow derived epithelial cells, and propose standards for detection methods that provide the most definitive data. Identification of BM derived epithelial cells requires reliable and sensitive techniques for their detection, which must include cell identification based on the presence of an epithelial marker and the absence of blood cell markers as well as a marker for donor BM origin. In order for these studies to be rigorous, they must also use approaches to rule out cell overlap by microscopy or single cell isolation. Once these stringent criteria for identification of marrow derived epithelial cells are used universally, then the field can move forward to address the critical questions regarding which bone marrow derived cells are responsible for engraftment as epithelial cells, the mechanisms by which this occurs, whether these cells play a role in normal tissue repair, and whether specific cell subsets can be used for therapeutic benefit. PMID:20447442

  12. [Erythrocyte removal from bone marrow by density gradient separation using the COBE 2991 cell processor with the triple-bag processing set].

    PubMed

    Cappellesso-Fleury, S; Rage, C; Tschaggeny, F; Gaudé, J; Gomez, M; Bourin, P

    2009-03-01

    ABO-incompatible bone marrow transplantation requires red blood cell depletion. Lots of laboratory adopted the technique of density gradient centrifugation (Ficoll-hypaque) using the COBE 2991 cell processor with simple-bag processing set. However, tubing of this set is not adapted to the currently available peristaltic pumps. Moreover, two other sets are required: one for the buffy-coat and one for postgradient cell washing. We developed a method using triple-bag processing set to conduct whole-step procedure (concentration, Ficoll and washing). Peristaltic PVC tubing is provided in one line of the set allowing a safe processing without several connections thus reducing risks of microbial contamination. First, we used buffy-coat of total blood for training, then, we carried out red cell depletion of healthy bone marrow donors. The red blood cell depletion was 97.9+/-1.1% and CD34+ recovery was 89.6+/-8.7%. These results are very close to those obtained with the simple-bag set (red cell depletion.=94.0+/-6.8% and CD34+ recovery=95.9+/-20.3%). We conclude that the triple-bag system, very little used in France, is practical, simplified the manipulation and is more safety than the simple-bag set.

  13. 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.

  14. 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...

  15. Effects of the extract of Ginkgo biloba on the differentiation of bone marrow mesenchymal stem cells in vitro.

    PubMed

    Wu, Zhe; Zhang, Jiadi; Gu, Xu; Zhang, Xiaoxiao; Shi, Shuman; Liu, Chang

    2016-01-01

    The balance of osteogenesis and adipogenesis in bone marrow mesenchymal stem cells (BMSCs) is disrupted in osteoporosis. This study was designed to investigate the effects of extract of Ginkgo biloba (EGB) on proliferation, osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells in vitro. The effect of EGB on proliferation was evaluated by CCK-8 assay and flow cytometry. Osteogenic differentiation was evaluated by Alizarin Red S staining and Alkaline phosphatase assay. Adipogenic differentiation was evaluated by Oil Red O staining. Quantitative real-time polymerase chain reaction (Real-time PCR) was used to detect the expression of osteogenic specific genes (BMP-2, Runx2 and Colla1) and adipogenic specific genes (ap2, PPARγ). EGB did not significantly affect proliferation of BMSCs. However, it increased the calcium accumulation and significantly promoted the activity of alkaline phosphatase, especially when the concentration of EGB reached 150 µg/mL. EGB dose-dependently inhibited the adipogenic ability of BMSCs. The osteogenic-related genes (BMP-2, Runx2, Colla1) were overexpressed while the expression of genes involved in adipogenesis, such as PPAR-γ and ap2, was decreasing with the increase of EGB concentration. Our data proves that EGB inhibited adipocyte differentiation and enhanced osteogenic differentiation in BMSCs, but had no effect on the proliferation of BMSCs. PMID:27508023

  16. Effects of the extract of Ginkgo biloba on the differentiation of bone marrow mesenchymal stem cells in vitro

    PubMed Central

    Wu, Zhe; Zhang, Jiadi; Gu, Xu; Zhang, Xiaoxiao; Shi, Shuman; Liu, Chang

    2016-01-01

    The balance of osteogenesis and adipogenesis in bone marrow mesenchymal stem cells (BMSCs) is disrupted in osteoporosis. This study was designed to investigate the effects of extract of Ginkgo biloba (EGB) on proliferation, osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells in vitro. The effect of EGB on proliferation was evaluated by CCK-8 assay and flow cytometry. Osteogenic differentiation was evaluated by Alizarin Red S staining and Alkaline phosphatase assay. Adipogenic differentiation was evaluated by Oil Red O staining. Quantitative real-time polymerase chain reaction (Real-time PCR) was used to detect the expression of osteogenic specific genes (BMP-2, Runx2 and Colla1) and adipogenic specific genes (ap2, PPARγ). EGB did not significantly affect proliferation of BMSCs. However, it increased the calcium accumulation and significantly promoted the activity of alkaline phosphatase, especially when the concentration of EGB reached 150 µg/mL. EGB dose-dependently inhibited the adipogenic ability of BMSCs. The osteogenic-related genes (BMP-2, Runx2, Colla1) were overexpressed while the expression of genes involved in adipogenesis, such as PPAR-γ and ap2, was decreasing with the increase of EGB concentration. Our data proves that EGB inhibited adipocyte differentiation and enhanced osteogenic differentiation in BMSCs, but had no effect on the proliferation of BMSCs. PMID:27508023

  17. Bone marrow hypoplasia in a cat treated with griseofulvin.

    PubMed

    Rottman, J B; English, R V; Breitschwerdt, E B; Duncan, D E

    1991-02-01

    Three weeks after initiation of griseofulvin treatment for dermatophytosis (40 mg/kg of body weight, q 12 h), an 8-yr-old domestic shorthair cat developed depression, vomiting, and pyrexia. Abnormalities found during physical examination included bilateral mydriasis, visual impairment, grade-II/V systolic murmur and multiple areas of alopecia. The cat was pancytopenic; serum biochemical abnormalities included hyperbilirubinemia, hyperglycemia, hyponatremia, and hypokalemia, and urinalysis revealed proteinuria, glycosuria, and bilirubinuria. Examination of a bone marrow aspirate revealed profound hypoplasia of all precursors. Griseofulvin toxicosis was diagnosed on the basis of the temporal relationship of drug administration with onset of clinical, hematologic, and biochemical abnormalities and failure to identify an infective or neoplastic cause for the bone marrow hypoplasia. The condition was refractory to treatment and the cat was euthanatized. Pathologic changes in the bone marrow were consistent with severe hypoplasia of all bone marrow precursors.

  18. [Bone marrow involvement in ovarian cancer determined by immunohistochemical methods].

    PubMed

    Gabriel, M; Obrebowska, A; Spaczyński, M

    2000-01-01

    Atypical epithelial cells in the bone marrow of patients with ovarian cancer were evaluated using immunohistochemical techniques. We investigated cytospin preparations of bone marrow taken from 9 women with benign ovarian tumors and 59 women with malignant ovarian tumors. Two monoclonal antibodies (NCL-C11 and NCL-CA 125) were used. With both antibodies we were able to detect keratin and CA 125 antigen expression in the bone marrow of 9 (18.4%) of the patients with ovarian cancer. With regard to the wide histological differentiation of ovarian carcinomas, the presence of atypical epithelial cells in the bone marrow was required as a prognostic factor for survival and relapses. This should be investigated in a larger study group. PMID:11326158

  19. 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

  20. 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.

  1. CNS inflammation and bone marrow neuropathy in type 1 diabetes.

    PubMed

    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

    2013-11-01

    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.

  2. 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.

  3. [Bone and Stem Cells. Intravital imaging of bone marrow microenvironment].

    PubMed

    Mizuno, Hiroki; Kikuta, Junichi; Ishii, Masaru

    2014-04-01

    Various kinds of cell types, such as osteoclasts, osteoblasts, hematopoietic cells, and mesenchymal cells, have been reported to exist in the bone marrow and communicate with each other. Although there have been many previous studies about bone marrow microenvironment, most of them were analyzed by conventional methods such as histological analysis and flow cytometry. These methods could not observe the dynamic cell movement in living bone marrow. Recently rapid development of fluorescent imaging techniques enables us to understand the cellular dynamics in vivo . That's why we have originally established an advanced imaging system for visualizing living bone tissues with intravital two-photon microscopy. Here we show the latest data and the detailed methodology of intravital imaging of bone marrow microenvironment, and also discuss its further application.

  4. Understanding Bone Marrow Transplantation as a Treatment Option

    MedlinePlus

    ... you have had, and your overall health. Transplant Process A bone marrow or cord blood transplant is ... The Transplant Process . For more about the search process, HLA matching, and steps of a transplant, such ...

  5. Distinct bone marrow blood vessels differentially regulate haematopoiesis.

    PubMed

    Itkin, Tomer; Gur-Cohen, Shiri; Spencer, Joel A; Schajnovitz, Amir; Ramasamy, Saravana K; Kusumbe, Anjali P; Ledergor, Guy; Jung, Yookyung; Milo, Idan; Poulos, Michael G; Kalinkovich, Alexander; Ludin, Aya; Kollet, Orit; Shakhar, Guy; Butler, Jason M; Rafii, Shahin; Adams, Ralf H; Scadden, David T; Lin, Charles P; Lapidot, Tsvee

    2016-04-21

    Bone marrow endothelial cells (BMECs) form a network of blood vessels that regulate both leukocyte trafficking and haematopoietic stem and progenitor cell (HSPC) maintenance. However, it is not clear how BMECs balance these dual roles, and whether these events occur at the same vascular site. We found that mammalian bone marrow stem cell maintenance and leukocyte trafficking are regulated by distinct blood vessel types with different permeability properties. Less permeable arterial blood vessels maintain haematopoietic stem cells in a low reactive oxygen species (ROS) state, whereas the more permeable sinusoids promote HSPC activation and are the exclusive site for immature and mature leukocyte trafficking to and from the bone marrow. A functional consequence of high permeability of blood vessels is that exposure to blood plasma increases bone marrow HSPC ROS levels, augmenting their migration and differentiation, while compromising their long-term repopulation and survival. These findings may have relevance for clinical haematopoietic stem cell transplantation and mobilization protocols.

  6. 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)

  7. Bone marrow metastasis presenting as bicytopenia originating from hepatocellular carcinoma

    PubMed Central

    Hong, Young Mi; Yoon, Ki Tae; Cho, Mong; Kang, Dae Hwan; Kim, Hyung Wook; Choi, Cheol Woong; Park, Su Bum; Heo, Jeong; Woo, Hyun Young; Lim, Won; Bakhtiar UI Islam, SM

    2016-01-01

    The bone is a common site for metastasis in hepatocellular carcinoma (HCC). However, bone marrow metastasis from HCC is rarely reported, and its frequency is unclear. Here we report a rare case of bone marrow metastasis that presented as bicytopenia originating from HCC without bone metastasis. A 58-year-old man was admitted for investigation of a liver mass with extensive lymph node enlargement that was detected when examining his general weakness and weight loss. Laboratory findings revealed anemia, thrombocytopenia, mild elevated liver enzymes, normal prothrombin time percentage and high levels of tumor markers (α-fetoprotein and des-γ-carboxyprothrombin). Abdominal computed tomography showed multiple enhanced masses in the liver and multiple enlarged lymph nodes in the abdomen. A bone marrow biopsy revealed only a few normal hematopoietic cells and abundant tumor cells. Despite its rarity, bone marrow metastasis should always be suspected in HCC patients even if accompanied by cirrhosis. PMID:27184470

  8. A marker chromosome in post-transplant bone marrow.

    PubMed

    Morsberger, Laura; Powell, Kerry; Ning, Yi

    2016-01-01

    Detection of small supernumerary marker chromosomes in karyotype analysis represents a diagnostic challenge. While such markers are usually detected during cytogenetic studies of constitutional chromosome abnormalities, they have also been found in specimens submitted from patients with acquired malignancies. We report here the detection of a marker chromosome in a bone marrow specimen from a patient who received a bone marrow transplantation. We discuss the importance of proper characterization and interpretation of marker chromosomes in clinical practice. PMID:27252781

  9. 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

  10. Great Red Spot (GRS)

    NASA Astrophysics Data System (ADS)

    Murdin, P.

    2000-11-01

    A huge permanent anticyclone in Jupiter's southern hemisphere, visible as a reddish oval at just over 20 °S. The earliest unequivocal observation was by Heinrich Schwabe in 1831 (the often-quoted sighting by Robert Hooke in 1664 now seems to have been of a similar but different spot). The GRS became a striking feature around 1880, when it developed a deep red coloration. It was also prominent in ...

  11. Activation of bone marrow phagocytes following benzene treatment of mice.

    PubMed Central

    Laskin, D L; MacEachern, L; Snyder, R

    1989-01-01

    Techniques in flow cytometry/cell sorting were used to characterize the effects of benzene and its metabolites on subpopulations of bone marrow cells. Treatment of male Balb/c mice with benzene (880 mg/kg) or a combination of its metabolites, hydroquinone and phenol (50 mg/kg), resulted in a 30 to 40% decrease in bone marrow cellularity. Flow cytometric analysis revealed two subpopulations of bone marrow cells that could be distinguished by their size and density or granularity. The larger, more dense subpopulation was found to consist predominantly of macrophages and granulocytes as determined by monoclonal antibody binding and by cell sorting. Benzene treatment had no selective cytotoxic effects on subpopulations of bone marrow cells. To determine if benzene treatment activated bone marrow phagocytes, we quantified production of hydrogen peroxide by these cells using the fluorescent indicator dye, 2',7'-dichlorofluorescein diacetate. We found that macrophages and granulocytes from bone marrow of treated mice produced 50% more hydrogen peroxide in response to the phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate than did cells from control animals. It is hypothesized that phagocyte activation and production of cytotoxic reactive oxygen intermediates may contribute to hematotoxicity induced by benzene. PMID:2676504

  12. Benzene toxicokinetics in humans: exposure of bone marrow to metabolites.

    PubMed Central

    Watanabe, K H; Bois, F Y; Daisey, J M; Auslander, D M; Spear, R C

    1994-01-01

    A three compartment physiologically based toxicokinetic model was fitted to human data on benzene disposition. Two separate groups of model parameter derivations were obtained, depending on which data sets were being fitted. The model was then used to simulate five environmental or occupational exposures. Predicted values of the total bone marrow exposure to benzene and cumulative quantity of metabolites produced by the bone marrow were generated for each scenario. The relation between cumulative quantity of metabolites produced by the bone marrow and continuous benzene exposure was also investigated in detail for simulated inhalation exposure concentrations ranging from 0.0039 ppm to 150 ppm. At the level of environmental exposures, no dose rate effect was found for either model. The occupational exposures led to only slight dose rate effects. A 32 ppm exposure for 15 minutes predicted consistently higher values than a 1 ppm exposure for eight hours for the total exposure of bone marrow to benzene and the cumulative quantity of metabolites produced by the bone marrow. The general relation between the cumulative quantity of metabolites produced by the bone marrow and the inhalation concentration of benzene is not linear. An inflection point exists in some cases leading to a slightly S shaped curve. At environmental levels (0.0039-10 ppm) the curve bends upward, and it saturates at high experimental exposures (greater than 100 ppm). PMID:8044234

  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. Endocrine complications following pediatric bone marrow transplantation.

    PubMed

    Ho, Josephine; Lewis, Victor; Guilcher, Gregory M T; Stephure, David K; Pacaud, Danièle

    2011-01-01

    Pediatric bone marrow transplantation (BMT) for various diseases can lead to endocrine system dysfunction owing to preparative regimens involving chemotherapy and radiation therapy. We assessed the prevalence of post-BMT endocrine complications in children treated at the Alberta Children's Hospital (ACH) from 1991 to 2001. Time of onset of endocrine dysfunction, underlying disease processes, chemotherapy, radiation therapy and age at BMT were characterized. Subjects of <18 years of age at the time of allogeneic or autologous BMT for whom 1-year follow-up through the ACH and a chart were available for review were included in the study. Subjects with a pre-existing endocrine condition were excluded. Of the 194 pediatric BMT procedures performed at the ACH between January 1, 1991 and December 31, 2001, 150 complete charts were available for review. Sixty five subjects received follow-up care at other centers and were excluded. Therefore, a total of 85 subjects were included in the review. The prevalence of endocrine complications identified was: primary hypothyroidism 1.2%, compensated hypothyroidism 7.0%, hyperthyroidism 2.4%, hypergonadotrophic hypogonadism 22.4%, abnormal bone density 2.4%, and secondary diabetes mellitus 1.2%. These findings emphasize the need to screen for endocrine system dysfunction, particularly hypergonadotrophic hypogonadism, in children who have undergone BMT. Children need long-term follow-up so that endocrine complications can be diagnosed and treated promptly. PMID:21823531

  15. Scanning Electron Microscopy Reveals Two Distinct Classes of Erythroblastic Island Isolated from Adult Mammalian Bone Marrow.

    PubMed

    Yeo, Jia Hao; McAllan, Bronwyn M; Fraser, Stuart T

    2016-04-01

    Erythroblastic islands are multicellular clusters in which a central macrophage supports the development and maturation of red blood cell (erythroid) progenitors. These clusters play crucial roles in the pathogenesis observed in animal models of hematological disorders. The precise structure and function of erythroblastic islands is poorly understood. Here, we have combined scanning electron microscopy and immuno-gold labeling of surface proteins to develop a better understanding of the ultrastructure of these multicellular clusters. The erythroid-specific surface antigen Ter-119 and the transferrin receptor CD71 exhibited distinct patterns of protein sorting during erythroid cell maturation as detected by immuno-gold labeling. During electron microscopy analysis we observed two distinct classes of erythroblastic islands. The islands varied in size and morphology, and the number and type of erythroid cells interacting with the central macrophage. Assessment of femoral marrow isolated from a cavid rodent species (guinea pig, Cavis porcellus) and a marsupial carnivore species (fat-tailed dunnarts, Sminthopsis crassicaudata) showed that while the morphology of the central macrophage varied, two different types of erythroblastic islands were consistently identifiable. Our findings suggest that these two classes of erythroblastic islands are conserved in mammalian evolution and may play distinct roles in red blood cell production. PMID:26898901

  16. 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

  17. Acquired pure red cell aplasia: updated review of treatment

    PubMed Central

    Sawada, Kenichi; Fujishima, Naohito; Hirokawa, Makoto

    2008-01-01

    Pure red cell aplasia (PRCA) is a syndrome characterized by a severe normocytic anaemia, reticulocytopenia, and absence of erythroblasts from an otherwise normal bone marrow. Primary PRCA, or secondary PRCA which has not responded to treatment of the underlying disease, is treated as an immunologically-mediated disease. Although vigorous immunosuppressive treatments induce and maintain remissions in a majority of patients, they carry an increased risk of serious complications. Corticosteroids were used in the treatment of PRCA and this has been considered the treatment of first choice although relapse is not uncommon. Cyclosporine A (CsA) has become established as one of the leading drugs for treatment of PRCA. However, common concerns have been the number of patients treated with CsA who achieve sustained remissions and the number that relapse. This article reviews the current status of CsA therapy and compares it to other treatments for diverse PRCAs. PMID:18510682

  18. The red ear syndrome

    PubMed Central

    2013-01-01

    Red Ear Syndrome (RES) is a very rare disorder, with approximately 100 published cases in the medical literature. Red ear (RE) episodes are characterised by unilateral or bilateral attacks of paroxysmal burning sensations and reddening of the external ear. The duration of these episodes ranges from a few seconds to several hours. The attacks occur with a frequency ranging from several a day to a few per year. Episodes can occur spontaneously or be triggered, most frequently by rubbing or touching the ear, heat or cold, chewing, brushing of the hair, neck movements or exertion. Early-onset idiopathic RES seems to be associated with migraine, whereas late-onset idiopathic forms have been reported in association with trigeminal autonomic cephalalgias (TACs). Secondary forms of RES occur with upper cervical spine disorders or temporo-mandibular joint dysfunction. RES is regarded refractory to medical treatments, although some migraine preventative treatments have shown moderate benefit mainly in patients with migraine-related attacks. The pathophysiology of RES is still unclear but several hypotheses involving peripheral or central nervous system mechanisms have been proposed. PMID:24093332

  19. 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

  20. The survival of cryopreserved human bone marrow stem cells.

    PubMed

    Hill, R S; Mackinder, C A; Postlewaight, B F; Blacklock, H A

    1979-07-01

    Two methods for cryopreservation of bone marrow stem cells were compared using bone marrow obtained from 36 patients. Included in this group were 21 persons with the diagnosis of leukaemia including 14 either with acute myeloid or lymphoblastic leukaemia in remission following intensive remission induction chemotherapy. After freeze-preservation and reconstitution, all marrow samples were tested for nucleated cell (NC) recovery and grown on agar to assess colony forming units (CFUC) and cluster forming units in culture (CluFUc). A slow dilution reconstitution method using freezing media containing AB negative plasma resulted in recovery of 85% of the CFUc activity of fresh marrow. This result was significantly better than the 47% CFUc recovery obtained when freezing media without plasma and a rapid dilution reconstitution technique were used. NC recoveries following slow dilution (51%) and rapid dilution (44%) were not significantly different. CluFUc were disproportionately reduced compared with CFUc although yielding similar results with both methods (26% and 32%). No correlation was found for either method between CFUc and NC recovery or between CFUc and CluFUc recovery in cryopreserved bone marrow. PMID:392422

  1. 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.

  2. 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.

  3. Murine Hind Limb Long Bone Dissection and Bone Marrow Isolation.

    PubMed

    Amend, Sarah R; Valkenburg, Kenneth C; Pienta, Kenneth J

    2016-01-01

    Investigation of the bone and the bone marrow is critical in many research fields including basic bone biology, immunology, hematology, cancer metastasis, biomechanics, and stem cell biology. Despite the importance of the bone in healthy and pathologic states, however, it is a largely under-researched organ due to lack of specialized knowledge of bone dissection and bone marrow isolation. Mice are a common model organism to study effects on bone and bone marrow, necessitating a standardized and efficient method for long bone dissection and bone marrow isolation for processing of large experimental cohorts. We describe a straightforward dissection procedure for the removal of the femur and tibia that is suitable for downstream applications, including but not limited to histomorphologic analysis and strength testing. In addition, we outline a rapid procedure for isolation of bone marrow from the long bones via centrifugation with limited handling time, ideal for cell sorting, primary cell culture, or DNA, RNA, and protein extraction. The protocol is streamlined for rapid processing of samples to limit experimental error, and is standardized to minimize user-to-user variability. PMID:27168390

  4. [Marrow donor registration and cord blood banking: current issues].

    PubMed

    Takanashi, Minoko

    2016-03-01

    Marrow donor registration and cord blood banking are essential components of the infrastructure required for unrelated haemopoietic stem cell transplantations. We now have a new law to support and regulate the Marrow Donor Coordination Agency, Cord Blood Banks and the Haematopoietic Stem Cell Provision Support Organization. We also need to have a specific goal for bone marrow and peripheral blood stem cell donor registration, a minimum cord blood bank size, and the demographic data to back the medical needs for unrelated haemopoietic stem cell transplantations. To improve bone marrow and peripheral blood stem cell transplantations, we need to recruit younger adults for marrow registration and make greater efforts to shorten the coordinating period. For cord blood transplantations, uniting and empowering the cord blood collection sites is needed, to encourage and motivate obstetricians and other staff, as the quality of cord blood units is primarily determined during collection. Also, the cord blood banks must work cooperatively to provide cord blood internationally, which includes coordinating with international agencies and their regulations. PMID:27076238

  5. Murine Hind Limb Long Bone Dissection and Bone Marrow Isolation

    PubMed Central

    Amend, Sarah R.; Valkenburg, Kenneth C.; Pienta, Kenneth J.

    2016-01-01

    Investigation of the bone and the bone marrow is critical in many research fields including basic bone biology, immunology, hematology, cancer metastasis, biomechanics, and stem cell biology. Despite the importance of the bone in healthy and pathologic states, however, it is a largely under-researched organ due to lack of specialized knowledge of bone dissection and bone marrow isolation. Mice are a common model organism to study effects on bone and bone marrow, necessitating a standardized and efficient method for long bone dissection and bone marrow isolation for processing of large experimental cohorts. We describe a straightforward dissection procedure for the removal of the femur and tibia that is suitable for downstream applications, including but not limited to histomorphologic analysis and strength testing. In addition, we outline a rapid procedure for isolation of bone marrow from the long bones via centrifugation with limited handling time, ideal for cell sorting, primary cell culture, or DNA, RNA, and protein extraction. The protocol is streamlined for rapid processing of samples to limit experimental error, and is standardized to minimize user-to-user variability. PMID:27168390

  6. Safety of bone marrow stem cell donation: a review.

    PubMed

    Bosi, A; Bartolozzi, B

    2010-01-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) represents the first choice of treatment or an important therapeutic option for several diseases, but it is still marked by morbidity and mortality. In contrast, the donation of hematopoietic stem cells (HSCs) is considered to be a safe procedure. The invaluable ethical source of donation and its central role in transplantation implies that the greatest attention be due to the donor and to the donation process through a serious monitoring protocol for donor safety. Both the Joint Accreditation Committee and the European Committee pay particular attention to the notification of adverse events and adverse reactions. Bone marrow donation is a well established procedure, that has now been performed for >30 years. Although it does not require drug administration, there is hospital admission for 1-3 days with 7-10 days off work. The main risk is related to the anesthesia. Pain in the aspiration area, together with astenia are considered to be the most frequent side effects, as shown by the USA National Marrow Donor Program experience in 1,193 donations. In the European Group for Blood and Marrow Transplantation analysis performed between 1993 and 2005 on 27,770 first HSCTs from bone marrow, only 1 fatal event (pulmonary embolism) and 12 serious adverse events were observed. The most frequent adverse events were cardiac. The incidence of adverse events was significantly lower (P < .05) compared with peripheral blood HSC donors, which confirms the necessity of accurate attention to donor selection and evaluation in bone marrow donation.

  7. [Marrow donor registration and cord blood banking: current issues].

    PubMed

    Takanashi, Minoko

    2016-03-01

    Marrow donor registration and cord blood banking are essential components of the infrastructure required for unrelated haemopoietic stem cell transplantations. We now have a new law to support and regulate the Marrow Donor Coordination Agency, Cord Blood Banks and the Haematopoietic Stem Cell Provision Support Organization. We also need to have a specific goal for bone marrow and peripheral blood stem cell donor registration, a minimum cord blood bank size, and the demographic data to back the medical needs for unrelated haemopoietic stem cell transplantations. To improve bone marrow and peripheral blood stem cell transplantations, we need to recruit younger adults for marrow registration and make greater efforts to shorten the coordinating period. For cord blood transplantations, uniting and empowering the cord blood collection sites is needed, to encourage and motivate obstetricians and other staff, as the quality of cord blood units is primarily determined during collection. Also, the cord blood banks must work cooperatively to provide cord blood internationally, which includes coordinating with international agencies and their regulations.

  8. Seeing red on the road.

    PubMed

    Díaz-Romnán, Amparo; Megías, Alberto; Díaz-Piedra, Carolina; Catena, Andrés; 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

  9. Red cell aging in vivo

    PubMed Central

    Ganzoni, A. M.; Oakes, R.; Hillman, R. S.

    1971-01-01

    Previous studies of red cell structure and metabolism during the aging process have relied upon in vitro techniques of cell separation into various age populations. Probably the most common approach is to isolate the older red cells with the assumption that they are more dense. This may lead to a number of inconsistencies in observations, and may certainly raise questions about possible cell changes secondary to manipulative procedures. For this reason, an experimental system was devised where a normal red cell population could be studied, while aging, in an in vivo environment. The initial red cell mass of a large number of inbred rats was transferred repeatedly into an ever smaller number of animals, making it possible to follow an aging population of red cells up to 48 days while preventing contamination with newly produced cells by suppression of erythropoiesis with transfusion-induced polycythemia. During this period, samples of progressively older red cells could be obtained for measurements of red cell constant. It was noted that the normal rat red cell undergoes both volume reduction and significant hemoglobin content loss with aging. In addition, the hemoglobin concentration within the cell demonstrated an early rise after a return to nearly normal values. These findings are noteworthy in that they help to explain the characteristics of life-spans of cohort labeled red cell populations in small animals, and provide a possible example of a cell's remodeling process within the spleen. PMID:5090053

  10. 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

  11. 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

  12. 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

  13. Communication between bone marrow niches in normal bone marrow function and during hemopathies progression

    PubMed Central

    Lamorte, Sara; Remédio, Leonor; Dias, Sergio

    2009-01-01

    Hematopoietic stem cell (HSC) chemotaxis, adhesion, proliferation, quiescence and differentiation are regulated by interactions with bone marrow (BM) niches. Two niches have been identified in the adult BM: the endosteal (close to the bone) and the perivascular niche (close to blood vessels). A vast body of literature has revealed the molecular basis for the interaction of HSCs with the two niches. However, the signals that regulate the communication between the two niches have not been well defined. Taking in consideration several clinical and experimental arguments this review highlights the molecular cues, involved in the communication between the BM niches, which regulate the basic properties of HSCs in physiological and malignant conditions. As such, it aims at clarifying the most important advances in basic and clinical research focusing on the role of different factors in the regulation of the BM microenvironment.

  14. The phytochrome red/far-red photoreceptor superfamily

    PubMed Central

    Sharrock, Robert A

    2008-01-01

    Proteins of the phytochrome superfamily of red/far-red light receptors have a variety of biological roles in plants, algae, bacteria and fungi and demonstrate a diversity of spectral sensitivities and output signaling mechanisms. Over the past few years the first three-dimensional structures of phytochrome light-sensing domains from bacteria have been determined. PMID:18771590

  15. AI-05IMPACT OF GBM MICROENVIRONMENT ON EXPRESSION PROFILE OF BONE MARROW DERIVED PROGENITOR CELLS

    PubMed Central

    Burrell, Kelly; Singh, Sanjay; Agnihotri, Sameer; Hill, Richard; Aldape, Kenneth; Zadeh, Gelareh

    2014-01-01

    We have recently shown that bone marrow derived cells (BMDC) provide a distinct tumor region dependent contribution to glioblastoma multiforme (GBM) neovascularization. The influence of GBM microenvironment on differentiation and modulation of expression factors by BMDC however remains unknown. In this study we establish the differential expression profile of BMDC as a consequence of recruitment and interaction with the GBM microenvironment and in response to radiation (RTx) and anti-angiogenic therapy (AATx). Chimeric mice with reconstituted green-fluorescent bone marrow were used to create intracranial GBM xenografts, by implanting red fluorescent glioma stem cells or U87 into the frontal lobes. Subsequently, BMDC recruited to the GBM were isolated from the GBM cells using FACS during GBM growth, and following treatment (RTx and AATx). RNA was extracted from both FACS-purified BMDC and GBM cells, and mRNA and miRNA array analyses were performed. We compared the expression profiles to systemic BMDC derived from control donor mice. BMDCs were found to exhibit significant plasticity and altered their expression profiles based on stage of GBM growth and in response to therapy. TGFb was significantly upregulated in BMDCs following recruitment to GBMs, with a compensatory increase in expression of IL6,4,8 by GBM cells. BMDC up-regulate cytokines, IFNG, CXCL and TNF pathways, and transcriptional regulators, SMAD2, all of which are able to influence the tumor microenvironment. BMDCs also prove to express angiogenic factors and angioMIRs, with a distinct differential expression pattern based on stage of GBM growth and in response to therapy. We demonstrate that a significant cross-talk exists between BMDC in the tumor microenvironment and GBM cells. There is a distinct angiogenic and invasive profile of BMDC once recruited to the GBM. Furthermore, recruited BMDC provide a source of angiogenic factors, that are differentially expressed based on the stage of GBM growth and

  16. Erythropoietin is involved in the angiogenic potential of bone marrow macrophages in multiple myeloma.

    PubMed

    De Luisi, Annunziata; Binetti, Laura; Ria, Roberto; Ruggieri, Simona; Berardi, Simona; Catacchio, Ivana; Racanelli, Vito; Pavone, Vincenzo; Rossini, Bernardo; Vacca, Angelo; Ribatti, Domenico

    2013-10-01

    Erythropoietin (Epo) is the crucial cytokine regulator of red blood cell production, and recombinant human erythropoietin (rHuEpo) is widely used in clinical practice for the treatment of anemia, primarily in kidney disease and in cancer. Increasing evidence suggests several biological roles for Epo and its receptor, Epo-R, unrelated to erythropoiesis, including angiogenesis. Epo-R has been found expressed in various non-haematopoietic cells and tissues, and in cancer cells. Here, we detected the expression of Epo-R in bone marrow-derived macrophages (BMMAs) from multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) patients and assessed whether Epo/Epo-R axis plays a role in MM macrophage-mediated angiogenesis. We found that Epo-R is over-expressed in BMMAs from MM patients with active disease compared to MGUS patients. The treatment of BMMAs with rHuEpo significantly increased the expression and secretion of key pro-angiogenic mediators, such as vascular endothelial growth factor, hepatocyte growth factor and monocyte chemotactic protein (MCP-1/CCL-2), through activation of JAK2/STAT5 and PI3 K/Akt pathways. In addition, the conditioned media harvested from rHuEpo-treated BMMAs enhanced bone marrow-derived endothelial cell migration and capillary morphogenesis in vitro, and induced angiogenesis in the chorioallantoic membrane of chick embryos in vivo. Furthermore, we found an increase in the circulating levels of several pro-angiogenic cytokines in serum of MM patients with anemia under treatment with Epo. Our findings highlight the direct effect of rHuEpo on macrophage-mediated production of pro-angiogenic factors, suggesting that Epo/Epo-R pathway may be involved in the regulation of angiogenic response occurring in MM.

  17. Erythropoietin is involved in the angiogenic potential of bone marrow macrophages in multiple myeloma.

    PubMed

    De Luisi, Annunziata; Binetti, Laura; Ria, Roberto; Ruggieri, Simona; Berardi, Simona; Catacchio, Ivana; Racanelli, Vito; Pavone, Vincenzo; Rossini, Bernardo; Vacca, Angelo; Ribatti, Domenico

    2013-10-01

    Erythropoietin (Epo) is the crucial cytokine regulator of red blood cell production, and recombinant human erythropoietin (rHuEpo) is widely used in clinical practice for the treatment of anemia, primarily in kidney disease and in cancer. Increasing evidence suggests several biological roles for Epo and its receptor, Epo-R, unrelated to erythropoiesis, including angiogenesis. Epo-R has been found expressed in various non-haematopoietic cells and tissues, and in cancer cells. Here, we detected the expression of Epo-R in bone marrow-derived macrophages (BMMAs) from multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) patients and assessed whether Epo/Epo-R axis plays a role in MM macrophage-mediated angiogenesis. We found that Epo-R is over-expressed in BMMAs from MM patients with active disease compared to MGUS patients. The treatment of BMMAs with rHuEpo significantly increased the expression and secretion of key pro-angiogenic mediators, such as vascular endothelial growth factor, hepatocyte growth factor and monocyte chemotactic protein (MCP-1/CCL-2), through activation of JAK2/STAT5 and PI3 K/Akt pathways. In addition, the conditioned media harvested from rHuEpo-treated BMMAs enhanced bone marrow-derived endothelial cell migration and capillary morphogenesis in vitro, and induced angiogenesis in the chorioallantoic membrane of chick embryos in vivo. Furthermore, we found an increase in the circulating levels of several pro-angiogenic cytokines in serum of MM patients with anemia under treatment with Epo. Our findings highlight the direct effect of rHuEpo on macrophage-mediated production of pro-angiogenic factors, suggesting that Epo/Epo-R pathway may be involved in the regulation of angiogenic response occurring in MM. PMID:23881169

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. 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 Tukey’s 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

  5. Spinal nociceptive transmission by mechanical stimulation of bone marrow

    PubMed Central

    Tanaka, Satoshi; Sekiguchi, Takemi; Sugiyama, Daisuke; Kawamata, Mikito

    2016-01-01

    Background Since bone marrow receives innervation from A-delta and C-fibers and since an increase in intramedullary pressure in bone marrow may induce acute pain in orthopedic patients during surgery and chronic pain in patients with bone marrow edema, skeletal pain may partly originate from bone marrow. Intraosseous lesions, such as osteomyelitis and bone cancer, are also known to produce cutaneous hypersensitivity, which might be referred pain from bone. However, little is known about pain perception in bone marrow and referred pain induced by bone disease. Thus, we carried out an in vivo electrophysiological study and behavioral study to determine whether increased intraosseous pressure of the femur induces acute pain and whether increased intraosseous pressure induces referred pain in the corresponding receptive fields of the skin. Results Intraosseous balloon inflation caused spontaneous pain-related behavior and mechanical hyperalgesia and allodynia in the lumbosacral region. Single neuronal activities of spinal dorsal horn neurons were extracellularly isolated, and then evoked responses to non-noxious and noxious cutaneous stimuli and intraosseous balloon inflation were recorded. Ninety-four spinal dorsal horn neurons, which had somatic receptive fields at the lower back and thigh, were obtained. Sixty-two percent of the wide-dynamic-range neurons (24/39) and 86% of the high-threshold neurons (12/14) responded to intraosseous balloon inflation, while none of the low-threshold neurons (0/41) responded to intraosseous balloon inflation. Spinally administered morphine (1 µg) abolished balloon inflation-induced spontaneous pain-related behavior and mechanical hyperalgesia in awake rats and also suppressed evoked activities of wide-dynamic-range neurons to noxious cutaneous stimulation and intraosseous balloon inflation. Conclusions The results suggest that mechanical stimulation to bone marrow produces nociception, concomitantly producing its referred pain

  6. Diverse Osteoclastogenesis of Bone Marrow From Mandible versus Long Bone

    PubMed Central

    Chaichanasakul, Thawinee; Kang, Benjamin; Bezouglaia, Olga; Aghaloo, Tara L.; Tetradis, Sotirios

    2015-01-01

    Background Mandible (MB) and maxilla possess unique metabolic and functional properties and demonstrate discrete responses to homeostatic, mechanical, hormonal and developmental stimuli. Osteogenic potential of bone marrow stromal cells (BMSCs) differs between MB versus long bones (LB). Furthermore, MB versus LB derived osteoclasts (OCs) have disparate functional properties. Here, we explored the osteoclastogenic potential of rat MB versus LB marrow in vitro and in vivo under basal and stimulated conditions. Methods Bone marrow from rat MB and LB was cultured in osteoblastic or osteoclastic differentiation media. Tartrate resistant acid phosphatase (TRAP) staining, resorption pit assays, and real-time PCR were performed. Additionally, osmotic mini-pumps were implanted in animals, mandibles and tibiae were isolated and multinucleated cells (MNCs) were measured. Results MB versus LB marrow cultures differentiated with RANKL and M-CSF produced more TRAP+ multinucleated cells (MNCs) and greater resorptive area. To explore MB versus LB BMSC supported osteoclastogenesis, confluent BMSCs were cultured with parathyroid hormone (PTH), 1α,25-dihydroxyvitaminD3 (1,25D3), or PTH+1,25D3. 1,25D3 or PTH+1,25D3 treated LB BMSCs expressed significantly higher RANKL and lower OPG mRNA and increased RANKL:OPG ratio. When whole marrow was cultured with PTH+1,25D3, more TRAP+ MNCs were seen in LB versus MB cultures. Ultimately, rats were infused with PTH+1,25D3 and MB versus tibia MNCs were measured. Hormonal stimulation increased osteoclastogenesis in both MB and tibia. However, higher TRAP+ MNC numbers were observed in tibia versus MB under basal and hormonal stimulation. Conclusions Collectively, our data illustrate differences both on osteoclastogenic potential and OC numbers of MB versus LB marrow. PMID:24003963

  7. 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.

  8. Autologous bone-marrow mesenchymal cell induced chondrogenesis (MCIC).

    PubMed

    Huh, Sung Woo; Shetty, Asode Ananthram; Ahmed, Saif; Lee, Dong Hwan; Kim, Seok Jung

    2016-01-01

    Degenerative and traumatic articular cartilage defects are common, difficult to treat, and progressive lesions that cause significant morbidity in the general population. There have been multiple approaches to treat such lesions, including arthroscopic debridement, microfracture, multiple drilling, osteochondral transplantation and autologous chondrocyte implantation (ACI) that are currently being used in clinical practice. Autologous bone-marrow mesenchymal cell induced chondrogenesis (MCIC) is a single-staged arthroscopic procedure. This method combines a modified microfracture technique with the application of a bone marrow aspirate concentrate (BMAC), hyaluronic acid and fibrin gel to treat articular cartilage defects. We reviewed the current literatures and surgical techniques for mesenchymal cell induced chondrogenesis. PMID:27489409

  9. 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-1β, IL-18, TNF-α 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.

  10. Bone marrow chimera experiments to determine the contribution of hematopoietic stem cells to cerebral angiogenesis.

    PubMed

    Machein, Marcia Regina; Plate, Karl H

    2014-01-01

    The generation of bone marrow chimera in mice is a valuable tool to study a variety of cellular processes. Donor bone marrow cells expressing reporter genes have been used to study the process of cell differentiation and the mechanisms involved in bone marrow cell recruitment. Bone marrow cells bearing genetic manipulation have been used in bone marrow chimeras to elucidate the role of molecules in different physiological and pathological settings. Since in the normal adult brain angiogenesis does not occur, models of brain injury like ischemia and tumor growth have been used to study the contribution of bone marrow-derived cells to the cerebral vasculature. This chapter describes the procedures to perform bone marrow transplantation in order to study the contribution of bone marrow-derived cells to vascularization in an orthotopic glioma model.

  11. 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 ...

  12. The Compton Effect Red Shift

    NASA Astrophysics Data System (ADS)

    Kierein, John

    2004-05-01

    In 1923 (Phil Mag. 46, 897.) A. H. Compton noted that the Compton effect produces a red shift for all wavelengths when the scattered electron is free and not bound to an atom or molecule. He suggested that the red shift in the visible spectrum at the limb of the sun is larger than that at the center due to the Compton effect from the greater number of free electrons in the sun's atmosphere along the line of sight. Kierein and Sharp (1968, Solar Physics 3, 450) quantified this and showed a good correlation of red shift observations with the variation in the number of these electrons along the line of sight from center to limb and suggested that the quasar red shift and cosmological red shift could be similarly explained. Grote Reber mapped and measured the background hectometric radiation and found it to be unexpectedly bright. In 1968 (J. Franklin Inst. 285,1), while describing these measurements and maps he explained this brightness as being due to the Compton effect causing the cosmological red shift and accelerating intergalactic electrons. The resulting universe is static. The predicted red shift from the Compton effect deviates from Hubble's law only at large red shifts.

  13. 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.

  14. Polysaccharides of the red algae.

    PubMed

    Usov, Anatolii I

    2011-01-01

    Red algae (Rhodophyta) are known as the source of unique sulfated galactans, such as agar, agarose, and carrageenans. The wide practical uses of these polysaccharides are based on their ability to form strong gels in aqueous solutions. Gelling polysaccharides usually have molecules built up of repeating disaccharide units with a regular distribution of sulfate groups, but most of the red algal species contain more complex galactans devoid of gelling ability because of various deviations from the regular structure. Moreover, several red algae may contain sulfated mannans or neutral xylans instead of sulfated galactans as the main structural polysaccharides. This chapter is devoted to a description of the structural diversity of polysaccharides found in the red algae, with special emphasis on the methods of structural analysis of sulfated galactans. In addition to the structural information, some data on the possible use of red algal polysaccharides as biologically active polymers or as taxonomic markers are briefly discussed.

  15. Bone marrow transplantation reverses new-onset immunoinflammatory diabetes in a mouse model.

    PubMed

    Lv, Cheng-Lan; Wang, Jing; Xie, Ting; Ouyang, Jian

    2014-01-01

    Bone marrow transplantation might be an effective method to cure type 1 diabetes mellitus. This study aimed to investigate whether bone marrow transplantation could reverse hyperglycemia in diabetic mice and whether high-dose total body irradiation followed by high-dose bone marrow mononuclear cell infusion could improve the efficiency of bone marrow transplantation in treating diabetic mice. Diabetic mice after multiple low doses of streptozotocin injection were irradiated followed by infusion with approximately 1×10(7) bone marrow mononuclear cells intravenously. Before and after bone marrow transplantation, fasting blood glucose, intraperitoneal glucose tolerance test, serum insulin, pancreatic histology, and the examination of insulin and glucagon in islets were processed. All recipients returned to near euglycemic within 1 week after undergoing bone marrow transplantation. No mice became hyperglycemia again during investigation period. The change of serum insulin, glucose tolerance test, pancreatic histology and the expression of insulin and glucagon in recipient islets after bone marrow transplantation all revealed islets regeneration and significant amelioration when compared respectively with those of diabetic mice without bone marrow transplantation. Bone marrow transplantation contributed to reduce blood glucose, prevent further blood glucose hike in diabetic recipients, and promote islets regeneration. High-dose total body irradiation in combination with high-dose bone marrow monoclear cell infusion could improve the efficiency of bone marrow transplantation in treating streptozotocin-induced diabetes.

  16. Mature adipocytes in bone marrow protect myeloma cells against chemotherapy through autophagy activation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A major problem in patients with multiple myeloma is chemotherapy resistance, which develops in myeloma cells upon interaction with bone marrow stromal cells. However, few studies have determined the role of bone marrow adipocytes, a major component of stromal cells in the bone marrow, in myeloma ch...

  17. 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.

  18. 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.

  19. [T lymphocyte receptors after allogenic bone marrow transplantation].

    PubMed

    Vilmer, E; Schumpp, M; Sigaux, F; Boiron, M; Bensussan, A

    1988-01-01

    Following allogeneic bone marrow transplantation, prominent expansion of peripheral T cells (40%) bearing gamma T cell receptor was observed in some patients. Biochemical, functional and molecular analyses were performed to characterize this T cell receptor and to understand its role in the immunodeficient state after transplantation.

  20. 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)

  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. Archival bone marrow samples: suitable for multiple biomarker analysis.

    PubMed

    Lund, Bendik; Najmi, Laeya A; Wesolowska-Andersen, Agata; Landsem, Veslemøy M; Rasmussen, Kirsten K; Borst, Louise; Gupta, Ramneek; Schmiegelow, Kjeld; Klungland, Helge

    2015-01-01

    AB Archival samples represent a significant potential for genetic studies, particularly in severe diseases with risk of lethal outcome, such as in cancer. In this pilot study, we aimed to evaluate the usability of archival bone marrow smears and biopsies for DNA extraction and purification, whole genome amplification (WGA), multiple marker analysis including 10 short tandem repeats, and finally a comprehensive genotyping of 33,683 single nucleotide polymorphisms (SNPs) with multiplexed targeted next-generation sequencing. A total of 73 samples from 21 bone marrow smears and 13 bone marrow biopsies from 18 Danish and Norwegian childhood acute lymphoblastic leukemia patients were included and compared with corresponding blood samples. Samples were grouped according to the age of sample and whether WGA was performed or not. We found that measurements of DNA concentration after DNA extraction was dependent on detection method and that spectrophotometry overestimated DNA amount compared with fluorometry. In the short tandem repeat analysis, detection rate dropped slightly with longer fragments. After WGA, this drop was more pronounced. Samples stored for 0 to 3 years showed better results compared with samples stored for 4 to 10 years. Acceptable call rates for SNPs were detected for 7 of 42 archival samples. In conclusion, archival bone marrow samples are suitable for DNA extraction and multiple marker analysis, but WGA was less successful, especially when longer fragments were analyzed. Multiple SNP analysis seems feasible, but the method has to be further optimized.

  3. Clinical significance of bone marrow micrometastases in esophageal cancer.

    PubMed

    Inoue, H; Kajiyama, Y; Tsurumaru, M

    2004-01-01

    Using the reverse transcriptase-polymerase chain reaction (RT-PCR), we investigated the clinical significance of bone marrow micrometastases in patients with esophageal cancer. Bone marrow samples from 57 patients with esophageal cancer, who underwent esophagotomy, were investigated by specific RT-PCR for carcinoembryonic antigens (CEA). A total of 40 out of 57 patients (70.1%) were positive for CEA mRNA in the bone marrow. Among curatively resected cases, 34 of 50 patients (68.0%) were positive for CEA. Ten of 13 T1 patients (76.9%) were positive for CEA. Although the CEA-positive rate was high, there was no significant correlation between CEA positivity and any clinical characteristics. Among the 40 CEA-positive patients, 50% have shown recurrence so far. Detection of cancer cells in the bone marrow by RT-PCR may not always correspond to the malignant potential or other characteristics of the tumor. CEA-positive 'micrometastases' might actually represent isolated circulating tumor cells without much biological significance.

  4. Neurological complications of bone marrow transplantation in childhood.

    PubMed

    Wiznitzer, M; Packer, R J; August, C S; Burkey, E D

    1984-11-01

    Bone marrow transplantation, used in the treatment of cancer, aplastic anemia, and metabolic diseases, involves the use of potentially neurotoxic agents to suppress immunity and eradicate malignancy. Fifty-seven patients with a median age of 11 years (age range, 6 months to 24 years) underwent bone marrow transplantation at the Children's Hospital of Philadelphia. Fifty-nine percent developed neurological abnormalities. Twenty-six patients (46%) had central nervous system (CNS) dysfunction, including infection (8), cerebrovascular accident (5), CNS leukemia (7), metabolic encephalopathy (5), and paraparesis with CNS toxoplasmosis (1). Neuropsychological dysfunction was present in 4 of 5 long-term survivors who were tested. Fourteen of 19 patients (74%) on whom postmortem examination was performed were found to have CNS abnormalities, including cerebral atrophy (10), focal cerebral injury (6), leukemia (5), and infection (3). Fourteen patients (24%) had peripheral nervous system dysfunction. CNS dysfunction was more common in patients with lymphoreticular malignancies. Cerebrovascular accidents (in patients with lymphoreticular malignancies) and infections (in our general population and in patients with lymphoreticular malignancies) occurred more often in our patients than in patients with similar illnesses who did not undergo bone marrow transplantation. The combination of prior treatment and preparative therapy for bone marrow transplantation predisposes patients to neurological and neuropsychological sequelae.

  5. Cell Fate and Differentiation of Bone Marrow Mesenchymal Stem Cells

    PubMed Central

    Jimi, Eijiro

    2016-01-01

    Osteoblasts and bone marrow adipocytes originate from bone marrow mesenchymal stem cells (BMMSCs) and there appears to be a reciprocal relationship between adipogenesis and osteoblastogenesis. Alterations in the balance between adipogenesis and osteoblastogenesis in BMMSCs wherein adipogenesis is increased relative to osteoblastogenesis are associated with decreased bone quality and quantity. Several proteins have been reported to regulate this reciprocal relationship but the exact nature of the signals regulating the balance between osteoblast and adipocyte formation within the bone marrow space remains to be determined. In this review, we focus on the role of Transducin-Like Enhancer of Split 3 (TLE3), which was recently reported to regulate the balance between osteoblast and adipocyte formation from BMMSCs. We also discuss evidence implicating canonical Wnt signalling, which plays important roles in both adipogenesis and osteoblastogenesis, in regulating TLE3 expression. Currently, there is demand for new effective therapies that target the stimulation of osteoblast differentiation to enhance bone formation. We speculate that reducing TLE3 expression or activity in BMMSCs could be a useful approach towards increasing osteoblast numbers and reducing adipogenesis in the bone marrow environment. PMID:27298623

  6. Agent-Based Deterministic Modeling of the Bone Marrow Homeostasis.

    PubMed

    Kurhekar, Manish; Deshpande, Umesh

    2016-01-01

    Modeling of stem cells not only describes but also predicts how a stem cell's environment can control its fate. The first stem cell populations discovered were hematopoietic stem cells (HSCs). In this paper, we present a deterministic model of bone marrow (that hosts HSCs) that is consistent with several of the qualitative biological observations. This model incorporates stem cell death (apoptosis) after a certain number of cell divisions and also demonstrates that a single HSC can potentially populate the entire bone marrow. It also demonstrates that there is a production of sufficient number of differentiated cells (RBCs, WBCs, etc.). We prove that our model of bone marrow is biologically consistent and it overcomes the biological feasibility limitations of previously reported models. The major contribution of our model is the flexibility it allows in choosing model parameters which permits several different simulations to be carried out in silico without affecting the homeostatic properties of the model. We have also performed agent-based simulation of the model of bone marrow system proposed in this paper. We have also included parameter details and the results obtained from the simulation. The program of the agent-based simulation of the proposed model is made available on a publicly accessible website. PMID:27340402

  7. Impaired function of bone marrow stromal cells in systemic mastocytosis.

    PubMed

    Nemeth, Krisztian; Wilson, Todd M; Ren, Jiaqiang J; Sabatino, Marianna; Stroncek, David M; Krepuska, Miklos; Bai, Yun; Robey, Pamela G; Metcalfe, Dean D; Mezey, Eva

    2015-07-01

    Patients with systemic mastocytosis (SM) have a wide variety of problems, including skeletal abnormalities. The disease results from a mutation of the stem cell receptor (c-kit) in mast cells and we wondered if the function of bone marrow stromal cells (BMSCs; also known as MSCs or mesenchymal stem cells) might be affected by the invasion of bone marrow by mutant mast cells. As expected, BMSCs from SM patients do not have a mutation in c-kit, but they proliferate poorly. In addition, while osteogenic differentiation of the BMSCs seems to be deficient, their adipogenic potential appears to be increased. Since the hematopoietic supportive abilities of BMSCs are also important, we also studied the engraftment in NSG mice of human CD34(+) hematopoietic progenitors, after being co-cultured with BMSCs of healthy volunteers vs. BMSCs derived from patients with SM. BMSCs derived from the bone marrow of patients with SM could not support hematopoiesis to the extent that healthy BMSCs do. Finally, we performed an expression analysis and found significant differences between healthy and SM derived BMSCs in the expression of genes with a variety of functions, including the WNT signaling, ossification, and bone remodeling. We suggest that some of the symptoms associated with SM might be driven by epigenetic changes in BMSCs caused by dysfunctional mast cells in the bone marrow of the patients.

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

    NASA Astrophysics Data System (ADS)

    Benkő, Klára; Pintye, Éva; Szabó, Boglárka; Géresi, Krisztina; Megyeri, Attila; Benkő, 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 γ—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.

  9. Quantitative image analysis of cell colocalization in murine bone marrow.

    PubMed

    Mokhtari, Zeinab; Mech, Franziska; Zehentmeier, Sandra; Hauser, Anja E; Figge, Marc Thilo

    2015-06-01

    Long-term antibody production is a key property of humoral immunity and is accomplished by long-lived plasma cells. They mainly reside in the bone marrow, whose importance as an organ hosting immunological memory is becoming increasingly evident. Signals provided by stromal cells and eosinophils may play an important role for plasma cell maintenance, constituting a survival microenvironment. In this joint study of experiment and theory, we investigated the spatial colocalization of plasma cells, eosinophils and B cells by applying an image-based systems biology approach. To this end, we generated confocal fluorescence microscopy images of histological sections from murine bone marrow that were subsequently analyzed in an automated fashion. This quantitative analysis was combined with computer simulations of the experimental system for hypothesis testing. In particular, we tested the observed spatial colocalization of cells in the bone marrow against the hypothesis that cells are found within available areas at positions that were drawn from a uniform random number distribution. We find that B cells and plasma cells highly colocalize with stromal cells, to an extent larger than in the simulated random situation. While B cells are preferentially in contact with each other, i.e., form clusters among themselves, plasma cells seem to be solitary or organized in aggregates, i.e., loosely defined groups of cells that are not necessarily in direct contact. Our data suggest that the plasma cell bone marrow survival niche facilitates colocalization of plasma cells with stromal cells and eosinophils, respectively, promoting plasma cell longevity.

  10. 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.

  11. Investigation of macrophage polarization using bone marrow derived macrophages.

    PubMed

    Ying, Wei; Cheruku, Patali S; Bazer, Fuller W; Safe, Stephen H; Zhou, Beiyan

    2013-06-23

    The article describes a readily easy adaptive in vitro model to investigate macrophage polarization. In the presence of GM-CSF/M-CSF, hematopoietic stem/progenitor cells from the bone marrow are directed into monocytic differentiation, followed by M1 or M2 stimulation. The activation status can be tracked by changes in cell surface antigens, gene expression and cell signaling pathways.

  12. Marrow hypoplasia associated with congenital neurologic anomalies in two siblings.

    PubMed

    Drachtman, R; Weinblatt, M; Sitarz, A; Gold, A; Kochen, J

    1990-10-01

    Two siblings with congenital neurologic structural anomalies and delayed-onset selective bone marrow hypoplasia in a previously undescribed constellation of symptoms are presented. Differences between these cases and other well known syndromes are discussed. The importance of this association is the implication that children with congenital neurologic abnormalities may be at increased risk for the development of hypoplastic hematopoietic conditions. PMID:2264478

  13. 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.

  14. Presumptive invasive Chrysosporium infection in a bone marrow transplant recipient.

    PubMed

    Warwick, A; Ferrieri, P; Burke, B; Blazar, B R

    1991-10-01

    Chrysosporium species caused an invasive infection in an 18-year-old patient following allogeneic sibling bone marrow transplant for T lineage acute lymphoblastic leukemia. This infection began as a facial swelling and extended into the central nervous system. Fungal disease spread rapidly despite antifungal agents. An autopsy showed fungal involvement of brain, lungs, liver and kidneys.

  15. Red Clump Stars

    NASA Astrophysics Data System (ADS)

    Girardi, Léo

    2016-09-01

    Low-mass stars in their core-helium-burning stage define the sharpest feature present in the color-magnitude diagrams of nearby galaxy systems: the red clump (RC). This feature has given rise to a series of methods aimed at measuring the distributions of stellar distances and extinctions, especially in the Magellanic Clouds and Milky Way Bulge. Because the RC is easily recognizable within the data of large spectroscopic and asteroseismic surveys, it is a useful probe of stellar densities, kinematics, and chemical abundances across the Milky Way disk; it can be applied up to larger distances than that allowed by dwarfs; and it has better accuracy than is possible with other kinds of giants. Here, we discuss the reasons for the RC narrowness in several sets of observational data, its fine structure, and the presence of systematic changes in the RC properties as regards age, metallicity, and the observed passband. These factors set the limits on the validity and accuracy of several RC methods defined in the literature.

  16. 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

  17. 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.

  18. 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

  19. 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

  20. The effect of different implant biomaterials on the behavior of canine bone marrow stromal cells during their differentiation into osteoblasts.

    PubMed

    Özdal-Kurt, F; Tuğlu, I; Vatansever, H S; Tong, S; Şen, B H; Deliloğlu-Gürhan, S I

    2016-08-01

    We investigated the effects of different implant biomaterials on cultured canine bone marrow stromal cells (BMSC) undergoing differentiation into osteoblasts (dBMSC). BMSC were isolated from canine humerus by marrow aspiration, cultured and differentiated on calcium phosphate scaffold (CPS), hydroxyapatite, hydroxyapatite in gel form and titanium mesh. We used the MTT method to determine the effects of osteogenic media on proliferation. The characteristics of dBMSC were assessed using alizarin red (AR), immunocytochemistry and osteoblastic markers including alkaline phosphatase/von Kossa (ALP/VK), osteocalcin (OC) and osteonectin (ON), and ELISA. The morphology of dBMSC on the biomaterials was investigated using inverted phase contrast microscopy and scanning electron microscopy. We detected expression of ALP/VK, AR, OC and ON by day 7 of culture; expression increased from day 14 until day 21. CPS supported the best adhesion, cell spreading, proliferation and differentiation of BMSCs. The effects of the biomaterials depended on their surface properties. Expression of osteoblastic markers showed that canine dBMSCs became functional osteoblasts. Tissue engineered stem cells can be useful clinically for autologous implants for treating bone wounds. PMID:27182756

  1. 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

  2. Romantic red: red enhances men's attraction to women.

    PubMed

    Elliot, Andrew J; Niesta, Daniela

    2008-11-01

    In many nonhuman primates, the color red enhances males' attraction to females. In 5 experiments, the authors demonstrate a parallel effect in humans: Red, relative to other achromatic and chromatic colors, leads men to view women as more attractive and more sexually desirable. Men seem unaware of this red effect, and red does not influence women's perceptions of the attractiveness of other women, nor men's perceptions of women's overall likeability, kindness, or intelligence. The findings have clear practical implications for men and women in the mating game and, perhaps, for fashion consultants, product designers, and marketers. Furthermore, the findings document the value of extending research on signal coloration to humans and of considering color as something of a common language, both within and across species.

  3. Significance of bone marrow edema in pathogenesis of rheumatoid arthritis

    PubMed Central

    Sudoł-Szopińska, Iwona; Kontny, Ewa; Maśliński, Włodzimierz; Prochorec-Sobieszek, Monika; Warczyńska, Agnieszka; Kwiatkowska, Brygida

    2013-01-01

    Summary Assessing the pathology of the synovium, its thickening and increased vascularity through ultrasound and magnetic resonance examinations (more often an ultrasound study alone) is still considered a sensitive parameter in the diagnosis of rheumatoid arthritis and in monitoring of treatment efficacy. Magnetic resonance studies showed that, aside from the joint pannus, the subchondral bone tissue constitutes an essential element in the development of rheumatoid arthritis. Bone marrow edema correlates with inflammation severity, joint destruction, clinical signs and symptoms of rheumatoid arthritis, and thus is considered a predictor of rapid radiological progression of the disease. The newest studies reveal that bone marrow edema may be a more sensitive indicator of the response to therapy than appearance of the synovium. Bone marrow edema presents with increased signal in T2-weighted images, being most visible in fat saturation or IR sequences (STIR, TIRM). On the other hand, it is hypointense and less evident in T1-weighted images. It becomes enhanced (hyperintense) after contrast administration. Histopathological studies confirmed that it is a result of bone inflammation (osteitis/osteomyelitis), i.e. replacememt of bone marrow fat by inflammatory infiltrates containing macrophages, T lymphocytes, B lymphocytes, plasma cells and osteoclasts. Bone marrow edema appears after a few weeks from occurrence of symptoms and therefore is considered an early marker of inflammation. It correlates with clinical assessment of disease activity and elevated markers of acute inflammatory phase, i.e. ESR and CRP. It is a reversible phenomenon and may become attenuated due to biological treatment. It is considered a “herald” of erosions, as the risk of their formation is 6-fold higher in sites where BME was previously noted PMID:23493495

  4. Late pulmonary sequelae after childhood bone marrow transplantation

    PubMed Central

    Cerveri, I.; Zoia, M.; Fulgoni, P.; Corsico, A.; Casali, L.; Tinelli, C.; Zecca, M.; Giorgiani, G.; Locatelli, F.

    1999-01-01

    BACKGROUND—Respiratory function in transplanted children is important because of the long life expectancy of bone marrow transplant recipients, particularly children. Attention is now being focused on the late sequelae of treatment on organ system function. A few papers have been published but available data are somewhat conflicting.
METHODS—A cross sectional study aimed at evaluating the late effects of transplantation on lung function was performed in a group of 52 young patients who were given autologous or allogeneic bone marrow transplants during childhood for haematological malignancies.
RESULTS—No patients reported chronic respiratory symptoms. The distribution of respiratory function patterns showed that only 62% of patients had respiratory function within the normal limits; 23% had a restrictive pattern and 15% had isolated transfer factor impairment. The percentage of patients with lung function abnormalities was higher in those who (1) received a bone marrow transplant after two or three complete remissions compared with those who were transplanted immediately after the first remission (54% vs 21%; p<0.02), (2) underwent allogeneic bone marrow transplantation rather than an autologous transplantation (45% vs 26%; p = 0.06), and (3) had a pulmonary infection compared with those without (56% vs 26%; p = 0.07).
CONCLUSIONS—In spite of the absence of chronic respiratory symptoms there is a high prevalence of children with late pulmonary sequelae after bone marrow transplantation. Regular testing is recommended after transplantation, in particular in subjects at higher risk of lung injuries, such as those receiving transplants after more than one remission, those receiving allogeneic transplants, and those having suffered from pulmonary infections. When lung function abnormalities become apparent, long term follow up is necessary to see whether they become clinically relevant. All patients should remain non-smokers after transplantation and

  5. 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

  6. A patient with familial bone marrow failure and an inversion of chromosome 8.

    PubMed

    Buchbinder, David Kyle; Zadeh, Touran; Nugent, Diane

    2011-12-01

    Familial bone marrow failure has been associated with a variety of chromosomal aberrations. Chromosome 8 abnormalities have been described in association with neoplastic and hematologic disorders; however, to our knowledge, inversion of the long arm of chromosome 8 has not been described in the context of familial bone marrow failure. We describe a 9-year-old female with familial bone marrow failure and an inversion of chromosome 8 [inv (8) (q22, q24.3)]. Given the importance of considering the genetic determinants of familial bone marrow failure, the potential role of chromosome 8 abnormalities in the development of marrow failure is discussed.

  7. Characteristics of mesenchymal stem cells isolated from bone marrow of giant panda.

    PubMed

    Liu, Yuliang; Liu, Yang; Yie, Shangmian; Lan, Jingchao; Pi, Jinkui; Zhang, Zhihe; Huang, He; Cai, Zhigang; Zhang, Ming; Cai, Kailai; Wang, Hairui; Hou, Rong

    2013-09-01

    In present study, we report on bone marrow (BM) mesenchymal stem cells (MSCs) that are isolated from giant pandas. Cells were collected from the BM of two stillborn giant pandas. The cells were cultured and expanded in 10% fetal bovine serum medium. Cell morphology was observed under an inverted microscopy, and the proliferation potential of the cells was evaluated by counting cell numbers for eight consecutive days. Differentiation potentials of the cells were determined by using a variety of differentiation protocols for osteocytes, adipocytes, neuron cells, and cardiomyocytes. Meanwhile, the specific gene expressions for MSCs or differentiated cells were analyzed by RT-PCR. The isolated cells exhibited a fibroblast-like morphology; expressed mesenchymal specific markers such as cluster of differentiation 73 (CD73), SRY (sex determining region Y)-box 2 (SOX-2), guanine nucleotide-binding protein-like 3 (GNL3), and stem cell factor receptor (SCFR); and could be differentiated into osteocytes and adipocytes that were characterized by Alizarin Red and Oil Red O staining. Under appropriate induction conditions, these cells were also able to differentiate into neuroglial-like or myocardial-like cells that expressed specific myocardial markers such as GATA transcription factors 4 (GATA-4), cardiac troponin T (cTnT), and myosin heavy chain 7B (MYH7B), or neural specific markers such as Nestin and glial fibrillary acidic protein (GFAP). This study demonstrated stem cells recovery and growth from giant pandas. The findings suggest that cells isolated from the BM of giant pandas have a high proliferative capacity and multiple differentiation potential in vitro which might aid conservation efforts.

  8. Increased Differentiation Capacity of Bone Marrow-Derived Mesenchymal Stem Cells in Aquaporin-5 Deficiency

    PubMed Central

    Yi, Fei; Khan, Muhammad; Gao, Hongwen; Hao, Feng; Sun, Meiyan; Zhong, Lili; Lu, Changzheng; Feng, Xuechao

    2012-01-01

    Mesenchymal stem cells (MSCs) are adult stem cells with a self-renewal and multipotent capability and express extensively in multitudinous tissues. We found that water channel aquaporin-5 (AQP5) is expressed in bone marrow-derived MSCs (BMMSCs) in the plasma membrane pattern. BMMSCs from AQP5−/− mice showed significantly lower plasma membrane water permeability than those from AQP5+/+ mice. In characterizing the cultured BMMSCs from AQP5−/− and AQP5+/+ mice, we found no obvious differences in morphology and proliferation between the 2 genotypes. However, the multiple differentiation capacity was significantly higher in AQP5−/− than AQP5+/+ BMMSCs as revealed by representative staining by Oil Red O (adipogenesis); Alizarin Red S and alkaline phosphatase (ALP; osteogenesis); and type II collagen and Safranin O (chondrogenesis) after directional induction. Relative mRNA expression levels of 3 lineage differentiation markers, including PPARγ2, C/EBPα, adipsin, collagen 1a, osteopontin, ALP, collagen 11a, collagen 2a, and aggrecan, were significantly higher in AQP5−/− -differentiating BMMSCs, supporting an increased differentiation capacity of AQP5−/− BMMSCs. Furthermore, a bone-healing process was accelerated in AQP5−/− mice in a drill-hole injury model. Mechanistic studies indicated a significantly lower apoptosis rate in AQP5−/− than AQP5+/+ BMMSCs. Apoptosis inhibitor Z-VAD-FMK increased the differentiation capacity to a greater extent in AQP5+/+ than AQP5−/− BMMSCs. We conclude that AQP5-mediated high plasma membrane water permeability enhances the apoptosis rate of differentiating BMMSCs, thus decreasing their differentiation capacity. These data implicate AQP5 as a novel determinant of differentiation of BMMSCs and therefore a new molecular target for regulating differentiation of BMMSCs during tissue repair and regeneration. PMID:22420587

  9. Characteristics of mesenchymal stem cells isolated from bone marrow of giant panda.

    PubMed

    Liu, Yuliang; Liu, Yang; Yie, Shangmian; Lan, Jingchao; Pi, Jinkui; Zhang, Zhihe; Huang, He; Cai, Zhigang; Zhang, Ming; Cai, Kailai; Wang, Hairui; Hou, Rong

    2013-09-01

    In present study, we report on bone marrow (BM) mesenchymal stem cells (MSCs) that are isolated from giant pandas. Cells were collected from the BM of two stillborn giant pandas. The cells were cultured and expanded in 10% fetal bovine serum medium. Cell morphology was observed under an inverted microscopy, and the proliferation potential of the cells was evaluated by counting cell numbers for eight consecutive days. Differentiation potentials of the cells were determined by using a variety of differentiation protocols for osteocytes, adipocytes, neuron cells, and cardiomyocytes. Meanwhile, the specific gene expressions for MSCs or differentiated cells were analyzed by RT-PCR. The isolated cells exhibited a fibroblast-like morphology; expressed mesenchymal specific markers such as cluster of differentiation 73 (CD73), SRY (sex determining region Y)-box 2 (SOX-2), guanine nucleotide-binding protein-like 3 (GNL3), and stem cell factor receptor (SCFR); and could be differentiated into osteocytes and adipocytes that were characterized by Alizarin Red and Oil Red O staining. Under appropriate induction conditions, these cells were also able to differentiate into neuroglial-like or myocardial-like cells that expressed specific myocardial markers such as GATA transcription factors 4 (GATA-4), cardiac troponin T (cTnT), and myosin heavy chain 7B (MYH7B), or neural specific markers such as Nestin and glial fibrillary acidic protein (GFAP). This study demonstrated stem cells recovery and growth from giant pandas. The findings suggest that cells isolated from the BM of giant pandas have a high proliferative capacity and multiple differentiation potential in vitro which might aid conservation efforts. PMID:23557186

  10. 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 β1 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

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

    PubMed

    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

    2015-05-01

    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.

  12. Red blood cells, spherocytosis (image)

    MedlinePlus

    Spherocytosis is a hereditary disorder of the red blood cells (RBCs), which may be associated with a mild anemia. Typically, the affected RBCs are small, spherically shaped, and lack the light centers seen ...

  13. Red Blood Cell Antibody Identification

    MedlinePlus

    ... be limited. Home Visit Global Sites Search Help? RBC Antibody Identification Share this page: Was this page helpful? Also known as: Alloantibody Identification; Antibody ID, RBC; RBC Ab ID Formal name: Red Blood Cell ...

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

    PubMed

    Green, Danielle E; Rubin, Clinton T

    2014-06-01

    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

  15. 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

  16. 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

  17. {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.

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

    PubMed

    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.

  19. 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.

  20. [Effect of bone marrow cells transplantation on the decidua formation in pseudopregnant rats].

    PubMed

    Domnina, A P; Mikhaĭlov, V M; Nikol'skiĭ, N N

    2014-01-01

    One of the most common causes of the current pregnancy loss is the failure of the decidual reaction of endometrial cells. It is assumed that a partial source of decidual cells in endometrial tissue is bone marrow cells (BMCs). In the present work, we have studied possible effect of BMCs transplantation on the process of decidualization using the model of pseudopregnancy in rats. BMCs were flushed from the rat femurs and tibias. The obtained suspension of single BMCs was injected into one of rat uterine horns on the 5th day of pseudopregnancy. PBS without cells was injected into the contralateral horn served as the control. Rats were sacrificed on the 11th day of pseudopregnancy. Decidua formed in the experimental uterine horn showed an increase in the meso-antimezometral direction of their diameter of about 1.5-2 times as compared with a control horn. The weight of decidual tissue in the experimental horn exceeded 3 times the weight of the control one. The presence of transplanted BMCs in decidual tissue was documented by preliminary double staining of BMCs with membrane dye PKH 26 Red and nuclear dye Hoechst 33342. Histological analysis of decidua sections after transplantation revealed any alterations neither in cell differentiation nor in tissue structure. We conclude that BMCs transplantation stimulates decidualization in animals.

  1. Recognization of receptors on bone marrow-derived dendritic cells bound with Pholiota nameko polysaccharides.

    PubMed

    Li, Haiping; Tao, Yongqing; Zhao, Pei; Ban, Xiaopan; Zhi, Dexian; Li, Guoliang; Wang, Fenlin; Yang, Xiaoli; Huai, Lihua

    2015-01-01

    Three major active polysaccharides isolated from Pholiota nameko (PNPS), including PNPS-1, PNPS-2 and PNPS-3, had been proved to inhibit the maturation of the murine bone marrow-derived dendritic cells (BMDCs). This paper recognized the affinity bind between PNPS and the five receptors (TLR2, TLR4, CD14, Dectin-1 and Mannose receptor) on BMDCs, using the bio-layer interferometry (BLI)-based biosensor technology developed by ForteBio on Octet RED system (Fortebio, Inc.). From the primary binding experiment, the gradient binding experiment and the inhibition binding experiment between the receptor proteins and PNPS, combined with the binding experiment between PNPS and the BMDCs membranes, we found that PNPS-1, PNPS-2 and PNPS-3 presented strong affinity bind with both TLR2 and Dectin-1 on BMDCs, only PNPS-3 with Mannose receptor. These data confirmed that PNPS could interact with TLR2, Dectin-1 and Mannose receptor that were very important for the affinity bind of these receptors and PNPS, which triggered the further stimulation on BMDCs. PMID:25158288

  2. High-Frequency Vibration Treatment of Human Bone Marrow Stromal Cells Increases Differentiation toward Bone Tissue

    PubMed Central

    Prè, D.; Ceccarelli, G.; Visai, L.; Benedetti, L.; Imbriani, M.; Cusella De Angelis, M. G.; Magenes, G.

    2013-01-01

    In order to verify whether differentiation of adult stem cells toward bone tissue is promoted by high-frequency vibration (HFV), bone marrow stromal cells (BMSCs) were mechanically stimulated with HFV (30 Hz) for 45 minutes a day for 21 or 40 days. Cells were seeded in osteogenic medium, which enhances differentiation towards bone tissue. The effects of the mechanical treatment on differentiation were measured by Alizarin Red test, (q) real-time PCR, and protein content of the extracellular matrix. In addition, we analyzed the proliferation rate and apoptosis of BMSC subjected to mechanical stimulation. A strong increase in all parameters characterizing differentiation was observed. Deposition of calcium was almost double in the treated samples; the expression of genes involved in later differentiation was significantly increased and protein content was higher for all osteogenic proteins. Lastly, proliferation results indicated that stimulated BMSCs have a decreased growth rate in comparison with controls, but both treated and untreated cells do not enter the apoptosis process. These findings could reduce the gap between research and clinical application for bone substitutes derived from patient cells by improving the differentiation protocol for autologous cells and a further implant of the bone graft into the patient. PMID:23585968

  3. Derivation of an equation to estimate marrow content of bovine cervical vertebrae.

    PubMed

    Gebault, R A; Field, R A; Means, W J; Russell, W C

    1998-08-01

    Marrow content of bovine cervical vertebrae from Choice- and Select-grade carcasses weighing 294 to 343 kg was determined so that a method to monitor the amount of marrow in meat from advanced meat/bone separation machinery and recovery (AMR) systems could be developed. The marrow determination requires cleaning and then ashing bones. Because a large difference in ash content of bone and bone marrow exists and because cartilage content of cervical vertebrae in Choice and Select beef is relatively constant, it was possible to derive the following equation: Weight of marrow = [weight of cartilage (% ash in cartilage - % ash in bone) + % ash in bone (total weight) - (total ash)]/[(% ash in bone - % ash in marrow)]. Constants for ash in fresh bone, marrow, and cartilage were 58.51, .57, and 2.14% with SD of 2.23, .15, and .30%, respectively. A cartilage content of 9.5% along with cervical vertebrae weight and total ash weight were also used to calculate 33.9% marrow in cervical vertebrae. Means for marrow pressed or centrifuged from bovine cervical vertebrae were lower than those obtained from the equation. Therefore, pressing and centrifuging left some marrow in spongy bone. Our ashing method for determining the amount of marrow in whole cervical vertebrae should be useful for determining marrow remaining in cervical vertebrae of bone cakes from AMR systems. Percentage ash in pressed bones is higher and the calculated marrow content is lower when pressed bones are compared to cervical vertebrae that are not pressed. The amount of marrow in whole cervical vertebrae minus the amount left in cervical vertebrae from bone cakes equals the amount in meat from AMR systems.

  4. Phenotypic and functional analysis of bone marrow progenitor cell compartment in bone marrow failure.

    PubMed

    Maciejewski, J P; Anderson, S; Katevas, P; Young, N S

    1994-06-01

    Many laboratory findings have demonstrated that the haemopoietic stem cell compartment is defective in aplastic anaemia (AA). AA bone marrow (BM) and peripheral blood (PB) are profoundly deficient in colony-forming cells, and AA progenitors fail to proliferate in long-term assays even in the presence of an intact stroma. Our study was designed to characterize some quantitative and qualitative aspects of the progenitor cell defect in AA. Using flow cytometric analysis of BM from new AA patients and from those recovering after immunosuppressive therapy, we determined that the numbers of CD34+ and CD33+ cells were markedly decreased in AA. Although PB neutrophil counts did not correlate with BM CD34+ cell numbers in acute disease, there was an association between the overall severity of the disease and the degree of CD34+ cell reduction. A decrease in BM CD33+ cells was a common finding in MDS patients, but reduction in CD34+ cells was found only in some hypoplastic MDS cases. Sorting experiments demonstrated lower plating efficiency for purified CD34+ cells from AA BM in comparison to controls. Thus, diminished colony formation of total BM appeared to result from both quantitative and qualitative defects. Based on the association between increased cycling and c-kit receptor expression on CD34+ cells, we found that the mitotically active CD34+ cells bearing the c-kit antigen were reduced in AA. With clinical improvement, CD34+ and CD33+ cells increased in correlation with PB parameters, but they did not return to normal values. Sorted CD34+ cells from recovered patents showed improved plating efficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. 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.

  6. Primary splenic histiocytic sarcoma complicated with prolonged idiopathic thrombocytopenia and secondary bone marrow involvement: a unique surgical case presenting with splenomegaly but non-nodular lesions

    PubMed Central

    2012-01-01

    Abstract A 67-year-old Japanese female was followed up due to prolonged idiopathic thrombocytopenia with non-response to steroid therapy for 4 years, but recent progressive pancytopenia, hypo-albuminemia, and hypo-γ-globulinemia were presented. An abdominal CT scan revealed heterogeneously enhanced splenomegaly without any nodular lesions. A splenectomy was performed, and gross examination showed markedly hyperemic red pulp, weighing 760 g, accompanied by multiple foci of peripheral anemic infarction. Surprisingly, microscopic findings exhibited a diffuse proliferation of medium-sized to large tumor cells having pleomorphic nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm, predominantly within the sinuses and cords of the red pulp, which occasionally displayed conspicuous hemophagocytosis and vascular permeation. In immunohistochemistry, these atypical cells were specifically positive for CD68 (KP-1), CD163, and lysozyme, which was consistent with histiocytic sarcoma (HS) of the spleen. Subsequently, section from the aspiration of bone marrow showed infiltration of the neoplastic cells associated with erythrophagocytosis 2 months after the operation, but never before it. Therefore, primary splenic HS presenting with secondary bone marrow involvement was conclusively diagnosed. Since early diagnosis and treatment are necessary for the HS patients with poor outcomes, splenic HS should be considered as a differential diagnosis in cases with chronic thrombocytopenia and splenomegaly. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1009474924812827 PMID:23075171

  7. Habitability of planets around red dwarf stars.

    PubMed

    Heath, M J; Doyle, L R; Joshi, M M; Haberle, R M

    1999-08-01

    Recent models indicate that relatively moderate climates could exist on Earth-sized planets in synchronous rotation around red dwarf stars. Investigation of the global water cycle, availability of photosynthetically active radiation in red dwarf sunlight, and the biological implications of stellar flares, which can be frequent for red dwarfs, suggests that higher plant habitability of red dwarf planets may be possible.

  8. 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...

  9. 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

  10. Shared oxidative pathways in response to gravity-dependent loading and gamma-irradiation of bone marrow-derived skeletal cell progenitors.

    PubMed

    Kondo, H; Limoli, C; Searby, N D; Almeida, E A C; Loftus, D J; Vercoutere, W; Morey-Holton, E; Giedzinski, E; Mojarrab, R; Hilton, D; Globus, R K

    2007-01-01

    Astronauts are exposed to radiation during space travel under conditions of dramatically reduced weightbearing activity. However, we know little about how gravity-dependent loading affects tissue sensitivity to radiation. We hypothesize gravity-dependent loading and irradiation share common molecular signaling pathways in bone cell progenitors that are sensitive to stress-induced reactive oxygen species (ROS), species capable of impacting skeletal health. To address this, progenitor cells with potential to differentiate into bone-forming osteoblasts were extracted from bone marrow, then cells were centrifuged (from 5-gravity (g) to 50-g for 5-180 min) on day 2 in culture, or were exposed to a single dose (1-5 Gy) of irradiation (137Cs 1 Gy/min) on day 3 or 4. Production of ROS was measured via fluorescence-activated cell sorting (FACS) using an oxidation-sensitive dye. Cell numbers were assessed by measurement of DNA content (CyQUANT). Osteoblastogenesis was estimated by measurement of alkaline phosphatase (ALP) activity and production of mineralized matrix (Alizarin Red staining). Transient centrifugation was a potent stimulus to bone marrow stromal cells, increasing production of ROS (1.2-fold), cell number (1.5-fold to 2.2-fold), and ALP activity (2.7-fold). Radiation also caused dose- and time-dependent increases in ROS production (1.1-fold to 1.4-fold) by bone marrow stromal cells, but inhibited subsequent osteoblast differentiation. In summary, gravity-dependent loading by centrifugation stimulated ROS production and increased numbers of osteoblasts. Although radiation increased production of ROS by bone marrow stromal cells, cell number and differentiation of osteoprogenitors appeared reduced. We conclude gravity-dependent loading and radiation both stimulate production of ROS and affect critical bone cell functions including growth and differentiation.

  11. Bone marrow stem cell as a potential treatment for diabetes.

    PubMed

    Li, Ming; Ikehara, Susumu

    2013-01-01

    Diabetes mellitus (DM) is a group of metabolic diseases in which a person has high blood glucose levels resulting from defects in insulin secretion and insulin action. The chronic hyperglycemia damages the eyes, kidneys, nerves, heart, and blood vessels. Curative therapies mainly include diet, insulin, and oral hypoglycemic agents. However, these therapies fail to maintain blood glucose levels in the normal range all the time. Although pancreas or islet-cell transplantation achieves better glucose control, a major obstacle is the shortage of donor organs. Recently, research has focused on stem cells which can be classified into embryonic stem cells (ESCs) and tissue stem cells (TSCs) to generate functional β cells. TSCs include the bone-marrow-, liver-, and pancreas-derived stem cells. In this review, we focus on treatment using bone marrow stem cells for type 1 and 2 DM. PMID:23671865

  12. Ethical issues in bone marrow transplantation in children.

    PubMed

    Bendorf, Aric; Kerridge, Ian H

    2011-09-01

    In the 50 years since the first successful human bone marrow transplant (BMT) was performed in 1959, BMT has become the optimal therapy for a wide variety of life-threatening paediatric haematological, immunological and genetic disorders. Unfortunately, while BMT generally provides the only possibility of cure for such afflicted children, few (25%) have a matched sibling available, and suitably matched unrelated donors are often not identified for many children in need of BMT. And even where BMT is possible, treatment is complex and arduous and associated with significant mortality and morbidity. The issues raised when either or both the donor and recipient are children and lack the capacity to make informed and rational decisions relating to BMT pose great challenges for all involved. This paper examines some of the ethical dilemmas that confront patients, families and medical practitioners when considering bone marrow transplantation in a child. PMID:21951444

  13. Male genital lichen sclerosus in recipients of bone marrow transplants.

    PubMed

    Thomas, L J; Shim, T N; Borysiewicz, C; Dinneen, M; Fawcett, H; Roy, A; Francis, N; Bunker, C B

    2016-07-01

    We describe two patients who received haematopoietic stem cell marrow transplantation, and developed male genital lichen sclerosus (MGLSc), one of whom also had squamous carcinoma in situ (Bowen disease). MGLSc has previously been associated with graft-versus-host disease. Various aetiological factors for LSc have been proposed, including a role for chronic occluded epithelial exposure to urine. A number of factors imply that the risk of malignant transformation in this bone marrow transplant group is likely to be higher than the overall figure of 2-9% cited for MGLSc. It is vital, therefore, that clinicians involved in the care of those with haematological malignancies are adequately prepared to examine the genitals of their patients, and to recognize and refer any suspect penile lesions. PMID:26936088

  14. Overview of bone marrow and peripheral blood stem cell transplantation.

    PubMed

    Poliquin, C M

    1997-01-01

    Bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT) are treatments used with increasing frequency for a growing number of cancers. As technology develops, so, too, does the complexity of nursing care. In addition, as the number of patients who receive BMT or PBSCT increases, more and more nurses will be involved in their care. Knowledge of what problems to anticipate, comprehensive assessment, clear patient and family education, and strong emotional support provide the key to successful patient management.

  15. Primary cutaneous aspergillosis and idiopathic bone marrow aplasia*

    PubMed Central

    Furlan, Karina Colossi; Pires, Mario Cezar; Kakizaki, Priscila; Chartuni, Juliana Cabral Nunes; Valente, Neusa Yuriko Sakai

    2016-01-01

    We describe the case of a 9-year-old boy with idiopathic bone marrow aplasia and severe neutropenia, who developed skin ulcers under cardiac monitoring electrodes. The diagnosis of primary cutaneous aspergillosis was made after the second biopsy and culture. Imaging investigation did not reveal internal fungal infection. The child was treated, but did not improve and died 3 months after admission. The report highlights and discusses the preventable risk of aspergillus skin infection in immunocompromised patients. PMID:27438213

  16. Intractable bone marrow edema syndrome of the hip.

    PubMed

    Gao, Fuqiang; Sun, Wei; Li, Zirong; Guo, Wanshou; Kush, Nepali; Ozaki, Koji

    2015-04-01

    There is a need for an effective and noninvasive treatment for intractable bone marrow edema syndrome of the hip. Forty-six patients with intractable bone marrow edema syndrome of the hip were retrospectively studied to compare the short-term clinical effects of treatment with high-energy extracorporeal shock wave therapy vs femoral head core decompression. The postoperative visual analog scale score decreased significantly more in the extracorporeal shock wave therapy group compared with the femoral head core decompression group (P<.05). For unilateral lesions, postoperative Harris Hip Scores for all hips in the extracorporeal shock wave therapy group were more significantly improved than Harris Hip Scores for all hips in the femoral head core decompression group (P<.05). Patients who underwent extracorporeal shock wave therapy also resumed daily activities significantly earlier. Average overall operative time was similar in both groups. Symptoms disappeared significantly sooner in the extracorporeal shock wave therapy group in patients with both unilateral (P<.01) and bilateral lesions (P<.05). Hospital costs were significantly lower with extracorporeal shock wave therapy compared with femoral head core decompression. The intraoperative fluoroscopy radiation dose was lower in extracorporeal shock wave therapy than in femoral head core decompression for both unilateral (P<.05) and bilateral lesions (P<.01). On magnetic resonance imaging (MRI), bone marrow edema improved in all patients during the follow-up period. After extracorporeal shock wave therapy, all patients remained pain-free and had normal findings on posttreatment radiographs and MRI scans. Extracorporeal shock wave therapy appears to be a valid, reliable, and noninvasive tool for rapidly resolving intractable bone marrow edema syndrome of the hip, and it has a low complication rate and relatively low cost compared with other conservative and surgical treatment approaches.

  17. Primary cutaneous aspergillosis and idiopathic bone marrow aplasia.

    PubMed

    Furlan, Karina Colossi; Pires, Mario Cezar; Kakizaki, Priscila; Chartuni, Juliana Cabral Nunes; Valente, Neusa Yuriko Sakai

    2016-01-01

    We describe the case of a 9-year-old boy with idiopathic bone marrow aplasia and severe neutropenia, who developed skin ulcers under cardiac monitoring electrodes. The diagnosis of primary cutaneous aspergillosis was made after the second biopsy and culture. Imaging investigation did not reveal internal fungal infection. The child was treated, but did not improve and died 3 months after admission. The report highlights and discusses the preventable risk of aspergillus skin infection in immunocompromised patients. PMID:27438213

  18. Pancytopenia after allogeneic bone marrow transplant due to copper deficiency.

    PubMed

    Hudspeth, Michelle; Turner, Amy; Miller, Nicole; Lazarchick, John

    2014-05-01

    Pancytopenia occurring 1 year or later after allogeneic bone marrow transplantation typically prompts a primary consideration for relapse. We present the case of a 15-year old-girl who underwent transplantation for therapy-related myelodysplasia secondary to Ewing sarcoma treatment who developed pancytopenia with myelodysplasia 1 year after transplant due to copper deficiency. Copper deficiency is an important consideration in the evaluation of pancytopenia and myelodysplasia in pediatric patients.

  19. Bone Marrow Diseases - Multiple Languages: MedlinePlus

    MedlinePlus

    ... page, please enable JavaScript. French (français) Japanese (日本語) Korean (한국어) Russian (Русский) Somali (af Soomaali) Spanish (español) ... 骨髄生検 - 日本語 (Japanese) Bilingual PDF Health Information Translations Korean (한국어) Bone Marrow Biopsy 골수 생체조직 검사 - 한국어 ( ...

  20. Spine Fusion Using Cell Matrix Composites Enriched in Bone Marrow-Derived Cells

    PubMed Central

    Nitto, Hironori; Matsukura, Yoichi; Boehm, Cynthia; Valdevit, Antonio; Kambic, Helen; Davros, William; Powell, Kimerly; Easley, Kirk

    2005-01-01

    Bone marrow-derived cells including osteoblastic progenitors can be concentrated rapidly from bone marrow aspirates using the surface of selected implantable matrices for selective cell attachment. Concentration of cells in this way to produce an enriched cellular composite graft improves graft efficacy. The current study was designed to test the hypothesis that the biologic milieu of a bone marrow clot will significantly improve the efficacy of such a graft. An established posterior spinal fusion model and cancellous bone matrix was used to compare an enriched cellular composite bone graft alone, bone matrix plus bone marrow clot, and an enriched bone matrix composite graft plus bone marrow clot. Union score, quantitative computed tomography, and mechanical testing were used to define outcome. The union score for the enriched bone matrix plus bone marrow clot composite was superior to the enriched bone matrix alone and the bone matrix plus bone marrow clot. The enriched bone matrix plus bone marrow clot composite also was superior to the enriched bone matrix alone in fusion volume and in fusion area. These data confirm that the addition of a bone marrow clot to an enriched cell-matrix composite graft results in significant improvement in graft performance. Enriched composite grafts prepared using this strategy provide a rapid, simple, safe, and inexpensive method for intraoperative concentration and delivery of bone marrow-derived cells and connective tissue progenitors that may improve the outcome of bone grafting. PMID:12567137

  1. A Single-center Experience in Splenic Diffuse Red Pulp Lymphoma Diagnosis.

    PubMed

    Julhakyan, Hunan L; Al-Radi, L S; Moiseeva, T N; Danishyan, K I; Kovrigina, A M; Glebova, S M; Lugovskaya, S A; Dvirnik, V N; Khvastunova, A N; Yakutik, I A; Savchenko, V G

    2016-08-01

    The World Health Organization 2008 classification highlighted a new nosology-splenic diffuse red pulp lymphoma (SDRPL) with clinical and laboratory features similar to both splenic marginal zone lymphoma and hairy cell leukemia (HCL) and variant form of HCL. Experience of hematologists on the diagnosis and differential diagnosis of SDRPL is extremely limited. The aim of our report was to characterize the clinical and immunomorphologic features of SDRPL on our own observations. During 2013-2014, in National Research Center for Hematology, 87 spleen specimens removed from various B-cell lymphomas were analyzed. In four (4.6%) cases, the diagnosis SDRPL was made based on morphologic, immunohistochemical, immunophenotypic, molecular examination of spleen biopsies, blood and bone marrow samples. In all cases of SDRPL were observed significant splenomegaly, lymphocytosis from 56% to 94% (in two cases with leukocytosis 55.000 and 75.000 109/l). The circulating "villous" lymphocytes phenotype was CD20+ (bright), CD11c+/±, CD103 (weakly)+/±, LAIR-1+, CD25-, CD5-, CD10-, and CD23-. Mutation BRAFV600E was not detected. Bone marrow with minor lymphoid CD20+, CD25-, Annexin1-, Cyclin D1- cell infiltration. The average weight of the spleen was 3900 g (1450-9500 g), and morphologically, there was revealed lymphoid infiltration of red pulp with phenotype CD20+, DBA.44+, CD25-, Annexin1-, Cyclin D1-, CD103-, CD123-, CD27-, focal SD11c± and TRAP±. Now patients are observed in remission: two patients after splenectomy, two after splenectomy and cladribine+rituximab chemotherapy. SRDPL-a rare lymphoma that is suspected in the cases with significant splenomegaly and lymphocytosis with villous lymphocytes forms that have only a part of the classic markers HCL, with minor bone marrow infiltration. The standard diagnosis and treatment is splenectomy. Differential diagnosis of SMZL and HCL has clear criteria, but criteria of differentiation with variant HCL are still unknown. PMID

  2. 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.

  3. 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...-0263 to read as follows: Sec. 165.T09-0263 Safety zone; Red River Safety Zone, Red River, MN....

  4. Mobilised bone marrow-derived cells accelerate wound healing.

    PubMed

    Wang, Yu; Sun, Yu; Yang, Xiao-Yan; Ji, Shi-Zhao; Han, Shu; Xia, Zhao-Fan

    2013-08-01

    Massive skin defects caused by severe burn and trauma are a clinical challenge to surgeons. Timely and effective wound closure is often hindered by the lack of skin donor site. Bone marrow-derived cells (BMDCs) have been shown to 'differentiate' into multiple tissue cells. In this study we focused on the direct manipulation of endogenous BMDCs, avoiding the immunocompatibility issues and complicated cell isolation, purification, identification and amplification procedures in vitro on wound repair. We found that mobilisation of the BMDCs into the circulation significantly increased the amount of BMDCs at the injury site which in turn accelerated healing of large open wound. We used a chimeric green fluorescent protein (GFP) mouse model to track BMDCs and to investigate their role in full-thickness skin excisional wounds. We have shown that bone marrow mobilisation by granulocyte colony stimulating factor (G-CSF) exerted multiple beneficial effects on skin repair, both by increasing the engraftment of BMDCs into the skin to differentiate into multiple skin cell types and by upregulating essential cytokine mRNAs critical to wound repair. The potential trophic effects of G-CSF on bone marrow stem cells to accelerate wound healing could have a significant clinical impact.

  5. 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.

  6. How I vaccinate blood and marrow transplant recipients.

    PubMed

    Carpenter, Paul A; Englund, Janet A

    2016-06-01

    Vaccination guidelines for recipients of blood and marrow transplantation (BMT) have been published by 3 major societies: American Blood and Marrow Transplantation, European Group of Blood and Marrow Transplantation, and Infectious Disease Society of America. Despite these extensive review articles, clinicians caring for BMT recipients continue to field frequently asked questions (FAQs) regarding the "who, when, and how" of feasible and effective posttransplant vaccination, frequently in the absence of adequate data. This may reflect discomfort with a "one size fits all" policy that makes no adjustments for different posttransplant clinical scenarios. Existing guidelines also lack practical dose clarifications when administering vaccines to patients who differ by age, underlying diagnosis, or amount of immunosuppressive therapy. Frequently, little or conflicting guidance is given regarding age-related schedules for certain vaccines (eg, meningococcal; tetanus toxoid, reduced diphtheria toxoid, and reduced acellular pertussis; and human papillomavirus vaccines) in addition to time posttransplant or other factors. FAQs and their answers form the body of this article and are shared with readers as a concise practical review, with the intent to facilitate good clinical practice. PMID:27048212

  7. Organotypic culture of human bone marrow adipose tissue.

    PubMed

    Uchihashi, Kazuyoshi; Aoki, Shigehisa; Shigematsu, Masamori; Kamochi, Noriyuki; Sonoda, Emiko; Soejima, Hidenobu; Fukudome, Kenji; Sugihara, Hajime; Hotokebuchi, Takao; Toda, Shuji

    2010-04-01

    The precise role of bone marrow adipose tissue (BMAT) in the marrow remains unknown. The purpose of the present study was therefore to describe a novel method for studying BMAT using 3-D collagen gel culture of BMAT fragments, immunohistochemistry, ELISA and real-time reverse transcription-polymerase chain reaction. Mature adipocytes and CD45+ leukocytes were retained for >3 weeks. Bone marrow stromal cells (BMSC) including a small number of lipid-laden preadipocytes and CD44+/CD105+ mesenchymal stem cell (MSC)-like cells, developed from BMAT. Dexamethasone (10 micromol/L), but not insulin (20 mU/mL), significantly increased the number of preadipocytes. Dexamethasone and insulin also promoted leptin production and gene expression in BMAT. Adiponectin production by BMAT was <0.8 ng/mL under all culture conditions. Dexamethasone promoted adiponectin gene expression, while insulin inhibited it. This finding suggests that dexamethasone, but not insulin, may serve as a powerful adipogenic factor for BMAT, in which adiponectin protein secretion is normally very low, and that BMAT may exhibit a different phenotype from that of the visceral and subcutaneous adipose tissues. BMAT-osteoblast interactions were also examined, and it was found that osteoblasts inhibited the development of BMSC and reduced leptin production, while BMAT inhibited the growth and differentiation of osteoblasts. The present novel method proved to be useful for the study of BMAT biology.

  8. 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.

  9. Bone marrow leishmaniasis: a review of situation in Thailand.

    PubMed

    Wiwanitkit, Viroj

    2011-10-01

    Leishmaniasis is an important tropical vector-borne disease. This infection can be seen in tropical area and it is considered to be one of the most important vector-borne infections at present. The general situation of the leishmaniasis in Thailand is hereby reviewed. Although Thailand is a tropical country, the leishmaniasis is not endemic but sporadic. The imported cases are documented in some literatures. The serious form of leishmaniasis, the visceral leishmaniasis is also detectable in Thailand. Also, the author performed an in depth literature review of the reports of bone marrow leishmaniasis, a specific kind of visceral leishmaniasis, in Thailand in order to summarize the characteristics of this infection among Thai patients. According to this review, there have been at least 5 reports in the literature of 6 cases of bone marrow leishmaniasis in the Thai population, of which no case was lethal. Concerning the clinical manifestations, all except had prolonged fever with unknown origin. From physical examination, all had hepatosplenomegaly. The striking findings were active hemophagocytosis with increased proliferation of lymphoidplasma cell line in the bone marrow and amastigotes of Leishmania donovani was demonstrated. Considering the treatment, pantavalent antimony compound was used and the excellent improvement and complete recovery. Finally, the author also discussed on the importance of leishmaniasis in Thailand relating to the present globalization and good traveling system.

  10. 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.

  11. Red eyes in renal failure.

    PubMed Central

    Klaassen-Broekema, N; van Bijsterveld, O P

    1992-01-01

    Of 57 patients with chronic renal failure who all had deposition of calcium salts in the conjunctival and corneal tissue two developed a brief episode of painful irritation and redness of the conjunctiva and subconjunctiva. This hyperaemia was adjacent to erosions of the corneal epithelium of the eye as a consequence of exfoliation of calcium concretions from the superficial corneal epithelium. Eight patients showed inflammatory reactions of the conjunctivae that were clinically identical to inflamed pingueculae. Three patients showed an inflammatory reaction of the eye that was characterised by a waxy red, more or less diffuse, episcleral and conjunctival hyperaemia extending beyond the palpebral fissure. The average value of the serum calcium concentration in these patients was particularly high and statistically significantly higher than in patients with calcification but without inflammatory signs and also higher than in patients who showed pingueculitis. We propose to reserve the term 'red eye of renal failure' for the latter group of patients. Images PMID:1390507

  12. [Kinetic study of splenocytes after allogeneic murine bone marrow transplantation].

    PubMed

    Liu, Jing-Hua; Zhou, Fan; Dou, Li-Ping; Wang, Li-Li; Wang, Xin-Rong; Li, Li; Yu, Li

    2010-08-01

    The study was purposed to understand immunological reconstitution of peripheral immune organs after transplantation, through establishing allogeneic murine bone marrow transplantation model and detecting the kinetic change of splenocytes after transplantation. C57BL/6 mice were donors, BALB/c mice were recipients. Recipient mice were divided into irradiation group (R), irradiation plus inoculating bone marrow mononuclear cells (MNC) group (B), and irradiation plus inoculating bone marrow mononuclear cells and spleno-MNC group (S). After transplantation, the mice were examined daily for the symptoms such as weight, hunched posture, activity, ruffled fur, diarrhea, and survival. Blood routine test was done once a week, splenocyte was counted and CD3, CD4, CD8, B220, CD11c positive cell relative count was detected by FACS on day 2, 7, 14, 27, 60 after transplantation, Liver, skin and intestine were biopsied for histopathological examination before dying. The results indicated that 89% mice in S group died of acute graft-versus-host disease (aGVHD) during day 6 to 78. The spleno-mononuclear cell count quickly decreased and reached to lowest level on day 2, then gradually recovered to level of pretransplantation on day 14; CD8 and B220 positive cells decreased to lowest level on day 12, in which CD8(+) cells quickly recovered and reached to level of pretransplantation, but the B220(+) recovered most slowly and sustained to be with low level, then gradually recovered to level of pretransplantation on day 60; CD3 and CD4 positive cells decreased relatively slowly, and reached to lowest level on day 14, then both gradually recovered to level of pretransplantation on day 60; CD11c positive cell count changed unstrikingly except day 14. It is concluded that when C57BL/6 mice are donors, and BALB/c mice are recipients treated with irradiation of 7.5 Gy and inoculated with 1 x 10⁷ bone marrow MNC and 1 x 10⁷ spleno-MNC, allogeneic murine bone marrow transplantation model

  13. Effect of Increasing Doses of γ-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 γ-radiation on BMSCs on SLA and PT (polished titanium) surfaces. Rat BMSCs were radiated with 2, 4, and 8 Gy γ-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, PPARγ) gene expression at days 7 and 14 postirradiation. Results showed that γ-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 γ-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

  14. Development of a single probe for documentation of chimerism following bone marrow transplantation.

    PubMed Central

    Yam, P; Petz, L D; Ali, S; Stock, A D; Wallace, R B

    1987-01-01

    Although numerous genetic markers are available for studying chimerism after bone marrow transplantation (BMT), there remains a need for a practical and highly informative method that is applicable in the early posttransplantation period. Using DNA restriction-fragment-length polymorphisms (RFLPs), we have evaluated the feasibility of developing a single synthetic oligonucleotide probe to study post-BMT chimerism. We have thus tested three candidate probes, termed O-3315-32, O-3315-80, and O-AY-29, that are homologous to tandemly repetitive sequences. Our results demonstrated donor-specific and recipient-specific fragments in 11 of 11 HLA-matched sibling pairs tested using probes O-3315-32 and O-3315-80. When probe O-AY-29 was used, 14 of 17 sibling pairs showed both donor and recipient markers, one had only a recipient marker, and two were identical. We showed that each of the three synthetic probes was effective in documenting donor marrow engraftment, mixed hematopoietic chimerism, the patient's pre-BMT phenotype (by using cultured skin fibroblasts obtained after BMT), and the origin of the malignant hematopoietic cells (i.e., of donor or recipient origin) in patients who developed recurrent hematologic malignancy following BMT. Compared with the use of cloned genomic probes, there are several important advantages to the use of synthetic oligonucleotide probes in studying post-BMT chimerism. Synthetic probes have absolute hybridization specificity and can be designed to suit the purposes of an individual study, since they have adjustable specificity that can be altered by changes in the length of the probe and by changes in the hybridization temperature. A single synthetic probe analogous to several highly polymorphic loci can have a polymorphism information content sufficiently high so that all but a small percentage of BMT patients could be followed easily; for example, if a probe were complementary to three highly polymorphic unlinked loci, it would

  15. Coleman v. American Red Cross.

    PubMed

    1990-04-01

    Cheryl Coleman became infected with the human immunodeficiency virus (HIV) after receiving a blood transfusion. Alleging that the blood she received was infected, she sued its supplier, the American Red Cross, to compel discovery of the donor's identity. Coleman asserted that without discovery of the donor's name, it would be impossible to determine whether the Red Cross adequately had screened blood donors (there was no test to identify HIV in blood at that time) and therefore to establish a claim of negligence and the necessary proximate cause. The District Court held that the potential danger to the nation's volunteer blood supply system outweighed Coleman's need to discover the donor's identity.

  16. 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.

  17. 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.

  18. The Application of Bone Marrow Transplantation to the Treatment of Genetic Diseases

    NASA Astrophysics Data System (ADS)

    Parkman, Robertson

    1986-06-01

    Genetic diseases can be treated by transplantation of either normal allogeneic bone marrow or, potentially, autologous bone marrow into which the normal gene has been inserted in vitro (gene therapy). Histocompatible allogeneic bone marrow transplantation is used for the treatment of genetic diseases whose clinical expression is restricted to lymphoid or hematopoietic cells. The therapeutic role of bone marrow transplantation in the treatment of generalized genetic diseases, especially those affecting the central nervous system, is under investigation. The response of a generalized genetic disease to allogeneic bone marrow transplantation may be predicted by experiments in vitro. Gene therapy can be used only when the gene responsible for the disease has been characterized. Success of gene therapy for a specific genetic disease may be predicted by its clinical response to allogeneic bone marrow transplantation.

  19. Detection of disseminated cancer cells in rib marrow of patients with esophageal cancer.

    PubMed

    Noguchi, Tsuyoshi; Shibata, Tomotaka; Fumoto, Shoichi; Sato, Tetsuro; Uchida, Yuzo; Daa, Tsutomu; Yokoyama, Shigeo; Gabbert, Helmut E; Mueller, Wolfram; Takeno, Shinsuke

    2003-01-01

    In the present study, micrometastasis in the rib marrow of 24 patients with esophageal cancer was examined using RT-PCR. RT-PCR was done using primers corresponding to cytokeratin 18 (CK18), squamous cell carcinoma antigen (SCC), and carcinoembryonic antigen (CEA). In 18 cases, CK18 was also detected in the rib marrow. Only one patient exhibited CEA amplification in the rib marrow. No cases demonstrated SCC amplification as a marker of micrometastasis in the rib marrow. The information from micrometastasis detected in the rib marrow using RT-PCR is useful in deciding whether or not adjuvant therapy is necessary after surgery. However, combined analysis using plural markers should be required since sensitivity or specificity of each marker may vary. Further follow-up of the patients is necessary to clarify the clinical impact of micrometastasis in rib marrow.

  20. Osteoinduction by a collagen mineral composite combined with isologous bone marrow in a subcutaneous rat model.

    PubMed

    Alvis, Mark; Lalor, Peggy; Brown, Melissa K C; Thorn, Malahki R; Block, Jon E; Hornby, Samantha; Berg, Richard; Reddi, A Hari

    2003-01-01

    In a subcutaneous implant rat model, Collagraft alone (n=8), Collagraft plus isologous bone marrow (n=8), and marrow alone (n=8) were evaluated. Twelve rats were euthanized at 11 days and 12 at 21 days. Explants were evaluated histologically for evidence of bone formation, and osteogenic activity was determined by an assay for alkaline phosphatase. Histological bone formation was absent in all groups at 11 days. At 21 days, in the Collagraft alone and bone marrow alone groups, no bone induction was noted. In contrast, 21-day specimens from the Collagraft plus bone marrow group showed newly formed bone. Alkaline phosphatase activity was negligible (<0.05 units/mg) in all 11-day specimens. Activity in Collagraft plus bone marrow specimens at 21 days (0.38 units/mg) was significantly higher than any other group (P<.001 for all comparisons). This study demonstrates that Collagraft plus bone marrow is an osteoinductive matrix. PMID:12555839

  1. 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

  2. A case of synovial sarcoma with bone metastasis identified by bone marrow scintigraphy

    SciTech Connect

    Otsuka, N.; Morita, R.; Yamamoto, T.; Muranaka, A.; Tomomitsu, T.; Yanagimoto, S.; Sone, T.; Fukunaga, M.

    1985-04-01

    In a patient with synovial sarcoma, routine bone survey showed no abnormality, while bone marrow scintigraphy with Tc-99m sulfur colloid revealed a defect in the fifth lumbar vertebra. At surgery, tumorous invasion was noted in the fifth lumbar vertebra and the surrounding tissues. It was suggested that the bone marrow scintigraphy was particularly useful in the detection of tumorous invasion into the bone marrow at the early stage before the destruction of skeletal tissue.

  3. Incorporation of Bone Marrow Cells in Pancreatic Pseudoislets Improves Posttransplant Vascularization and Endocrine Function

    PubMed Central

    Wittig, Christine; Laschke, Matthias W.; Scheuer, Claudia; Menger, Michael D.

    2013-01-01

    Failure of revascularization is known to be the major reason for the poor outcome of pancreatic islet transplantation. In this study, we analyzed whether pseudoislets composed of islet cells and bone marrow cells can improve vascularization and function of islet transplants. Pancreatic islets isolated from Syrian golden hamsters were dispersed into single cells for the generation of pseudoislets containing 4×103 cells. To create bone marrow cell-enriched pseudoislets 2×103 islet cells were co-cultured with 2×103 bone marrow cells. Pseudoislets and bone marrow cell-enriched pseudoislets were transplanted syngeneically into skinfold chambers to study graft vascularization by intravital fluorescence microscopy. Native islet transplants served as controls. Bone marrow cell-enriched pseudoislets showed a significantly improved vascularization compared to native islets and pseudoislets. Moreover, bone marrow cell-enriched pseudoislets but not pseudoislets normalized blood glucose levels after transplantation of 1000 islet equivalents under the kidney capsule of streptozotocin-induced diabetic animals, although the bone marrow cell-enriched pseudoislets contained only 50% of islet cells compared to pseudoislets and native islets. Fluorescence microscopy of bone marrow cell-enriched pseudoislets composed of bone marrow cells from GFP-expressing mice showed a distinct fraction of cells expressing both GFP and insulin, indicating a differentiation of bone marrow-derived cells to an insulin-producing cell-type. Thus, enrichment of pseudoislets by bone marrow cells enhances vascularization after transplantation and increases the amount of insulin-producing tissue. Accordingly, bone marrow cell-enriched pseudoislets may represent a novel approach to increase the success rate of islet transplantation. PMID:23875013

  4. 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.

  5. 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.

  6. Factors that influence Greeks' decision to register as potential bone marrow donors.

    PubMed

    Galanis, P A; Sparos, L D; Katostaras, T; Velonakis, E; Kalokerinou, A

    2008-06-01

    Hemopoietic stem cells can be used from bone marrow or blood or umbilical cord blood of matched siblings or appropriately matched unrelated volunteers. Today, large bone marrow registries have been established to help identify volunteer unrelated bone marrow donors for patients lacking a family donor. Despite there being almost 10 million registered potential bone marrow donors (PBMD) worldwide, only 50% of white patients have a suitable bone marrow match. Growth in the number of PBMD increases the likelihood of finding a compatible donor for a patient. The attitudes and knowledge of 250 registered PBMD and 315 not registered PBMD toward bone marrow donation, tissues and organs donation, and blood donation were surveyed, using a questionnaire with 27 items. Multivariate logistic regression identified gender (females more often than males), regular blood donation, having a relative or a friend who has already been registered as PBMD, having a relative or a friend who needs bone marrow transplantation, family discussion about tissue and organ donation, knowledge about bone marrow transplantation, information about bone marrow transplantation, and trust in health professionals were independent predictive factors influencing people's decision to register as PBMD. Knowledge of these factors is important to target recruitment efforts.

  7. Skeletal cell fate decisions within periosteum and bone marrow during bone regeneration.

    PubMed

    Colnot, Céline

    2009-02-01

    Bone repair requires the mobilization of adult skeletal stem cells/progenitors to allow deposition of cartilage and bone at the injury site. These stem cells/progenitors are believed to come from multiple sources including the bone marrow and the periosteum. The goal of this study was to establish the cellular contributions of bone marrow and periosteum to bone healing in vivo and to assess the effect of the tissue environment on cell differentiation within bone marrow and periosteum. Results show that periosteal injuries heal by endochondral ossification, whereas bone marrow injuries heal by intramembranous ossification, indicating that distinct cellular responses occur within these tissues during repair. [corrected] Next, lineage analyses were used to track the fate of cells derived from periosteum, bone marrow, and endosteum, a subcompartment of the bone marrow. Skeletal progenitor cells were found to be recruited locally and concurrently from periosteum and/or bone marrow/endosteum during bone repair. Periosteum and bone marrow/endosteum both gave rise to osteoblasts, whereas the periosteum was the major source of chondrocytes. Finally, results show that intrinsic and environmental signals modulate cell fate decisions within these tissues. In conclusion, this study sheds light into the origins of skeletal stem cells/progenitors during bone regeneration and indicates that periosteum, endosteum, and bone marrow contain pools of stem cells/progenitors with distinct osteogenic and chondrogenic potentials that vary with the tissue environment.

  8. 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.

  9. Induction of allogeneic unresponsiveness by supralethal irradiation and bone marrow reconstitution. [Dogs

    SciTech Connect

    Rapaport, F.T.; Bachvaroff, R.J.; Akiyama, N.; Sato, T.

    1980-09-01

    Supralethally irradiated dogs were reconstituted wth their own stored bone marrow and were challenged at various time intervals with a kidney allograft. The data suggest that transplanted bone marrow cells may participate directly in the events leading to allogenic unresponsiveness. The time interval between marrow cell replacement and kidney allotransplantation required for optimal results suggest that at least one cycle of cell turnover by the replaced stem cells is needed in order to produce unresponsiveness. Host irradiation and reconstitution with stored autologous marrow may be useful in the treatment of certain forms of cancer.

  10. Past and future of providing matched, unrelated donors for marrow transplantation.

    PubMed

    Roeckel, I E; Baker, J

    1997-01-01

    Prior to 1979, bone marrow transplants were only performed with histocompatible sibling donors. Once it was established that histocompatible, unrelated donors could donate marrow for transplantation, the recruitment of such donors needed to be standardized. Blood donor centers had already identified the histocompatibility locus antigen (HLA) typing for donors who could be recruited to donate bone marrow. Recruiting a large number of donors required systematic evaluation and testing according to defined standards which were published in 1988 by the National Marrow Donor Program (NMDP). Peripheral stem cell collection (PBS) has been added as a transplant source. It promises additional therapeutic modalities, such as gene splicing to address other than cancer therapy.

  11. Bone marrow mesenchymal stem cell therapy in ischemic stroke: mechanisms of action and treatment optimization strategies.

    PubMed

    Li, Guihong; Yu, Fengbo; Lei, Ting; Gao, Haijun; Li, Peiwen; Sun, Yuxue; Huang, Haiyan; Mu, Qingchun

    2016-06-01

    Animal and clinical studies have confirmed the therapeutic effect of bone marrow mesenchymal stem cells on cerebral ischemia, but their mechanisms of action remain poorly understood. Here, we summarize the transplantation approaches, directional migration, differentiation, replacement, neural circuit reconstruction, angiogenesis, neurotrophic factor secretion, apoptosis, immunomodulation, multiple mechanisms of action, and optimization strategies for bone marrow mesenchymal stem cells in the treatment of ischemic stroke. We also explore the safety of bone marrow mesenchymal stem cell transplantation and conclude that bone marrow mesenchymal stem cell transplantation is an important direction for future treatment of cerebral ischemia. Determining the optimal timing and dose for the transplantation are important directions for future research. PMID:27482235

  12. Bone marrow mesenchymal stem cell therapy in ischemic stroke: mechanisms of action and treatment optimization strategies

    PubMed Central

    Li, Guihong; Yu, Fengbo; Lei, Ting; Gao, Haijun; Li, Peiwen; Sun, Yuxue; Huang, Haiyan; Mu, Qingchun

    2016-01-01

    Animal and clinical studies have confirmed the therapeutic effect of bone marrow mesenchymal stem cells on cerebral ischemia, but their mechanisms of action remain poorly understood. Here, we summarize the transplantation approaches, directional migration, differentiation, replacement, neural circuit reconstruction, angiogenesis, neurotrophic factor secretion, apoptosis, immunomodulation, multiple mechanisms of action, and optimization strategies for bone marrow mesenchymal stem cells in the treatment of ischemic stroke. We also explore the safety of bone marrow mesenchymal stem cell transplantation and conclude that bone marrow mesenchymal stem cell transplantation is an important direction for future treatment of cerebral ischemia. Determining the optimal timing and dose for the transplantation are important directions for future research. PMID:27482235

  13. Characterization of functions of neutrophils from bone marrow of cattle with leukocyte adhesion deficiency.

    PubMed

    Nagahata, H; Nochi, H; Tamoto, K; Yamashita, K; Noda, H; Kociba, G J

    1995-02-01

    Marked differences in bone marrow cellularity were observed between cattle affected with leukocyte adhesion deficiency (LAD) and control cattle. The number of nucleated cells in bone marrow was 2.9 to 8.8 times higher in cattle affected with LAD, compared with controls. The myeloid-to-erythroid ratio of bone marrow from 3 cattle affected with LAD ranged from 2.4 to 12. Deficient CD18 expression on neutrophils isolated from bone marrow of cattle with LAD was clearly detected by flow cytometric analysis. Neutrophils from bone marrow of cattle affected with LAD appeared round and not flat, after adherence to plastic wells under agarose, whereas neutrophils from bone marrow of clinically normal cattle were firmly spread on the surface of plastic wells. In the chemotaxis under-agarose assay, many pseudopodia were detected on bone marrow neutrophils from clinically normal cattle, but were not detected on bone marrow neutrophils from cattle with LAD. Activities of chemotactic movements and phagocytosis of neutrophils isolated from bone marrow of cattle affected with LAD were documented to be severely impaired. PMID:7717579

  14. Muscle-specific kinase antibody associated myasthenia gravis after bone marrow transplantation.

    PubMed

    Heidarzadeh, Zeinab; Mousavi, Seyyed-Asadollah; Ostovan, Vahid Reza; Nafissi, Shahriar

    2014-02-01

    Myasthenia gravis is a rare complication of bone marrow transplantation and graft versus host disease. We report a 30-year-old woman presented with oculobulbar and proximal limb weakness after allogeneic bone marrow transplantation for chronic myelogenous leukemia. Also, she developed graft versus host disease following bone marrow transplantation. Investigations led to the diagnosis of muscle specific kinase antibody related myasthenia gravis. There have been only two case reports of muscle specific kinase antibody positive myasthenia gravis after bone marrow transplantation in the literature, but none of the previously reported cases had graft versus host disease.

  15. Evaluation of bone-marrow scanning with technetium-99m sulfur colloid in pediatric oncology.

    PubMed

    Siddiqui, A R; Oseas, R S; Wellman, H N; Doerr, D R; Baehner, R L

    1979-05-01

    Eighty-six technetium-99m sulfur colloid (Tc-SC) bone-marrow scans in 56 pediatric oncology patients were reviewed. The distribution of the sulfur colloid was similar to that in adult bone marrow in normal children older than 10 yr, and involved progressively more marrow of the extremities in normal children under 10 years of age. After irradiation or chemotherapy there was an extension of the Tc-SC to peripheral marrow sites. There was also diminished uptake of the tracer in sites corresponding to irradiated areas. In most patients there was recovery of these defects by 6 mo after completion of therapy. Tumor replacement of the marrow was reflected in the scans, and the extent of the scan defect paralleled the course of the disease. In four patients, despite normal bone scans and radiographs, marrow-scan abnormalities due to tumor replacement were present and confirmed by needle aspiration and/or biopsy. In two other patients, the marrow-scan abnormality preceded radiographic and histologic evidence of tumor metastasis. Two patients who responded clinically showed persistent defects; biopsy in one revealed fibrosis. Technetium-99m sulfur colloid bone-marrow scanning appears to be a sensitive monitor of marrow alteration caused by metastases, irradiation damage, or tissue fibrosis in children receiving treatment for cancer.

  16. "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…

  17. 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.

  18. Chemical Contamination of Red Meat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chemical residues have been present in red meat products since meat eating began. Only in the last few decades, however has man been able to identify and quantify these residues in meat products and to ascribe to them specific risks to human health. For some residues, uncertainties with respect to q...

  19. 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.

  20. The role of bone marrow-derived cells during the bone healing process in the GFP mouse bone marrow transplantation model.

    PubMed

    Tsujigiwa, Hidetsugu; Hirata, Yasuhisa; Katase, Naoki; Buery, Rosario Rivera; Tamamura, Ryo; Ito, Satoshi; Takagi, Shin; Iida, Seiji; Nagatsuka, Hitoshi

    2013-03-01

    Bone healing is a complex and multistep process in which the origin of the cells participating in bone repair is still unknown. The involvement of bone marrow-derived cells in tissue repair has been the subject of recent studies. In the present study, bone marrow-derived cells in bone healing were traced using the GFP bone marrow transplantation model. Bone marrow cells from C57BL/6-Tg (CAG-EGFP) were transplanted into C57BL/6 J wild mice. After transplantation, bone injury was created using a 1.0-mm drill. Bone healing was histologically assessed at 3, 7, 14, and 28 postoperative days. Immunohistochemistry for GFP; double-fluorescent immunohistochemistry for GFP-F4/80, GFP-CD34, and GFP-osteocalcin; and double-staining for GFP and tartrate-resistant acid phosphatase were performed. Bone marrow transplantation successfully replaced the hematopoietic cells into GFP-positive donor cells. Immunohistochemical analyses revealed that osteoblasts or osteocytes in the repair stage were GFP-negative, whereas osteoclasts in the repair and remodeling stages and hematopoietic cells were GFP-positive. The results indicated that bone marrow-derived cells might not differentiate into osteoblasts. The role of bone marrow-derived cells might be limited to adjustment of the microenvironment by differentiating into inflammatory cells, osteoclasts, or endothelial cells in immature blood vessels.

  1. Still red light for red light cameras? An update.

    PubMed

    Høye, Alena

    2013-06-01

    The present study has replicated the results from a previous meta-analysis by Erke (2009) [Erke, A., 2009. Red light for red-light cameras? A meta-analysis of the effects of red-light cameras on crashes. Accident Analysis & Prevention 41 (5), 897-905.] based on a larger sample of RLC-studies, and provides answers to the criticisms that were raised by Lund et al. (2009) [Lund, A.K., Kyrychenko, S.Y., Retting, R.A., 2009. Caution: a comment on Alena Erke's red light for red-light cameras? A meta-analysis of the effects of red-light cameras on crashes. Accident Analysis and Prevention 41, 895-896.] against the previous meta-analysis. The addition of recent studies to the meta-analysis and a more thorough investigation of potential moderator variables lead to a slight improvement of the estimated effects of RLC in the previous meta-analysis. The present study found a non-significant increase of all crashes by 6% and a non-significant decrease of all injury crashes by 13%. Right-angle collisions were found to decrease by 13% and rear-end collisions were found to increase by 39%. For right-angle injury collisions a decrease by 33% was found and for rear-end injury collisions a smaller increase was found (+19%). The effects of RLC are likely to be more favorable when RLC-warning signs are set up at main entrances to areas with RLC enforcement than when each RLC-intersection is signposted. The effects of RLC may become more favorable over time, this could however not be investigated empirically. Several results indicate that spillover effects may occur for right-angle collisions, but most likely not for rear-end and other crashes. If spillover effects do not occur for rear-end crashes, which increase at RLC intersection, this would be a positive result for RLC. However, the results seem to be affected to some degree by publication bias and the effects may therefore be somewhat less favorable than indicated by the results from meta-analysis.

  2. Genetic Basis for Red Coloration in Birds.

    PubMed

    Lopes, Ricardo J; Johnson, James D; Toomey, Matthew B; Ferreira, Mafalda S; Araujo, Pedro M; Melo-Ferreira, José; Andersson, Leif; Hill, Geoffrey E; Corbo, Joseph C; Carneiro, Miguel

    2016-06-01

    The yellow and red feather pigmentation of many bird species [1] plays pivotal roles in social signaling and mate choice [2, 3]. To produce red pigments, birds ingest yellow carotenoids and endogenously convert them into red ketocarotenoids via an oxidation reaction catalyzed by a previously unknown ketolase [4-6]. We investigated the genetic basis for red coloration in birds using whole-genome sequencing of red siskins (Spinus cucullata), common canaries (Serinus canaria), and "red factor" canaries, which are the hybrid product of crossing red siskins with common canaries [7]. We identified two genomic regions introgressed from red siskins into red factor canaries that are required for red coloration. One of these regions contains a gene encoding a cytochrome P450 enzyme, CYP2J19. Transcriptome analysis demonstrates that CYP2J19 is significantly upregulated in the skin and liver of red factor canaries, strongly implicating CYP2J19 as the ketolase that mediates red coloration in birds. Interestingly, a second introgressed region required for red feathers resides within the epidermal differentiation complex, a cluster of genes involved in development of the integument. Lastly, we present evidence that CYP2J19 is involved in ketocarotenoid formation in the retina. The discovery of the carotenoid ketolase has important implications for understanding sensory function and signaling mediated by carotenoid pigmentation. PMID:27212400

  3. Genetic Basis for Red Coloration in Birds.

    PubMed

    Lopes, Ricardo J; Johnson, James D; Toomey, Matthew B; Ferreira, Mafalda S; Araujo, Pedro M; Melo-Ferreira, José; Andersson, Leif; Hill, Geoffrey E; Corbo, Joseph C; Carneiro, Miguel

    2016-06-01

    The yellow and red feather pigmentation of many bird species [1] plays pivotal roles in social signaling and mate choice [2, 3]. To produce red pigments, birds ingest yellow carotenoids and endogenously convert them into red ketocarotenoids via an oxidation reaction catalyzed by a previously unknown ketolase [4-6]. We investigated the genetic basis for red coloration in birds using whole-genome sequencing of red siskins (Spinus cucullata), common canaries (Serinus canaria), and "red factor" canaries, which are the hybrid product of crossing red siskins with common canaries [7]. We identified two genomic regions introgressed from red siskins into red factor canaries that are required for red coloration. One of these regions contains a gene encoding a cytochrome P450 enzyme, CYP2J19. Transcriptome analysis demonstrates that CYP2J19 is significantly upregulated in the skin and liver of red factor canaries, strongly implicating CYP2J19 as the ketolase that mediates red coloration in birds. Interestingly, a second introgressed region required for red feathers resides within the epidermal differentiation complex, a cluster of genes involved in development of the integument. Lastly, we present evidence that CYP2J19 is involved in ketocarotenoid formation in the retina. The discovery of the carotenoid ketolase has important implications for understanding sensory function and signaling mediated by carotenoid pigmentation.

  4. 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

  5. Mouse bone marrow cytogenetic damage produced by residues of tequila.

    PubMed

    Madrigal-Bujaidar, E; Rojas, A; Ramos, A; Rosas, E; Díaz Barriga-Arceo, S

    1990-06-01

    Five concentrations (50-860 mg/kg) of residues obtained after distillation and lyophilization of commercial tequila were injected into mice for evaluation of chromosome aberrations, sister-chromatid exchanges, and proliferation kinetics in mouse bone marrow cells. Appropriate positive and negative controls were included. Our results showed significant dose-related increases of chromosomal aberrations starting at 50 mg/kg and for sister-chromatid exchanges at 430 mg/kg. Cellular proliferation kinetics showed no alterations. With these data we demonstrated that the residues of tequila are genotoxic in vivo.

  6. 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

  7. The bone marrow niche for haematopoietic stem cells.

    PubMed

    Morrison, Sean J; Scadden, David T

    2014-01-16

    Niches are local tissue microenvironments that maintain and regulate stem cells. Haematopoiesis provides a model for understanding mammalian stem cells and their niches, but the haematopoietic stem cell (HSC) niche remains incompletely defined and beset by competing models. Recent progress has been made 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.

  8. 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

  9. Psychiatric Sequelae in Adolescent Bone Marrow Transplantation Survivors

    PubMed Central

    STUBER, MARGARET L.; NADER, KATHLEEN O.

    1995-01-01

    Survivors of life-threatening pediatric illness and their families present a number of psychotherapeutic challenges. The authors present pilot data evaluating the long-term psychiatric impact of pediatric bone marrow transplantation on 10 adolescent transplantation survivors compared with a matched control group. On a quantitative assessment of posttraumatic stress symptoms, the survivors reported a consistent but low level of symptoms. Their narratives about the experience suggest the need for ongoing mental health assessment in addition to specific interventions with families early in the treatment. PMID:22700211

  10. 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

  11. Red blood cells, sickle cell (image)

    MedlinePlus

    ... 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 ...

  12. GATA2 regulates differentiation of bone marrow-derived mesenchymal stem cells.

    PubMed

    Kamata, Mayumi; Okitsu, Yoko; Fujiwara, Tohru; Kanehira, Masahiko; Nakajima, Shinji; Takahashi, Taro; Inoue, Ai; Fukuhara, Noriko; Onishi, Yasushi; Ishizawa, Kenichi; Shimizu, Ritsuko; Yamamoto, Masayuki; Harigae, Hideo

    2014-11-01

    The bone marrow microenvironment comprises multiple cell niches derived from bone marrow mesenchymal stem cells. However, the molecular mechanism of bone marrow mesenchymal stem cell differentiation is poorly understood. The transcription factor GATA2 is indispensable for hematopoietic stem cell function as well as other hematopoietic lineages, suggesting that it may maintain bone marrow mesenchymal stem cells in an immature state and also contribute to their differentiation. To explore this possibility, we established bone marrow mesenchymal stem cells from GATA2 conditional knockout mice. Differentiation of GATA2-deficient bone marrow mesenchymal stem cells into adipocytes induced accelerated oil-drop formation. Further, GATA2 loss- and gain-of-function analyses based on human bone marrow mesenchymal stem cells confirmed that decreased and increased GATA2 expression accelerated and suppressed bone marrow mesenchymal stem cell differentiation to adipocytes, respectively. Microarray analysis of GATA2 knockdowned human bone marrow mesenchymal stem cells revealed that 90 and 189 genes were upregulated or downregulated by a factor of 2, respectively. Moreover, gene ontology analysis revealed significant enrichment of genes involved in cell cycle regulation, and the number of G1/G0 cells increased after GATA2 knockdown. Concomitantly, cell proliferation was decreased by GATA2 knockdown. When GATA2 knockdowned bone marrow mesenchymal stem cells as well as adipocytes were cocultured with CD34-positive cells, hematopoietic stem cell frequency and colony formation decreased. We confirmed the existence of pathological signals that decrease and increase hematopoietic cell and adipocyte numbers, respectively, characteristic of aplastic anemia, and that suppress GATA2 expression in hematopoietic stem cells and bone marrow mesenchymal stem cells.

  13. Photoconversion in orange and red fluorescent proteins.

    PubMed

    Kremers, Gert-Jan; Hazelwood, Kristin L; Murphy, Christopher S; Davidson, Michael W; Piston, David W

    2009-05-01

    We found that photoconversion is fairly common among orange and red fluorescent proteins, as in a screen of 12 proteins, 8 exhibited photoconversion. Specifically, three red fluorescent proteins could be switched to a green state, and two orange variants could be photoconverted to a far-red state. The orange proteins are ideal for dual-probe highlighter applications, and they exhibited the most red-shifted excitation of all fluorescent proteins described to date.

  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 Euzébio Pereira Dias; Manso, Pedro Paulo de Abreu; Caputo, Luzia Fátima Gonçalves; 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. 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

  17. 7 CFR 29.1053 - Red (R).

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 2 2012-01-01 2012-01-01 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....

  18. Grape (Vitis spp.) - Grapevine Red Blotch Disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Grapevine red blotch disease is caused by Grapevine red blotch-associated virus (GRBaV), which was first reported in 2012 from New York and subsequently in California, Washington, Oregon, Idaho and elsewhere in the U.S. The discovery occurred when grapevines with red leaf symptoms that tested negati...

  19. 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...

  20. 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...

  1. 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... 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...

  2. 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...

  3. 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... 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...

  4. 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)…

  5. 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...

  6. 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....

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. Genotoxicity of Copper Oxide Nanoparticles with Different Surface Chemistry on Rat Bone Marrow Mesenchymal Stem Cells.

    PubMed

    Zhang, Wenjing; Jiang, Pengfei; Chen, Wei; Zheng, Botuo; Mao, Zhengwei; Antipov, Alexei; Correia, Manuel; Larsen, Erik H; Gao, Changyou

    2016-06-01

    The surface chemistry of nanoparticles (NPs) is one of the critical factors determining their cellular responses. In this study, the cytotoxicity and genotoxicity of copper oxide (CuO) NPs with a similar size but different surface chemistry to rat bone marrow mesenchymal stem cells (MSCs) were investigated. The morphology, size and surface charge of four types of CuO NPs, i.e., CuO-core, CuO-COOH, CuO-NH2 and CuO-PEG NPs, were characterized by TEM, dynamic light scattering (DLS) and zeta-potential measurement, respectively. All of the four CuO NPs had a negative surface charge around -10 mV and showed a similar tendency to form agglomerates with a size of -200 nm in cell culture environment. The cytotoxicity of CuO NPs to MSCs at various concentrations and incubation periods were firstly evaluated. The CuO NPs showed dose-dependent and time-dependent toxicity to MSCs, and their surface chemistry had influence on the toxicity to some extent too. The intracellular reactive oxygen species (ROS) level of MSCs was then quantified. Finally, the genotoxicity of the CuO NPs was studied by comet assay. The results suggest that the genotoxicity of CuO NPs was mainly dependent on NPs concentration, and was only slightly influenced by their surface chemistry. The osteogenic and adipogenic differentiation abilities of the MSCs exposed to different CuO NPs were studied by Alizarin Res S and Oil Red O staining. The preliminary results showed that the exposure to 10 μg/mL CuO NPs will, not lead to significant impact on the differentiation potential of the MSCs. PMID:27427588

  13. Genotoxicity of Copper Oxide Nanoparticles with Different Surface Chemistry on Rat Bone Marrow Mesenchymal Stem Cells.

    PubMed

    Zhang, Wenjing; Jiang, Pengfei; Chen, Wei; Zheng, Botuo; Mao, Zhengwei; Antipov, Alexei; Correia, Manuel; Larsen, Erik H; Gao, Changyou

    2016-06-01

    The surface chemistry of nanoparticles (NPs) is one of the critical factors determining their cellular responses. In this study, the cytotoxicity and genotoxicity of copper oxide (CuO) NPs with a similar size but different surface chemistry to rat bone marrow mesenchymal stem cells (MSCs) were investigated. The morphology, size and surface charge of four types of CuO NPs, i.e., CuO-core, CuO-COOH, CuO-NH2 and CuO-PEG NPs, were characterized by TEM, dynamic light scattering (DLS) and zeta-potential measurement, respectively. All of the four CuO NPs had a negative surface charge around -10 mV and showed a similar tendency to form agglomerates with a size of -200 nm in cell culture environment. The cytotoxicity of CuO NPs to MSCs at various concentrations and incubation periods were firstly evaluated. The CuO NPs showed dose-dependent and time-dependent toxicity to MSCs, and their surface chemistry had influence on the toxicity to some extent too. The intracellular reactive oxygen species (ROS) level of MSCs was then quantified. Finally, the genotoxicity of the CuO NPs was studied by comet assay. The results suggest that the genotoxicity of CuO NPs was mainly dependent on NPs concentration, and was only slightly influenced by their surface chemistry. The osteogenic and adipogenic differentiation abilities of the MSCs exposed to different CuO NPs were studied by Alizarin Res S and Oil Red O staining. The preliminary results showed that the exposure to 10 μg/mL CuO NPs will, not lead to significant impact on the differentiation potential of the MSCs.

  14. 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.; Licínio, 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 µM) reduced the growth of CFU-GM in clonogenic assays. In culture assays with stromal cells, fibroblast proliferation and α-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 µM. 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 µM IM, although there was gradual growth inhibition of fibroblastic cells while the number of round cells (macrophage-like cells) increased. At higher concentrations (15 µM), 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 µM. These results suggest that IM differentially inhibits the survival of different types of BM cells since toxic effects were achieved. PMID:23011404

  15. Foxc2 regulates osteogenesis and angiogenesis of bone marrow mesenchymal stem cells

    PubMed Central

    2013-01-01

    Background The Forkhead/Fox transcription factor Foxc2 is a critical regulator of osteogenesis and angiogenesis of cells. Bone marrow mesenchymal stem cells (BMSCs) have the capacity to differentiate into osteoblasts, chondrocytes, adipocytes, myocytes and fibroblasts. The present study investigates the role of Foxc2 overexpression in osteogenesis and angiogenesis of BMSCs in vitro. Methods BMSCs were isolated from SD rat femurs and tibias, and characterized by cell surface antigen identification and osteoblasts and adipocytes differentiation. The cells were transfected with lentiviral Foxc2 (Lv-Foxc2) or green fluorescent protein (Lv-GFP). Seventy hours later, Foxc2 expression was observed using real time-PCR and Western blot. The transfected cells were stained with Alizarin red S or alkaline phosphatase (ALP) after osteogenic induction. Meanwhile, the expression levels of osteocalcin (OCN), Runt-related transcription factor 2 (Runx2), vascular endothelial growth factor (VEGF) and platelet-derived growth factor-β (PDGF-β) were measured by real time-PCR, Western blot and immunostaining. Results Results of cell characterization showed that the cells were positive to CD44 (99.56%) and negative to CD34 (0.44%), and could differentiate into osteoblasts and adipocytes. Foxc2 overexpression not only increased the numbers of mineralized nodes and ALP activity, but also enhanced the expressions of Runx2, OCN, VEGF and PDGF-β in transfected BMSCs after osteogenic induction. The effects of Foxc2 on osteogenesis and angiogenesis were significantly different between Lv-Foxc2 transfected BMSCs and Lv-GFP transfected BMSCs (P<0.05). In addition, the MAPK-specific inhibitors, PD98059 and LY294002, blocked the Foxc2-induced regulation of BMSC differentiation. Conclusions Foxc2 gene is successfully transfected into BMSCs with stable and high expression. The overexpression of Foxc2 acts on BMSCs to stimulate osteogenesis and angiogenesis. The effect of Foxc2 on angiogenesis of

  16. ME-03BONE MARROW DERIVED MICROGLIA AND THEIR FUNCTION WITHIN TUMOR MICROENVIRONMENT

    PubMed Central

    Burrell, Kelly; Singh, Sanjay; Agnihotri, Sameer; Hill, Richard; Aldape, Kenneth; Zadeh, Gelareh

    2014-01-01

    We have previously demonstrated that BMDC are recruited to Glioblastoma Multiforme (GBM), in a highly tumor-growth and region-dependent pattern, demonstrating that the majority of BMDCs differentiate into inflammatory cells, MAC3 + , and CD11b+ IBA1+ microglia-like cells. The majority of microglia seen in GBM microenvironment are derived from the BMDC rather than being resident brain microglia. The role of microglial cells in GBMs remains unknown, with evidence supporting both an anti- and pro- tumorgenic function. In this study we aimed to understand the contribution of microglia to GBM growth and tumor vascularity. Chimeric mice with reconstituted green-fluorescent bone marrow were used to create intracranial GBM xenografts, by implanting red fluorescent glioma stem cells or U87 into the frontal lobe. Using a known inhibitor of microglial activation, minocycline, we show that treatment with this agent increased tumor cell growth and invasiveness and reduced animal survival compared to controls. We show that Minocycline decreases activation of microglia, inhibits the phagocytic activity of microglia in GBMs and decreases the perivascular localization of microglia. The mRNA expression profile of microglia isolated from the GBM microenvironment showed, through Ingenuity Pathway Analysis (IPA), a loss of engulfment and migration of cells and phaocytotic pathways in BM-derived microglia, additionally we see a reorganization of cytoskeletal pathways leading to an increase in the migration and invasiveness of GBM cells following treatment with Minocycline. We also have preliminary data to suggest that this property of Minocycline is dependent on VEGF levels, where in the context of low VEGF Minocycline does not provide a significant anti-angiogenic role. We demonstrate that microglia in GBM microenvironment, are primarily recruited and differentiated from the BM and not resident, and that these cells have an anti-tumorgenic functions, and inhibition of the activated

  17. “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...

  18. 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...

  19. Unrelated donor marrow transplantation: an update of the experience of the Italian Bone Marrow Transplant Group (GITMO).

    PubMed

    Dini, G; Cancedda, R; Locatelli, F; Bosi, A; Bandini, G; Alessandrino, E P; Porta, F; Uderzo, C; Messina, C; Fagioli, F; Arcese, W; Marenco, P; Fanin, R; Falda, M; Soligo, D; La Nasa, G; Giardini, C; Pession, A; Scimè, R; Di Bartolomeo, P; Bruno, B; Garbarino, L; Lamparelli, T; Giorgiani, G; Lanino, E; Manzitti, C; Bacigalupo, A

    2000-11-01

    Unrelated donor bone marrow transplant (UD-BMT) has become an attractive alternative source of hematopoietic cells for patients lacking a matched sibling. The aim of this paper was to report on results of the 696 UD BMTs performed in 31 Italian institutions during the first 10 years of activity of the Italian Bone Marrow Donor Registry (IBMDR). In 1989 the Italian Bone Marrow Transplant Group (GITMO) established the IBMDR to facilitate donor search and marrow procurement for patients lacking an HLA identical sibling. By end of December 1999, 260,000 HLA-A, B typed volunteer donors had been cumulatively registered and 2,620 searches had been activated for Italian patients. At least one HLA-A, B, DRB1 matched donor was found for 54% of the patients and 696 UD BMTs were performed. In 50% of cases the donor was found in the IBMDR and in 50% in 15 other Registries. The average time from search activation to transplant was 6 months for disease other than CML. For CML it was 14 months. Actuarial 12-month transplant-related mortality (TRM) was 68% in patients grafted between 1979 and 1992 and 44% for patients grafted after 1993. Twenty-eight per cent of patients developed grade III or IV acute GvHD and 24% developed extensive chronic GvHD. The rate of disease free survival at three years was 57% for patients with 1st chronic phase CML, 37% for patients with 1st or 2nd CR ALL, 31% for AML or MDS patients < or = 18 years of age and 54% for patients with inborn errors. We conclude that the IBMDR has benefited a substantial number of patients lacking a matched sibling and has facilitated the recruitment of UDs into the international donor pool. The long time required for the search is the major obstacle to the success of this programme. This suggests that early transplant and a decrease in TRM could further improve these encouraging results.

  20. 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.

  1. 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.

  2. Hyaluronan scaffold supports osteogenic differentiation of bone marrow concentrate cells.

    PubMed

    Cavallo, C; Desando, G; Ferrari, A; Zini, N; Mariani, E; Grigolo, B

    2016-01-01

    Osteochondral lesions are considered a challenge for orthopedic surgeons. Currently, the treatments available are often unsatisfactory and unable to stimulate tissue regeneration. Tissue engineering offers a new therapeutic strategy, taking into account the role exerted by cells, biomaterial and growth factors in restoring tissue damage. In this light, Mesenchymal Stem Cells (MSCs) have been indicated as a fascinating tool for regenerative medicine thanks to their ability to differentiate into bone, cartilage and adipose tissue. However, in vitro-cultivation of MSCs could be associated with some risks such as de-differentiation/reprogramming, infection and contaminations of the cells. To overcome these shortcomings, a new approach is represented by the use of Bone Marrow Concentrate (BMC), that could allow the delivery of cells surrounded by their microenvironment in injured tissue. For this purpose, cells require a tridimensional scaffold that can support their adhesion, proliferation and differentiation. This study is focused on the potentiality of BMC seeded onto a hyaluronan-based scaffold (Hyaff-11) to differentiate into osteogenic lineage. This process depends on the specific interaction between cells derived from bone marrow (surrounded by their niche) and scaffold, that create an environment able to support the regeneration of damaged tissue. The data obtained from the present study demonstrate that BMC grown onto Hyaff-11 are able to differentiate toward osteogenic sense, producing specific osteogenic genes and matrix proteins.

  3. Degradation of polysaccharide hydrogels seeded with bone marrow stromal cells.

    PubMed

    Jahromi, Shiva H; Grover, Liam M; Paxton, Jennifer Z; Smith, Alan M

    2011-10-01

    In order to produce hydrogel cell culture substrates that are fit for the purpose, it is important that the mechanical properties are well understood not only at the point of cell seeding but throughout the culture period. In this study the change in the mechanical properties of three biopolymer hydrogels alginate, low methoxy pectin and gellan gum have been assessed in cell culture conditions. Samples of the gels were prepared encapsulating rat bone marrow stromal cells which were then cultured in osteogenic media. Acellular samples were also prepared and incubated in standard cell culture media. The rheological properties of the gels were measured over a culture period of 28 days and it was found that the gels degraded at very different rates. The degradation occurred most rapidly in the order alginate > Low methoxy pectin > gellan gum. The ability of each hydrogel to support differentiation of bone marrow stromal cells to osteoblasts was also verified by evidence of mineral deposits in all three of the materials. These results highlight that the mechanical properties of biopolymer hydrogels can vary greatly during in vitro culture, and provide the potential of selecting hydrogel cell culture substrates with mechanical properties that are tissue specific.

  4. Hyaluronan scaffold supports osteogenic differentiation of bone marrow concentrate cells.

    PubMed

    Cavallo, C; Desando, G; Ferrari, A; Zini, N; Mariani, E; Grigolo, B

    2016-01-01

    Osteochondral lesions are considered a challenge for orthopedic surgeons. Currently, the treatments available are often unsatisfactory and unable to stimulate tissue regeneration. Tissue engineering offers a new therapeutic strategy, taking into account the role exerted by cells, biomaterial and growth factors in restoring tissue damage. In this light, Mesenchymal Stem Cells (MSCs) have been indicated as a fascinating tool for regenerative medicine thanks to their ability to differentiate into bone, cartilage and adipose tissue. However, in vitro-cultivation of MSCs could be associated with some risks such as de-differentiation/reprogramming, infection and contaminations of the cells. To overcome these shortcomings, a new approach is represented by the use of Bone Marrow Concentrate (BMC), that could allow the delivery of cells surrounded by their microenvironment in injured tissue. For this purpose, cells require a tridimensional scaffold that can support their adhesion, proliferation and differentiation. This study is focused on the potentiality of BMC seeded onto a hyaluronan-based scaffold (Hyaff-11) to differentiate into osteogenic lineage. This process depends on the specific interaction between cells derived from bone marrow (surrounded by their niche) and scaffold, that create an environment able to support the regeneration of damaged tissue. The data obtained from the present study demonstrate that BMC grown onto Hyaff-11 are able to differentiate toward osteogenic sense, producing specific osteogenic genes and matrix proteins. PMID:27358127

  5. 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

  6. Bone marrow mesenchymal stem cells are abnormal in multiple myeloma.

    PubMed

    Corre, J; Mahtouk, K; Attal, M; Gadelorge, M; Huynh, A; Fleury-Cappellesso, S; Danho, C; Laharrague, P; Klein, B; Rème, T; Bourin, P

    2007-05-01

    Recent literature suggested that cells of the microenvironment of tumors could be abnormal as well. To address this hypothesis in multiple myeloma (MM), we studied bone marrow mesenchymal stem cells (BMMSCs), the only long-lived cells of the bone marrow microenvironment, by gene expression profiling and phenotypic and functional studies in three groups of individuals: patients with MM, patients with monoclonal gamopathy of undefined significance (MGUS) and healthy age-matched subjects. Gene expression profile independently classified the BMMSCs of these individuals in a normal and in an MM group. MGUS BMMSCs were interspersed between these two groups. Among the 145 distinct genes differentially expressed in MM and normal BMMSCs, 46% may account for a tumor-microenvironment cross-talk. Known soluble factors implicated in MM pathophysiologic features (i.e. IL (interleukin)-6, DKK1) were revealed and new ones were found which are involved in angiogenesis, osteogenic differentiation or tumor growth. In particular, GDF15 was found to induce dose-dependent growth of MOLP-6, a stromal cell-dependent myeloma cell line. Functionally, MM BMMSCs induced an overgrowth of MOLP-6, and their capacity to differentiate into an osteoblastic lineage was impaired. Thus, MM BMMSCs are abnormal and could create a very efficient niche to support the survival and proliferation of the myeloma cells.

  7. A novel metric for bone marrow cells chromosome pairing.

    PubMed

    Khmelinskii, Artem; Ventura, Rodrigo; Sanches, João

    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

  8. Regenerate augmentation with bone marrow concentrate after traumatic bone loss.

    PubMed

    Gessmann, Jan; Köller, Manfred; Godry, Holger; Schildhauer, Thomas Armin; Seybold, Dominik

    2012-01-01

    Distraction osteogenesis after post-traumatic segmental bone loss of the tibia is a complex and time-consuming procedure that is often complicated due to prolonged consolidation or complete insufficiency of the regenerate. The aim of this feasibility study was to investigate the potential of bone marrow aspiration concentrate (BMAC) for percutaneous regenerate augmentation to accelerate bony consolidation of the regenerate. Eight patients (age 22-64) with an average posttraumatic bone defect of 82.4 mm and concomitant risk factors (nicotine abuse, soft-tissue defects, obesity and/or circulatory disorders) were treated with a modified Ilizarov external frame using an intramedullary cable transportation system. At the end of the distraction phase, each patient was treated with a percutaneously injection of autologous BMAC into the centre of the regenerate. The concentration factor was analysed using flow cytometry. The mean follow up after frame removal was 10 (4-15) months. With a mean healing index (HI) of 36.9 d/cm, bony consolidation of the regenerate was achieved in all eight cases. The mean concentration factor of the bone marrow aspirate was 4.6 (SD 1.23). No further operations concerning the regenerate were needed and no adverse effects were observed with the BMAC procedure. This procedure can be used for augmentation of the regenerate in cases of segmental bone transport. Further studies with a larger number of patients and control groups are needed to evaluate a possible higher success rate and accelerating effects on regenerate healing.

  9. 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

  10. Evaluation of sodium alginate for bone marrow cell tissue engineering.

    PubMed

    Wang, L; Shelton, R M; Cooper, P R; Lawson, M; Triffitt, J T; Barralet, J E

    2003-09-01

    Sodium alginate has applications as a material for the encapsulation and immobilisation of a variety of cell types for immunoisolatory and biochemical processing applications. It forms a biodegradable gel when crosslinked with calcium ions and it has been exploited in cartilage tissue engineering since chondrocytes do not dedifferentiate when immobilised in it. Despite its attractive properties of degradability, ease of processing and cell immobilisation, there is little work demonstrating the efficacy of alginate gel as a substrate for cell proliferation, except when RGD is modified. In this study we investigated the ability of rat bone marrow cells to proliferate and differentiate on alginates of differing composition and purity. The mechanical properties of the gels were investigated. It was found that high purity and high G-type alginate retained 27% of its initial strength after 12 days in culture and that comparable levels of proliferation were observed on this material and tissue culture plastic. Depending on composition, calcium crosslinked alginate can act as a substrate for rat marrow cell proliferation and has potential for use as 3D degradable scaffold.

  11. DIRECT AND INDIRECT CONTRIBUTION OF BONE MARROW DERIVED CELLS TO CANCER

    PubMed Central

    Guest, Ian; Ilic, Zoran; Ma, Jun; Grant, Denise; Glinsky, Gennadi; Sell, Stewart

    2010-01-01

    Summary Stromal-epithelial interactions may control the growth and initiation of cancers. Here we not only test the hypothesis that bone marrow derived cells may effect development of cancers arising from other tissue cells by forming tumor stroma, but also that sarcomas may arise by transformation of stem cells from the bone marrow and epithelial cancers may arise by transdifferentiation of bone marrow stem cells to epithelial cancers. Lethally irradiated female FVB/N mice were restored with bone marrow (BM) transplants from a male transgenic mouse carrying the polyoma middle T-oncoprotein under the control of the mouse mammary tumor virus promoter (MMTV-PyMT) and followed for development of lesions. Eight of 8 lethally irradiated female FVB/N recipient mice, restored with BM transplants from a male MMTV-PyMT transgenic mouse, developed Ychromosome negative (Y−) cancers of various organs surrounded by Y+ stroma. One of the female FVB/N recipient mice also developed fibrosarcoma and one a diploid breast adenocarcinoma (BCA) containing Ychromosomes. In contrast, only 1 of 12 control female mice restored with normal male bone marrow developed a tumor (lymphoma) during the same time period.. These results indicate not only that the transgenic bone marrow derived stromal cells may indirectly contribute to development of tumors in recipient mice, but also that sarcomas may arise by transformation of bone marrow stem cells and that breast cancers arise by transdifferentiation of bone marrow stem cells, presumably by mesenchymal-epithelial transition. PMID:19816927

  12. 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.

  13. Bone marrow necrosis at transformation of chronic granulocytic leukaemia treated with interferon.

    PubMed Central

    Kendra, J R; Pickens, S; Singh, A K; Singh, K

    1992-01-01

    A patient with chronic myeloid leukaemia was treated with interferon without using conventional cytotoxic agents. Bone marrow necrosis developed at the onset of blast transformation. It is suggested that cytotoxic drugs should be given before treatment with interferon for chronic myeloid leukaemia. Cytotoxic drugs may also be needed to prevent rapid bone marrow growth once interferon has been withdrawn. PMID:1401221

  14. Steroid changes adipokine concentration in the blood and bone marrow fluid.

    PubMed

    Fukushima, Tatsuya; Hozumi, Akira; Tomita, Masato; Yonekura, Akihiko; Miyata, Noriaki; Miyamoto, Takashi; Taguchi, Kenji; Goto, Hisataka; Tsuda, Keiichi; Osaki, Makoto

    2016-01-01

    Our previous study has shown that plasminogen activator inhibitor 1 (PAI-1) gene expression and secretion from bone marrow adipocytes increased markedly with dexamethasone administration. The purpose of the present study was to measure the secretion of various adipokines from human bone marrow and blood, and investigate how adipokine secretion changes in a steroid environment. Human blood and bone marrow fluid were collected from a steroid treatment group and a control group during hip replacement surgery, and an enzyme-linked immunosorbent assay (ELISA) was used to measure the adiponectin, leptin, and PAI-1 levels. Adiponectin and leptin showed no significant differences between bone marrow and blood levels, but PAI-1 was significantly higher in bone marrow. The steroid treatment group had higher levels of leptin and PAI-1 in both the blood and bone marrow than the control group. PAI-1 was present at high concentrations in the bone marrow and increased by steroid treatment. High levels of PAI-1 in bone marrow may influence intraosseous hemodynamics and may induce necrotic bone disorders. PMID:27356609

  15. Perfusion Method for Intra-bone Marrow Collection and Stem Cell Transplantation: A Critical Review.

    PubMed

    Korrapati, Narasimhulu; Nanganuru, Harikrishna Yadav

    2014-03-19

    A bone marrow transplant is a procedure to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Bone marrow is the soft, fatty tissue inside our bones. Bone marrow transplantation (BMT) is a powerful strategy for the treatment of leukemia, aplastic anemia, congenital immunodeficiency and autoimmune diseases. In humans, bone marrow cells (BMCs) have usually been collected by multiple bone marrow aspirations from the iliac crest. We have established a new "perfusion" method for collecting BMCs with minimal contamination with the peripheral blood using the long bones of cynomolgus monkeys. This method has proven to be a simple and safe method for harvesting BMCs and reduces the risk of acute graft versus host disease in allogeneic BMT. Intra-bone marrow-BMT (IBM-BMT) provides distinct advantages because it recruits donor-derived hematopoietic stem cells and mesenchymal stem cells. IBM-BMT has been shown to currently be the best strategy for allogeneic BMT. Here we review the perfusion method (for harvesting BMCs) and IBM-BMT (for their transplantation) and show that this combination will become a powerful new clinical strategy for allogeneic BMT.

  16. 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

  17. MR-Based Assessment of Bone Marrow Fat in Osteoporosis, Diabetes, and Obesity

    PubMed Central

    Cordes, Christian; Baum, Thomas; Dieckmeyer, Michael; Ruschke, Stefan; Diefenbach, Maximilian N.; Hauner, Hans; Kirschke, Jan S.; Karampinos, Dimitrios C.

    2016-01-01

    Bone consists of the mineralized component (i.e., cortex and trabeculae) and the non-mineralized component (i.e., bone marrow). Most of the routine clinical bone imaging uses X-ray-based techniques and focuses on the mineralized component. However, bone marrow adiposity has been also shown to have a strong linkage with bone health. Specifically, multiple previous studies have demonstrated a negative association between bone marrow fat fraction (BMFF) and bone mineral density. Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) are ideal imaging techniques for non-invasively investigating the properties of bone marrow fat. In the present work, we first review the most important MRI and MRS methods for assessing properties of bone marrow fat, including methodologies for measuring BMFF and bone marrow fatty acid composition parameters. Previous MRI and MRS studies measuring BMFF and fat unsaturation in the context of osteoporosis are then reviewed. Finally, previous studies investigating the relationship between bone marrow fat, other fat depots, and bone health in patients with obesity and type 2 diabetes are presented. In summary, MRI and MRS are powerful non-invasive techniques for measuring properties of bone marrow fat in osteoporosis, obesity, and type 2 diabetes and can assist in future studies investigating the pathophysiology of bone changes in the above clinical scenarios. PMID:27445977

  18. 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

  19. Computational modelling of the mechanics of trabecular bone and marrow using fluid structure interaction techniques.

    PubMed

    Birmingham, E; Grogan, J A; Niebur, G L; McNamara, L M; McHugh, P E

    2013-04-01

    Bone marrow found within the porous structure of trabecular bone provides a specialized environment for numerous cell types, including mesenchymal stem cells (MSCs). Studies have sought to characterize the mechanical environment imposed on MSCs, however, a particular challenge is that marrow displays the characteristics of a fluid, while surrounded by bone that is subject to deformation, and previous experimental and computational studies have been unable to fully capture the resulting complex mechanical environment. The objective of this study was to develop a fluid structure interaction (FSI) model of trabecular bone and marrow to predict the mechanical environment of MSCs in vivo and to examine how this environment changes during osteoporosis. An idealized repeating unit was used to compare FSI techniques to a computational fluid dynamics only approach. These techniques were used to determine the effect of lower bone mass and different marrow viscosities, representative of osteoporosis, on the shear stress generated within bone marrow. Results report that shear stresses generated within bone marrow under physiological loading conditions are within the range known to stimulate a mechanobiological response in MSCs in vitro. Additionally, lower bone mass leads to an increase in the shear stress generated within the marrow, while a decrease in bone marrow viscosity reduces this generated shear stress.

  20. 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

  1. Changes in Vertebral Bone Marrow Fat and Bone Mass After Gastric Bypass Surgery: A Pilot Study

    PubMed Central

    Schafer, AL; Li, X; Schwartz, AV; Tufts, LS; Wheeler, AL; Grunfeld, C; Stewart, L; Rogers, SJ; Carter, JT; Posselt, AM; Black, DM; Shoback, DM

    2015-01-01

    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

  2. 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.

  3. Propofol promotes spinal cord injury repair by bone marrow mesenchymal stem cell transplantation

    PubMed Central

    Zhou, Ya-jing; Liu, Jian-min; Wei, Shu-ming; Zhang, Yun-hao; Qu, Zhen-hua; Chen, Shu-bo

    2015-01-01

    Propofol is a neuroprotective anesthetic. Whether propofol can promote spinal cord injury repair by bone marrow mesenchymal stem cells remains poorly understood. We used rats to investigate spinal cord injury repair using bone marrow mesenchymal stem cell transplantation combined with propofol administration via the tail vein. Rat spinal cord injury was clearly alleviated; a large number of newborn non-myelinated and myelinated nerve fibers appeared in the spinal cord, the numbers of CM-Dil-labeled bone marrow mesenchymal stem cells and fluorogold-labeled nerve fibers were increased and hindlimb motor function of spinal cord-injured rats was markedly improved. These improvements were more prominent in rats subjected to bone marrow mesenchymal cell transplantation combined with propofol administration than in rats receiving monotherapy. These results indicate that propofol can enhance the therapeutic effects of bone marrow mesenchymal stem cell transplantation on spinal cord injury in rats. PMID:26487860

  4. Early MR changes in vertebral bone marrow for patients following radiotherapy.

    PubMed

    Onu, M; Savu, M; Lungu-Solomonescu, C; Harabagiu, I; Pop, T

    2001-01-01

    Our study aimed to evaluate the vertebral marrow changes in patients following radiotherapy (RT) by measuring the T2 relaxation times before and during RT. We were mostly interested in evaluating early MR marrow changes during RT. Fifteen patients treated by RT for cervical cancer were submitted to MR examination before and during RT (5-23 days of RT). T2 values were calculated for irradiated and non-irradiated tissues (lumbar and sacral vertebral bone marrow, symphysis pubis marrow, and regional muscle). Fourteen patients presented increased T2 values for irradiated vertebral bone marrow (VBM), and 3 patients showed increased T2 values even for non-irradiated VBM. We found T2 variations for VBM as early as in the fifth day of RT for an absorbed dose as small as 9 Gy. Calculated T2 values in irradiated and also in non-irradiated tissues prove very early tissue alterations.

  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.

  6. Marrow Fat and the Bone Microenvironment: Developmental, Functional, and Pathological Implications

    PubMed Central

    Rosen, Clifford J.; Ackert-Bicknell, Cheryl; Rodriguez, Juan Pablo; Pino, Ana Maria

    2008-01-01

    Bone marrow adipogenesis is a normal physiologic process in all mammals. However, its function is unknown. The mesenchymal stem cell is the marrow precursor for adipocytes as well as osteoblasts, and PPARγ is an essential differentiation factor for entrance into the fat lineage. Mouse models have provided significant insight into the molecular cues that define stromal cell fate. In humans, accelerated marrow adipogenesis has been associated with aging and several chronic conditions including diabetes mellitus and osteoporosis. Newer imaging techniques have been used to determine the developmental time course of fat generation in bone marrow. However, more studies are needed to understand the interrelationship among hematopoietic, osteoblastic, and adipogenic cells within the marrow niche. PMID:19392647

  7. 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.

  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. Bone Marrow Adipose Tissue: A New Player in Cancer Metastasis to Bone

    PubMed Central

    Morris, Emma V.; Edwards, Claire M.

    2016-01-01

    The bone marrow is a favored site for a number of cancers, including the hematological malignancy multiple myeloma, and metastasis of breast and prostate cancer. This specialized microenvironment is highly supportive, not only for tumor growth and survival but also for the development of an associated destructive cancer-induced bone disease. The interactions between tumor cells, osteoclasts and osteoblasts are well documented. By contrast, despite occupying a significant proportion of the bone marrow, the importance of bone marrow adipose tissue is only just emerging. The ability of bone marrow adipocytes to regulate skeletal biology and hematopoiesis, combined with their metabolic activity, endocrine functions, and proximity to tumor cells means that they are ideally placed to impact both tumor growth and bone disease. This review discusses the recent advances in our understanding of how marrow adipose tissue contributes to bone metastasis and cancer-induced bone disease. PMID:27471491

  10. Adult bone marrow: which stem cells for cellular therapy protocols in neurodegenerative disorders?

    PubMed

    Wislet-Gendebien, Sabine; Laudet, Emerence; Neirinckx, Virginie; Rogister, Bernard

    2012-01-01

    The generation of neuronal cells from stem cells obtained from adult bone marrow is of significant clinical interest in order to design new cell therapy protocols for several neurological disorders. The recent identification in adult bone marrow of stem cells derived from the neural crests (NCSCs) might explain the neuronal phenotypic plasticity shown by bone marrow cells. However, little information is available about the nature of these cells compared to mesenchymal stem cells (MSCs). In this paper, we will review all information available concerning NCSC from adult tissues and their possible use in regenerative medicine. Moreover, as multiple recent studies showed the beneficial effect of bone marrow stromal cells in neurodegenerative diseases, we will discuss which stem cells isolated from adult bone marrow should be more suitable for cell replacement therapy.

  11. 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.

  12. [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

  13. 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

  14. Quantitative Analysis of Mechanisms That Govern Red Blood Cell Age Structure and Dynamics during Anaemia

    PubMed Central

    Savill, Nicholas J.; Chadwick, William; Reece, Sarah E.

    2009-01-01

    Mathematical modelling has proven an important tool in elucidating and quantifying mechanisms that govern the age structure and population dynamics of red blood cells (RBCs). Here we synthesise ideas from previous experimental data and the mathematical modelling literature with new data in order to test hypotheses and generate new predictions about these mechanisms. The result is a set of competing hypotheses about three intrinsic mechanisms: the feedback from circulating RBC concentration to production rate of immature RBCs (reticulocytes) in bone marrow, the release of reticulocytes from bone marrow into the circulation, and their subsequent ageing and clearance. In addition we examine two mechanisms specific to our experimental system: the effect of phenylhydrazine (PHZ) and blood sampling on RBC dynamics. We performed a set of experiments to quantify the dynamics of reticulocyte proportion, RBC concentration, and erythropoietin concentration in PHZ-induced anaemic mice. By quantifying experimental error we are able to fit and assess each hypothesis against our data and recover parameter estimates using Markov chain Monte Carlo based Bayesian inference. We find that, under normal conditions, about 3% of reticulocytes are released early from bone marrow and upon maturation all cells are released immediately. In the circulation, RBCs undergo random clearance but have a maximum lifespan of about 50 days. Under anaemic conditions reticulocyte production rate is linearly correlated with the difference between normal and anaemic RBC concentrations, and their release rate is exponentially correlated with the same. PHZ appears to age rather than kill RBCs, and younger RBCs are affected more than older RBCs. Blood sampling caused short aperiodic spikes in the proportion of reticulocytes which appear to have a different developmental pathway than normal reticulocytes. We also provide evidence of large diurnal oscillations in serum erythropoietin levels during anaemia

  15. 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 ρsh/ρolinec and

  16. Red facts: Dibromodicyanobutane. Fact sheet

    SciTech Connect

    1996-06-01

    This fact sheet summarizes the information in the RED document for reregistration case 2780, dibromodicyanobutane. Dibromodicyanobutane (1,2-dibromo-2,4-dicyanobutane) is a microbiocide/microbiostat used to control slime-forming bacteria and fungi in commercial/industrial water cooling systems (recirculating), oil recovery drilling muds/packer fluids, pulp/paper mill water systems, secondary oil recovery rejection water, industrial adhesives and coatings, resin/latex/polymer emulsions, metalworking cutting fluids, paints, specialty industrial products (including fiber processing fluids, waxes, polishes, and inks), and wet-end additives/industrial processing chemicals.

  17. Allogeneic and autologous bone marrow transplantation for acute nonlymphocytic leukemia.

    PubMed

    Hurd, D D

    1987-12-01

    Current results show that 50% of young patients with ANLL who undergo allogeneic BMT experience prolonged DFS and may be cured. Encouraging results with high-dose chemo/radiotherapy and autologous BMT are likewise being reported. In addition, some studies using intensive postremission treatment without BMT have shown results comparable to many transplant series. As better ways of preventing GVHD are found, the morbidity and mortality of allogeneic BMT should be reduced and the benefits of transplantation for curing patients with ANLL should be increased. However, the applicability of allogeneic BMT will remain limited due to the availability of compatible donors whether related or unrelated. Further studies are needed in the use of postremission intensive therapy with and without autologous bone marrow support. However, results to date should engender the same degree of enthusiastic optimism that followed the early reports of improved outcome with allogeneic BMT when applied to first remission patients. PMID:3321445

  18. 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

  19. 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.

  20. Pericardial Tamponade: a Rare Complication of Sternal Bone Marrow Biopsy

    PubMed Central

    Santavy, Petr; Troubil, Martin; Lonsky, Vladimir

    2013-01-01

    Injury of the heart with concomitant pericardial tamponade as a result of sternal bone marrow biopsy is rare. An 80-year-old man was admitted with dehydration and non-specified abdominal pain to the regional hospital. Sternal aspiration biopsy was performed because of anemia and thrombocytopenia. Later on, because of the back pain, general weakness and blood pressure drop, an echocardiography examination was indicated. Pericardial fluid collection was found. Anticipated ascending aortic dissection was excluded on computed tomography scan, but pericardial fluid collection was confirmed. Transfer to our cardiac surgical facility ensued. Limited heart tamponade was affirmed on echocardiography and surgery was immediately indicated. Blood effusion was found in upper mediastinal fat tissue and 300 mL of blood were evacuated from opened pericardial space. Stab wound by sternal biopsy needle at the upper part of ascending aorta was repaired by pledgeted suture. Postoperative course was uneventful. PMID:24179668

  1. 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

  2. Prevention and treatment of fungal infections in bone marrow transplantation.

    PubMed

    Mossad, Sherif B

    2003-07-01

    There has not been as much success in the prevention and treatment of invasive fungal infections, particularly aspergillosis, compared to the prevention and treatment of cytomegalovirus infection and graft-versus-host disease in bone marrow transplant (BMT) recipients. Allogeneic BMT recipients who develop graft-versus-host disease and remain immunosuppressed for long periods are at major risk for development of these infections. Prevention of environmental exposure, antifungal chemoprophylaxis, and attempts at early diagnosis are essential for the reduction of mortality from invasive fungal infections. Chest computerized axial tomography is extremely useful in diagnosing pulmonary aspergillosis. However, microbiologic or histologic identification of infection remains essential. Unfortunately, the response to therapy in BMT recipients remains suboptimal. With the development of the lipid formulations of amphotericin B, the newer azoles, and the echinocandins, safer and more efficacious options have become available. The optimal use of antifungal agents or their combinations remains to be determined. PMID:12901327

  3. 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

  4. [The effect of nutrition on bone marrow transplantation].

    PubMed

    Olóriz, M R; del Campo, M; Sierra, D; Tamayo, B; Fuente, E

    1991-01-01

    Malnutrition alone may provoke considerable immune alterations, mainly in the immunocellular function, and in particular in the T lymphocyte and macrophage-monocytic function. This gives rise to an increase in proneness to infections, which in patients subjected to bone marrow transplants, will be increased by the intense neutropenia suffered by them. This study shows the greater incidence of infection among badly nourished patients compared to nourished patients. It was also observed that short bouts of high temperature mainly occurred in a subgroup of patients with an acceptable nutritional level, which in our opinion was the cause for none of them developing the infectious illness. Finally, one of the germs most often found in these patients is Staphylococcus epidermis, and the most common method of entry is through the catheters used in the administration of medicines and artificial nutrition. Emphasis is placed on the role played by nursing in preventing this type of infection. PMID:1760483

  5. Bone Marrow Aspirate in the Treatment of Chondral Injuries

    PubMed Central

    Holton, James; Imam, Mohamed A.; Snow, Martin

    2016-01-01

    The ability of mesenchymal stem cells (MSCs) to transdifferentiate into a desired cell lineage has captured the imagination of scientists and clinicians alike. The limited ability for chondrocytes to regenerate in chondral injuries has raised the concept of using MSCs to help regenerate and repair damaged tissue. The expansion of cells in a laboratory setting to be delivered back to the patient is too costly for clinical use in the present tough economic climate. This process is slow with due to the complexity of trying to imitate the natural environment and biological stimulation of chondral cell replication and proliferation. Bone marrow aspirate concentrate (BMAC) has the potential to provide an easily accessible and readily available source of MSCs with key growth factors that can be used in treating chondral injuries. This review summarizes the underlying basic science of MSCs and the therapeutic potential of BMAC. PMID:27379241

  6. Bone marrow processing on the Haemonetics V50 cell separator.

    PubMed

    Anderson, N A; Cornish, J M; Godwin, V; Gunstone, M J; Oakhill, A; Pamphilon, D H

    1990-01-01

    We have processed 27 bone marrow (BM) harvests using the Haemonetics V50 cell separator with a paediatric plasmapheresis set and programmed for lymphocyte collection. The mean starting volume of 843 mL was processed in 6-8 cycles to a buffy coat (BC) with a mean volume of 230 mL. The mean starting mononuclear cell (MNC) count was 1.22 x 10 8/kg recipient weight, and recovery was 92%. Clonogenic potential of the BC was assessed using CFU-GM assays and recovery was measured after cryopreservation or purging. On 4 occasions where major ABO incompatibility existed between donor and recipient, both BM and BC were consecutively diluted in compatible blood and processed twice. This achieved a calculated reduction in donor erythrocytes of 98%. The procedure was efficient and yielded a BC fraction suitable for cryopreservation and purging. Adequate stem-cells were retained as verified by CFU-GM assays and documentation of stable engraftment.

  7. Discordant bone marrow involvement in non-Hodgkin lymphoma.

    PubMed

    Brudno, Jennifer; Tadmor, Tamar; Pittaluga, Stefania; Nicolae, Alina; Polliack, Aaron; Dunleavy, Kieron

    2016-02-25

    A discordant lymphoma occurs where 2 distinct histologic subtypes coexist in at least 2 separate anatomic sites. Histologic discordance is most commonly observed between the bone marrow (BM) and lymph nodes (LNs), where typically aggressive lymphoma is found in a LN biopsy with indolent lymphoma in a BM biopsy. Although the diagnosis of discordance relied heavily on histopathology alone in the past, the availability of flow cytometry and molecular studies have aided the identification of this entity. The true prevalence and clinical ramifications of discordance remain controversial as available data are principally retrospective, and there is therefore little consensus to guide optimal management strategies. In this review, we examine the available literature on discordant lymphoma and its outcome, and discuss current therapeutic approaches. Future studies in discordant lymphoma should ideally focus on a large series of patients with adequate tissue samples and incorporate molecular analyses. PMID:26679865

  8. Transplanted Bone Marrow-Derived Cells Contribute to Human Adipogenesis.

    PubMed

    Rydén, Mikael; Uzunel, Mehmet; Hård, Joanna L; Borgström, 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; Frisén, 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 may contribute 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

  9. Engineering bone grafts with enhanced bone marrow and native scaffolds.

    PubMed

    Hung, Ben P; Salter, Erin K; Temple, Josh; Mundinger, Gerhard S; Brown, Emile N; Brazio, Philip; Rodriguez, Eduardo D; Grayson, Warren L

    2013-01-01

    The translation of tissue engineering approaches to the clinic has been hampered by the inability to find suitable multipotent cell sources requiring minimal in vitro expansion. Enhanced bone marrow (eBM), which is obtained by reaming long bone medullary canals and isolating the solid marrow putty, has large quantities of stem cells and demonstrates significant potential to regenerate bone tissues. eBM, however, cannot impart immediate load-bearing mechanical integrity or maintain the gross anatomical structure to guide bone healing. Yet, its putty-like consistency creates a challenge for obtaining the uniform seeding necessary to effectively combine it with porous scaffolds. In this study, we examined the potential for combining eBM with mechanically strong, osteoinductive trabecular bone scaffolds for bone regeneration by creating channels into scaffolds for seeding the eBM. eBM was extracted from the femurs of adult Yorkshire pigs using a Synthes reamer-irrigator-aspirator device, analyzed histologically, and digested to extract cells and characterize their differentiation potential. To evaluate bone tissue formation, eBM was seeded into the channels in collagen-coated or noncoated scaffolds, cultured in osteogenic conditions for 4 weeks, harvested and assessed for tissue distribution and bone formation. Our data demonstrates that eBM is a heterogenous tissue containing multipotent cell populations. Furthermore, coating scaffolds with a collagen hydrogel significantly enhanced cellular migration, promoted uniform tissue development and increased bone mineral deposition. These findings suggest the potential for generating customized autologous bone grafts for treating critical-sized bone defects by combining a readily available eBM cell source with decellularized trabecular bone scaffolds.

  10. Bone marrow necrosis in acute leukemia: Clinical characteristic and outcome.

    PubMed

    Badar, Talha; Shetty, Aditya; Bueso-Ramos, Carlos; Cortes, Jorge; Konopleva, Marina; Borthakur, Gautam; Pierce, Sherry; Huang, Xuelin; Chen, Hsiang-Chun; Kadia, Tapan; Daver, Naval; Dinardo, Courtney; O'Brien, Susan; Garcia-Manero, Guillermo; Kantarjian, Hagop; Ravandi, Farhad

    2015-09-01

    Bone marrow necrosis (BMN) is characterized by infarction of the medullary stroma, leading to marrow necrosis with preserved cortical bone. In reported small series, BMN in hematological malignancies is associated with poor prognosis. We sought to find the impact of BMN on clinical outcome in a relatively larger cohort of patients with acute leukemias. Overall we evaluated 1,691 patients; 1,051 with acute myeloid leukemia (AML) and 640 with acute lymphocytic leukemia referred to our institution between 2002 and 2013. Patients with AML and acute lymphoblastic leukemia (ALL) were evaluated separately to determine the incidence of BMN, associated clinical features and its prognostic significance. At initial diagnosis, BMN was observed in 25 (2.4%) patients with AML and 20 (3.2%) patients with ALL. In AML, BMN was significantly associated with French-American-British AML M5 morphology (32% vs. 10%, P = 0.002). The complete remission (CR) rate in AML with and without BMN was 32% and 59% respectively (P = 0.008). Likewise, CR rate in ALL with BMN was also inferior, 70% vs. 92% (P = 0.005). The median overall survival (OS) in AML with BMN was significantly poorer, 3.7 months compared to 14 months without BMN (P = 0.003). Similarly, the median OS in ALL with and without BMN was 61.7 and 72 months respectively (P = 0.33). BMN is not a rare entity in AML and ALL, but is infrequent. BMN in AML and in ALL is suggestive of inferior response and poor prognosis.

  11. Modification of bone marrow radiosensensitivity by medicinal plant extracts.

    PubMed

    Ganasoundari, A; Zare, S M; Devi, P U

    1997-06-01

    Withaferin A (WA), a steroidal lactone, and Plumbagin (Pl), a naphthoquinone, from the roots of Withania somnifera and Plumbago rosea, respectively, have been shown to possess growth inhibitory and radiosensitizing effects on experimental mouse tumours. An aqueous extract of the leaves of Ocimum sanctum (OE) was found to protect mice against radiation lethality. Therefore, the radiomodifying effects of the above plant products on the bone marrow of the adult Swiss mouse was studied. Single doses of WA (30 mg kg-1) or Pl (5 mg kg-1) were injected intraperitoneally (ip) and OE (10 mg kg-1) was injected ip once daily for five consecutive days. Administration of extracts was followed by 2 Gy whole body gamma irradiation. Bone marrow stem cell survival was studied by an exogenous spleen colony unit (CFU-S) assay. The effects of WA and Pl were compared with that of cyclophosphamide (CP) and radioprotection by OE was compared with that of WR-2721 (WR). Radiation reduced the CFU-S to less than 50% of normal. WA, CP and Pl significantly enhanced this effect and reduced the CFU-S to almost the same extent (to < 20% of normal), although individually WA and Pl were less cytotoxic than CP. These results indicate that radiosensitization by WA and Pl is not tumour specific. OE significantly increased CFU-S compared with radiotherapy (RT) alone. OE+RT gave a higher stem cell survival (p < 0.05) than that produced by WR+RT. While WR alone had a toxic effect, OE treatment showed no such effect, suggesting that the latter may have an advantage over WR in clinical application. PMID:9227253

  12. Regenerate augmentation with bone marrow concentrate after traumatic bone loss

    PubMed Central

    Gessmann, Jan; Köller, Manfred; Godry, Holger; Schildhauer, Thomas Armin; Seybold, Dominik

    2012-01-01

    Distraction osteogenesis after post-traumatic segmental bone loss of the tibia is a complex and time-consuming procedure that is often complicated due to prolonged consolidation or complete insufficiency of the regenerate. The aim of this feasibility study was to investigate the potential of bone marrow aspiration concentrate (BMAC) for percutaneous regenerate augmentation to accelerate bony consolidation of the regenerate. Eight patients (age 22–64) with an average posttraumatic bone defect of 82.4 mm and concomitant risk factors (nicotine abuse, soft-tissue defects, obesity and/or circulatory disorders) were treated with a modified Ilizarov external frame using an intramedullary cable transportation system. At the end of the distraction phase, each patient was treated with a percutaneously injection of autologous BMAC into the centre of the regenerate. The concentration factor was analysed using flow cytometry. The mean follow up after frame removal was 10 (4–15) months. With a mean healing index (HI) of 36.9 d/cm, bony consolidation of the regenerate was achieved in all eight cases. The mean concentration factor of the bone marrow aspirate was 4.6 (SD 1.23). No further operations concerning the regenerate were needed and no adverse effects were observed with the BMAC procedure. This procedure can be used for augmentation of the regenerate in cases of segmental bone transport. Further studies with a larger number of patients and control groups are needed to evaluate a possible higher success rate and accelerating effects on regenerate healing. PMID:22577502

  13. Cartilage Repair With Autologous Bone Marrow Mesenchymal Stem Cell Transplantation

    PubMed Central

    Yamasaki, Shinya; Mera, Hisashi; Itokazu, Maki; Hashimoto, Yusuke

    2014-01-01

    Clinical trials of various procedures, including bone marrow stimulation, mosaicplasty, and autologous chondrocyte implantation, have been explored to treat articular cartilage defects. However, all of them have some demerits. We focused on autologous culture-expanded bone marrow mesenchymal stem cells (BMSC), which can proliferate without losing their capacity for differentiation. First, we transplanted BMSC into the defective articular cartilage of rabbit and succeeded in regenerating osteochondral tissue. We then applied this transplantation in humans. Our previous reports showed that treatment with BMSC relieves the clinical symptoms of chondral defects in the knee and elbow joint. We investigated the efficacy of BMSC for osteoarthritic knee treated with high tibial osteotomy, by comparing 12 BMSC-transplanted patients with 12 cell-free patients. At 16-month follow-up, although the difference in clinical improvement between both groups was not significant, the arthroscopic and histological grading score was better in the cell-transplanted group. At the over 10-year follow-up, Hospital for Special Surgery knee scores improved to 76 and 73 in the BMSC-transplanted and cell-free groups, respectively, which were better than preoperative scores. Additionally, neither tumors nor infections were observed in all patients, and in the clinical study, we have never observed hypertrophy of repaired tissue, thereby guaranteeing the clinical safety of this therapy. Although we have never observed calcification above the tidemark in rabbit model and human histologically, the repair cartilage was not completely hyaline cartilage. To elucidate the optimum conditions for cell therapy, other stem cells, culture conditions, growth factors, and gene transfection methods should be explored. PMID:26069698

  14. A study of membrane protein defects and alpha hemoglobin chains of red blood cells in human beta thalassemia

    SciTech Connect

    Rouyer-Fessard, P.; Garel, M.C.; Domenget, C.; Guetarni, D.; Bachir, D.; Colonna, P.; Beuzard, Y. )

    1989-11-15

    The soluble pool of alpha hemoglobin chains present in blood or bone marrow cells was measured with a new affinity method using a specific probe, beta A hemoglobin chain labeled with ({sup 3}H)N-ethylmaleimide. This pool of soluble alpha chains was 0.067 {plus minus} 0.017% of hemoglobin in blood of normal adult, 0.11 {plus minus} 0.03% in heterozygous beta thalassemia and ranged from 0.26 to 1.30% in homozygous beta thalassemia intermedia. This elevated pool of soluble alpha chains observed in human beta thalassemia intermedia decreased 33-fold from a value of 10% of total hemoglobin in bone marrow cells to 0.3% in the most dense red blood cells. The amount of insoluble alpha chains was measured by using the polyacrylamide gel electrophoresis in urea and Triton X-100. In beta thalassemia intermedia the amount of insoluble alpha chains was correlated with the decreased spectrin content of red cell membrane and was associated with a decrease in ankyrin and with other abnormalities of the electrophoretic pattern of membrane proteins. The loss and topology of the reactive thiol groups of membrane proteins was determined by using ({sup 3}H)N-ethylmaleimide added to membrane ghosts prior to urea and Triton X-100 electrophoresis. Spectrin and ankyrin were the major proteins with the most important decrease of thiol groups.

  15. Histological Development of the Immune Tissues of a Marsupial, the Red-Tailed Phascogale (Phascogale calura).

    PubMed

    Borthwick, Casey R; Old, Julie M

    2016-02-01

    Red-tailed phascogale (Phascogale calura) pouch young at birth were relatively underdeveloped in comparison with their eutherian counterparts, and the lymphoid tissues of the immune system were found to be histologically immature. The phascogale thymus rapidly developed in the first few days of pouch life and was quickly populated with lymphocytes. By the end of pouch life, involution of the thymus was underway. The bone marrow started to develop in the early stage of pouch life, although adipocytes and megakaryocytes were not observed until slightly later. The liver was hematopoietic from birth and reached histological maturity toward the end of pouch life. The lymph nodes were difficult to detect macroscopically because of their small size, but were easily identified microscopically later in pouch life, particularly in the mesentery, and these lymph nodes exhibited germinal centers by the end of pouch life. The early spleen was predominately mesenchymal, but exhibited some erythropoiesis. Follicles with well-developed germinal centers were not observed until the latest stage of pouch life. Although intraepithelial lymphocytes were detected in the intestines early in pouch life, the discrete lymphoid aggregates and Peyer's patches characteristic of the gut-associated lymphoid tissue (GALT) were not detected until later in pouch life. This is the first report of histological development in phascogale pouch young, as well as the first report of the thymus, bone marrow, and lymph nodes in this dasyurid species at any age.

  16. The second transferrin receptor regulates red blood cell production in mice.

    PubMed

    Nai, Antonella; Lidonnici, Maria Rosa; Rausa, Marco; Mandelli, Giacomo; Pagani, Alessia; Silvestri, Laura; Ferrari, Giuliana; Camaschella, Clara

    2015-02-12

    Transferrin receptor 2 (TFR2) contributes to hepcidin regulation in the liver and associates with erythropoietin receptor in erythroid cells. Nevertheless, TFR2 mutations cause iron overload (hemochromatosis type 3) without overt erythroid abnormalities. To clarify TFR2 erythroid function, we generated a mouse lacking Tfr2 exclusively in the bone marrow (Tfr2(BMKO)). Tfr2(BMKO) mice have normal iron parameters, reduced hepcidin levels, higher hemoglobin and red blood cell counts, and lower mean corpuscular volume than normal control mice, a phenotype that becomes more evident in iron deficiency. In Tfr2(BMKO) mice, the proportion of nucleated erythroid cells in the bone marrow is higher and the apoptosis lower than in controls, irrespective of comparable erythropoietin levels. Induction of moderate iron deficiency increases erythroblasts number, reduces apoptosis, and enhances erythropoietin (Epo) levels in controls, but not in Tfr2(BMKO) mice. Epo-target genes such as Bcl-xL and Epor are highly expressed in the spleen and in isolated erythroblasts from Tfr2(BMKO) mice. Low hepcidin expression in Tfr2(BMKO) is accounted for by erythroid expansion and production of the erythroid regulator erythroferrone. We suggest that Tfr2 is a component of a novel iron-sensing mechanism that adjusts erythrocyte production according to iron availability, likely by modulating the erythroblast Epo sensitivity. PMID:25499454

  17. [Pure red cell aplasia and hypogammaglobulinemia after administration of Dioscorea rhizome and Poria cocos].

    PubMed

    Sato, Takayuki; Ueda, Yasunori

    2015-11-01

    A 56-year-old woman was referred to our department for detailed examination of anemia. She was diagnosed with pure red cell aplasia (PRCA) associated with severe reticulocytopenia based on blood testing and severe erythroblastopenia based on bone marrow aspiration. Blood tests revealed severe hypogammaglobulinemia, but monoclonal protein was not detected in either serum or urine by immunoelectrophoresis. Plasma cells were not increased in bone marrow aspirates or the biopsy specimen. Neither osteolytic lesions nor plasmacytoma was detected by computed tomography. We thus ruled out multiple myeloma. She had been treated with various Chinese herbal medicines prescribed at the referring hospital. We suspected PRCA induced by one of the Chinese herbal medicines and completely discontinued all of these herbal preparations. Hematologic testing revealed that the reticulocyte count and hemoglobin concentration began to recover on day 7 and the hemoglobin concentration and IgG levels had reached reference ranges on day 73 after discontinuation of the Chinese herbal medicines. We suspected Sanyaku (Dioscorea rhizome) or Bukuryou (Poria cocos) to have induced PRCA and hypogammaglobulinemia in this patient. To the best of our knowledge, this is the first report of PRCA and hypogammaglobulinemia induced by a Chinese herbal medicine. Clinicians must consider the possibility of drug-induced PRCA and hypogammaglobulinemia in patients taking Chinese herbal preparations.

  18. 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.

  19. Effect of bone marrow-derived stem cells on chondrocytes from patients with osteoarthritis.

    PubMed

    Zhang, Qiangzhi; Chen, Yong; Wang, Qiang; Fang, Chaoyong; Sun, Yu; Yuan, Tao; Wang, Yuebei; Bao, Rongni; Zhao, Ningjian

    2016-02-01

    Increasing numbers of individuals are suffering from osteoarthritis every year, and the directed intra-articular injection of bone marrow stem cells has provided a promising treatment strategy for osteoarthritis. Although a number of studies have demonstrated that intra-articular injection of bone marrow stem cells produced desirable results, the mechanism underlying this effect has not been elucidated. In the current study, the effect of bone marrow stem cells on chondrocytes from patients with osteoarthritis was observed in a co-culture system. Human chondrocytes were obtained from patients with osteoarthritis who underwent surgical procedures and bone marrow stem cells were obtained from bone marrow aspirates, and then the chondrocytes were then cultured alone or cocultured with bone marrow stem cells in 0.4-µm Transwell inserts. The differentiation and biological activity of chondrocytes in the culture system were measured, and the inflammatory factors and OA-associated markers were also measured. The results indicated that coculture with human bone marrow stem cells increases cell proliferation of chondrocytes and inhibits inflammatory activity in osteoarthritis.

  20. Histopathological perspective on bone marrow oedema, reactive bone change and haemorrhage.

    PubMed

    Thiryayi, W A; Thiryayi, S A; Freemont, A J

    2008-07-01

    This article presents a systematic review of the current biomedical literature surrounding the aetiopathogenesis and histopathological features of bone marrow oedema, reactive bone change and haemorrhage. Bone marrow oedema is generally demonstrated as a non-specific finding on magnetic resonance imaging in association with infections, tumours and avascular necrosis. When it occurs in isolation as a primary event not triggered by any obvious bony pathology in the clinical setting of debilitating joint pain, it constitutes the "bone marrow oedema syndrome". Although the latter diagnosis is based on magnetic resonance (MR) imaging, showing the lesion as areas of signal hyperintensity within the marrow, recent radiology-histology correlational studies have shown variably interstitial marrow oedema, necrosis, fibrosis and trabecular bone abnormalities. In light of these facts, the use of the term bone marrow oedema syndrome in a radiological context might be considered questionable, but histopathological techniques are not sensitive in detecting increased extracellular fluid. Reactive bone changes may be focal or diffuse and usually amount to increased bone formation. Bone marrow haemorrhage, due to trauma, results in bone bruising, a condition in which the size of the bruise and associated osteochondral injury determines the outcome, although the natural history of these lesions is still being researched. PMID:18337044

  1. Increasing utilization of bone marrow transplantation. II. Results of the 1985-1987 survey.

    PubMed

    Bortin, M M; Rimm, A A

    1989-09-01

    The International Bone Marrow Transplant REgistry conducts periodic surveys to determine activity in the field of allogeneic and syngeneic bone marrow transplantation. Data were reported to the IBMTR by 258 institutions in 41 countries regarding their patients who received bone marrow transplants during the period 1985-1987. To the best of our knowledge, the data represent essentially all bone marrow transplants (exclusive of autologous transplants) performed in the past 3 years. A total of 10,887 patients received bone marrow transplants; 73% were for leukemia, 11% for other malignant diseases, 9% for severe aplastic anemia and related disorders, 3% for immune deficiency diseases, 2% for thalassemia major, and 2% for genetic, metabolic, and several other rare diseases. 161 (62%) of the 258 institutions performed fewer than one transplant per month. More than 50% of the patients were transplanted in 37 institutions. 46% of the world's bone marrow transplants were performed in North America, 42% in Western Europe, 5% in Asia, 3% in Australia and New Zealand, 2% in the Mideast and Africa, 1% in South and Central America, and 1% in Eastern Europe and the USSR. The data reflect continued growth in utilization of allogeneic and syngeneic bone marrow transplantation and quantify the annual increases in the number of patients receiving transplants.

  2. In vitro growth of hematopoietic progenitors and stromal bone marrow cells from patients with multiple myeloma.

    PubMed

    Martínez-Jaramillo, Guadalupe; Vela-Ojeda, Jorge; Flores-Guzmán, Patricia; Mayani, Hector

    2011-02-01

    In the present study we have determined the content of hematopoietic and stromal progenitors in multiple myeloma (MM) bone marrow, and assessed their in vitro growth. Marrow cells were obtained from 17 MM patients at the time of diagnosis, and from 6 hematologically normal subjects. When mononuclear cells (MNC) from MM marrow were cultured, reduced numbers of hematopoietic progenitors were detected and their growth in long-term cultures was deficient, as compared to cultures of normal cells. When cell fractions enriched for CD34(+) Lin(-) cells were obtained, the levels of hematopoietic progenitors from MM marrow were within the normal range, and so was their growth kinetics in liquid suspension cultures. The levels of fibroblast progenitors in MM were not statistically different from those in normal marrow; however, their proliferation potential was significantly reduced. Conditioned media from MM-derived MNC and stroma cells contained factors that inhibited normal progenitor cell growth. Our observations suggest that hematopoietic progenitors in MM marrow are intrinsically normal; however, their growth in LTMC may be hampered by the presence of abnormal accessory and stroma cells. These results suggest that besides its role in the generation of osteolytic lesions and the expansion of the myeloma clone, the marrow microenvironment in MM may have a negative effect on hematopoiesis. PMID:20621354

  3. 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

  4. The Challenge and the Promise of Bone Marrow Cells for Human Cartilage Repair

    PubMed Central

    2015-01-01

    The cartilage repair potential of bone marrow–derived stem cells has been well described. Harnessing this potential for human articular cartilage repair remains challenging. Accessing bone marrow repair cells through marrow stimulation techniques such as microfracture is readily achieved with generally good but inconsistent results. Animal and human studies show feasibility for ex vivo processing of bone marrow to isolate, concentrate, and culture mesenchymal stem cells. Nevertheless, it has been difficult to show consistent and clinically meaningful improvement using bone marrow cell preparations above what has been achieved with microfracture. Consequently, microfracture continues to be the simplest and most commonly used method to enhance repair of focal articular cartilage defects. Emerging preclinical work in the equine model suggests a role for enhancing marrow-stimulation techniques through the use of natural scaffolds such as autologous platelet enriched fibrin as well as optimization of joint biology through localized gene therapy to support cartilage repair. In contrast to joint replacement where inert materials of known mechanical properties are used, host biology determines the relative success, failure, and durability of cartilage repair. As such, development of personalized strategies to improve the quality and durability of bone marrow cell–based articular cartilage repair represent exciting new areas of inquiry. Continued advances in stem cell biology, scaffold technologies, and methods to delineate and enhance host biology, both systemically and within the joint, hold promise for harnessing the full power of bone marrow cells to facilitate cartilage repair and regeneration. PMID:27340515

  5. Histological and In Vivo Microscopic Analysis of the Bone Marrow Microenvironment in a Murine Model of Chronic Myelogenous Leukemia.

    PubMed

    Weissenberger, Eva S; Krause, Daniela S

    2016-01-01

    Imaging of the leukemic bone marrow microenvironment, also called the leukemic bone marrow niche, is an essential method to determine and to evaluate the progression of chronic myelogenous leukemia (CML) and other leukemias in murine models. In this chapter we introduce the murine model of CML primarily used in our laboratory by describing blood and bone marrow analysis as well as the method of histological sectioning and immunohistochemistry in combination with various stainings that can help to understand the complex interaction between leukemic cells, their normal hematopoietic counterparts, and the bone marrow microenvironment. We conclude with describing how to image the bone marrow niche using in vivo microscopy. PMID:27581139

  6. The clinical impact of staging bone marrow examination on treatment decisions and prognostic assessment of lymphoma patients.

    PubMed

    Painter, Dan; Smith, Alexandra; de Tute, Ruth; Crouch, Simon; Roman, Eve; Jack, Andrew

    2015-07-01

    This study investigates the value of performing a staging bone marrow in patients with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and classical hodgkin lymphoma (CHL). The results of 3112 staging bone marrow examinations were assessed for impact on prognostic assessment and critical treatment decisions. The detection of marrow involvement altered the disease-specific prognostic index for 4·3% of DLBCL, 6·2% of FL and 0·6% of CHL but marrow involvement in DLBCL was an independent prognostic factor. Knowing the marrow status potentially changed treatment in 92 patients, detection of these patients would have required 854 examinations to be performed.

  7. 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

  8. Pressure and shear stress in trabecular bone marrow during whole bone loading.

    PubMed

    Metzger, Thomas A; Schwaner, Stephen A; LaNeve, Anthony J; Kreipke, Tyler C; Niebur, Glen L

    2015-09-18

    Skeletal adaptation to mechanical loading is controlled by mechanobiological signaling. Osteocytes are highly responsive to applied strains, and are the key mechanosensory cells in bone. However, many cells residing in the marrow also respond to mechanical cues such as hydrostatic pressure and shear stress, and hence could play a role in skeletal adaptation. Trabecular bone encapsulates marrow, forming a poroelastic solid. According to the mechanical theory, deformation of the pores induces motion in the fluid-like marrow, resulting in pressure and velocity gradients. The latter results in shear stress acting between the components of the marrow. To characterize the mechanical environment of trabecular bone marrow in situ, pore pressure within the trabecular compartment of whole porcine femurs was measured with miniature pressure transducers during stress-relaxation and cyclic loading. Pressure gradients ranging from 0.013 to 0.46 kPa/mm were measured during loading. This range was consistent with calculated pressure gradients from continuum scale poroelastic models with the same permeability. Micro-scale computational fluid dynamics models created from computed tomography images were used to calculate the micromechanical stress in the marrow using the measured pressure differentials as boundary conditions. The volume averaged shear stress in the marrow ranged from 1.67 to 24.55 Pa during cyclic loading, which exceeds the mechanostimulatory threshold for mesenchymal lineage cells. Thus, the loading of bone through activities of daily living may be an essential component of bone marrow health and mechanobiology. Additional studies of cell-level interactions during loading in healthy and disease conditions will provide further incite into marrow mechanobiology.

  9. 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 α-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.

  10. 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

  11. 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 non-erythrotoxic 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 non-erythrotoxic 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.

  12. Architecture of the marrow vasculature in three amphibian species and its significance in hematopoietic development.

    PubMed

    Tanaka, Y

    1976-04-01

    Architecture of the bone marrow vasculature, particularly that of the femur, was analyzed in three amphibian species in relation to the early phylogeny of marrow hematopoiesis. A dye-injection method and histological techniques, including both serial sectioning and reconstruction methods, were used for this purpose. From these observations the following conclusions may be drawn. (1) Marrow hematopoiesis is absent from the femur of the urodelan (Triturus pyrrhogaster) and appears first in the femur of the primitive anuran (Xenopus laevis) (2) The site of primitive hematopoiesis (granulopoiesis) is the subendosteal region where the venous vascular net develops. (3) The primitive vascular architecture observed in the femur of Xenopus is characterized by the absence of a central vein. Subendosteal veins drain the blood from the bone marrow. A vein collateral to the primary artery appears in the femur of Rana catesbeiana, an advanced anuran, in which further development of both the subendosteal venous plexus and hematopoietic activity are noted. In both anura examined, the primitive blood sinuses form near the mid-shaft of the femur. The proliferation of mesenchymal elements containing dark pigment, presumably melanin, was also noted in this area. (4) The architecture of marrow vessels in Rana approaches the structure noted in mammalian bone marrow. (5) Fat tissue is observed in the urodelan bone marrow prior to the appearance of hematopoietic activity. This indicates that the formation of marrow fat is phylogenetically unrelated to the development of hematopoiesis. The present investigation on primitive hematopoiesis suggests that the development of hematopoietic activity is intimately related to the development of the marrow vasculature, particularly that of the subendosteal venous plexus. A favorable vascular arrangement may be necessary to allow active hematopoiesis.

  13. Zinc enhances bone metabolism in ovariectomized rats and exerts anabolic osteoblastic/adipocytic marrow effects ex vivo.

    PubMed

    Li, Binbin; Liu, Hao; Jia, Shengnan

    2015-02-01

    Investigations of bone mass and marrow adiposity are critical for defining the role of zinc (Zn) in bone metabolism. Rats used for study were grouped as follows: control (sham), ovariectomy (OVX), ovariectomy + estradiol (OVX-E), ovariectomy + Zn treatment (OVX-Zn). Bone mineral density (BMD) was quantified (microCT); serum osteocalcin, adiponectin, RANKL, and TRAP levels were assayed (ELISA); and biochemical determinations of serum alkaline phosphatase (ALP), calcium (Ca), and phosphorus (P) were done. Cells derived from bone mesenchymal stem cell (BMSC) isolates of respective test groups were compared, identifying primary osteoblasts by MTT assay and adipocytes by Oil Red O stain. Osteocalcin and adiponectin levels in culture supernatants were determined by ELISA. Zn supplementation resulted in a modest increase in BMD, but serum osteocalcin and ALP activity increased significantly (P < 0.01, both). Serum levels of RANKL and TRAP were lower in OVX-Zn (vs OVX) rats (P < 0.01), whereas serum concentrations of adiponectin, Ca, and P did not differ by group. Osteocalcin level was significantly upregulated ex vivo (P < 0.01) in the supernatant of cultured OVX-Zn (vs OVX) cells, accompanied by a slight upturn in osteoblastic differentiation. However, Oil Red O uptake and adiponectin level in supernatant were sharply diminished in cultured OVX-Zn (vs OVX) cells (P < 0.01). Overall, we concluded that Zn contributes to bone mass by marginally stimulating differentiation and proliferation of osteoblasts and by effectively inhibiting osteoclastic and adipocytic differentiation of BMSCs.

  14. Bone marrow-derived mesenchymal stem cells effectively regenerate fibrotic liver in bile duct ligation rat model

    PubMed Central

    Elswefy, Sahar E; Rashed, Laila A; Younis, Nahla N; Shaheen, Mohamed A; Ghanim, Amal MH

    2016-01-01

    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 × 106 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

  15. 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 M H

    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.

  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. Acquired loss of red cell Kell antigens.

    PubMed

    Vengelen-Tyler, V; Gonzalez, B; Garratty, G; Kruppe, C; Johnson, C L; Mueller, K A; Marsh, W L

    1987-02-01

    A 19-year-old patient with a long history of idiopathic thrombocytopenic purpura developed a potent antibody against a high-incidence antigen in the Kell blood group system. The direct antiglobulin test on his red cells was negative. His cells exhibited profound depression of Kell blood group antigens, but antigens of other blood groups were normal. Transfusion of incompatible blood was well tolerated and differential agglutination tests, using selected Rh antisera, showed in vivo survival of the transfused red cells for more than 8 weeks. However, the transfused red cells also showed acquired loss of Kell antigens. Five months after the initial findings, Kell-related antibody disappeared and Kell antigens reappeared on his red cells. The patient's serum stored from the initial investigation now reacted with his freshly collected red cells. These data suggest that an environmental agent in the patient's plasma was responsible for the temporary loss of Kell antigens from red cells in his circulation.

  18. 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.

  19. Stress responses after pediatric bone marrow transplantation: preliminary results of a prospective longitudinal study.

    PubMed

    Stuber, M L; Nader, K; Yasuda, P; Pynoos, R S; Cohen, S

    1991-11-01

    This paper reports the preliminary findings of a longitudinal prospective study of young children undergoing bone marrow transplantation. Symptoms of post-traumatic stress were seen in these children up to 12 months after transplant. The bone marrow transplantation survivors demonstrated more denial and avoidance and fewer arousal symptoms than has been noted in children traumatized by a violent life threat, such as a sniper attack. These data suggest the use of post-traumatic stress as a model in understanding some of the symptoms of pediatric bone marrow transplantation survivors and may be applicable to other children exposed to the double life threat of serious illness and intensive medical intervention.

  20. Heart and kidney transplantation using total lymphoid irradiation and donor bone marrow in mongrel dogs

    SciTech Connect

    Kahn, D.R.; Dufek, J.H.; Hong, R.; Caldwell, W.L.; Thomas, F.J.; Kolenda, D.R.; Swanson, D.K.; Struble, R.A.

    1980-07-01

    Heart and kidney allografts showed markedly prolonged survival in unrelated mongrel dogs following total lymphoid irradiation (TLI) and donor bone marrow without any other immunosuppression. In every animal the heart survived longer than the kidney. Placing the kidney allograft in the abdomen with the bone marrow given intraperitoneally doubled kidney survival over placement in the neck, but heart survival was equally prolonged in the abdomen or neck. Splenectomy before TLI or after TLI, but just before transplantation, almost completely eliminated the prolonged survival of both heart and kidney allografts. Thus there is suggestive evidence that TLI plus bone marrow from the donor may be valuable for transplantation in man, particularly heart transplantation.

  1. Bone marrow stromal cell assays – in vitro and in vivo

    PubMed Central

    Robey, Pamela Gehron; Kuznetsov, Sergei A.; Riminucci, Mara; Bianco, Paolo

    2014-01-01

    Summary Populations of bone marrow stromal cells (BMSCs, also known as bone marrow-derived “mesenchymal stem cells”) contain a a subset of cells that are able to recapitulate the formation of a bone/marrow organ (skeletal stem cells, SSCs). The biological properties of BMSC cultures are assessed by a variety of assays, both in vitro and in vivo. Application of these assays in an appropriate fashion provide a great deal of information on the role of BMSCs, and the subset of SSCs, in health and in disease. PMID:24482181

  2. Large-scale gene expression profiling data of bone marrow stromal cells from osteoarthritic donors.

    PubMed

    Stiehler, Maik; Rauh, Juliane; Bünger, Cody; Jacobi, Angela; Vater, Corina; Schildberg, Theresa; Liebers, Cornelia; Günther, Klaus-Peter; Bretschneider, Henriette

    2016-09-01

    This data article contains data related to the research article entitled, "in vitro characterization of bone marrow stromal cells from osteoarthritic donors" [1]. Osteoarthritis (OA) represents the main indication for total joint arthroplasty and is one of the most frequent degenerative joint disorders. However, the exact etiology of OA remains unknown. Bone marrow stromal cells (BMSCs) can be easily isolated from bone marrow aspirates and provide an excellent source of progenitor cells. The data shows the identification of pivotal genes and pathways involved in osteoarthritis by comparing gene expression patterns of BMSCs from osteoarthritic versus healthy donors using an array-based approach.

  3. Enhancing mental health services to bone marrow transplant recipients through a mindfulness-based therapeutic intervention.

    PubMed

    Horton-Deutsch, Sara; O'Haver Day, Pamela; Haight, Regina; Babin-Nelson, Michele

    2007-05-01

    Complementary and alternative therapies are gaining recognition in the treatment of many disease states. The importance of treating psychological and emotional problems associated with bone marrow transplant has been substantiated by research evidence. This feasibility study tested a mindfulness-based therapeutic intervention to treat such problems in this context. Pretests and post-tests were administered to patients (n=24) undergoing bone marrow transplant. Results indicate that the mindfulness-based therapeutic intervention has the potential to be an effective therapy for bone marrow transplant recipients.

  4. The preparation of primary hematopoietic cell cultures from murine bone marrow for electroporation.

    PubMed

    Kroeger, Kelly; Collins, Michelle; Ugozzoli, Luis

    2009-01-01

    It is becoming increasingly apparent that electroporation is the most effective way to introduce plasmid DNA or siRNA into primary cells. The Gene Pulser MXcell electroporation system and Gene Pulser electroporation buffer were specifically developed to transfect nucleic acids into mammalian cells and difficult-to-transfect cells, such as primary and stem cells.This video demonstrates how to establish primary hematopoietic cell cultures from murine bone marrow, and then prepare them for electroporation in the MXcell system. We begin by isolating femur and tibia. Bone marrow from both femur and tibia are then harvested and cultures are established. Cultured bone marrow cells are then transfected and analyzed. PMID:19229174

  5. Bone marrow hypoplasia and intestinal crypt cell necrosis associated with fenbendazole administration in five painted storks.

    PubMed

    Weber, Martha A; Terrell, Scott P; Neiffer, Donald L; Miller, Michele A; Mangold, Barbara J

    2002-08-01

    Five painted storks were treated with fenbendazole for 5 days for internal parasitism. Four birds died following treatment. Profound heteropenia was a consistent finding in all samples evaluated; additionally, the 1 surviving bird had progressive anemia. Consistent necropsy findings in the 4 birds that died were small intestinal crypt cell necrosis and severe bone marrow depletion and necrosis. Fenbendazole has been associated with bone marrow hypoplasia and enteric damage in mammals and other species of birds. The dosages of fenbendazole used in birds are often substantially higher than those recommended for mammals, which may contribute to bone marrow hypoplasia and intestinal crypt cell necrosis associated with fenbendazole administration in birds.

  6. Prognostic value of in vitro bone marrow culture in refractory anaemia with excess of myeloblasts.

    PubMed

    Faille, A; Dresch, C; Poirier, O; Balitrand, N; Najean, Y

    1978-03-01

    Bone marrow from 17 patients with refractory anaemia with excess of myeloblasts (RAEM) was cultured in methylcellulose semi-solid medium. Compared with normal bone marrow, 3 patterns of growth occurred corresponding with different clinical stages of the condition. Patients whose bone marrow grew normal colonies and those who produced a predominance of microclusters had the longest life expectance, while those who produced a predominance of macroclusters had the shortest life expectancy with a high rate of acute leukaemic transformation. Colony culture appears to be a useful prognostic tool in the condition.

  7. Antitumor immunomodulatory activity of allogenic bone marrow cells on TiNi scaffold

    NASA Astrophysics Data System (ADS)

    Kokorev, O. V.; Hodorenko, V. N.; Cherdyntseva, N. V.; Gunther, V. E.

    2016-08-01

    The present study was undertaken to evaluate the feasibility of modulation of anti-tumor response by allogenic bone marrow cell transplantation into porous TiNi-based scaffold. Transplantation of bone marrow cells into porous TiNi-based scaffold leads to antitumor (35%) and antimetastatic (55%) effects. The lifetime of tumor-bearing animals and implanted allogenic bone marrow cells in incubator of TiNi increases up to 60%. The possible mechanisms of the effect of allogenic cells on tumor process are the stimulation of endogenous effectors of antitumor immunity.

  8. Enhancing mental health services to bone marrow transplant recipients through a mindfulness-based therapeutic intervention.

    PubMed

    Horton-Deutsch, Sara; O'Haver Day, Pamela; Haight, Regina; Babin-Nelson, Michele

    2007-05-01

    Complementary and alternative therapies are gaining recognition in the treatment of many disease states. The importance of treating psychological and emotional problems associated with bone marrow transplant has been substantiated by research evidence. This feasibility study tested a mindfulness-based therapeutic intervention to treat such problems in this context. Pretests and post-tests were administered to patients (n=24) undergoing bone marrow transplant. Results indicate that the mindfulness-based therapeutic intervention has the potential to be an effective therapy for bone marrow transplant recipients. PMID:17400146

  9. An Autologous Bone Marrow Mesenchymal Stem Cell–Derived 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 cell–derived 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

  10. Malignant Melanoma Arising in Red Tattoo Ink

    PubMed Central

    Duff, Gerald; McKenna, Dermot; Regan, Padraic James

    2015-01-01

    We report the case of a 33-year-old male who presented with a malignant melanoma on his anterior chest wall. The lesion was only found in the red ink pigment of the tattoo, as were several in-transit dermal metastases. Possible explanations include a pre-existing lesion which was seeded with red ink or the possibility of the red ink causing an inflammatory reaction leading to malignant transformation. This is the first reported case of a melanoma developing in the red ink pigment of a multi-colored tattoo. PMID:26217569

  11. Amelioration of murine sickle cell disease by nonablative conditioning and γ-globin gene-corrected bone marrow cells.

    PubMed

    Pestina, Tamara I; Hargrove, Phillip W; Zhao, Huifen; Mead, Paul E; Smeltzer, Matthew P; Weiss, Mitchell J; Wilber, Andrew; Persons, Derek A

    2015-01-01

    Patients with severe sickle cell disease (SCD) are candidates for gene therapy using autologous hematopoietic stem cells (HSCs), but concomitant multi-organ disease may contraindicate pretransplant conditioning with full myeloablation. We tested whether nonmyeloablative conditioning, a regimen used successfully for allogeneic bone marrow transplantation of adult SCD patients, allows engraftment of γ-globin gene-corrected cells to a therapeutic level in the Berkeley mouse model of SCD. Animals transplanted according to this regimen averaged 35% engraftment of transduced hematopoietic stem cells with an average vector copy < 2.0. Fetal hemoglobin (HbF) levels ranged from 20 to 44% of total hemoglobin and approximately two-thirds of circulating red blood cells expressed HbF detected by immunofluorescence (F-cells). Gene therapy treatment of SCD mice ameliorated anemia, reduced hyperleukocytosis, improved renal function, and reduced iron accumulation in liver, spleen, and kidneys. Thus, modest levels of chimerism with donor cells expressing high levels of HbF from an insulated γ-globin lentiviral vector can improve the pathology of SCD in mice, thereby illustrating a potentially safe and effective strategy for gene therapy in humans. PMID:26665131

  12. Effect of substrate stiffness on the osteogenic differentiation of bone marrow stem cells and bone-derived cells.

    PubMed

    Witkowska-Zimny, Malgorzata; Walenko, Katarzyna; Wrobel, Edyta; Mrowka, Piotr; Mikulska, Agnieszka; Przybylski, Jacek

    2013-06-01

    There is a profound dependence of cell behaviour on the stiffness of its microenvironment. To gain a better understanding of the regulation of cellular differentiation by mechanical cues, we investigated the influence of matrix stiffness (E = 1.46 kPa and E = 26.12 kPa) on differentiated osteogenic cell lineage of bone marrow stem cells (BM-MSCs) and bone-derived cells (BDCs) using flexible collagen-coated polyacrylamide substrates. Differentiation potential was determined by measuring alkaline phosphatase activity, expression of osteoblast-specific markers including alkaline phosphatase, osteocalcin, Runx2 and collagen type I, as well as assessment of mineralisation (Alizarin Red S staining). We found that osteogenic differentiation can be regulated by the rigidity of the substrate, which may depend on the commitment in multi- or uni-potent targeting cells. Osteogenic differentiation of BM-MSCs was enhanced on a stiff substrate compared to a soft one, whereas BDCs osteogenic differentiation did not vary depending on the substrate stiffness. The data help in understanding the role of the external mechanical determinants in stem cell differentiation, and can also be useful in translational approach in functional tissue engineering.

  13. Amelioration of murine sickle cell disease by nonablative conditioning and γ-globin gene-corrected bone marrow cells

    PubMed Central

    Pestina, Tamara I; Hargrove, Phillip W; Zhao, Huifen; Mead, Paul E; Smeltzer, Matthew P; Weiss, Mitchell J; Wilber, Andrew; Persons, Derek A

    2015-01-01

    Patients with severe sickle cell disease (SCD) are candidates for gene therapy using autologous hematopoietic stem cells (HSCs), but concomitant multi-organ disease may contraindicate pretransplant conditioning with full myeloablation. We tested whether nonmyeloablative conditioning, a regimen used successfully for allogeneic bone marrow transplantation of adult SCD patients, allows engraftment of γ-globin gene-corrected cells to a therapeutic level in the Berkeley mouse model of SCD. Animals transplanted according to this regimen averaged 35% engraftment of transduced hematopoietic stem cells with an average vector copy < 2.0. Fetal hemoglobin (HbF) levels ranged from 20 to 44% of total hemoglobin and approximately two-thirds of circulating red blood cells expressed HbF detected by immunofluorescence (F-cells). Gene therapy treatment of SCD mice ameliorated anemia, reduced hyperleukocytosis, improved renal function, and reduced iron accumulation in liver, spleen, and kidneys. Thus, modest levels of chimerism with donor cells expressing high levels of HbF from an insulated γ-globin lentiviral vector can improve the pathology of SCD in mice, thereby illustrating a potentially safe and effective strategy for gene therapy in humans. PMID:26665131

  14. Histopathological Comparison between Bone Marrow- and Periodontium-derived Stem Cells for Bone Regeneration in Rabbit Calvaria

    PubMed Central

    Kadkhoda, Z.; Safarpour, A.; Azmoodeh, F.; Adibi, S.; Khoshzaban, A.; Bahrami, N.

    2016-01-01

    Background: Periodontitis is an important oral disease. Stem cell therapy has found its way in treatment of many diseases. Objective: To evaluate the regenerative potential of periodontal ligament-derived stem cells (PDLSCs) and osteoblast differentiated from PDLSC in comparison with bone marrow-derived mesenchymal stem cells (BM-MSCs) and pre-osteoblasts in calvarial defects. Methods: After proving the existence of surface markers by flow cytometry, BM-MSCs were differentiated into osteoblasts. 5 defects were made on rabbit calvaria. 3 of them were first covered with collagen membrane and then with BM-MSCs, PDLSCs, and pre-osteoblasts. The 4th defect was filled with collagen membrane and the 5th one was served as control. After 4 weeks, histological (quantitative) and histomorphological (qualitative) surveys were performed. Results: Both cell lineages were positive for CD-90 cell marker, which was specifically related to stem cells. Alizarin red staining was done for showing mineral material. RT-PCR set up for the expression of Cbfa1 gene, BMP4 gene, and PGLAP gene, confirmed osteoblast differentiation. The findings indicated that although PDLSCs and pre-osteoblasts could be used for bone regeneration, the rate of regeneration in BM-MSCs-treated cavities was more significant (p<0.0001). Conclusion: The obtained results are probably attributable to the effective micro-environmental signals caused by different bone types and the rate of cell maturation. PMID:26889369

  15. Naringin Stimulates Osteogenic Differentiation of Rat Bone Marrow Stromal Cells via Activation of the Notch Signaling Pathway

    PubMed Central

    Yu, Guo-yong; Zheng, Gui-zhou; Chang, Bo; Hu, Qin-xiao; Lin, Fei-xiang; Liu, De-zhong; Wu, Chu-cheng; Du, Shi-xin

    2016-01-01

    Naringin is a major flavonoid found in grapefruit and is an active compound extracted from the Chinese herbal medicine Rhizoma Drynariae. Naringin is a potent stimulator of osteogenic differentiation and has potential application in preventing bone loss. However, the signaling pathway underlying its osteogenic effect remains unclear. We hypothesized that the osteogenic activity of naringin involves the Notch signaling pathway. Rat bone marrow stromal cells (BMSCs) were cultured in osteogenic medium containing-naringin, with or without DAPT (an inhibitor of Notch signaling), the effects on ALP activity, calcium deposits, osteogenic genes (ALP, BSP, and cbfa1), adipogenic maker gene PPARγ2 levels, and Notch expression were examined. We found that naringin dose-dependently increased ALP activity and Alizarin red S staining, and treatment at the optimal concentration (50 μg/mL) increased mRNA levels of osteogenic genes and Notch1 expression, while decreasing PPARγ2 mRNA levels. Furthermore, treatment with DAPT partly reversed effects of naringin on BMSCs, as judged by decreases in naringin-induced ALP activity, calcium deposits, and osteogenic genes expression, as well as upregulation of PPARγ2 mRNA levels. These results suggest that the osteogenic effect of naringin partly involves the Notch signaling pathway. PMID:27069482

  16. Amelioration of murine sickle cell disease by nonablative conditioning and γ-globin gene-corrected bone marrow cells.

    PubMed

    Pestina, Tamara I; Hargrove, Phillip W; Zhao, Huifen; Mead, Paul E; Smeltzer, Matthew P; Weiss, Mitchell J; Wilber, Andrew; Persons, Derek A

    2015-01-01

    Patients with severe sickle cell disease (SCD) are candidates for gene therapy using autologous hematopoietic stem cells (HSCs), but concomitant multi-organ disease may contraindicate pretransplant conditioning with full myeloablation. We tested whether nonmyeloablative conditioning, a regimen used successfully for allogeneic bone marrow transplantation of adult SCD patients, allows engraftment of γ-globin gene-corrected cells to a therapeutic level in the Berkeley mouse model of SCD. Animals transplanted according to this regimen averaged 35% engraftment of transduced hematopoietic stem cells with an average vector copy < 2.0. Fetal hemoglobin (HbF) levels ranged from 20 to 44% of total hemoglobin and approximately two-thirds of circulating red blood cells expressed HbF detected by immunofluorescence (F-cells). Gene therapy treatment of SCD mice ameliorated anemia, reduced hyperleukocytosis, improved renal function, and reduced iron accumulation in liver, spleen, and kidneys. Thus, modest levels of chimerism with donor cells expressing high levels of HbF from an insulated γ-globin lentiviral vector can improve the pathology of SCD in mice, thereby illustrating a potentially safe and effective strategy for gene therapy in humans.

  17. Human tonsil-derived mesenchymal stromal cells enhanced myelopoiesis in a mouse model of allogeneic bone marrow transplantation

    PubMed Central

    Ryu, Jung-Hwa; Park, Minhwa; Kim, Bo-Kyung; Kim, Yu-Hee; Woo, So-Youn; Ryu, Kyung-Ha

    2016-01-01

    Mesenchymal stromal cells (MSCs) have therapeutic potential for repairing tissue damage and are involved in immune regulation. MSCs are predominantly isolated from bone marrow (BM), adipose tissue or placental tissue. Further to these well-known sources, the isolation of MSCs from human tonsils was previously reported. The aim of the present study was to investigate a potential role for tonsil-derived MSCs (T-MSCs) in BM reconstitution and application towards supplementing hematopoiesis in a mouse model of BM transplantation (BMT). Eight-week-old BALB/c female mice received 80 mg/kg busulfan (Bu)/200 mg/kg cyclophosphamide (Cy) conditioning chemotherapy for BM ablation. Subsequently, human T-MSCs were injected into the Bu/Cy-treated mice with or without BM cells (BMCs) obtained from allogeneic C57BL/6 male mice. After 3 weeks, peripheral blood and BM was collected for analysis. The red blood cell count in the group that received BMCs had almost returned to normal, whereas mononuclear cell counts and BM cellularity were most improved in the T-MSCs + BMCs group. These results indicate that the T-MSCs enhanced myelopoiesis in the allogeneic BMT mouse model, as evidenced by the restoration of BM with hematopoietic cells, as well as increased myeloid colony formation in vitro. Therefore, T-MSCs may provide a source of MSCs to facilitate myelopoiesis and megakaryocytosis following BMT. PMID:27511380

  18. The effect of a red leaf pigment on the relationship between red edge and chlorophyll concentration

    NASA Technical Reports Server (NTRS)

    Curran, Paul J.; Dungan, Jennifer L.; Macler, Bruce A.; Plummer, Stephen E.

    1991-01-01

    The effect of a leaf pigment - red amaranthin - on red edge and chlorophyll concentration is investigated in amaranth leaves by means of treatments with nitrate and salts. A near-linear relationship between red edge and chlorophyll concentration is observed for leaves with low amaranthin concentration, and no relationship is noted at high concentrations. The study demonstrates the limitation inherent in estimating chlorophyll concentration by using remotely sensed red edge.

  19. Asteroseismology of Red Giant stars

    NASA Astrophysics Data System (ADS)

    Tarrant, N. J.; Chaplin, W. J.; Elsworth, Y. P.; Spreckley, S. A.; Stevens, I. R.

    2008-12-01

    Sun-like oscillations, that is p-modes excited stochastically by convective noise, have now been observed in a number of Red Giant stars. Compared to those seen in the Sun, these modes are of large amplitude and long period, making the oscillations attractive prospects for observation. However, the low Q-factor of these modes, and issues relating to the rising background at low frequencies, present some interesting challenges for identifying modes and determining the related asteroseismic parameters. We report on the analysis procedure adopted for peak-bagging by our group at Birming- ham, and the techniques used to robustly ensure these are not a product of noise. I also show results from a number of giants extracted from multi-year observations with the SMEI instrument

  20. Voyager 1 Red Spot Movie

    NASA Technical Reports Server (NTRS)

    2000-01-01

    This movie shows the portion of Jupiter around the Great Red Spot as it swirls through more than 60 Jupiter days. Notice the difference in speed and direction of the various zones of the atmosphere. The interaction of the atmospheric clouds and storm shows how dynamic the Jovian atmosphere is.

    As Voyager 1 approached Jupiter in 1979, it took images of the planet at regular intervals. This sequence is made from 66 images taken once every Jupiter rotation period (about 10 hours). This time-lapse movie uses images taken every time Jupiter longitude 68W passed under the spacecraft. These images were acquired in the Blue filter from Jan. 6 to Feb. 3 1979. The spacecraft flew from 58 million kilometers to 31 million kilometers from Jupiter during that time.

    This time-lapse movie was produced at JPL by the Image Processing Laboratory in 1979.

  1. Demonstration project cuts red tape

    NASA Astrophysics Data System (ADS)

    Katzoff, Judith A.

    Results from a demonstration project aimed at cutting red tape in federal grants for basic research at universities are "very encouraging" so far, according to Don I. Phillips, executive director of the Government-University-Industry Research Roundtable. The roundtable is coordinating the experimental effort, with the participation of five major federal agencies as well as the Florida state university system and the University of Miami (a private institution in Coral Gables, Fla.).Under the project, special conditions apply to grants from the participating agencies to individual researchers at the participating universities: Investigators do not have to ask the agency's permission for changes in budget allocations, purchases of permanent equipment, or foreign travel. Grant money can be spent up to a year after the grant ends without a special request. Under this plan, researchers, with agency approval, can also ask to have their entire research program covered as a single administrative entity, rather than as several individual projects.

  2. Chemical toxicity of red cells.

    PubMed Central

    Piomelli, S

    1981-01-01

    Exposure to toxic chemicals may result in alterations of red cell function. In certain cases, the toxic effect requires a genetic predisposition and thus affects only a restricted number of individuals; in other instances, the toxic effect is exerted on the hematopoietic system of every person. Glucose-6-phosphate dehydrogenase deficiency is probably the most widespread genetic disorder. It is observed at highest frequency in populations from subtropical countries as a result of its selective advantage vis à vis falciparum malaria. The gene controlling this enzyme is located on the X-chromosome; thus, the defect is sex-linked. Individuals with a genetic defect of this enzyme are extremely susceptible to hemolysis, when exposed to oxidant drugs (such as certain antimalarials and sulfonamides) because of the inability of their red cells to regenerate NADPH. Lead poisoning result in profound effects on the process of heme synthesis. Among the steps most sensitive to lead toxicity are the enzyme delta-aminolevulinic acid dehydratase and the intramitochondrial step that leads to the incorporation of iron into protoporphyrin. By these mechanisms, in severe lead intoxication there is an accumulation of large amounts of delta-aminolevulinic acid (a compound with inherent neurotoxicity), and there are abnormalities of mitochondrial function in all cells of the body. Individuals living in an industrialized society are unavoidably exposed to some environmental lead. Recent evidence indicates that, even at levels of exposure which do not increase the blood lead level above values presently considered normal, abnormalities of heme synthesis are clearly detectable. PMID:7016524

  3. Bone marrow fat: linking adipocyte-induced inflammation with skeletal metastases

    PubMed Central

    Hardaway, Aimalie L.; Herroon, Mackenzie K.; Rajagurubandara, Erandi

    2014-01-01

    Adipocytes are important but underappreciated components of bone marrow microenvironment, and their numbers greatly increase with age, obesity, and associated metabolic pathologies. Age and obesity are also significant risk factors for development of metastatic prostate cancer. Adipocytes are metabolically active cells that secrete adipokines, growth factors, and inflammatory mediators; influence behavior and function of neighboring cells; and have a potential to disturb local milleu and dysregulate normal bone homeostasis. Increased marrow adiposity has been linked to bone marrow inflammation and osteoporosis of the bone, but its effects on growth and progression of prostate tumors that have metastasized to the skeleton are currently not known. This review focuses on fat-bone relationship in a context of normal bone homeostasis and metastatic tumor growth in bone. We discuss effects of marrow fat cells on bone metabolism, hematopoiesis, and inflammation. Special attention is given to CCL2- and COX-2-driven pathways and their potential as therapeutic targets for bone metastatic disease. PMID:24398857

  4. Osteogenetic activity in composite grafts of demineralized compact bone and marrow

    SciTech Connect

    Wittbjer, J.; Palmer, B.; Rohlin, M.; Thorngren, K.G.

    1983-03-01

    The effects of a composite graft of autologous marrow and demineralized autologous compact bone on the healing of a surgically created bone defect were observed in adult rabbits. A segment of the radius was bilaterally resected, demineralized, and replaced. On one side the bone graft was supplemented with autologous marrow. The new bone formation was measured 14 and 28 days after operation by roentgenography, including planimetry with scintigraphy and autoradiography using /sup 99m/Tc-labelled MDP. The composite graft, i.e., demineralized compact bone and marrow, had a significantly higher (p less than 0.01) bone formation rate 14 days after operation compared with the graft with demineralized compact bone in the opposite radius. At 28 days, however, there were no differences between the sides. Viable autologous marrow cells and demineralized autologous compact bone graft accelerate the rate of osteogenesis, but only at the beginning of the healing process.

  5. Specific allogeneic unresponsiveness in irradiated dogs reconstituted with autologous bone marrow. [/sup 60/Co

    SciTech Connect

    Rapaport, F.T.; Bachvaroff, R.J.; Akiyama, N.; Sato, T.; Ferrebee, J.W.

    1980-07-01

    Hemopoietic reconstitution of supralethally irradiated adult dogs of the Cooperstown colony with their own stored bone marrow can produce long-term unresponsiveness to DLA-identical kidney allografts with no need for any additional immunosuppression. Eleven of 18 kidneys transplanted 12 h after replacement of autologous marrow into irradiated recipients currently survive with normal function for as long as 1417 d; 8 of 13 organs transplanted 28 h after marrow replacement, and 8 of 13 organs transplanted 36 h after marrow injection, currently survive up to 502 d, with no further treatment. Alterations in the timing and sequence of each procedure decrease the incidence of unresponsiveness. Survival and function of the kidney allografts were not affected by the rejection of successive skin grafts from the kidney donor. Skin grafts from other DLA-identical donors and DLA-incompatible skin grafts were rejected by the same recipients in uniform fashion.

  6. Bone marrow fat: linking adipocyte-induced inflammation with skeletal metastases.

    PubMed

    Hardaway, Aimalie L; Herroon, Mackenzie K; Rajagurubandara, Erandi; Podgorski, Izabela

    2014-09-01

    Adipocytes are important but underappreciated components of bone marrow microenvironment, and their numbers greatly increase with age, obesity, and associated metabolic pathologies. Age and obesity are also significant risk factors for development of metastatic prostate cancer. Adipocytes are metabolically active cells that secrete adipokines, growth factors, and inflammatory mediators; influence behavior and function of neighboring cells; and have a potential to disturb local milleu and dysregulate normal bone homeostasis. Increased marrow adiposity has been linked to bone marrow inflammation and osteoporosis of the bone, but its effects on growth and progression of prostate tumors that have metastasized to the skeleton are currently not known. This review focuses on fat-bone relationship in a context of normal bone homeostasis and metastatic tumor growth in bone. We discuss effects of marrow fat cells on bone metabolism, hematopoiesis, and inflammation. Special attention is given to CCL2- and COX-2-driven pathways and their potential as therapeutic targets for bone metastatic disease.

  7. Stem Cell Transplant (Peripheral Blood, Bone Marrow, and Cord Blood Transplants)

    MedlinePlus

    ... donor cells may be harvested (removed) in an operating room, and then processed in the lab right ... called bone marrow harvest . It’s done in an operating room, while the donor is under general anesthesia ( ...

  8. Marrow granulomas in coal workers' pneumoconiosis. A histologic study with elemental analysis

    SciTech Connect

    Pelstring, R.J.; Kim, C.K.; Lower, E.E.; Swerdlow, S.H.

    1988-04-01

    The differential diagnosis of bone marrow granulomas is lengthy but has not previously included coal workers' pneumoconiosis. This report describes the first case in which noncaseating epithelioid granulomas containing anthracotic pigment and birefringent silica containing crystals were discovered in the marrow of a patient with progressive massive fibrosis of coal workers' pneumoconiosis. The silicotic nature of the crystals was confirmed using energy dispersive x-ray microanalysis. There was no evidence of a mycobacterial, fungal, or other etiology for the granulomas. This case demonstrates that coal workers' pneumoconiosis should be added to the differential diagnosis of bone marrow granulomas and that marrow examination may be a source of tissue for documentation of specific occupational exposures.

  9. Selection of patients with Hodgkin's disease and non-Hodgkin's lymphoma for bone marrow transplantation.

    PubMed

    Sullivan, K M; Appelbaum, F R; Horning, S J; Rosenberg, S A; Thomas, E D

    1986-01-01

    Despite substantial progress in curative therapy of malignant lymphomas, some patients fail current treatment and die of refractory disease. Although Although high-dose chemotherapy and supralethal total body irradiation followed by bone marrow transplantation may salvage and cure a proportion of these refractory patients, treatment of such end-stage patients with marrow grafting often fails because of resistant disease or transplant-related complications. Using the analogy of transplantation in the early phases of acute and chronic leukemias, results of marrow transplant in Hodgkin's disease and non-Hodgkin's lymphoma might be improved if performed earlier in the course of the malignancy. The following collaborative report by the Seattle and Stanford groups examines current results of conventional lymphoma therapy to define subgroups of patients with "high-risk" lymphoma for whom early marrow transplant might be offered to control otherwise incurable disease. PMID:3528333

  10. Rectal cancer with disseminated carcinomatosis of the bone marrow: report of a case.

    PubMed

    Nakashima, Yuichiro; Takeishi, Kazuki; Guntani, Atsushi; Tsujita, Eiji; Yoshinaga, Keiji; Matsuyama, Ayumi; Hamatake, Motoharu; Maeda, Takashi; Tsutsui, Shinichi; Matsuda, Hiroyuki; Fujihara, Megumu; Ishida, Teruyoshi

    2014-01-01

    We report a rare case of disseminated carcinomatosis of the bone marrow from rectal cancer with disseminated intravascular coagulation (DIC). A 65-year-old man was admitted with melena and low back pain at rest. X-ray examination showed rectal cancer with multiple bone metastases. Laboratory examination showed severe anemia and DIC. Histologic examination showed disseminated carcinomatosis of the bone marrow. The DIC was considered to be caused by disseminated carcinomatosis of the bone marrow from rectal cancer, and we immediately started treatment with anti-DIC therapy and anticancer chemotherapy with the modified FOLFOX6 regimen (mFOLFOX6). After some response to therapy, the patient's general condition deteriorated, and he died 128 days after admission. This is the first English report showing disseminated carcinomatosis of the bone marrow from colorectal cancer treated with mFOLFOX6.

  11. Allogeneic bone marrow transplantation for postpolycythemic myeloid metaplasia with myelofibrosis: a case report.

    PubMed

    de Revel, T; Giraudier, S; Nedellec, G; Joussemet, M; Bourin, P; Schill, H; Gaillard, J F; Auzanneau, G

    1995-07-01

    Myeloid metaplasia with myelofibrosis develops in about 10% of patients with polycythemia vera. We report a case of a 48-year-old female with postpolycythemic myelofibrosis successfully treated with allogeneic HLA-matched bone marrow transplantation.

  12. In-vitro circadian rhythm of murine bone marrow progenitor production.

    PubMed

    Bourin, Philippe; Ledain, Arnaud F; Beau, Jacques; Mille, Dominique; Lévi, Francis

    2002-01-01

    Hematopoietic processes display 24h rhythms both in rodents and in human beings. We hypothesized these rhythms to be in part generated by a circadian oscillator within the bone marrow. The ability of murine bone marrow granulo-monocytic (GM) precursors to form colonies following colony-stimulating factor (rm GM-CSF) exposure was investigated in liquid culture samples obtained every 3 h for a span of up to 198 h. The CFU-GM count varied rhythmically over the first 4 d of culture, with a reproducible maximum in the early morning hours, similar to that observed in vivo. These experiments provide the first evidence that bone marrow progenitors sustain in vitro circadian rhythmicity, and they demonstrate the presence of a circadian time-keeping system within these cells. The results support the potential usefulness of bone marrow cultures for investigating chronopharmacologic effects of anticancer drugs and cytokines on this target system.

  13. The secret life of a megakaryocyte: emerging roles in bone marrow homeostasis control

    PubMed Central

    Malara, Alessandro; Abbonante, Vittorio; Buduo, Christian A. Di; Tozzi, Lorenzo; Currao, Manuela; Balduini, Alessandra

    2015-01-01

    SUMMARY Megakaryocytes are rare cells found in the bone marrow, responsible for the everyday production and release of millions of platelets into the bloodstream. Since the discovery and cloning, in 1994, of their principal humoral factor, thrombopoietin, and its receptor c-Mpl, many efforts have been directed to define the mechanisms underlying an efficient platelet production. However, more recently different studies have pointed out new roles for megakaryocytes as regulators of bone marrow homeostasis and physiology. In this review we discuss the interaction and the reciprocal regulation of megakaryocytes with the different cellular and extracellular components of the bone marrow environment. Finally, we provide evidence that these processes may concur to the reconstitution of the bone marrow environment after injury and their deregulation may lead to the development of a series of inherited or acquired pathologies. PMID:25572292

  14. Glycol methacrylate embedding for light microscopy. I. enzyme histochemistry on semithin sections of undecalcified marrow cores.

    PubMed

    Islam, A; Henderson, E S

    1987-10-01

    A simple, routine procedure for water miscible glycol methacrylate (GMA) embedding of undecalcified bone marrow cores, which preserves the activity of enzymes useful in diagnosing various haematopoietic disorders, is described. The GMA used in this study has a low acid content that eliminates background staining, and the modified May-Grünwald-Giemsa stain provides good definition and excellent colour differentiation of various haematopoietic cells in the bone marrow, thereby providing optimal conditions for the study of the morphology and enzyme activity of bone marrow cells in the same preparation. The method is simple, reproducible, requires no expensive equipment, and is suitable for routine processing of small bone marrow cores in any histopathology or haematology laboratory.

  15. Bone marrow is a major site of long-term antibody production after acute viral infection.

    PubMed Central

    Slifka, M K; Matloubian, M; Ahmed, R

    1995-01-01

    Antiviral antibody production is often sustained for long periods after resolution of an acute viral infection. Despite extensive documentation of this phenomenon, the mechanisms involved in maintaining long-term antibody production remain poorly defined. As a first step towards understanding the nature of long-term humoral immunity, we examined the anatomical location of antibody-producing cells during acute viral infection. Using the lymphocytic choriomeningitis virus (LCMV) model, we found that after resolution of the acute infection, when antiviral plasma cells in the spleen decline, a population of virus-specific plasma cells appears in the bone marrow and constitutes the major source of long-term antibody production. Following infection of adult mice, LCMV-specific antibody-secreting cells (ASC) peaked in the spleen at 8 days postinfection but were undetectable in the bone marrow at that time. The infection was essentially cleared by 15 days, and the ASC numbers in the spleen rapidly declined while an increasing population of LCMV-specific ASC began to appear in the bone marrow. Compared with the peak response at 8 days postinfection, time points from 30 days to more than 1 year later demonstrated greater-than-10-fold reductions in splenic ASC. In contrast, LCMV-specific plasma cell numbers in the bone marrow remained high and correlated with the high levels of antiviral serum antibody. The presence of LCMV-specific plasma cells in the bone marrow was not due to persistent infection at this site, since the virus was cleared from both the spleen and bone marrow with similar kinetics as determined by infectivity and PCR assays. The immunoglobulin G subclass profile of antibody-secreting cells derived from bone marrow and the spleen correlated with the immunoglobulin G subclass distribution of LCMV-specific antibody in the serum. Upon rechallenge with LCMV, the spleen exhibited a substantial increase in virus-specific plasma cell numbers during the early phase

  16. Total marrow irradiation using Helical TomoTherapy

    NASA Astrophysics Data System (ADS)

    Garcia-Fernandez, Lourdes Maria

    Clinical dose response data of human tumours are limited or restricted to a radiation dose range determined by the level of toxicity to the normal tissues. This is the case for the most common disseminated plasma cell neoplasm, multiple myeloma, where the maximum dose deliverable to the entire bony skeleton using a standard total body irradiation (TBI) technique is limited to about 12 Gy. This study is part of scientific background of a phase I/II dose escalation clinical trial for multiple myeloma using image-guided intensity modulated radiotherapy (IG-IMRT) to deliver high dose to the entire volume of bone marrow with Helical TomoTherapy (HT). This relatively new technology can deliver highly conformal dose distributions to complex target shapes while reducing the dose to critical normal tissues. In this study tools for comparing and predicting the effectiveness of different approaches to total marrow irradiation (TMI) using HT were provided. The expected dose response for plasma cell neoplasms was computed and a radiobiological evaluation of different treatment cohorts in a dose escalating study was performed. Normal tissue complication probability (NTCP) and tumour control probability (TCP) models were applied to an actual TMI treatment plan for a patient and the implications of using different longitudinal field widths were assessed. The optimum dose was ˜39 Gy for which a predicted tumour control of 95% (+/-3%) was obtained, with a predicted 3% (0, 8%) occurrence of radiation pneumonitis. Tissue sparing was seen by using smaller field widths only in the organs of the head. This suggests it would be beneficial to use the small fields in the head only since using small fields for the whole treatment would lead to long treatment times. In TMI it may be necessary to junction two longitudinally adjacent treatment volumes to form a contiguous planning target volume PTV. For instance, this is the case when a different SUP-INF spatial resolution is required or when

  17. Primary cilia expression in bone marrow in response to mechanical stimulation in explant bioreactor culture.

    PubMed

    Coughlin, T R; Schiavi, J; Alyssa Varsanik, M; Voisin, M; Birmingham, E; Haugh, M G; McNamara, L M; Niebur, G L

    2016-01-01

    Bone marrow contains a multitude of mechanically sensitive cells that may participate in mechanotransduction. Primary cilia are sensory organelles expressed on mesenchymal stem cells (MSCs), osteoblasts, osteocytes, and other cell types that sense fluid flow in monolayer culture. In marrow, cilia could similarly facilitate the sensation of relative motion between adjacent cells or interstitial fluid. The goal of this study was to determine the response of cilia to mechanical stimulation of the marrow. Bioreactors were used to supply trabecular bone explants with low magnitude mechanical stimulation (LMMS) of 0.3 ×g at 30 Hz for 1 h/d, 5 d/week, inducing shear stresses in the marrow. Four groups were studied: unstimulated (UNSTIM), stimulated (LMMS), and with and without chloral hydrate (UNSTIM+CH and LMMS+CH, respectively), which was used to disrupt cilia. After 19 days of culture, immunohistochemistry for acetylated α-tubulin revealed that more cells expressed cilia in culture compared to in vivo controls. Stimulation decreased the number of cells expressing cilia in untreated explants, but not in CH-treated explants. MSCs represented a greater fraction of marrow cells in the untreated explants than CH-treated explants. MSCs harvested from the stimulated groups were more proliferative than in the unstimulated explants, but this effect was absent from CH treated explants. In contrast to the marrow, neither LMMS nor CH treatment affected bone formation as measured by mineralising surface. Computational models indicated that LMMS does not induce bone strain, and the reported effects were thus attributed to shear stress in the marrow. From a clinical perspective, genetic or pharmaceutical alterations of cilia expression may affect marrow health and function. PMID:27434268

  18. A blinded study of bone marrow examinations in patients with primary immune thrombocytopenia

    PubMed Central

    Mahabir, Vishwanath K.; Ross, Catherine; Popovic, Snezana; Sur, Mona Lisa; Bourgeois, Jacqueline; Lim, Wendy; George, James N.; Wang, Grace; Cook, Richard J.; Toltl, Lisa J.; Nazi, Ishac; Kelton, John G.; Arnold, Donald M.

    2014-01-01

    Objective The role of bone marrow examinations in patients with primary immune thrombocytopenia (ITP) is uncertain. The objectives of this study were to determine the inter-rater reliability of bone marrow examinations and to identify distinguishing morphological features of ITP bone marrows under controlled conditions. Methods Histological slides of bone marrow biopsy specimens and aspirates from 32 adult patients with severe primary ITP who had failed a median of two treatments, and 51 non-thrombocytopenic controls were retrieved from hospital archives. Slides were arranged in random order in a slide box and coded. Blinded to the diagnosis and platelet counts, three independent hematopathologists were asked to identify the ITP bone marrows and to evaluate megakaryocyte number, morphology, and distribution. Results Overall chance-corrected agreement on ITP classification among the three raters was poor [kappa (κ) = 0.30; 95% confidence interval 0.22–0.38]. Raters were generally unable to correctly identify the ITP bone marrows from controls. Increased number of megakaryocytes, while an uncommon finding, was more frequent among ITP patients compared with controls (6/32, 18.8%; vs. 2/51, 3.9%; P = 0.05), and abnormal megakaryocyte morphology often led individual raters to reach a diagnosis of ITP. Overall sensitivity and specificity of bone marrow examinations were 24% and 90%, respectively. Conclusions This study confirms methodologically that bone marrow examinations are unreliable and frequently non-diagnostic in ITP. Thus, they are not useful for patients with typical disease. Rare subsets of patients with severe ITP demonstrated unique features such as increased number of megakaryocytes. PMID:23140198

  19. 33 CFR 117.135 - Red River.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Red River. 117.135 Section 117.135 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Arkansas § 117.135 Red River. The draws of the bridges...

  20. 33 CFR 117.135 - Red River.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Red River. 117.135 Section 117.135 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Arkansas § 117.135 Red River. The draws of the bridges...